ID   TPA_HUMAN               Reviewed;         562 AA.
AC   P00750; A8K022; B2R8E8; Q15103; Q503B0; Q6PJA5; Q7Z7N2; Q86YK8;
AC   Q9BU99; Q9BZW1;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   05-OCT-2010, entry version 160.
DE   RecName: Full=Tissue-type plasminogen activator;
DE            Short=t-PA;
DE            Short=t-plasminogen activator;
DE            Short=tPA;
DE            EC=3.4.21.68;
DE   AltName: INN=Alteplase;
DE   AltName: INN=Reteplase;
DE   Contains:
DE     RecName: Full=Tissue-type plasminogen activator chain A;
DE   Contains:
DE     RecName: Full=Tissue-type plasminogen activator chain B;
DE   Flags: Precursor;
GN   Name=PLAT;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Melanoma;
RX   MEDLINE=83115262; PubMed=6337343; DOI=10.1038/301214a0;
RA   Pennica D., Holmes W.E., Kohr W.J., Harkins R.N., Vehar G.A.,
RA   Ward C.A., Bennett W.F., Yelverton E., Seeburg P.H., Heyneker H.L.,
RA   Goeddel D.V., Collen D.;
RT   "Cloning and expression of human tissue-type plasminogen activator
RT   cDNA in E. coli.";
RL   Nature 301:214-221(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=84298137; PubMed=6089198; DOI=10.1073/pnas.81.17.5355;
RA   Ny T., Elgh F., Lund B.;
RT   "The structure of the human tissue-type plasminogen activator gene:
RT   correlation of intron and exon structures to functional and structural
RT   domains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 81:5355-5359(1984).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=86196143; PubMed=3009482;
RA   Friezner Degen S.J., Rajput B., Reich E.;
RT   "The human tissue plasminogen activator gene.";
RL   J. Biol. Chem. 261:6972-6985(1986).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   MEDLINE=86284200; PubMed=3090401;
RA   Harris T.J., Patel T., Marston F.A., Little S., Emtage J.S.,
RA   Opdenakker G., Volckaert G., Rombauts W., Billiau A., Somer P.;
RT   "Cloning of cDNA coding for human tissue-type plasminogen activator
RT   and its expression in Escherichia coli.";
RL   Mol. Biol. Med. 3:279-292(1986).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   MEDLINE=88054470; PubMed=2824147;
RA   Reddy V.B., Garramone A.J., Sasak H., Wei C.-M., Watkins P., Galli J.,
RA   Hsiung N.;
RT   "Expression of human uterine tissue-type plasminogen activator in
RT   mouse cells using BPV vectors.";
RL   DNA 6:461-472(1987).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Fetal lung;
RX   MEDLINE=88262579; PubMed=3133640; DOI=10.1093/nar/16.12.5695;
RA   Sasaki H., Saito Y., Hayashi M., Otsuka K., Niwa M.;
RT   "Nucleotide sequence of the tissue-type plasminogen activator cDNA
RT   from human fetal lung cells.";
RL   Nucleic Acids Res. 16:5695-5695(1988).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Umbilical vein;
RX   MEDLINE=90192129; PubMed=2107528; DOI=10.1093/nar/18.4.1086;
RA   Siebert P.D., Fong K.;
RT   "Variant tissue-type plasminogen activator (PLAT) cDNA obtained from
RT   human endothelial cells.";
RL   Nucleic Acids Res. 18:1086-1086(1990).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA   Dou D.;
RT   "A brain-type plasminogen activator.";
RL   Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Liu Y., Xu L., Zeng Y., He X.;
RT   "cDNA of tissue plasminogen activator.";
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Testis;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [12]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-34; SER-136;
RP   THR-146 AND TRP-164.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [13]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [14]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Brain, Placenta, and Skin;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [15]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36.
RX   MEDLINE=85289338; PubMed=3161893;
RA   Fisher R., Waller E.K., Grossi G., Thompson D., Tizard R.,
RA   Schleuning W.-D.;
RT   "Isolation and characterization of the human tissue-type plasminogen
RT   activator structural gene including its 5' flanking region.";
RL   J. Biol. Chem. 260:11223-11230(1985).
RN   [16]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 31-562.
RX   MEDLINE=91291340; PubMed=1368681;
RA   Itagaki Y., Yasuda H., Morinaga T., Mitsuda S., Higashio K.;
RT   "Purification and characterization of tissue plasminogen activator
RT   secreted by human embryonic lung diploid fibroblasts, IMR-90 cells.";
RL   Agric. Biol. Chem. 55:1225-1232(1991).
RN   [17]
RP   PROTEIN SEQUENCE OF 33-52 AND 311-330.
RC   TISSUE=Melanoma;
RX   MEDLINE=83209620; PubMed=6682760;
RX   DOI=10.1111/j.1432-1033.1983.tb07418.x;
RA   Wallen P., Pohl G., Bergsdorf N., Raanby M., Ny T., Joernvall H.;
RT   "Purification and characterization of a melanoma cell plasminogen
RT   activator.";
RL   Eur. J. Biochem. 132:681-686(1983).
RN   [18]
RP   PROTEIN SEQUENCE OF 36-562.
RC   TISSUE=Melanoma;
RX   MEDLINE=85000468; PubMed=6433976; DOI=10.1021/bi00311a020;
RA   Pohl G., Kaellstroem M., Bergsdorf N., Wallen P., Joernvall H.;
RT   "Tissue plasminogen activator: peptide analyses confirm an indirectly
RT   derived amino acid sequence, identify the active site serine residue,
RT   establish glycosylation sites, and localize variant differences.";
RL   Biochemistry 23:3701-3707(1984).
RN   [19]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 251-358.
RX   MEDLINE=83169656; PubMed=6572897; DOI=10.1073/pnas.80.2.349;
RA   Edlund T., Ny T., Raanby M., Heden L.-O., Palm G., Holmgren E.,
RA   Josephson S.;
RT   "Isolation of cDNA sequences coding for a part of human tissue
RT   plasminogen activator.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:349-352(1983).
RN   [20]
RP   PARTIAL PROTEIN SEQUENCE, AND SIGNAL SEQUENCE CLEAVAGE SITE.
RA   Jalah R., Pavlakis G.N., Felber B.J.;
RL   Submitted (JUL-2007) to UniProtKB.
RN   [21]
RP   STRUCTURE OF CARBOHYDRATES.
RX   MEDLINE=90092112; PubMed=2513186;
RX   DOI=10.1111/j.1432-1033.1989.tb15206.x;
RA   Pfeiffer G., Schmidt M., Strube K.-H., Geyer R.;
RT   "Carbohydrate structure of recombinant human uterine tissue
RT   plasminogen activator expressed in mouse epithelial cells.";
RL   Eur. J. Biochem. 186:273-286(1989).
RN   [22]
RP   GLYCOSYLATION AT THR-96.
RX   MEDLINE=91159408; PubMed=1900431; DOI=10.1021/bi00223a004;
RA   Harris R.J., Leonard C.K., Guzzetta A.W., Spellman M.W.;
RT   "Tissue plasminogen activator has an O-linked fucose attached to
RT   threonine-61 in the epidermal growth factor domain.";
RL   Biochemistry 30:2311-2314(1991).
RN   [23]
RP   DISULFIDE BONDS IN KRINGLE 2.
RX   MEDLINE=91244765; PubMed=1645336;
RA   Vlahos C.J., Wilhelm O.G., Hassell T., Jaskunas S.R., Bang N.U.;
RT   "Disulfide pairing of the recombinant kringle-2 domain of tissue
RT   plasminogen activator produced in Escherichia coli.";
RL   J. Biol. Chem. 266:10070-10072(1991).
RN   [24]
RP   INTERACTION WITH LRP1B.
RX   MEDLINE=21369943; PubMed=11384978; DOI=10.1074/jbc.M102727200;
RA   Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G.;
RT   "The putative tumor suppressor LRP1B, a novel member of the low
RT   density lipoprotein (LDL) receptor family, exhibits both overlapping
RT   and distinct properties with the LDL receptor-related protein.";
RL   J. Biol. Chem. 276:28889-28896(2001).
RN   [25]
RP   SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX   PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA   Hillman R.T., Green R.E., Brenner S.E.;
RT   "An unappreciated role for RNA surveillance.";
RL   Genome Biol. 5:R8.1-R8.16(2004).
RN   [26]
RP   STRUCTURE BY NMR OF KRINGLE 2.
RX   MEDLINE=90122799; PubMed=2558718; DOI=10.1021/bi00450a016;
RA   Byeon I.-J.L., Kelley R.F., Llinas M.;
RT   "1H NMR structural characterization of a recombinant kringle 2 domain
RT   from human tissue-type plasminogen activator.";
RL   Biochemistry 28:9350-9360(1989).
RN   [27]
RP   STRUCTURE BY NMR OF KRINGLE 2.
RX   MEDLINE=91200042; PubMed=1901789;
RX   DOI=10.1111/j.1432-1033.1991.tb15894.x;
RA   Byeon I.-J.L., Kelley R.F., Llinas M.;
RT   "Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR
RT   assignments and secondary structure.";
RL   Eur. J. Biochem. 197:155-165(1991).
RN   [28]
RP   STRUCTURE BY NMR OF KRINGLE 2.
RX   MEDLINE=92106329; PubMed=1762144; DOI=10.1016/0022-2836(91)90592-T;
RA   Byeon I.-J.L., Llinas M.;
RT   "Solution structure of the tissue-type plasminogen activator kringle 2
RT   domain complexed to 6-aminohexanoic acid an antifibrinolytic drug.";
RL   J. Mol. Biol. 222:1035-1051(1991).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2.
RX   MEDLINE=92118803; PubMed=1310033; DOI=10.1021/bi00116a037;
RA   de Vos A., Ultsch M.H., Kelley R.F., Padmanabhan K., Tulinskly A.,
RA   Westbrook M.L., Kossiakof A.A.;
RT   "Crystal structure of the kringle 2 domain of tissue plasminogen
RT   activator at 2.4-A resolution.";
RL   Biochemistry 31:270-279(1992).
RN   [30]
RP   STRUCTURE BY NMR OF 38-85.
RX   MEDLINE=92292163; PubMed=1602484; DOI=10.1016/0022-2836(92)90403-7;
RA   Downing A.K., Driscoll P.C., Harvey T.S., Dudgeon T.J., Smith B.O.,
RA   Baron M., Campbell I.D.;
RT   "Solution structure of the fibrin binding finger domain of tissue-type
RT   plasminogen activator determined by 1H nuclear magnetic resonance.";
RL   J. Mol. Biol. 225:821-833(1992).
RN   [31]
RP   STRUCTURE BY NMR OF 36-126.
RX   MEDLINE=96027104; PubMed=7582899; DOI=10.1016/S0969-2126(01)00217-9;
RA   Smith B.O., Downing A.K., Driscoll P.C., Dudgeon T.J., Campbell I.D.;
RT   "The solution structure and backbone dynamics of the fibronectin type
RT   I and epidermal growth factor-like pair of modules of tissue-type
RT   plasminogen activator.";
RL   Structure 3:823-833(1995).
RN   [32]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN.
RX   MEDLINE=96200985; PubMed=8613982; DOI=10.1006/jmbi.1996.0238;
RA   Lamba D., Bauer M., Huber R., Fischer S., Rudolph R., Kohnert U.,
RA   Bode W.;
RT   "The 2.3 A crystal structure of the catalytic domain of recombinant
RT   two-chain human tissue-type plasminogen activator.";
RL   J. Mol. Biol. 258:117-135(1996).
RN   [33]
RP   X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN.
RX   MEDLINE=97449126; PubMed=9305622; DOI=10.1093/emboj/16.16.4797;
RA   Renatus M., Engh R.A., Stubbs M.T., Huber R., Fischer S., Kohnert U.,
RA   Bode W.;
RT   "Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray
RT   crystal structure of single-chain human tPA.";
RL   EMBO J. 16:4797-4805(1997).
CC   -!- FUNCTION: Converts the abundant, but inactive, zymogen plasminogen
CC       to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By
CC       controlling plasmin-mediated proteolysis, it plays an important
CC       role in tissue remodeling and degradation, in cell migration and
CC       many other physiopathological events. Play a direct role in
CC       facilitating neuronal migration.
CC   -!- CATALYTIC ACTIVITY: Specific cleavage of Arg-|-Val bond in
CC       plasminogen to form plasmin.
CC   -!- SUBUNIT: Heterodimer of chain A and chain B held by a disulfide
CC       bond. Binds to fibrin with high affinity. This interaction leads
CC       to an increase in the catalytic efficiency of the enzyme between
CC       100-fold and 1000-fold, due to an increase in affinity for
CC       plasminogen. Similarly, binding to heparin increases the
CC       activation of plasminogen. Binds to annexin A2, cytokeratin-8,
CC       fibronectin and laminin. Binds to mannose receptor and the low-
CC       density lipoprotein receptor-related protein (LRP1); these
CC       proteins are involved in TPA clearance. Yet unidentified
CC       interactions on endothelial cells and vascular smooth muscle cells
CC       (VSMC) lead to a 100-fold stimulation of plasminogen activation.
CC       In addition, binding to VSMC reduces TPA inhibition by PAI-1 by
CC       30-fold. Binds LRP1B; binding is followed by internalization and
CC       degradation.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1; Synonyms=Long;
CC         IsoId=P00750-1; Sequence=Displayed;
CC       Name=2; Synonyms=Short;
CC         IsoId=P00750-2; Sequence=VSP_005411, VSP_005412;
CC         Note=May be produced at very low levels due to a premature stop
CC         codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC       Name=3;
CC         IsoId=P00750-3; Sequence=VSP_015957;
CC         Note=No experimental confirmation available;
CC       Name=4; Synonyms=Neonatal;
CC         IsoId=P00750-4; Sequence=VSP_028029, VSP_028030;
CC         Note=No experimental confirmation available;
CC   -!- TISSUE SPECIFICITY: Synthesized in numerous tissues (including
CC       tumors) and secreted into most extracellular body fluids, such as
CC       plasma, uterine fluid, saliva, gingival crevicular fluid, tears,
CC       seminal fluid, and milk.
CC   -!- DOMAIN: Both FN1 and one of the kringle domains are required for
CC       binding to fibrin.
CC   -!- DOMAIN: Both FN1 and EGF-like domains are important for binding to
CC       LRP1.
CC   -!- DOMAIN: The FN1 domain mediates binding to annexin A2.
CC   -!- DOMAIN: The second kringle domain is implicated in binding to
CC       cytokeratin-8 and to the endothelial cell surface binding site.
CC   -!- PTM: The single chain, almost fully active enzyme, can be further
CC       processed into a two-chain fully active form by a cleavage after
CC       Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa.
CC   -!- PTM: Differential cell-specific N-linked glycosylation gives rise
CC       to two glycoforms, type I (glycosylated at Asn-219) and type II
CC       (not glycosylated at Asn-219). The single chain type I glycoform
CC       is less readily converted into the two-chain form by plasmin, and
CC       the two-chain type I glycoform has a lower activity than the two-
CC       chain type II glycoform in the presence of fibrin.
CC   -!- PTM: N-glycosylation of Asn-152; the bound oligomannosidic glycan
CC       is involved in the interaction with the mannose receptor.
CC   -!- PTM: Characterization of O-linked glycan was studied in Bowes
CC       melanoma cell line.
CC   -!- DISEASE: Note=Increased activity of TPA results in increased
CC       fibrinolysis of fibrin blood clots that is associated with
CC       excessive bleeding. Defective release of TPA results in
CC       hypofibrinolysis that can lead to thrombosis or embolism.
CC   -!- PHARMACEUTICAL: Available under the names Activase (Genentech) and
CC       Retavase (Centocor and Roche) [Retavase is a fragment of TPA that
CC       contains kringle 2 and the protease domain; it was also known as
CC       BM 06.022]. Used in Acute Myocardial Infarction (AMI), in Acute
CC       Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate
CC       fibrinolysis.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family.
CC   -!- SIMILARITY: Contains 1 EGF-like domain.
CC   -!- SIMILARITY: Contains 1 fibronectin type-I domain.
CC   -!- SIMILARITY: Contains 2 kringle domains.
CC   -!- SIMILARITY: Contains 1 peptidase S1 domain.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Tissue plasminogen activator
CC       entry;
CC       URL="http://en.wikipedia.org/wiki/Tissue_plasminogen_Activator";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/plat/";
CC   -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC       polymorphism database;
CC       URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PLAT";
CC   -!- WEB RESOURCE: Name=Activase; Note=Clinical information on
CC       Activase;
CC       URL="http://www.gene.com/gene/products/information/cardiovascular/activase/index.jsp";
CC   -!- WEB RESOURCE: Name=Retavase; Note=Clinical information on
CC       Retavase;
CC       URL="http://www.retavase.com/pdf/Retavase_PI.pdf";
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DR   EMBL; L00153; AAB59510.1; -; Genomic_DNA.
DR   EMBL; L00141; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00142; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00143; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00144; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00145; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00146; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00147; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00148; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00149; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00150; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; L00151; AAB59510.1; JOINED; Genomic_DNA.
DR   EMBL; K03021; AAA98809.1; -; Genomic_DNA.
DR   EMBL; M15518; AAA60111.1; -; mRNA.
DR   EMBL; M18182; AAA36800.1; -; mRNA.
DR   EMBL; X07393; CAA30302.1; -; mRNA.
DR   EMBL; X13097; CAA31489.1; -; mRNA.
DR   EMBL; AF260825; AAK11956.1; -; mRNA.
DR   EMBL; AY221101; AAO34406.1; -; mRNA.
DR   EMBL; AK289387; BAF82076.1; -; mRNA.
DR   EMBL; AK290575; BAF83264.1; -; mRNA.
DR   EMBL; AK313342; BAG36145.1; -; mRNA.
DR   EMBL; BT007060; AAP35709.1; -; mRNA.
DR   EMBL; AY291060; AAP34246.1; -; Genomic_DNA.
DR   EMBL; CH471080; EAW63235.1; -; Genomic_DNA.
DR   EMBL; CH471080; EAW63233.1; -; Genomic_DNA.
DR   EMBL; BC002795; AAH02795.3; -; mRNA.
DR   EMBL; BC007231; AAH07231.1; -; mRNA.
DR   EMBL; BC013968; AAH13968.3; -; mRNA.
DR   EMBL; BC018636; AAH18636.3; -; mRNA.
DR   EMBL; BC095403; AAH95403.1; -; mRNA.
DR   EMBL; M11890; AAA61213.1; -; Genomic_DNA.
DR   EMBL; M11889; AAA61213.1; JOINED; Genomic_DNA.
DR   EMBL; D01096; BAA00881.1; -; mRNA.
DR   EMBL; V00570; CAA23833.1; -; mRNA.
DR   IPI; IPI00019590; -.
DR   IPI; IPI00479511; -.
DR   IPI; IPI00910450; -.
DR   IPI; IPI00953228; -.
DR   PIR; A94004; UKHUT.
DR   PIR; I38098; I38098.
DR   RefSeq; NP_000921.1; -.
DR   RefSeq; NP_127509.1; -.
DR   UniGene; Hs.491582; -.
DR   PDB; 1A5H; X-ray; 2.90 A; A/B=311-562, C/D=298-304.
DR   PDB; 1BDA; X-ray; 3.35 A; A/B=298-562.
DR   PDB; 1PK2; NMR; -; A=209-298.
DR   PDB; 1PML; X-ray; 2.38 A; A/B/C=213-298.
DR   PDB; 1RTF; X-ray; 2.30 A; B=311-562.
DR   PDB; 1TPG; NMR; -; A=36-126.
DR   PDB; 1TPK; X-ray; 2.40 A; A/B/C=211-298.
DR   PDB; 1TPM; NMR; -; A=36-85.
DR   PDB; 1TPN; NMR; -; A=36-85.
DR   PDBsum; 1A5H; -.
DR   PDBsum; 1BDA; -.
DR   PDBsum; 1PK2; -.
DR   PDBsum; 1PML; -.
DR   PDBsum; 1RTF; -.
DR   PDBsum; 1TPG; -.
DR   PDBsum; 1TPK; -.
DR   PDBsum; 1TPM; -.
DR   PDBsum; 1TPN; -.
DR   ProteinModelPortal; P00750; -.
DR   SMR; P00750; 126-210, 174-299, 212-334.
DR   STRING; P00750; -.
DR   MEROPS; S01.232; -.
DR   GlycoSuiteDB; P00750; -.
DR   PRIDE; P00750; -.
DR   Ensembl; ENST00000220809; ENSP00000220809; ENSG00000104368.
DR   GeneID; 5327; -.
DR   KEGG; hsa:5327; -.
DR   UCSC; uc003xos.2; human.
DR   UCSC; uc003xot.2; human.
DR   UCSC; uc010lxf.1; human.
DR   CTD; 5327; -.
DR   GeneCards; GC08M042050; -.
DR   H-InvDB; HIX0007476; -.
DR   HGNC; HGNC:9051; PLAT.
DR   HPA; CAB009335; -.
DR   HPA; HPA003412; -.
DR   MIM; 173370; gene.
DR   PharmGKB; PA33381; -.
DR   eggNOG; prNOG16610; -.
DR   HOVERGEN; HBG008633; -.
DR   InParanoid; P00750; -.
DR   OMA; TCGLRQY; -.
DR   OrthoDB; EOG9TQPVK; -.
DR   PhylomeDB; P00750; -.
DR   BRENDA; 3.4.21.68; 247.
DR   Pathway_Interaction_DB; amb2_neutrophils_pathway; amb2 Integrin signaling.
DR   Reactome; REACT_16888; Signaling by PDGF.
DR   Reactome; REACT_604; Hemostasis.
DR   DrugBank; DB00009; Alteplase.
DR   DrugBank; DB00513; Aminocaproic Acid.
DR   DrugBank; DB00029; Anistreplase.
DR   DrugBank; DB01088; Iloprost.
DR   DrugBank; DB00015; Reteplase.
DR   DrugBank; DB00031; Tenecteplase.
DR   DrugBank; DB00302; Tranexamic Acid.
DR   DrugBank; DB00013; Urokinase.
DR   NextBio; 20622; -.
DR   PMAP-CutDB; P00750; -.
DR   ArrayExpress; P00750; -.
DR   Bgee; P00750; -.
DR   Genevestigator; P00750; -.
DR   GermOnline; ENSG00000104368; Homo sapiens.
DR   GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR   GO; GO:0005515; F:protein binding; IPI:BHF-UCL.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR   GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR   GO; GO:0045861; P:negative regulation of proteolysis; IDA:BHF-UCL.
DR   GO; GO:0006464; P:protein modification process; TAS:ProtInc.
DR   GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR   InterPro; IPR016060; Complement_control_module.
DR   InterPro; IPR006209; EGF.
DR   InterPro; IPR006210; EGF-like.
DR   InterPro; IPR013032; EGF-like_reg_CS.
DR   InterPro; IPR000742; EGF_3.
DR   InterPro; IPR000083; Fibrnctn1.
DR   InterPro; IPR000001; Kringle.
DR   InterPro; IPR013806; Kringle-like.
DR   InterPro; IPR018056; Kringle_CS.
DR   InterPro; IPR018114; Peptidase_S1/S6_AS.
DR   InterPro; IPR001254; Peptidase_S1_S6.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR009003; Ser/Cys_Pept_Trypsin-like.
DR   Gene3D; G3DSA:2.10.70.10; Complement_control_module; 1.
DR   Gene3D; G3DSA:2.40.20.10; Kringle; 2.
DR   Pfam; PF00008; EGF; 1.
DR   Pfam; PF00039; fn1; 1.
DR   Pfam; PF00051; Kringle; 2.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00181; EGF; 1.
DR   SMART; SM00058; FN1; 1.
DR   SMART; SM00130; KR; 2.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF57440; Kringle-like; 2.
DR   SUPFAM; SSF50494; Pept_Ser_Cys; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   PROSITE; PS01253; FN1_1; 1.
DR   PROSITE; PS51091; FN1_2; 1.
DR   PROSITE; PS00021; KRINGLE_1; 2.
DR   PROSITE; PS50070; KRINGLE_2; 2.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing;
KW   Cleavage on pair of basic residues; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Hydrolase; Kringle; Pharmaceutical;
KW   Plasminogen activation; Polymorphism; Protease; Repeat; Secreted;
KW   Serine protease; Signal; Zymogen.
FT   SIGNAL        1     22
FT   PROPEP       23     32
FT                                /FTId=PRO_0000028348.
FT   PROPEP       33     35       Removed by plasmin.
FT                                /FTId=PRO_0000028349.
FT   CHAIN        36    562       Tissue-type plasminogen activator.
FT                                /FTId=PRO_0000028350.
FT   CHAIN        36    310       Tissue-type plasminogen activator chain
FT                                A.
FT                                /FTId=PRO_0000028351.
FT   CHAIN       311    562       Tissue-type plasminogen activator chain
FT                                B.
FT                                /FTId=PRO_0000028352.
FT   DOMAIN       39     81       Fibronectin type-I.
FT   DOMAIN       82    120       EGF-like.
FT   DOMAIN      127    208       Kringle 1.
FT   DOMAIN      215    296       Kringle 2.
FT   DOMAIN      311    561       Peptidase S1.
FT   REGION       42     52       Important for binding to annexin A2.
FT   ACT_SITE    357    357       Charge relay system.
FT   ACT_SITE    406    406       Charge relay system.
FT   ACT_SITE    513    513       Charge relay system.
FT   SITE        102    102       Important for binding to LRP1.
FT   SITE        253    253       Not glycosylated.
FT   SITE        464    464       Important for single-chain activity.
FT   SITE        512    512       Important for single-chain activity.
FT   CARBOHYD     96     96       O-linked (Fuc).
FT                                /FTId=CAR_000029.
FT   CARBOHYD    152    152       N-linked (GlcNAc...).
FT   CARBOHYD    219    219       N-linked (GlcNAc...); partial.
FT                                /FTId=CAR_000030.
FT   CARBOHYD    483    483       N-linked (GlcNAc...).
FT                                /FTId=CAR_000031.
FT   DISULFID     41     71
FT   DISULFID     69     78
FT   DISULFID     86     97
FT   DISULFID     91    108
FT   DISULFID    110    119
FT   DISULFID    127    208       By similarity.
FT   DISULFID    148    190       By similarity.
FT   DISULFID    179    203       By similarity.
FT   DISULFID    215    296
FT   DISULFID    236    278
FT   DISULFID    267    291
FT   DISULFID    299    430       Interchain (between A and B chains).
FT   DISULFID    342    358       By similarity.
FT   DISULFID    350    419       By similarity.
FT   DISULFID    444    519       By similarity.
FT   DISULFID    476    492       By similarity.
FT   DISULFID    509    537       By similarity.
FT   VAR_SEQ       1     40       MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVI
FT                                -> MAS (in isoform 4).
FT                                /FTId=VSP_028029.
FT   VAR_SEQ      39     85       VICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCH
FT                                SVPVKS -> G (in isoform 3).
FT                                /FTId=VSP_015957.
FT   VAR_SEQ      79    208       Missing (in isoform 4).
FT                                /FTId=VSP_028030.
FT   VAR_SEQ     269    291       NPDGDAKPWCHVLKNRRLTWEYC -> TGRSVSSPATASMR
FT                                PCPLSIRSG (in isoform 2).
FT                                /FTId=VSP_005411.
FT   VAR_SEQ     292    562       Missing (in isoform 2).
FT                                /FTId=VSP_005412.
FT   VARIANT      34     34       A -> D (in dbSNP:rs8178733).
FT                                /FTId=VAR_020181.
FT   VARIANT     136    136       R -> S (in dbSNP:rs8178747).
FT                                /FTId=VAR_038732.
FT   VARIANT     146    146       A -> T (in dbSNP:rs8178748).
FT                                /FTId=VAR_038733.
FT   VARIANT     164    164       R -> W (in dbSNP:rs2020921).
FT                                /FTId=VAR_011783.
FT   CONFLICT     93     93       N -> T (in Ref. 2; AAB59510).
FT   CONFLICT    159    160       KP -> NA (in Ref. 7; CAA31489).
FT   CONFLICT    247    247       K -> N (in Ref. 9; AAO34406).
FT   CONFLICT    283    283       N -> S (in Ref. 14; AAH95403).
FT   CONFLICT    333    334       RR -> EE (in Ref. 8; AAK11956).
FT   CONFLICT    389    389       V -> C (in Ref. 8; AAK11956).
FT   STRAND       44     46
FT   STRAND       55     59
FT   STRAND       61     64
FT   STRAND       66     70
FT   STRAND       72     74
FT   STRAND       83     85
FT   STRAND       96    104
FT   STRAND      106    109
FT   STRAND      115    118
FT   HELIX       242    244
FT   STRAND      248    250
FT   HELIX       256    259
FT   STRAND      262    264
FT   STRAND      277    282
FT   STRAND      285    291
FT   STRAND      312    316
FT   HELIX       319    321
FT   STRAND      325    331
FT   STRAND      338    346
FT   STRAND      348    354
FT   HELIX       356    359
FT   HELIX       365    367
FT   STRAND      368    373
FT   STRAND      375    379
FT   STRAND      385    394
FT   TURN        400    402
FT   STRAND      408    412
FT   STRAND      415    417
FT   STRAND      443    449
FT   STRAND      464    470
FT   HELIX       473    475
FT   TURN        478    483
FT   STRAND      490    494
FT   STRAND      516    521
FT   STRAND      524    533
FT   STRAND      535    538
FT   STRAND      544    548
FT   HELIX       549    552
FT   HELIX       553    559
SQ   SEQUENCE   562 AA;  62917 MW;  B7EC9B1A5E3FDC4D CRC64;
     MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARSYQVI CRDEKTQMIY QQHQSWLRPV
     LRSNRVEYCW CNSGRAQCHS VPVKSCSEPR CFNGGTCQQA LYFSDFVCQC PEGFAGKCCE
     IDTRATCYED QGISYRGTWS TAESGAECTN WNSSALAQKP YSGRRPDAIR LGLGNHNYCR
     NPDRDSKPWC YVFKAGKYSS EFCSTPACSE GNSDCYFGNG SAYRGTHSLT ESGASCLPWN
     SMILIGKVYT AQNPSAQALG LGKHNYCRNP DGDAKPWCHV LKNRRLTWEY CDVPSCSTCG
     LRQYSQPQFR IKGGLFADIA SHPWQAAIFA KHRRSPGERF LCGGILISSC WILSAAHCFQ
     ERFPPHHLTV ILGRTYRVVP GEEEQKFEVE KYIVHKEFDD DTYDNDIALL QLKSDSSRCA
     QESSVVRTVC LPPADLQLPD WTECELSGYG KHEALSPFYS ERLKEAHVRL YPSSRCTSQH
     LLNRTVTDNM LCAGDTRSGG PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGQK
     DVPGVYTKVT NYLDWIRDNM RP
//
ID   CBBQ_CHRVI              Reviewed;          74 AA.
AC   P56540;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 1.
DT   10-AUG-2010, entry version 31.
DE   RecName: Full=Protein CbbQ;
DE   Flags: Fragment;
GN   Name=cbbQ;
OS   Chromatium vinosum (Allochromatium vinosum).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Chromatiales;
OC   Chromatiaceae; Allochromatium.
OX   NCBI_TaxID=1049;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=89213919; PubMed=2708310;
RA   Viale A.M., Kobayashi H., Akazawa T.;
RT   "Expressed genes for plant-type ribulose 1,5-bisphosphate
RT   carboxylase/oxygenase in the photosynthetic bacterium Chromatium
RT   vinosum, which possesses two complete sets of the genes.";
RL   J. Bacteriol. 171:2391-2400(1989).
RN   [2]
RP   IDENTIFICATION.
RX   MEDLINE=95189107; PubMed=7883189; DOI=10.1016/0378-1119(94)00808-6;
RA   Yokoyama K., Hayashi N.R., Arai H., Chung S.Y., Igarashi Y.,
RA   Kodama T.;
RT   "Genes encoding RubisCO in Pseudomonas hydrogenothermophila are
RT   followed by a novel cbbQ gene similar to nirQ of the denitrification
RT   gene cluster from Pseudomonas species.";
RL   Gene 153:75-79(1995).
CC   -!- FUNCTION: May affect the post-translational activation and/or
CC       assembly of the oligomeric structure of RuBisCO.
CC   -!- SIMILARITY: Belongs to the CbbQ/NirQ/NorQ/GpvN family.
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DR   EMBL; M26396; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   ProteinModelPortal; P56540; -.
DR   SMR; P56540; 10-72.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATPase activity; IEA:InterPro.
DR   InterPro; IPR011704; ATPase_AAA-5.
DR   Pfam; PF07728; AAA_5; 1.
PE   3: Inferred from homology;
KW   ATP-binding; Nucleotide-binding.
FT   CHAIN         1    >74       Protein CbbQ.
FT                                /FTId=PRO_0000219562.
FT   NP_BIND      41     48       ATP (Potential).
FT   NON_TER      74     74
SQ   SEQUENCE   74 AA;  8377 MW;  B7AB23BF4DEA291C CRC64;
     MSDIDRNQFL IDHEPYYRPV SNEVALYEAA YAARMPVMLK GPTGCGKTRF VEYMAWKLGK
     PLITVACNED MTAS
//
ID   CBBQ_PSEHY              Reviewed;         267 AA.
AC   Q51858;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   10-AUG-2010, entry version 36.
DE   RecName: Full=Protein CbbQ;
GN   Name=cbbQ;
OS   Pseudomonas hydrogenothermophila.
OC   Bacteria; Proteobacteria; Betaproteobacteria; Hydrogenophilales;
OC   Hydrogenophilaceae; Hydrogenophilus.
OX   NCBI_TaxID=297;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=TH-1;
RX   MEDLINE=95189107; PubMed=7883189; DOI=10.1016/0378-1119(94)00808-6;
RA   Yokoyama K., Hayashi N.R., Arai H., Chung S.Y., Igarashi Y.,
RA   Kodama T.;
RT   "Genes encoding RubisCO in Pseudomonas hydrogenothermophila are
RT   followed by a novel cbbQ gene similar to nirQ of the denitrification
RT   gene cluster from Pseudomonas species.";
RL   Gene 153:75-79(1995).
CC   -!- FUNCTION: May affect the post-translational activation and/or
CC       assembly of the oligomeric structure of RuBisCO.
CC   -!- SIMILARITY: Belongs to the CbbQ/NirQ/NorQ/GpvN family.
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DR   EMBL; D30764; BAA06439.1; -; Genomic_DNA.
DR   ProteinModelPortal; Q51858; -.
DR   SMR; Q51858; 21-191.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATPase activity; IEA:InterPro.
DR   InterPro; IPR011704; ATPase_AAA-5.
DR   InterPro; IPR013615; CbbQ_C.
DR   Pfam; PF07728; AAA_5; 1.
DR   Pfam; PF08406; CbbQ_C; 1.
PE   3: Inferred from homology;
KW   ATP-binding; Nucleotide-binding.
FT   CHAIN         1    267       Protein CbbQ.
FT                                /FTId=PRO_0000219563.
FT   NP_BIND      39     46       ATP (Potential).
FT   NP_BIND      99    106       ATP (Potential).
SQ   SEQUENCE   267 AA;  29613 MW;  EA99FE2DB05B0118 CRC64;
     MDLRNQYLVR SEPYYHAVGD EIERFEAAYA NRIPMMLKGP TGCGKSRFVE YMAWKLGKPL
     ITVACNEDMT AADLVGRFLL DKEGTRWQDG PLTTAARIGA ICYLDEVVEA RQDTTVVIHP
     LTDHRRILPL DKKGEVVEAH PDFQIVISYN PGYQSAMKDL KTSTKQRFAA MDFDYPAPEV
     ESEIVAHESG VDAATAKKLV EVAIRSRHLK GHGLDEGIST RLLVYAGSLI TKGIAPLIAC
     EMALICPITD DPDLRYALRA AAQTLFA
//
ID   NIRQ_PSEAE              Reviewed;         260 AA.
AC   Q51481;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   10-AUG-2010, entry version 66.
DE   RecName: Full=Denitrification regulatory protein nirQ;
GN   Name=nirQ; OrderedLocusNames=PA0520;
OS   Pseudomonas aeruginosa.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC   Pseudomonadaceae; Pseudomonas.
OX   NCBI_TaxID=287;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=PAO1161;
RX   MEDLINE=94362287; PubMed=7765251;
RA   Arai H., Igarashi Y., Kodama T.;
RT   "Structure and ANR-dependent transcription of the nir genes for
RT   denitrification from Pseudomonas aeruginosa.";
RL   Biosci. Biotechnol. Biochem. 58:1286-1291(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228;
RX   MEDLINE=20437337; PubMed=10984043; DOI=10.1038/35023079;
RA   Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA   Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA   Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA   Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA   Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T.,
RA   Reizer J., Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT   "Complete genome sequence of Pseudomonas aeruginosa PAO1, an
RT   opportunistic pathogen.";
RL   Nature 406:959-964(2000).
CC   -!- FUNCTION: Activator of nitrite and nitric oxide reductases.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm (Potential).
CC   -!- INDUCTION: Under denitrifying conditions.
CC   -!- SIMILARITY: Belongs to the CbbQ/NirQ/NorQ/GpvN family.
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DR   EMBL; D37883; BAA07123.1; -; Genomic_DNA.
DR   EMBL; AE004091; AAG03909.1; -; Genomic_DNA.
DR   PIR; JC2288; JC2288.
DR   RefSeq; NP_249211.1; -.
DR   ProteinModelPortal; Q51481; -.
DR   SMR; Q51481; 14-183.
DR   GeneID; 882214; -.
DR   GenomeReviews; AE004091_GR; PA0520.
DR   KEGG; pae:PA0520; -.
DR   NMPDR; fig|208964.1.peg.521; -.
DR   PseudoCAP; PA0520; -.
DR   HOGENOM; HBG295312; -.
DR   OMA; HEARILV; -.
DR   ProtClustDB; CLSK865916; -.
DR   BioCyc; PAER208964:PA0520-MONOMER; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATPase activity; IEA:InterPro.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0045449; P:regulation of transcription; IEA:UniProtKB-KW.
DR   GO; GO:0006350; P:transcription; IEA:UniProtKB-KW.
DR   InterPro; IPR011704; ATPase_AAA-5.
DR   InterPro; IPR013615; CbbQ_C.
DR   Pfam; PF07728; AAA_5; 1.
DR   Pfam; PF08406; CbbQ_C; 1.
PE   2: Evidence at transcript level;
KW   Activator; ATP-binding; Complete proteome; Cytoplasm; DNA-binding;
KW   Nucleotide-binding; Transcription; Transcription regulation.
FT   CHAIN         1    260       Denitrification regulatory protein nirQ.
FT                                /FTId=PRO_0000219569.
FT   NP_BIND      32     39       ATP (Potential).
FT   NP_BIND      92     99       ATP (Potential).
FT   DNA_BIND    234    253       H-T-H motif (Potential).
SQ   SEQUENCE   260 AA;  28904 MW;  3FD36F19BEBA38B5 CRC64;
     MRDATPFYEA TGHEIEVFER AWRHGLPVLL KGPTGCGKTR FVQYMARRLE LPLYSVACHD
     DLGAADLLGR HLIGADGTWW QDGPLTRAVR EGGICYLDEV VEARQDTTVA IHPLADDRRE
     LYLERTGETL QAPPSFMLVV SYNPGYQNLL KGLKPSTRQR FVALRFDYPA AQQEARILVG
     ESGCAETLAQ RLVQLGQALR RLEQHDLEEV ASTRLLIFAA RLIGDGMDPR EACRVALAEP
     LSDDPATVAA LMDIVDLHVA
//
ID   CHDH_HUMAN              Reviewed;         594 AA.
AC   Q8NE62; Q9NY17;
DT   16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 2.
DT   05-OCT-2010, entry version 72.
DE   RecName: Full=Choline dehydrogenase, mitochondrial;
DE            Short=CDH;
DE            Short=CHD;
DE            EC=1.1.99.1;
DE   Flags: Precursor;
GN   Name=CHDH;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA   Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA   Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA   Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA   Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA   Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA   Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA   Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA   Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA   Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA   Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA   Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA   Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA   Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA   Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA   Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-78.
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 113-594.
RC   TISSUE=Kidney;
RA   Bugert P., Hanke S., Chudek J., Kovacs G.;
RT   "Analysis of a putative tumor suppressor gene region of 100 kb at
RT   chromosome 3p21.1 in conventional renal cell carcinoma.";
RL   Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
CC   -!- CATALYTIC ACTIVITY: Choline + acceptor = betaine aldehyde +
CC       reduced acceptor.
CC   -!- COFACTOR: FAD (By similarity).
CC   -!- PATHWAY: Amine and polyamine biosynthesis; betaine biosynthesis
CC       via choline pathway; betaine aldehyde from choline (cytochrome c
CC       reductase route): step 1/1.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion (Potential).
CC   -!- SIMILARITY: Belongs to the GMC oxidoreductase family.
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DR   EMBL; AC012467; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC034502; AAH34502.1; -; mRNA.
DR   EMBL; AJ272267; CAB75961.1; -; mRNA.
DR   IPI; IPI00168603; -.
DR   RefSeq; NP_060867.2; -.
DR   UniGene; Hs.126688; -.
DR   ProteinModelPortal; Q8NE62; -.
DR   STRING; Q8NE62; -.
DR   PhosphoSite; Q8NE62; -.
DR   Ensembl; ENST00000315251; ENSP00000319851; ENSG00000016391.
DR   GeneID; 55349; -.
DR   KEGG; hsa:55349; -.
DR   UCSC; uc003dgz.1; human.
DR   CTD; 55349; -.
DR   GeneCards; GC03M053826; -.
DR   HGNC; HGNC:24288; CHDH.
DR   PharmGKB; PA134873121; -.
DR   eggNOG; prNOG07180; -.
DR   HOGENOM; HBG734713; -.
DR   HOVERGEN; HBG023639; -.
DR   InParanoid; Q8NE62; -.
DR   OMA; SRDEYSY; -.
DR   OrthoDB; EOG9962C6; -.
DR   PhylomeDB; Q8NE62; -.
DR   BRENDA; 1.1.99.1; 247.
DR   DrugBank; DB00122; Choline.
DR   NextBio; 59691; -.
DR   ArrayExpress; Q8NE62; -.
DR   Bgee; Q8NE62; -.
DR   CleanEx; HS_CHDH; -.
DR   Genevestigator; Q8NE62; -.
DR   GermOnline; ENSG00000016391; Homo sapiens.
DR   GO; GO:0008812; F:choline dehydrogenase activity; IEA:EC.
DR   GO; GO:0050660; F:FAD or FADH2 binding; IEA:InterPro.
DR   GO; GO:0006066; P:alcohol metabolic process; IEA:InterPro.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   InterPro; IPR012132; GMC_OxRdtase.
DR   InterPro; IPR000172; GMC_OxRdtase_N.
DR   InterPro; IPR007867; GMC_OxRtase_C.
DR   Pfam; PF05199; GMC_oxred_C; 1.
DR   Pfam; PF00732; GMC_oxred_N; 1.
DR   PIRSF; PIRSF000137; Alcohol_oxidase; 1.
DR   PROSITE; PS00623; GMC_OXRED_1; 1.
DR   PROSITE; PS00624; GMC_OXRED_2; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Complete proteome; FAD; Flavoprotein; Mitochondrion;
KW   Oxidoreductase; Polymorphism; Transit peptide.
FT   TRANSIT       1      ?       Mitochondrion (Potential).
FT   CHAIN         ?    594       Choline dehydrogenase, mitochondrial.
FT                                /FTId=PRO_0000012329.
FT   NP_BIND      42     71       FAD (By similarity).
FT   ACT_SITE    511    511       By similarity.
FT   MOD_RES     496    496       N6-acetyllysine (By similarity).
FT   VARIANT      40     40       E -> A (in dbSNP:rs9001).
FT                                /FTId=VAR_020421.
FT   VARIANT      78     78       L -> R (in dbSNP:rs12676).
FT                                /FTId=VAR_055097.
FT   VARIANT     441    441       N -> S (in dbSNP:rs34974961).
FT                                /FTId=VAR_049357.
FT   CONFLICT    113    113       R -> A (in Ref. 3; CAB75961).
SQ   SEQUENCE   594 AA;  65358 MW;  E9764CD0F325A501 CRC64;
     MWCLLRGLGR PGALARGALG QQQSLGARAL ASAGSESRDE YSYVVVGAGS AGCVLAGRLT
     EDPAERVLLL EAGPKDVLAG SKRLSWKIHM PAALVANLCD DRYNWCYHTE VQRGLDGRVL
     YWPRGRVWGG SSSLNAMVYV RGHAEDYERW QRQGARGWDY AHCLPYFRKA QGHELGASRY
     RGADGPLRVS RGKTNHPLHC AFLEATQQAG YPLTEDMNGF QQEGFGWMDM TIHEGKRWSA
     ACAYLHPALS RTNLKAEAET LVSRVLFEGT RAVGVEYVKN GQSHRAYASK EVILSGGAIN
     SPQLLMLSGI GNADDLKKLG IPVVCHLPGV GQNLQDHLEI YIQQACTRPI TLHSAQKPLR
     KVCIGLEWLW KFTGEGATAH LETGGFIRSQ PGVPHPDIQF HFLPSQVIDH GRVPTQQEAY
     QVHVGPMRGT SVGWLKLRSA NPQDHPVIQP NYLSTETDIE DFRLCVKLTR EIFAQEALAP
     FRGKELQPGS HIQSDKEIDA FVRAKADSAY HPSCTCKMGQ PSDPTAVVDP QTRVLGVENL
     RVVDASIMPS MVSGNLNAPT IMIAEKAADI IKGQPALWDK DVPVYKPRTL ATQR
//
ID   IVBKI_DENPO             Reviewed;          79 AA.
AC   P00981; Q91351;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2004, sequence version 2.
DT   10-AUG-2010, entry version 84.
DE   RecName: Full=Dendrotoxin-K;
DE            Short=DTX-K;
DE   AltName: Full=Venom basic protease inhibitor K;
DE   Flags: Precursor; Fragment;
OS   Dendroaspis polylepis polylepis (Black mamba).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Scleroglossa; Serpentes; Colubroidea;
OC   Elapidae; Elapinae; Dendroaspis.
OX   NCBI_TaxID=8620;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 23-39.
RX   MEDLINE=93277850; PubMed=8504088; DOI=10.1021/bi00072a026;
RA   Smith L.A., Lafaye P.J., LaPenotiere H.F., Spain T., Dolly J.O.;
RT   "Cloning and functional expression of dendrotoxin K from black mamba,
RT   a K+ channel blocker.";
RL   Biochemistry 32:5692-5697(1993).
RN   [2]
RP   PROTEIN SEQUENCE OF 23-79.
RC   TISSUE=Venom;
RX   MEDLINE=77158069; PubMed=857902; DOI=10.1016/0005-2795(77)90279-3;
RA   Strydom D.J.;
RT   "Snake venom toxins. The amino acid sequence of toxin Vi2, a homologue
RT   of pancreatic trypsin inhibitor, from Dendroaspis polylepis polylepis
RT   (black mamba) venom.";
RL   Biochim. Biophys. Acta 491:361-369(1977).
RN   [3]
RP   STRUCTURE BY NMR OF 23-79.
RX   MEDLINE=94076347; PubMed=8254670; DOI=10.1006/jmbi.1993.1623;
RA   Berndt K.D., Guentert P., Wuethrich K.;
RT   "Nuclear magnetic resonance solution structure of dendrotoxin K from
RT   the venom of Dendroaspis polylepis polylepis.";
RL   J. Mol. Biol. 234:735-750(1993).
CC   -!- FUNCTION: This protein is much less toxic to mice than is whole
CC       venom. It inhibits trypsin slightly, but chymotrypsin not at all.
CC       It is a highly selective blocker of voltage-gated potassium
CC       channels.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- TOXIC DOSE: LD(50) is 30 mg/kg by intravenous injection.
CC   -!- SIMILARITY: Contains 1 BPTI/Kunitz inhibitor domain.
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DR   EMBL; S61886; AAB26998.1; -; mRNA.
DR   PIR; A49291; TIEPVK.
DR   PDB; 1DTK; NMR; -; A=23-79.
DR   PDBsum; 1DTK; -.
DR   ProteinModelPortal; P00981; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0019870; F:potassium channel inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW.
DR   InterPro; IPR002223; Prot_inh_Kunz-m.
DR   InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR   Gene3D; G3DSA:4.10.410.10; Prot_inh_Kunz-m; 1.
DR   Pfam; PF00014; Kunitz_BPTI; 1.
DR   PRINTS; PR00759; BASICPTASE.
DR   SMART; SM00131; KU; 1.
DR   SUPFAM; SSF57362; Prot_inh_Kunz-m; 1.
DR   PROSITE; PS00280; BPTI_KUNITZ_1; 1.
DR   PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond;
KW   Ionic channel inhibitor; Neurotoxin; Potassium channel inhibitor;
KW   Protease inhibitor; Secreted; Serine protease inhibitor; Signal;
KW   Toxin.
FT   SIGNAL       <1      ?
FT   PROPEP        ?     22
FT                                /FTId=PRO_0000016869.
FT   CHAIN        23     79       Dendrotoxin-K.
FT                                /FTId=PRO_0000016870.
FT   DOMAIN       27     77       BPTI/Kunitz inhibitor.
FT   SITE         37     38       Reactive bond.
FT   DISULFID     27     77       By similarity.
FT   DISULFID     36     60       By similarity.
FT   DISULFID     52     73       By similarity.
FT   NON_TER       1      1
FT   HELIX        25     28
FT   STRAND       35     37
FT   STRAND       40     45
FT   TURN         47     49
FT   STRAND       50     57
FT   STRAND       59     61
FT   STRAND       67     69
FT   HELIX        70     77
SQ   SEQUENCE   79 AA;  8852 MW;  DCDFB9AFA07D7D46 CRC64;
     SGHLLLLLGL LTLWAELTPV SGAAKYCKLP LRIGPCKRKI PSFYYKWKAK QCLPFDYSGC
     GGNANRFKTI EECRRTCVG
//
ID   GRN_HUMAN               Reviewed;         593 AA.
AC   P28799; P23781; P23782; P23783; P23784; Q53Y88; Q540U8; Q9BWE7;
AC   Q9UCH0;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 2.
DT   02-NOV-2010, entry version 120.
DE   RecName: Full=Granulins;
DE   AltName: Full=Proepithelin;
DE            Short=PEPI;
DE   Contains:
DE     RecName: Full=Acrogranin;
DE   Contains:
DE     RecName: Full=Paragranulin;
DE   Contains:
DE     RecName: Full=Granulin-1;
DE     AltName: Full=Granulin G;
DE   Contains:
DE     RecName: Full=Granulin-2;
DE     AltName: Full=Granulin F;
DE   Contains:
DE     RecName: Full=Granulin-3;
DE     AltName: Full=Granulin B;
DE   Contains:
DE     RecName: Full=Granulin-4;
DE     AltName: Full=Granulin A;
DE   Contains:
DE     RecName: Full=Granulin-5;
DE     AltName: Full=Granulin C;
DE   Contains:
DE     RecName: Full=Granulin-6;
DE     AltName: Full=Granulin D;
DE   Contains:
DE     RecName: Full=Granulin-7;
DE     AltName: Full=Granulin E;
DE   Flags: Precursor;
GN   Name=GRN;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION.
RX   MEDLINE=93038704; PubMed=1417868; DOI=10.1016/0006-291X(92)92349-3;
RA   Bhandari V., Bateman A.;
RT   "Structure and chromosomal location of the human granulin gene.";
RL   Biochem. Biophys. Res. Commun. 188:57-63(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Kidney;
RX   MEDLINE=92317004; PubMed=1618805;
RA   Plowman G.D., Green J.M., Neubauer M.G., Buckley S.D., McDonald V.L.,
RA   Todaro G.J., Shoyab M.;
RT   "The epithelin precursor encodes two proteins with opposing activities
RT   on epithelial cell growth.";
RL   J. Biol. Chem. 267:13073-13078(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Bone marrow;
RX   MEDLINE=92179253; PubMed=1542665; DOI=10.1073/pnas.89.5.1715;
RA   Bhandari V., Palfree R.G.E., Bateman A.;
RT   "Isolation and sequence of the granulin precursor cDNA from human bone
RT   marrow reveals tandem cysteine-rich granulin domains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:1715-1719(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Lu R., Tian C., Serrero G.;
RT   "PCDGF sequence from lambda phage human Jurkat T cell cDNA library
RT   (Clontech).";
RL   Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RA   Yu W., Gibbs R.A.;
RL   Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Cervix, and Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   PROTEIN SEQUENCE OF 206-233; 281-336; 364-396 AND 442-447.
RC   TISSUE=Leukocyte;
RX   MEDLINE=91097544; PubMed=2268320; DOI=10.1016/S0006-291X(05)80908-8;
RA   Bateman A., Belcourt D.R., Bennett H.P., Lazure C., Solomon S.;
RT   "Granulins, a novel class of peptide from leukocytes.";
RL   Biochem. Biophys. Res. Commun. 173:1161-1168(1990).
RN   [10]
RP   PROTEIN SEQUENCE OF 281-295.
RX   PubMed=8471426;
RA   Kardana A., Bagshawe K.D., Coles B., Read D., Taylor M.;
RT   "Characterisation of UGP and its relationship with beta-core
RT   fragment.";
RL   Br. J. Cancer 67:686-692(1993).
RN   [11]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-265, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of
RT   multiple enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [12]
RP   STRUCTURE BY NMR OF 284-311.
RX   PubMed=10715107; DOI=10.1021/bi992130u;
RA   Tolkatchev D., Ng A., Vranken W., Ni F.;
RT   "Design and solution structure of a well-folded stack of two beta-
RT   hairpins based on the amino-terminal fragment of human granulin A.";
RL   Biochemistry 39:2878-2886(2000).
RN   [13]
RP   INVOLVEMENT IN UP-FTD.
RX   PubMed=16862116; DOI=10.1038/nature05016;
RA   Baker M., Mackenzie I.R., Pickering-Brown S.M., Gass J.,
RA   Rademakers R., Lindholm C., Snowden J., Adamson J., Sadovnick A.D.,
RA   Rollinson S., Cannon A., Dwosh E., Neary D., Melquist S.,
RA   Richardson A., Dickson D., Berger Z., Eriksen J., Robinson T.,
RA   Zehr C., Dickey C.A., Crook R., McGowan E., Mann D., Boeve B.,
RA   Feldman H., Hutton M.;
RT   "Mutations in progranulin cause tau-negative frontotemporal dementia
RT   linked to chromosome 17.";
RL   Nature 442:916-919(2006).
RN   [14]
RP   VARIANT UP-FTD ASP-9.
RX   PubMed=16983685; DOI=10.1002/ana.20963;
RA   Mukherjee O., Pastor P., Cairns N.J., Chakraverty S., Kauwe J.S.K.,
RA   Shears S., Behrens M.I., Budde J., Hinrichs A.L., Norton J.,
RA   Levitch D., Taylor-Reinwald L., Gitcho M., Tu P.-H.,
RA   Tenenholz Grinberg L., Liscic R.M., Armendariz J., Morris J.C.,
RA   Goate A.M.;
RT   "HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-
RT   positive, tau-negative inclusions caused by a missense mutation in the
RT   signal peptide of progranulin.";
RL   Ann. Neurol. 60:314-322(2006).
RN   [15]
RP   CHARACTERIZATION OF VARIANT UP-FTD ASP-9.
RX   PubMed=18183624; DOI=10.1002/humu.20681;
RA   Mukherjee O., Wang J., Gitcho M., Chakraverty S., Taylor-Reinwald L.,
RA   Shears S., Kauwe J.S.K., Norton J., Levitch D., Bigio E.H.,
RA   Hatanpaa K.J., White C.L., Morris J.C., Cairns N.J., Goate A.;
RT   "Molecular characterization of novel progranulin (GRN) mutations in
RT   frontotemporal dementia.";
RL   Hum. Mutat. 29:512-521(2008).
CC   -!- FUNCTION: Granulins have possible cytokine-like activity. They may
CC       play a role in inflammation, wound repair, and tissue remodeling.
CC   -!- FUNCTION: Granulin-4 promotes proliferation of the epithelial cell
CC       line A431 in culture while granulin-3 acts as an antagonist to
CC       granulin-4, inhibiting the growth.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P28799-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P28799-2; Sequence=VSP_001837;
CC   -!- TISSUE SPECIFICITY: In myelogenous leukemic cell lines of
CC       promonocytic, promyelocytic, and proerythroid lineage, in
CC       fibroblasts, and very strongly in epithelial cell lines. Present
CC       in inflammatory cells and bone marrow. Highest levels in kidney.
CC   -!- PTM: Granulins are disulfide bridged.
CC   -!- DISEASE: Defects in GRN are the cause of ubiquitin-positive
CC       frontotemporal dementia (UP-FTD) [MIM:607485]; also known as tau-
CC       negative frontotemporal dementia linked to chromosome 17.
CC       Frontotemporal dementia (FTD) is the second most common cause of
CC       dementia in people under the age of 65 years. It is an autosomal
CC       dominant neurodegenerative disease.
CC   -!- SIMILARITY: Belongs to the granulin family.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/GRNID40757ch17q21.html";
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GRN";
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DR   EMBL; X62320; CAA44196.1; -; mRNA.
DR   EMBL; AF055008; AAC09359.1; -; mRNA.
DR   EMBL; M75161; AAA58617.1; ALT_SEQ; mRNA.
DR   EMBL; AY124489; AAM94026.1; -; mRNA.
DR   EMBL; BT006844; AAP35490.1; -; mRNA.
DR   EMBL; CH471178; EAW51599.1; -; Genomic_DNA.
DR   EMBL; BC000324; AAH00324.1; -; mRNA.
DR   EMBL; BC010577; AAH10577.1; -; mRNA.
DR   IPI; IPI00182138; -.
DR   IPI; IPI00296713; -.
DR   PIR; JC1284; GYHU.
DR   RefSeq; NP_002078.1; -.
DR   UniGene; Hs.514220; -.
DR   PDB; 1G26; NMR; -; A=284-311.
DR   PDB; 2JYE; NMR; -; A=281-337.
DR   PDB; 2JYT; NMR; -; A=364-417.
DR   PDB; 2JYU; NMR; -; A=364-417.
DR   PDB; 2JYV; NMR; -; A=123-179.
DR   PDBsum; 1G26; -.
DR   PDBsum; 2JYE; -.
DR   PDBsum; 2JYT; -.
DR   PDBsum; 2JYU; -.
DR   PDBsum; 2JYV; -.
DR   ProteinModelPortal; P28799; -.
DR   SMR; P28799; 206-236.
DR   IntAct; P28799; 23.
DR   MINT; MINT-271687; -.
DR   STRING; P28799; -.
DR   PRIDE; P28799; -.
DR   Ensembl; ENST00000053867; ENSP00000053867; ENSG00000030582.
DR   GeneID; 2896; -.
DR   KEGG; hsa:2896; -.
DR   UCSC; uc002igp.1; human.
DR   CTD; 2896; -.
DR   GeneCards; GC17P042433; -.
DR   H-InvDB; HIX0013882; -.
DR   HGNC; HGNC:4601; GRN.
DR   HPA; CAB019394; -.
DR   HPA; HPA008763; -.
DR   HPA; HPA028747; -.
DR   MIM; 138945; gene.
DR   MIM; 607485; phenotype.
DR   Orphanet; 98929; Frontotemporal dementia with motor neuron-disease type inclusions.
DR   PharmGKB; PA24626; -.
DR   eggNOG; prNOG11069; -.
DR   HOVERGEN; HBG000845; -.
DR   InParanoid; P28799; -.
DR   OMA; CCEDRVH; -.
DR   OrthoDB; EOG9JQ6HG; -.
DR   PhylomeDB; P28799; -.
DR   NextBio; 11459; -.
DR   PMAP-CutDB; P28799; -.
DR   ArrayExpress; P28799; -.
DR   Bgee; P28799; -.
DR   CleanEx; HS_GRN; -.
DR   Genevestigator; P28799; -.
DR   GermOnline; ENSG00000030582; Homo sapiens.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0008083; F:growth factor activity; TAS:ProtInc.
DR   GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR   InterPro; IPR006150; Cys_repeat_1.
DR   InterPro; IPR000118; Granulin.
DR   Pfam; PF00396; Granulin; 7.
DR   SMART; SM00277; GRAN; 7.
DR   SMART; SM00289; WR1; 5.
DR   PROSITE; PS00799; GRANULINS; 7.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Complete proteome; Cytokine;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Polymorphism;
KW   Repeat; Secreted; Signal.
FT   SIGNAL        1     17       Potential.
FT   CHAIN        18    593       Acrogranin.
FT                                /FTId=PRO_0000012693.
FT   PEPTIDE      18    ?47       Paragranulin.
FT                                /FTId=PRO_0000012694.
FT   PEPTIDE     ?58   ?113       Granulin-1.
FT                                /FTId=PRO_0000012695.
FT   PEPTIDE    ?123   ?179       Granulin-2.
FT                                /FTId=PRO_0000012696.
FT   PEPTIDE     206    261       Granulin-3.
FT                                /FTId=PRO_0000012697.
FT   PEPTIDE     281    336       Granulin-4.
FT                                /FTId=PRO_0000012698.
FT   PEPTIDE     364   ?417       Granulin-5.
FT                                /FTId=PRO_0000012699.
FT   PEPTIDE     442   ?496       Granulin-6.
FT                                /FTId=PRO_0000012700.
FT   PEPTIDE    ?518   ?573       Granulin-7.
FT                                /FTId=PRO_0000012701.
FT   CARBOHYD    118    118       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    236    236       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    265    265       N-linked (GlcNAc...).
FT   CARBOHYD    368    368       N-linked (GlcNAc...).
FT   CARBOHYD    530    530       N-linked (GlcNAc...) (Potential).
FT   DISULFID    284    296
FT   DISULFID    290    306
FT   VAR_SEQ     377    531       Missing (in isoform 2).
FT                                /FTId=VSP_001837.
FT   VARIANT       9      9       A -> D (in UP-FTD; no significant
FT                                difference in the total mRNA between
FT                                cases and controls; although the mutant
FT                                protein is expressed it is not secreted
FT                                and appears to be trapped within an
FT                                intracellular compartment).
FT                                /FTId=VAR_044451.
FT   VARIANT     515    515       G -> A (in dbSNP:rs25647).
FT                                /FTId=VAR_014830.
FT   CONFLICT    219    219       S -> H (in Ref. 9; AA sequence).
FT   CONFLICT    290    290       C -> S (in Ref. 10; AA sequence).
FT   CONFLICT    386    386       W -> H (in Ref. 9; AA sequence).
FT   CONFLICT    454    454       Q -> G (in Ref. 3; AAA58617).
FT   STRAND      137    141
FT   STRAND      143    145
FT   STRAND      147    151
FT   STRAND      282    285
FT   STRAND      288    290
FT   STRAND      294    298
FT   STRAND      304    308
FT   STRAND      315    319
FT   TURN        330    333
FT   STRAND      377    380
FT   STRAND      382    384
FT   STRAND      386    389
FT   STRAND      409    411
FT   TURN        412    414
FT   STRAND      415    417
SQ   SEQUENCE   593 AA;  63544 MW;  4E5947F1B4EDE619 CRC64;
     MWTLVSWVAL TAGLVAGTRC PDGQFCPVAC CLDPGGASYS CCRPLLDKWP TTLSRHLGGP
     CQVDAHCSAG HSCIFTVSGT SSCCPFPEAV ACGDGHHCCP RGFHCSADGR SCFQRSGNNS
     VGAIQCPDSQ FECPDFSTCC VMVDGSWGCC PMPQASCCED RVHCCPHGAF CDLVHTRCIT
     PTGTHPLAKK LPAQRTNRAV ALSSSVMCPD ARSRCPDGST CCELPSGKYG CCPMPNATCC
     SDHLHCCPQD TVCDLIQSKC LSKENATTDL LTKLPAHTVG DVKCDMEVSC PDGYTCCRLQ
     SGAWGCCPFT QAVCCEDHIH CCPAGFTCDT QKGTCEQGPH QVPWMEKAPA HLSLPDPQAL
     KRDVPCDNVS SCPSSDTCCQ LTSGEWGCCP IPEAVCCSDH QHCCPQGYTC VAEGQCQRGS
     EIVAGLEKMP ARRASLSHPR DIGCDQHTSC PVGQTCCPSL GGSWACCQLP HAVCCEDRQH
     CCPAGYTCNV KARSCEKEVV SAQPATFLAR SPHVGVKDVE CGEGHFCHDN QTCCRDNRQG
     WACCPYRQGV CCADRRHCCP AGFRCAARGT KCLRREAPRW DAPLRDPALR QLL
//
ID   CEF_BPT4                Reviewed;          71 AA.
AC   Q01436;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   15-JUN-2010, entry version 37.
DE   RecName: Full=Protein cef;
GN   Name=cef; Synonyms=mb;
OS   Enterobacteria phage T4 (Bacteriophage T4).
OC   Viruses; dsDNA viruses, no RNA stage; Caudovirales; Myoviridae;
OC   T4-like viruses.
OX   NCBI_TaxID=10665;
OH   NCBI_TaxID=562; Escherichia coli.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=93015705; PubMed=1400206;
RA   Sanson B., Uzan M.;
RT   "Sequence and characterization of the bacteriophage T4 comC alpha gene
RT   product, a possible transcription antitermination factor.";
RL   J. Bacteriol. 174:6539-6547(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   MEDLINE=22514363; PubMed=12626685; DOI=10.1128/MMBR.67.1.86-156.2003;
RA   Miller E.S., Kutter E., Mosig G., Arisaka F., Kunisawa T., Ruger W.;
RT   "Bacteriophage T4 genome.";
RL   Microbiol. Mol. Biol. Rev. 67:86-156(2003).
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DR   EMBL; M89919; AAA32484.1; -; Genomic_DNA.
DR   EMBL; AF158101; AAD42588.1; -; Genomic_DNA.
DR   PIR; B45731; B45731.
DR   RefSeq; NP_049625.1; -.
DR   GeneID; 1258628; -.
DR   GenomeReviews; AF158101_GR; T4p011.
DR   ProtClustDB; CLSP2343268; -.
PE   4: Predicted;
KW   Virus reference strain.
FT   CHAIN         1     71       Protein cef.
FT                                /FTId=PRO_0000164920.
SQ   SEQUENCE   71 AA;  8465 MW;  031505CA6FE414FA CRC64;
     MKRKIVQNCT NDEFEDVLFD PNLVVVQKEH TSKFTHLTSV YVYEKVGDKQ PIYGVFREIT
     EDGTTYWKEI Y
//
