ID E9PIT3_HUMAN Unreviewed; 583 AA.
AC E9PIT3;
DT 05-APR-2011, integrated into UniProtKB/TrEMBL.
DT 05-APR-2011, sequence version 1.
DT 27-MAR-2024, entry version 91.
DE RecName: Full=Prothrombin {ECO:0000256|ARBA:ARBA00014840};
DE EC=3.4.21.5 {ECO:0000256|ARBA:ARBA00012174};
DE AltName: Full=Coagulation factor II {ECO:0000256|ARBA:ARBA00032835};
GN Name=F2 {ECO:0000313|Ensembl:ENSP00000433907.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000433907.1, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0000313|Ensembl:ENSP00000433907.1, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [2] {ECO:0007829|PubMed:24275569}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [3] {ECO:0000313|Ensembl:ENSP00000433907.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Thrombin, which cleaves bonds after Arg and Lys, converts
CC fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in
CC complex with thrombomodulin, protein C. Functions in blood homeostasis,
CC inflammation and wound healing. {ECO:0000256|ARBA:ARBA00025390}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of Arg-|-Gly bonds in fibrinogen to form
CC fibrin and release fibrinopeptides A and B.; EC=3.4.21.5;
CC Evidence={ECO:0000256|ARBA:ARBA00001621};
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00121}.
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DR EMBL; AC115088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; E9PIT3; -.
DR SMR; E9PIT3; -.
DR MEROPS; S01.217; -.
DR GlyCosmos; E9PIT3; 3 sites, No reported glycans.
DR MassIVE; E9PIT3; -.
DR MaxQB; E9PIT3; -.
DR PeptideAtlas; E9PIT3; -.
DR ProteomicsDB; 20913; -.
DR Antibodypedia; 857; 1316 antibodies from 42 providers.
DR Ensembl; ENST00000530231.5; ENSP00000433907.1; ENSG00000180210.15.
DR UCSC; uc058aym.1; human.
DR HGNC; HGNC:3535; F2.
DR VEuPathDB; HostDB:ENSG00000180210; -.
DR GeneTree; ENSGT00940000154234; -.
DR Proteomes; UP000005640; Chromosome 11.
DR Bgee; ENSG00000180210; Expressed in right lobe of liver and 101 other cell types or tissues.
DR ExpressionAtlas; E9PIT3; baseline and differential.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProt.
DR GO; GO:0005576; C:extracellular region; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00108; KR; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.20.10; Plasminogen Kringle 4; 2.
DR Gene3D; 4.10.140.10; Thrombin light chain domain; 1.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR InterPro; IPR035972; GLA-like_dom_SF.
DR InterPro; IPR000294; GLA_domain.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR003966; Prothrombin/thrombin.
DR InterPro; IPR018992; Thrombin_light_chain.
DR InterPro; IPR037111; Thrombin_light_chain_sf.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24254; PROTHROMBIN; 1.
DR PANTHER; PTHR24254:SF10; PROTHROMBIN; 1.
DR Pfam; PF00594; Gla; 1.
DR Pfam; PF00051; Kringle; 2.
DR Pfam; PF09396; Thrombin_light; 1.
DR Pfam; PF00089; Trypsin; 2.
DR PIRSF; PIRSF001149; Thrombin; 2.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR PRINTS; PR00001; GLABLOOD.
DR PRINTS; PR00018; KRINGLE.
DR PRINTS; PR01505; PROTHROMBIN.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00130; KR; 2.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF57630; GLA-domain; 1.
DR SUPFAM; SSF57440; Kringle-like; 2.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_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 Acute phase {ECO:0000256|ARBA:ARBA00022486};
KW Blood coagulation {ECO:0000256|ARBA:ARBA00023084};
KW Calcium {ECO:0000256|ARBA:ARBA00022837};
KW Cleavage on pair of basic residues {ECO:0000256|ARBA:ARBA00022685};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157,
KW ECO:0000256|PIRSR:PIRSR001149-4};
KW Gamma-carboxyglutamic acid {ECO:0000256|ARBA:ARBA00022479};
KW Hemostasis {ECO:0000256|ARBA:ARBA00022696};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU363034};
KW Kringle {ECO:0000256|ARBA:ARBA00022572, ECO:0000256|PROSITE-
KW ProRule:PRU00121};
KW Protease {ECO:0000256|ARBA:ARBA00022670, ECO:0000256|RuleBase:RU363034};
KW Proteomics identification {ECO:0007829|EPD:E9PIT3,
KW ECO:0007829|MaxQB:E9PIT3};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW Serine protease {ECO:0000256|RuleBase:RU363034};
KW Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP}.
FT SIGNAL 1..24
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 25..583
FT /note="Prothrombin"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5003245057"
FT DOMAIN 43..89
FT /note="Gla"
FT /evidence="ECO:0000259|PROSITE:PS50998"
FT DOMAIN 107..186
FT /note="Kringle"
FT /evidence="ECO:0000259|PROSITE:PS50070"
FT DOMAIN 212..291
FT /note="Kringle"
FT /evidence="ECO:0000259|PROSITE:PS50070"
FT DOMAIN 364..579
FT /note="Peptidase S1"
FT /evidence="ECO:0000259|PROSITE:PS50240"
FT SITE 198..199
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-2"
FT SITE 327..328
FT /note="Cleavage; by factor Xa"
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-2"
FT SITE 363..364
FT /note="Cleavage; by factor Xa"
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-2"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-3"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-3"
FT CARBOHYD 416
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-3"
FT DISULFID 60..65
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 90..103
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 108..186
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 129..169
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 157..181
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 213..291
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 234..274
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 262..286
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 391..407
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 497..511
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
FT DISULFID 525..555
FT /evidence="ECO:0000256|PIRSR:PIRSR001149-4"
SQ SEQUENCE 583 AA; 65409 MW; 9AA7C96D997C827C CRC64;
MAHVRGLQLP GCLALAALCS LVHSQHVFLA PQQARSLLQR VRRANTFLEE VRKGNLEREC
VEETCSYEEA FEALESSTAT DVFWAKYTAC ETARTPRDKL AACLEGNCAE GLGTNYRGHV
NITRSGIECQ LWRSRYPHKP EINSTTHPGA DLQENFCRNP DSSTTGPWCY TTDPTVRRQE
CSIPVCGQDQ VTVAMTPRSE GSSVNLSPPL EQCVPDRGQQ YQGRLAVTTH GLPCLAWASA
QAKALSKHQD FNSAVQLVEN FCRNPDGDEE GVWCYVAGKP GDFGYCDLNY CEEAVEEETG
DGLDEDSDRA IEGRTATSEY QTFFNPRTFG SGEADCGLRP LFEKKSLEDK TERELLESYI
DGRIVEGSDA EIGMSPWQVM LFRKSPQELL CGASLISDRW VLTAAHCLLY PPWDKNFTEN
DLLVRIGKHS RTRYERNIEK ISMLEKIYIH PSLLQAGYKG RVTGWGNLKE TWTANVGKGQ
PSVLQVVNLP IVERPVCKDS TRIRITDNMF CAGYKPDEGK RGDACEGDSG GPFVMKSPFN
NRWYQMGIVS WGEGCDRDGK YGFYTHVFRL KKWIQKVIDQ FGE
//
