THRB_PIG
ID THRB_PIG Reviewed; 623 AA.
AC Q19AZ8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Prothrombin;
DE EC=3.4.21.5;
DE AltName: Full=Coagulation factor II;
DE Contains:
DE RecName: Full=Activation peptide fragment 1;
DE Contains:
DE RecName: Full=Activation peptide fragment 2;
DE Contains:
DE RecName: Full=Thrombin light chain;
DE Contains:
DE RecName: Full=Thrombin heavy chain;
DE Flags: Precursor;
GN Name=F2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Chen Y., Tan W., Cheng J.;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
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 -!- ACTIVITY REGULATION: Inhibited by SERPINA5. {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer (named alpha-thrombin) of a light and a heavy
CC chain; disulfide-linked. Forms a heterodimer with SERPINA5. In plasma,
CC interacts (via N-terminus) with alpha-1-microglobulin; this interaction
CC does not prevent the activation of prothrombin to thrombin.
CC {ECO:0000250|UniProtKB:P00734}.
CC -!- PTM: The gamma-carboxyglutamyl residues, which bind calcium ions,
CC result from the carboxylation of glutamyl residues by a microsomal
CC enzyme, the vitamin K-dependent carboxylase. The modified residues are
CC necessary for the calcium-dependent interaction with a negatively
CC charged phospholipid surface, which is essential for the conversion of
CC prothrombin to thrombin (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Prothrombin is activated on the surface of a
CC phospholipid membrane that binds the amino end of prothrombin and
CC factors Va and Xa in Ca-dependent interactions; factor Xa removes the
CC activation peptide and cleaves the remaining part into light and heavy
CC chains. The activation process starts slowly because factor V itself
CC has to be activated by the initial, small amounts of thrombin (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Thrombin can itself cleave the N-terminal fragment
CC (fragment 1) of the prothrombin, prior to its activation by factor Xa.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; DQ530370; ABF82359.1; -; mRNA.
DR RefSeq; NP_001116457.1; NM_001122985.1.
DR AlphaFoldDB; Q19AZ8; -.
DR SMR; Q19AZ8; -.
DR STRING; 9823.ENSSSCP00000014081; -.
DR MEROPS; S01.217; -.
DR PaxDb; Q19AZ8; -.
DR PeptideAtlas; Q19AZ8; -.
DR PRIDE; Q19AZ8; -.
DR GeneID; 100144442; -.
DR KEGG; ssc:100144442; -.
DR CTD; 2147; -.
DR eggNOG; ENOG502QTSX; Eukaryota.
DR InParanoid; Q19AZ8; -.
DR OrthoDB; 1314811at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0030168; P:platelet activation; IBA:GO_Central.
DR GO; GO:0030194; P:positive regulation of blood coagulation; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00108; KR; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.20.10; -; 2.
DR Gene3D; 4.10.140.10; -; 1.
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:SF10; PTHR24254:SF10; 1.
DR Pfam; PF00594; Gla; 1.
DR Pfam; PF00051; Kringle; 2.
DR Pfam; PF09396; Thrombin_light; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001149; Thrombin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR PRINTS; PR00001; GLABLOOD.
DR PRINTS; PR01505; PROTHROMBIN.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00130; KR; 2.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57440; SSF57440; 2.
DR SUPFAM; SSF57630; SSF57630; 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 2: Evidence at transcript level;
KW Acute phase; Blood coagulation; Calcium;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Gamma-carboxyglutamic acid; Glycoprotein; Hemostasis; Hydrolase; Kringle;
KW Protease; Reference proteome; Repeat; Serine protease; Signal; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..43
FT /evidence="ECO:0000250"
FT /id="PRO_0000285892"
FT CHAIN 44..623
FT /note="Prothrombin"
FT /id="PRO_0000285893"
FT PEPTIDE 44..199
FT /note="Activation peptide fragment 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285894"
FT PEPTIDE 200..328
FT /note="Activation peptide fragment 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285918"
FT CHAIN 329..364
FT /note="Thrombin light chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285919"
FT CHAIN 365..622
FT /note="Thrombin heavy chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285920"
FT DOMAIN 44..90
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 108..187
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 213..292
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 365..619
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 552..574
FT /note="High affinity receptor-binding region which is also
FT known as the TP508 peptide"
FT /evidence="ECO:0000250"
FT ACT_SITE 407
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 463
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 569
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 199..200
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT SITE 328..329
FT /note="Cleavage; by factor Xa"
FT /evidence="ECO:0000250"
FT SITE 364..365
FT /note="Cleavage; by factor Xa"
FT /evidence="ECO:0000250"
FT MOD_RES 50
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 51
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 58
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 60
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 63
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 64
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 69
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 70
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 73
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 76
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 61..66
FT /evidence="ECO:0000250"
FT DISULFID 91..104
FT /evidence="ECO:0000250"
FT DISULFID 109..187
FT /evidence="ECO:0000250"
FT DISULFID 130..170
FT /evidence="ECO:0000250"
FT DISULFID 158..182
FT /evidence="ECO:0000250"
FT DISULFID 214..292
FT /evidence="ECO:0000250"
FT DISULFID 235..275
FT /evidence="ECO:0000250"
FT DISULFID 263..287
FT /evidence="ECO:0000250"
FT DISULFID 337..483
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121,
FT ECO:0000255|PROSITE-ProRule:PRU00274, ECO:0000255|PROSITE-
FT ProRule:PRU00463"
FT DISULFID 392..408
FT /evidence="ECO:0000250"
FT DISULFID 537..551
FT /evidence="ECO:0000250"
FT DISULFID 565..595
FT /evidence="ECO:0000250"
SQ SEQUENCE 623 AA; 70066 MW; B7FEDC2231735D4E CRC64;
MAHVGGLWLH GCLALAVLVS LVHSQHVFMA PQQALSLLQR ARRANSGFFE EMRKGNLERE
CVEEQCSREE AYEALESPSE TDAFWAKYTA CESVRKSREK LVECLEGNCA EGLGMNYRGN
ISVTRSGIEC QLWRSRYPHK PEVNSTMYPG ADLRENFCRN PDGSITGPWC YTTSPTVRRE
ACSIPVCGQG RVTAELIPRS GGSTVNVSPP LETCVPERGR QYQGRLAVTS HGSPCLAWGS
SQAKALSKDQ DFNPAVPLVE NFCRNPDGDQ EGAWCYVAGQ PGDFEYCDLD YCEEPVDEEV
GDALGENADA AIEGRTTADD FQPFFNEKTF GAGEADCGLR PLFEKSSLED KTEKELFESY
IEGRIVEGSD AEIGLAPWQV MIFRKSPQEL LCGASLISDR WVLTAAHCLL YPPWDKNFTE
NDLLVRIGKH SRTRYERNIE KISMLEKIYI HPRYNWRENL DRDIALLKLR KPITFSDYIH
PVCLPDKETA TKLLRAGYKG RVTGWGNLKE TWTTSASEVQ PSVLQVVNLP IVERLVCKAS
TRIRITDNMF CAGYKPDEGK RGDACEGDSG GPFVMKSPFN NRWYQMGIVS WGEGCDRDGK
YGFYTHVFRL KKWMQKVIDR FGG
