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Protein

Prothrombin

Gene

F2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.

Catalytic activityi

Selective cleavage of Arg-|-Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B.

Enzyme regulationi

Inhibited by SERPINA5.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei402 – 4021Charge relay systemBy similarity
Active sitei458 – 4581Charge relay systemBy similarity
Active sitei564 – 5641Charge relay systemBy similarity

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • serine-type endopeptidase activity Source: RGD

GO - Biological processi

  • acute-phase response Source: UniProtKB-KW
  • blood coagulation Source: RGD
  • cellular response to mechanical stimulus Source: RGD
  • positive regulation of blood coagulation Source: RGD
  • response to inactivity Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Acute phase, Blood coagulation, Hemostasis

Keywords - Ligandi

Calcium

Protein family/group databases

MEROPSiS01.217.

Names & Taxonomyi

Protein namesi
Recommended name:
Prothrombin (EC:3.4.21.5)
Alternative name(s):
Coagulation factor II
Cleaved into the following 4 chains:
Gene namesi
Name:F2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi61996. F2.

Subcellular locationi

GO - Cellular componenti

  • extracellular matrix Source: RGD
  • extracellular space Source: RGD
Complete GO annotation...

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL3078.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Propeptidei25 – 4319PRO_0000028177Add
BLAST
Chaini44 – 617574ProthrombinPRO_0000028178Add
BLAST
Peptidei44 – 200157Activation peptide fragment 1PRO_0000028179Add
BLAST
Peptidei201 – 323123Activation peptide fragment 2PRO_0000028180Add
BLAST
Chaini324 – 35936Thrombin light chainPRO_0000028181Add
BLAST
Chaini360 – 617258Thrombin heavy chainPRO_0000028182Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei50 – 5014-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei51 – 5114-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei58 – 5814-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei60 – 6014-carboxyglutamatePROSITE-ProRule annotationBy similarity
Disulfide bondi61 ↔ 66By similarity
Modified residuei63 – 6314-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei64 – 6414-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei69 – 6914-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei70 – 7014-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei73 – 7314-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei76 – 7614-carboxyglutamatePROSITE-ProRule annotationBy similarity
Disulfide bondi91 ↔ 104By similarity
Disulfide bondi109 ↔ 187By similarity
Glycosylationi120 – 1201N-linked (GlcNAc...)Sequence analysis
Disulfide bondi130 ↔ 170By similarity
Glycosylationi144 – 1441N-linked (GlcNAc...)Sequence analysis
Disulfide bondi158 ↔ 182By similarity
Disulfide bondi215 ↔ 292By similarity
Disulfide bondi236 ↔ 276By similarity
Disulfide bondi264 ↔ 287By similarity
Disulfide bondi332 ↔ 478Interchain (between light and heavy chains)PROSITE-ProRule annotation
Disulfide bondi387 ↔ 403By similarity
Glycosylationi412 – 4121N-linked (GlcNAc...)Sequence analysis
Disulfide bondi532 ↔ 546By similarity
Glycosylationi552 – 5521N-linked (GlcNAc...)Sequence analysis
Disulfide bondi560 ↔ 590By similarity

Post-translational modificationi

The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei200 – 2012Cleavage; by thrombin
Sitei323 – 3242Cleavage; by factor Xa
Sitei359 – 3602Cleavage; by factor Xa

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Gamma-carboxyglutamic acid, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP18292.
PRIDEiP18292.

PTM databases

iPTMnetiP18292.
PhosphoSiteiP18292.

Miscellaneous databases

PMAP-CutDBP18292.

Interactioni

Subunit structurei

Heterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with SERPINA5 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022233.

Chemistry

BindingDBiP18292.

Structurei

3D structure databases

ProteinModelPortaliP18292.
SMRiP18292. Positions 44-190, 209-615.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 9047GlaPROSITE-ProRule annotationAdd
BLAST
Domaini109 – 18779Kringle 1PROSITE-ProRule annotationAdd
BLAST
Domaini215 – 29278Kringle 2PROSITE-ProRule annotationAdd
BLAST
Domaini360 – 614255Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni547 – 56923High affinity receptor-binding region which is also known as the TP508 peptideAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 Gla (gamma-carboxy-glutamate) domain.PROSITE-ProRule annotation
Contains 2 kringle domains.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKPN. Eukaryota.
COG5640. LUCA.
HOGENOMiHOG000251824.
HOVERGENiHBG108381.
InParanoidiP18292.
PhylomeDBiP18292.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di4.10.140.10. 1 hit.
4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR000294. GLA_domain.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR003966. Prothrombin/thrombin.
IPR018992. Thrombin_light_chain.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PANTHERiPTHR24254:SF10. PTHR24254:SF10. 1 hit.
PfamiPF00594. Gla. 1 hit.
PF00051. Kringle. 2 hits.
PF09396. Thrombin_light. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001149. Thrombin. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
PR01505. PROTHROMBIN.
SMARTiSM00069. GLA. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
SSF57630. SSF57630. 1 hit.
PROSITEiPS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS00021. KRINGLE_1. 2 hits.
PS50070. KRINGLE_2. 2 hits.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P18292-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLHVRGLGLP GCLALAALAS LVHSQHVFLA PQQALSLLQR VRRANSGFLE
60 70 80 90 100
ELRKGNLERE CVEEQCSYEE AFEALESPQD TDVFWAKYTV CDSVRKPRET
110 120 130 140 150
FMDCLEGRCA MDLGLNYHGN VSVTHTGIEC QLWRSRYPHR PDINSTTHPG
160 170 180 190 200
ADLKENFCRN PDSSTSGPWC YTTDPTVRRE ECSIPVCGQE GRTTVKMTPR
210 220 230 240 250
SRGSKENLSP PLGECLLERG RLYQGNLAVT TLGSPCLAWD SLPTKTLSKY
260 270 280 290 300
QNFDPEVKLV QNFCRNPDRD EEGAWCFVAQ QPGFEYCSLN YCDEAVGEEN
310 320 330 340 350
HDGDESIAGR TTDAEFHTFF DERTFGLGEA DCGLRPLFEK KSLTDKTEKE
360 370 380 390 400
LLDSYIDGRI VEGWDAEKGI APWQVMLFRK SPQELLCGAS LISDRWVLTA
410 420 430 440 450
AHCILYPPWD KNFTENDLLV RIGKHSRTRY ERNVEKISML EKIYIHPRYN
460 470 480 490 500
WRENLDRDIA LLKLKKPVPF SDYIHPVCLP DKQTVTSLLQ AGYKGRVTGW
510 520 530 540 550
GNLRETWTTN INEIQPSVLQ VVNLPIVERP VCKASTRIRI TDNMFCAGFK
560 570 580 590 600
VNDTKRGDAC EGDSGGPFVM KSPYNHRWYQ MGIVSWGEGC DRNGKYGFYT
610
HVFRLKRWMQ KVIDQHR
Length:617
Mass (Da):70,412
Last modified:November 1, 1990 - v1
Checksum:iAD27D1B71445DB1D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52835 Transcribed RNA. Translation: CAA37017.1.
M81397 mRNA. Translation: AAA42240.1.
PIRiS10511.
UniGeneiRn.54498.

Genome annotation databases

UCSCiRGD:61996. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52835 Transcribed RNA. Translation: CAA37017.1.
M81397 mRNA. Translation: AAA42240.1.
PIRiS10511.
UniGeneiRn.54498.

3D structure databases

ProteinModelPortaliP18292.
SMRiP18292. Positions 44-190, 209-615.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022233.

Chemistry

BindingDBiP18292.
ChEMBLiCHEMBL3078.

Protein family/group databases

MEROPSiS01.217.

PTM databases

iPTMnetiP18292.
PhosphoSiteiP18292.

Proteomic databases

PaxDbiP18292.
PRIDEiP18292.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:61996. rat.

Organism-specific databases

RGDi61996. F2.

Phylogenomic databases

eggNOGiENOG410IKPN. Eukaryota.
COG5640. LUCA.
HOGENOMiHOG000251824.
HOVERGENiHBG108381.
InParanoidiP18292.
PhylomeDBiP18292.

Miscellaneous databases

PMAP-CutDBP18292.
PROiP18292.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di4.10.140.10. 1 hit.
4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR000294. GLA_domain.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR003966. Prothrombin/thrombin.
IPR018992. Thrombin_light_chain.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PANTHERiPTHR24254:SF10. PTHR24254:SF10. 1 hit.
PfamiPF00594. Gla. 1 hit.
PF00051. Kringle. 2 hits.
PF09396. Thrombin_light. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001149. Thrombin. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
PR01505. PROTHROMBIN.
SMARTiSM00069. GLA. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
SSF57630. SSF57630. 1 hit.
PROSITEiPS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS00021. KRINGLE_1. 2 hits.
PS50070. KRINGLE_2. 2 hits.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTHRB_RAT
AccessioniPrimary (citable) accession number: P18292
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: September 7, 2016
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Prothrombin is activated on the surface of a phospholipid membrane that binds the amino end of prothrombin and factors Va and Xa in Ca-dependent interactions; factor Xa removes the activation peptide and cleaves the remaining part into light and heavy chains. The activation process starts slowly because factor V itself has to be activated by the initial, small amounts of thrombin.
Thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa.
The peptide TP508 is able to accelerate repair of both soft and hard tissues.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.