Reviewed, UniProtKB/Swiss-Prot P12259 (FA5_HUMAN)

Names and origin

Protein names

Recommended name:
    Coagulation factor V
Alternative name(s):
    Activated protein C cofactor
Cleaved into the following 2 chains:
    1- Recommended name:
            Coagulation factor V heavy chain
    2- Recommended name:
            Coagulation factor V light chain

Gene names

Name:

F5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2224 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Coagulation factor V is a cofactor that participates with factor Xa to activate prothrombin to thrombin.
Subunit structure	Factor Va is composed of a heavy chain and a light chain, non-covalently bound. The interaction between the two chains is calcium-dependent.
Subcellular location	SecretedBy similarity.
Domain	Domain B contains 35 x 9 AA tandem repeats, and 2 x 17 AA repeats.
Post-translational modification	Thrombin activates factor V proteolytically to the active cofactor, factor Va (formation of a heavy chain at the N-terminus and a light chain at the C-terminus). Sulfation is required for efficient thrombin cleavage and activation and for full procoagulant activity.
Involvement in disease	Defects in F5 are the cause of factor V deficiency (FA5D) [MIM:227400]; also known as Owren parahemophilia. It is an hemorrhagic diastesis. Defects in F5 are the cause of thrombophilia due to activated protein C resistance (THR-APCR) [MIM:188055]. THR-APCR is a hemostatic disorder due to defective degradation of factor Va by activated protein C. It is characterized by a poor anticoagulant response to activated protein C resulting in tendency to thrombosis. Defects in F5 are a cause of susceptibility to Budd-Chiari syndrome [MIM:600880]. Budd-Chiari syndrome is a spectrum of disease states, including anatomic abnormalities and hypercoagulable disorders, resulting in hepatic venous outflow occlusion. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain, and abdominal ascites. Defects in F5 may be a cause of susceptibility to ischemic stroke [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
Sequence similarities	Belongs to the multicopper oxidase family. Contains 3 F5/8 type A domains. Contains 2 F5/8 type C domains. Contains 6 plastocyanin-like domains.

Ontologies

Keywords
Biological process	Blood coagulation
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Thrombophilia
Domain	Repeat Signal
Ligand	Calcium Copper Metal-binding
PTM	Glycoprotein Phosphoprotein Sulfation Zymogen
Technical term	3D-structure
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: ProtInc cell adhesion Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB plasma membrane Inferred from Experiment. Source: Reactome platelet alpha granule lumen Inferred from Experiment. Source: Reactome
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW copper ion binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28
	Chain	29 – 2224	2196	Coagulation factor V		PRO_0000002978
	Chain	29 – 737	709	Coagulation factor V heavy chain		PRO_0000002979
	Propeptide	738 – 1573	836	Activation peptide (connecting region)		PRO_0000002980
	Chain	1574 – 2224	651	Coagulation factor V light chain		PRO_0000002981
Regions
	Domain	30 – 329	300	F5/8 type A 1
	Domain	30 – 193	164	Plastocyanin-like 1
	Domain	203 – 329	127	Plastocyanin-like 2
	Domain	348 – 684	337	F5/8 type A 2
	Domain	348 – 526	179	Plastocyanin-like 3
	Domain	536 – 684	149	Plastocyanin-like 4
	Repeat	895 – 911	17	1-1
	Repeat	912 – 928	17	1-2
	Repeat	1185 – 1193	9	2-1
	Repeat	1194 – 1202	9	2-2
	Repeat	1203 – 1211	9	2-3
	Repeat	1212 – 1220	9	2-4
	Repeat	1221 – 1229	9	2-5
	Repeat	1230 – 1238	9	2-6
	Repeat	1239 – 1247	9	2-7
	Repeat	1248 – 1256	9	2-8
	Repeat	1257 – 1265	9	2-9
	Repeat	1266 – 1274	9	2-10
	Repeat	1275 – 1283	9	2-11
	Repeat	1284 – 1292	9	2-12
	Repeat	1293 – 1301	9	2-13
	Repeat	1302 – 1310	9	2-14
	Repeat	1311 – 1319	9	2-15
	Repeat	1320 – 1328	9	2-16
	Repeat	1329 – 1337	9	2-17
	Repeat	1338 – 1346	9	2-18
	Repeat	1347 – 1355	9	2-19
	Repeat	1356 – 1364	9	2-20
	Repeat	1365 – 1373	9	2-21
	Repeat	1374 – 1382	9	2-22
	Repeat	1383 – 1391	9	2-23
	Repeat	1392 – 1400	9	2-24
	Repeat	1401 – 1409	9	2-25
	Repeat	1410 – 1418	9	2-26
	Repeat	1419 – 1427	9	2-27
	Repeat	1428 – 1436	9	2-28
	Repeat	1437 – 1445	9	2-29
	Repeat	1446 – 1454	9	2-30
	Repeat	1455 – 1463	9	2-31
	Repeat	1464 – 1472	9	2-32
	Repeat	1473 – 1481	9	2-33
	Repeat	1482 – 1490	9	2-34
	Repeat	1493 – 1501	9	2-35
	Domain	1578 – 1907	330	F5/8 type A 3
	Domain	1578 – 1751	174	Plastocyanin-like 5
	Domain	1761 – 1907	147	Plastocyanin-like 6
	Domain	1907 – 2061	155	F5/8 type C 1
	Domain	2066 – 2221	156	F5/8 type C 2
	Region	692 – 1573	882	B
	Region	895 – 928	34	2 X 17 AA tandem repeats
	Region	1185 – 1501	317	35 X 9 AA approximate tandem repeats of [TNP]-L-S-P-D-L-S-Q-T
Sites
	Metal binding	139	1	Calcium By similarity
	Metal binding	140	1	Calcium By similarity
	Metal binding	1843	1	Copper By similarity
	Metal binding	1845	1	Copper By similarity
	Site	737 – 738	2	Cleavage; by thrombin
	Site	1046 – 1047	2	Cleavage; by thrombin
	Site	1573 – 1574	2	Cleavage; by thrombin
Amino acid modifications
	Modified residue	693	1	Sulfotyrosine Potential
	Modified residue	724	1	Sulfotyrosine Potential
	Modified residue	726	1	Sulfotyrosine Potential
	Modified residue	1150	1	Phosphoserine
	Modified residue	1522	1	Sulfotyrosine Potential
	Modified residue	1538	1	Sulfotyrosine Potential
	Modified residue	1543	1	Sulfotyrosine Potential
	Modified residue	1593	1	Sulfotyrosine Potential
	Glycosylation	51	1	N-linked (GlcNAc...) Potential
	Glycosylation	55	1	N-linked (GlcNAc...) Potential
	Glycosylation	239	1	N-linked (GlcNAc...) Potential
	Glycosylation	297	1	N-linked (GlcNAc...)
	Glycosylation	382	1	N-linked (GlcNAc...) Potential
	Glycosylation	460	1	N-linked (GlcNAc...)
	Glycosylation	468	1	N-linked (GlcNAc...) Potential
	Glycosylation	554	1	N-linked (GlcNAc...) Potential
	Glycosylation	741	1	N-linked (GlcNAc...) Potential
	Glycosylation	752	1	N-linked (GlcNAc...) Potential
	Glycosylation	760	1	N-linked (GlcNAc...) Potential
	Glycosylation	776	1	N-linked (GlcNAc...) Potential
	Glycosylation	782	1	N-linked (GlcNAc...) Potential
	Glycosylation	821	1	N-linked (GlcNAc...)
	Glycosylation	938	1	N-linked (GlcNAc...) Potential
	Glycosylation	977	1	N-linked (GlcNAc...)
	Glycosylation	1074	1	N-linked (GlcNAc...) Potential
	Glycosylation	1083	1	N-linked (GlcNAc...) Potential
	Glycosylation	1103	1	N-linked (GlcNAc...) Potential
	Glycosylation	1106	1	N-linked (GlcNAc...) Potential
	Glycosylation	1479	1	N-linked (GlcNAc...) Potential
	Glycosylation	1499	1	N-linked (GlcNAc...) Potential
	Glycosylation	1559	1	N-linked (GlcNAc...)
	Glycosylation	1703	1	N-linked (GlcNAc...) Potential
	Glycosylation	2010	1	N-linked (GlcNAc...) Potential
	Glycosylation	2209	1	N-linked (GlcNAc...) Potential
	Disulfide bond	167 ↔ 193		By similarity