PROZ (protein Z, vitamin K dependent plasma glycoprotein)

Gene

• Entrez ID: 8858
• Gene name: Protein Z, vitamin K dependent plasma glycoprotein
• Gene symbol: PROZ
• Synonyms (NCBI Gene): PZ
• Chromosome: 13
• Chromosome location: 13q34
• Summary: This gene encodes a liver vitamin K-dependent glycoprotein that is synthesized in the liver and secreted into the plasma. The encoded protein plays a role in regulating blood coagulation by complexing with protein Z-dependent protease inhibitor to directl

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004252	Function	Serine-type endopeptidase activity	IBA
GO:0004252	Function	Serine-type endopeptidase activity	IEA
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	20427285
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005788	Component	Endoplasmic reticulum lumen	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005796	Component	Golgi lumen	IEA
GO:0005796	Component	Golgi lumen	TAS
GO:0006508	Process	Proteolysis	IBA
GO:0006508	Process	Proteolysis	IEA
GO:0007596	Process	Blood coagulation	IBA
GO:0007596	Process	Blood coagulation	IEA
GO:0007596	Process	Blood coagulation	IEA
GO:0007599	Process	Hemostasis	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145

Other IDs

• MIM: 176895
• HGNC: 9460
• e!Ensembl: ENSG00000126231

Protein

• UniProt ID: P22891
• Protein name: Vitamin K-dependent protein Z
• Protein function: Appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles. Inhibits activity of the coagulation protease factor Xa in the presence of SERPINA10, calcium and phospholipids.
• PDB: 3F1S, 3H5C
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00594	Gla	46 → 86	Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain	Domain
  PF00008	EGF	91 → 121	EGF-like domain	Domain
  PF00089	Trypsin	177 → 395	Trypsin	Domain

• Tissue specificity: TISSUE SPECIFICITY: Plasma.
• Sequence:

  MAGCVPLLQGLVLVLALHRVEPSVFLPASKANDVLVRWKRAGSYLLEELFEGNLEKECYE
  EICVYEEAREVFENEVVTDEFWRRYKGGSPCISQPCLHNGSCQDSIWGYTCTCSPGYEGS
  NCELAKNECHPERTDGCQHFCLPGQESYTCSCAQGYRLGEDHKQCVPHDQCACGVLTSEK
  RAPDLQDLPWQVKLTNSEGKDFCGGVIIRENFVLTTAKCSLLHRNITVKTYFNRTSQDPL
  MIKITHVHVHMRYDADAGENDLSLLELEWPIQCPGAGLPVCTPEKDFAEHLLIPRTRGLL
  SGWARNGTDLGNSLTTRPVTLVEGEECGQVLNVTVTTRTYCERSSVAAMHWMDGSVVTRE
  HRGSWFLTGVLGSQPVGGQAHMVLVTKVSRYSLWFKQIMN

• Sequence length: 400

Pathways

Reactome:

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

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Abnormal bleeding	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BEHCET SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRAIN ISCHEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CEREBRAL SINOVENOUS THROMBOSIS	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Protein Z deficiency	Uncertain significance; Likely benign; Affects	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROZ-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thrombocytopenia	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Coronary Syndrome	Coronary Syndrome	LHGDN	15314579		★☆☆☆☆ Found in Text Mining only
Anemia Sickle Cell	Sickle cell anemia	Pubtator	28548215	Associate	★☆☆☆☆ Found in Text Mining only
Anemia, Sickle Cell	Anemia	BEFREE	28548215		★☆☆☆☆ Found in Text Mining only
Behcet Syndrome	Behcet Syndrome	LHGDN	14507116		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Brain Ischemia	Cerebral Ischemia	LHGDN	14671240		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36140703	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Cerebral Infarction	BEFREE	14671240, 27683756, 29746949		★☆☆☆☆ Found in Text Mining only
Cerebral sinovenous thrombosis	Cerebral Sinovenous Thrombosis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cerebrovascular accident	Stroke	LHGDN	12970515, 14671240		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	16155788, 27683756		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney Disease	LHGDN	18180611		★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Non rare thrombophilia	Non Rare Thrombophilia	Orphanet			★☆☆☆☆ Found in Text Mining only
PROTEIN Z DEFICIENCY	Protein Z Deficiency	GENOMICS_ENGLAND_DG	15638861		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pyelonephritis	Pyelonephritis	LHGDN	18828054		★☆☆☆☆ Found in Text Mining only
Thromboembolism	Thromboembolism	Pubtator	19050305	Associate	★☆☆☆☆ Found in Text Mining only
Thrombophilia	Thrombophilia	Pubtator	37098010	Associate	★☆☆☆☆ Found in Text Mining only