serpin family C member 1

Target id: 2632

Nomenclature: serpin family C member 1

Family: Blood coagulation components

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     serpin family C member 1 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 464 1q25.1 SERPINC1 serpin family C member 1
Mouse - 465 1 H2.1 Serpinc1 serine (or cysteine) peptidase inhibitor
Rat - - 13q22 Serpinc1 serpin family C member 1
Previous and Unofficial Names
antithrombin-III | ATIII | serpin peptidase inhibitor, clade C (antithrombin), member 1 | serpin peptidase inhibitor | serine (or cysteine) peptidase inhibitor, clade C (antithrombin), member 1
Database Links
Specialist databases
MEROPS I04.018 (Hs)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
heparin Hs Activation 7.8 pKd 4
pKd 7.8 (Kd 1.42x10-8 M) [4]
Description: Catalyses the inactivation of coagulation proteases by activatted antithrombin-III
fondaparinux Hs Activation 7.5 pKd 8
pKd 7.5 (Kd 3.2x10-8 M) [8]
Description: Catalyses the inactivation of coagulation proteases by activated antithrombin-III
dalteparin Hs Activation - - 5
[5]
Description: Catalyses the inactivation of coagulation proteases by activated antithrombin-III
danaparoid Hs Activation - - 1,6
[1,6]
Description: Catalyses the inactivation of coagulation proteases by activated antithrombin-III
enoxaparin Hs Activation - - 2
[2]
Description: Catalyses the inactivation of coagulation proteases by activated antithrombin-III
tinzaparin Hs Activation - - 3
[3]
Description: Catalyses the inactivation of coagulation proteases by activated antithrombin-III
Immunopharmacology Comments
Antithrombin-III, the protein product of the SERPINC1 gene, is believed to have some regulatory effect on inflammatory tone, principally anti-inflammatory action [7,12], but the mechanism of this action is poorly understood. A 2017 article by Smits et al. suggests that the HS3ST1 gene (that encodes a heparan sulfate biosynthetic enzyme) is required for AT's anti-inflammatory activity, and that this interaction provides protection against acute and chronic inflammatory disorders [9].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment:  Antithrombin-III, encoded by the SERPINC1 gene, has some anti-inflammatory action which is mediated via various potential mechanistic pathways [7,9,12]. The precise mechanism is still to be fully resolved.
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  acute inflammatory response to antigenic stimulus (GO:0002438) IEA
References: 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Thrombophilia due to antithrombin III deficiency
Synonyms: Thrombophilia [Disease Ontology: DOID:2452]
Disease Ontology: DOID:2452
OMIM: 613118
Orphanet: ORPHA82
General Comments
The low molecular weight heparins (LMWHs) and their derivatives above bind to the protease inhibitor antithrombin III (AT-III), inducing activation via a conformational change. This in turn inactivates thrombin and other proteases involved in blood clotting (e.g. factor Xa) resulting in an overall decrease in clotting ability (reviewed in [10]). Fondaparinux is specific against factor Xa via AT-III [11]. Since the heparins are technically mixtures specific binding constants are not available. However, the listed references give insights in to the function and uses of these compounds.

References

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1. Cziraky MJ, Spinler SA. (1993) Low-molecular-weight heparins for the treatment of deep-vein thrombosis. Clin Pharm12 (12): 892-9. [PMID:8137606]

2. Eriksson BI, Söderberg K, Widlund L, Wandeli B, Tengborn L, Risberg B. (1995) A comparative study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UH) in healthy volunteers. Thromb. Haemost.73 (3): 398-401. [PMID:7667822]

3. Friedel HA, Balfour JA. (1994) Tinzaparin. A review of its pharmacology and clinical potential in the prevention and treatment of thromboembolic disorders. Drugs48 (4): 638-60. [PMID:7528134]

4. Gotti R, Parma B, Spelta F, Liverani L. (2013) Affinity capillary electrophoresis in binding study of antithrombin to heparin from different sources. Talanta105: 366-71. [PMID:23598032]

5. Holmer E, Söderberg K, Bergqvist D, Lindahl U. (1986) Heparin and its low molecular weight derivatives: anticoagulant and antithrombotic properties. Haemostasis16 Suppl 2: 1-7. [PMID:3744129]

6. Nakase J, Toribatake Y, Mouri Y, Seki H, Kitaoka K, Tomita K. (2009) Heparin versus danaproid for prevention of venous thromboembolism after hip surgery. J Orthop Surg (Hong Kong)17 (1): 6-9. [PMID:19398784]

7. Oelschläger C, Römisch J, Staubitz A, Stauss H, Leithäuser B, Tillmanns H, Hölschermann H. (2002) Antithrombin III inhibits nuclear factor kappaB activation in human monocytes and vascular endothelial cells. Blood99 (11): 4015-20. [PMID:12010802]

8. Paolucci F, Claviés MC, Donat F, Necciari J. (2002) Fondaparinux sodium mechanism of action: identification of specific binding to purified and human plasma-derived proteins. Clin Pharmacokinet41 Suppl 2: 11-8. [PMID:12383040]

9. Smits NC, Kobayashi T, Srivastava PK, Skopelja S, Ivy JA, Elwood DJ, Stan RV, Tsongalis GJ, Sellke FW, Gross PL et al.. (2017) HS3ST1 genotype regulates antithrombin's inflammomodulatory tone and associates with atherosclerosis. Matrix Biol.63: 69-90. [PMID:28126521]

10. van Boven HH, Lane DA. (1997) Antithrombin and its inherited deficiency states. Semin. Hematol.34 (3): 188-204. [PMID:9241705]

11. Walenga JM, Jeske WP, Samama MM, Frapaise FX, Bick RL, Fareed J. (2002) Fondaparinux: a synthetic heparin pentasaccharide as a new antithrombotic agent. Expert Opin Investig Drugs11 (3): 397-407. [PMID:11866668]

12. Yamauchi T, Umeda F, Inoguchi T, Nawata H. (1989) Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells. Biochem. Biophys. Res. Commun.163 (3): 1404-11. [PMID:2675842]

How to cite this page

Blood coagulation components: serpin family C member 1. Last modified on 28/09/2017. Accessed on 13/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2632.