F2 (P00734) — curation notes

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Protein

Prothrombin: signal 1-24, propeptide 25-43, chain 44-622, with Gla and two kringle
domains and a chymotrypsin-like protease domain; alpha-thrombin is the disulfide-linked
light (315-363) and heavy (364-622) chain heterodimer.
[file:human/F2/F2-uniprot.txt "SUBCELLULAR LOCATION: Secreted, extracellular space."]
[file:human/F2/F2-uniprot.txt "Expressed by the liver and secreted in plasma."]

Localization conclusion: extracellular / secreted plasma protein. It is not a
membrane protein. The ER-lumen and Golgi-lumen rows are secretory transit compartments
(kept as non-core); the six Reactome plasma membrane rows were modified to
GO:0009897 external side of plasma membrane, which is where thrombin engages PARs,
GPIb-alpha and thrombomodulin, and which the gene already carries by IDA
(colocalizes_with).

Function

[file:human/F2/F2-uniprot.txt "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."]
PMID:10761923
PMID:1672265
PMID:12855810
PMID:20421939

Notable review decisions

• GO:0070053 thrombospondin receptor activity (IDA, PMID:2435757, assigned by BHF-UCL)
  was REMOVEd with a source_defects entry. The paper isolates an 88-kDa platelet
  membrane glycoprotein (the OKM5 antigen, CD36/GPIV) as the thrombospondin binding site;
  thrombin appears only as the platelet agonist, and a secreted protease cannot be a
  membrane receptor.
  PMID:2435757
• GO:0008083 growth factor activity and GO:0048018 receptor ligand activity were
  marked as over-annotations: thrombin activates PARs by cleaving them, the tethered
  ligand being the receptor's own N-terminus.
• Ten bare protein-binding rows (serpins, staphylocoagulase, alpha-1-microglobulin, APP,
  PAI-1, LRP1) were removed under the protein-binding policy; the informative LRP1 and
  GPIb-alpha interactions are retained as signaling receptor binding.
• Both positive regulation of blood coagulation and negative regulation of blood coagulation are accepted, because the switch is made by thrombomodulin binding; the
  parent regulation of blood coagulation is therefore TOO_GENERAL.
• Antimicrobial and immunomodulatory rows from PMID:20421939 are kept as non-core because
  they describe released C-terminal peptides rather than the coagulation protease.