PROC (protein C, inactivator of coagulation factors Va and VIIIa)

Gene

• Entrez ID: 5624
• Gene name: Protein C, inactivator of coagulation factors Va and VIIIa
• Gene symbol: PROC
• Synonyms: APC, PC, PROC1, THPH3, THPH4
• Chromosome: 2
• Chromosome location: 2q14.3
• Summary: This gene encodes a vitamin K-dependent plasma glycoprotein. The encoded protein is cleaved to its activated form by the thrombin-thrombomodulin complex. This activated form contains a serine protease domain and functions in degradation of the activated f

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918148	A>C	Pathogenic	Coding sequence variant, missense variant
rs121918149	G>A	Pathogenic	Coding sequence variant, missense variant
rs369504169	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs754243426	G>A	Likely-pathogenic	Splice acceptor variant, intron variant, coding sequence variant, missense variant
rs757583846	C>T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs1448630830	G>A,T	Likely-pathogenic	Coding sequence variant, missense variant, stop gained
rs1553423061	GTTATGG>-	Likely-pathogenic	Upstream transcript variant, frameshift variant, 5 prime UTR variant, genic upstream transcript variant, coding sequence variant
rs1553423955	G>A	Likely-pathogenic	Splice acceptor variant
rs1573442055	A>G	Likely-pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1265030	hsa-miR-3682-5p	CLIP-seq
MIRT1265031	hsa-miR-3907	CLIP-seq
MIRT1265032	hsa-miR-4797-3p	CLIP-seq
MIRT1265033	hsa-miR-552	CLIP-seq
MIRT1265034	hsa-miR-764	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ONECUT1	Activation	9553065

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004252	Function	Serine-type endopeptidase activity	IBA	21873635
GO:0004252	Function	Serine-type endopeptidase activity	IMP	25748729
GO:0004252	Function	Serine-type endopeptidase activity	TAS	15005336
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	15248212, 32296183
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005783	Component	Endoplasmic reticulum	IDA	25748729
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005794	Component	Golgi apparatus	IDA	25748729
GO:0005796	Component	Golgi lumen	TAS
GO:0006508	Process	Proteolysis	NAS	12052963
GO:0006888	Process	Endoplasmic reticulum to Golgi vesicle-mediated transport	TAS
GO:0007596	Process	Blood coagulation	TAS
GO:0030195	Process	Negative regulation of blood coagulation	IBA	21873635
GO:0030195	Process	Negative regulation of blood coagulation	TAS	15005336
GO:0043066	Process	Negative regulation of apoptotic process	IMP	12563316
GO:0043687	Process	Post-translational protein modification	TAS
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0050728	Process	Negative regulation of inflammatory response	IMP	25651845
GO:0050819	Process	Negative regulation of coagulation	IMP	25651845
GO:1903142	Process	Positive regulation of establishment of endothelial barrier	IMP	25651845

Other IDs

• MIM: 612283
• HGNC: 9451
• e!Ensembl: ENSG00000115718

Protein

• UniProt ID: P04070
• Protein name: Vitamin K-dependent protein C (EC 3.4.21.69) (Anticoagulant protein C) (Autoprothrombin IIA) (Blood coagulation factor XIV) [Cleaved into: Vitamin K-dependent protein C light chain; Vitamin K-dependent protein C heavy chain; Activation peptide]
• Protein function: Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a protective effect on the endothelial cell barr
• PDB: 1AUT, 1LQV, 3F6U, 3JTC, 4DT7, 6M3B, 6M3C, 8JRU, 8JRV, 9BVM
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00594	Gla	47 → 87	Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain	Domain
  PF00008	EGF	96 → 130	EGF-like domain	Domain
  PF14670	FXa_inhibition	140 → 175		Domain
  PF00089	Trypsin	212 → 445	Trypsin	Domain

• Sequence:

  MWQLTSLLLFVATWGISGTPAPLDSVFSSSERAHQVLRIRKRANSFLEELRHSSLERECI
  EEICDFEEAKEIFQNVDDTLAFWSKHVDGDQCLVLPLEHPCASLCCGHGTCIDGIGSFSC
  DCRSGWEGRFCQREVSFLNCSLDNGGCTHYCLEEVGWRRCSCAPGYKLGDDLLQCHPAVK
  FPCGRPWKRMEKKRSHLKRDTEDQEDQVDPRLIDGKMTRRGDSPWQVVLLDSKKKLACGA
  VLIHPSWVLTAAHCMDESKKLLVRLGEYDLRRWEKWELDLDIKEVFVHPNYSKSTTDNDI
  ALLHLAQPATLSQTIVPICLPDSGLAERELNQAGQETLVTGWGYHSSREKEAKRNRTFVL
  NFIKIPVVPHNECSEVMSNMVSENMLCAGILGDRQDACEGDSGGPMVASFHGTWFLVGLV
  SWGEGCGLLHNYGVYTKVSRYLDWIHGHIRDKEAPQKSWAP

• Sequence length: 461

Pathways

KEGG:

Complement and coagulation cascades

Reactome:

Intrinsic Pathway of Fibrin Clot Formation
Common Pathway of Fibrin Clot Formation
Gamma-carboxylation of protein precursors
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
Removal of aminoterminal propeptides from gamma-carboxylated proteins
Cell surface interactions at the vascular wall
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Post-translational protein phosphorylation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Asthma	Asthma	rs324981, rs121912630, rs150116809, rs4950928, rs708494, rs1581842283	21907864
Cerebral palsy	Cerebral Palsy	rs121918149, rs75184679, rs730880264, rs587777428, rs797045067, rs767399782, rs564185858, rs886039513
Developmental delay	Global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Hereditary thrombophilia	Severe hereditary thrombophilia due to congenital protein C deficiency	rs121918146, rs121918122, rs761776963
Hypertension	Hypertensive disease	rs13306026, rs13333226	22352330
Thrombophilia	Thrombophilia, Thrombophilia, Hereditary, Due To Protein C Deficiency, Autosomal Dominant, THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL RECESSIVE	rs118203912, rs118203911, rs121918141, rs121918142, rs121918143, rs121918144, rs121918145, rs121918146, rs121918147, rs121918148, rs121918149, rs121918151, rs121918152, rs121918153, rs121918154, rs1558715857, rs121918155, rs121918157, rs121918158, rs2104934553, rs121918159, rs121918160, rs121918477, rs121918473, rs121918474, rs267606981, rs2107137679, rs121918475, rs387906674, rs387907201, rs369504169, rs142742242, rs373983977, rs368074804, rs574132670, rs757583846, rs863224838, rs121918476, rs1333329860, rs1553424043, rs1553808038, rs5017717, rs374476971, rs1553809314, rs1553423955, rs767112991, rs1558718572, rs571278160, rs766261022, rs1321566264, rs1559926604, rs1241365457, rs759677822, rs1448630830, rs1305782685, rs1571577365, rs1247269491, rs777486993, rs201907715, rs769277939, rs199469503, rs1575904540, rs199469494, rs199469471, rs1189377845, rs1576182848, rs1688218776, rs1456533664, rs1709033502, rs1708668246, rs1708665916	8446940, 9840027, 7792728, 1301959, 7482420, 16867987, 8807339, 24028705, 9798967, 14642106, 2437584, 17635713, 1511989, 10942114, 7605880, 17152060, 1868249, 8505327, 1593215, 1347706, 1771629, 18954896, 28111891, 8477066, 19822351, 1498334, 25748729, 1347608, 22817391, 8398832, 8499568, 1464619, 8292730, 23332921, 15978566, 7865674, 25618265, 2602169, 24162787, 28468828, 27172833, 22545135, 8560401, 8829639, 8499565, 7878626, 7841323, 1611081, 1511988, 25618265, 7841324, 1593215

Unknown
Disease name	Disease term	dbSNP ID	References
Congenital thrombotic disease	Congenital thrombotic disease, due to Protein C deficiency		23521084, 25748729
Disseminated intravascular coagulation	Disseminated Intravascular Coagulation		18376272
Drachtman weinblatt sitarz syndrome	Congenital neurologic anomalies
Gangrene	Gangrene
Non rare thrombophilia	NON RARE IN EUROPE: Non rare thrombophilia
Protein c deficiency	Protein C Deficiency		14707701, 18376272, 31064749, 21445774, 23521084
Purpura fulminans	Purpura Fulminans		18376272
Septicemia	Septicemia		11820775, 17556722
Superficial thrombophlebitis	Superficial Thrombophlebitis
Thrombosis	Deep Vein Thrombosis, Thrombosis of cerebral veins		25748729, 31064749, 12730085
Venous insufficiency	Venous Insufficiency