SerpinD1

SerpinD1, also known as heparin cofactor II (HCâ…¡), is a member of Serpin superfamily of the serine proteinase inhibitors. HCII is a glycoprotein in human plasma that inhibits thrombin and chymotrypsin, and the rate of inhibition of thrombin is rapidly increased by Dermatan sulfate (DS), heparin (H) and glycosaminoglycans(GAG). The stimulatory effect of glycosaminoglycans on the inhibition is mediated, in part, by the N-terminal acidic domain of HCII. Interestingly, a C-terminal His-tagged recombinant HCII exhibits enhanced activity of thrombin inhibition. It has been suggested that HCII plays an unique and important role in vascular homeostasis, and accordingly mutations in this gene or congenital HCII deficiency is potentially associated with thrombosis. HCII specifically inhibits thrombin action at the site of vascular wall injury and HCII-thrombin complexes have been detected in human plasma. HCII protects against thrombin-induced vascular remodeling in both humans and mice and suggest that HCII is a predictive biomarker and therapeutic target for atherosclerosis. SerpinD1 also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.

SerpinD1 Related Areas

Enzyme>>Protease & Regulator>>Serine Protease & Regulator>>Serpin Superfamily>>SerpinD1

Immunology>>Innate Immunity>>Coagulation>>SerpinD1

Cardiovascular>>Coagulation>>SerpinD1

SerpinD1 Alternative Names

SERPIND1, HCII, HC2, HCF2, HLS2, LS2, D22S673, [Homo sapiens]

SerpinD1, HCII, Hcf2, AA985900, AI303446, MGC107662 [Mus musculus]

Summaries for SerpinD1

Entrez Gene summary for SerpinD1:

The product encoded by SerpinD1 gene is a serine proteinase inhibitor which rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. SerpinD1 gene contains five exons and four introns. This protein shares homology with antithrombin III and other members of the alpha 1-antitrypsin superfamily. Mutations in SerpinD1 gene are associated with heparin cofactor II deficiency. [provided by RefSeq, Jul 2008]

OMIM - description for SerpinD1:

Heparin cofactor II is a serine protease inhibitor in plasma that rapidly inhibits thrombin in the presence of dermatan sulfate or heparin (Kondo et al., 1996).

Wikipedia summary for SerpinD1:

Heparin cofactor II (HCII), a protein encoded by the SERPIND1 gene, is a coagulation factor that inhibits IIa, and is a cofactor for heparin and dermatan sulfate ("minor antithrombin"). The product encoded by this gene is a serine proteinase inhibitor which rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. The gene contains five exons and four introns. This protein shares homology with antithrombin III and other members of the alpha 1-antitrypsin superfamily. Mutations in this gene are associated with heparin cofactor II deficiency. Heparin Cofactor II deficiency can lead to increased thrombin generation and a hypercoagulable state.

Human SerpinD1 Protein General Information

 

• Protein names: SerpinD1
• Sequence length: 499 AA.
• Domain: The N-terminal acidic repeat region mediates, in part, the glycosaminoglycan-accelerated thrombin inhibition.
• Sequence similarities: Belongs to the serpin family.
• Post-translational modification: Phosphorylation sites are present in the extracelllular medium.
• Sequence caution: The sequence CAG30459.1 differs from that shown. Reason: Erroneous initiation.
• Tissue specificity: Expressed predominantly in liver. Also present in plasma.
• Involvement in disease: Defects in SERPIND1 are the cause of thrombophilia due to heparin cofactor 2 deficiency (THPH10) . A hemostatic disorder characterized by a tendency to recurrent thrombosis.

General information above from UniProt

Function for SerpinD1 Protein

UniProtKB:

SerpinD1 is thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also SerpinD1 inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.
SerpinD1 peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils.

Genatlas:

• SerpinD1 is inhibitor of thrombin and chymotrypsin
• SerpinD1 rapidly inhibits thrombin in the presence of dermatan sulfate or heparin

Homology for human SerpinD1

• homolog to AT3

Phenotype Information for SerpinD1

• Gene/Locus: HCF2, HC2, SERPIND1, THPH10
• Phenotype: Thrombophilia due to heparin cofactor II deficiency

Phenotype Information for SerpinD1 from OMIM (Online Mendelian Inheritance in Man)

Drugs for SerpinD1

Target	Drug Name	Disease	Drug Status
SerpinD1	Ardeparin	Deep vein thrombosis	Approved

Drugs for SerpinD1 from TTD (Therapeutic Targets Database)