Top ▲

serpin family C member 1

Click here for help

Target id: 2632

Nomenclature: serpin family C member 1

Abbreviated Name: antithrombin, antithrombin III

Family: Blood coagulation components

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 464 1q25.1 SERPINC1 serpin family C member 1
Mouse - 465 1 69.75 cM Serpinc1 serine (or cysteine) peptidase inhibitor, clade C (antithrombin), member 1
Rat - - 13q22 Serpinc1 serpin family C member 1
Previous and Unofficial Names Click here for help
antithrombin-III | ATIII | serine (or cysteine) peptidase inhibitor | serine (or cysteine) peptidase inhibitor, clade C (antithrombin), member 1 | serpin peptidase inhibitor | serpin peptidase inhibitor, clade C (antithrombin), member 1
Database Links Click here for help
Specialist databases
MEROPS I04.018 (Hs)
Other databases
Alphafold P01008 (Hs), P32261 (Mm)
ChEMBL Target CHEMBL1950 (Hs)
DrugBank Target P01008 (Hs)
Ensembl Gene ENSG00000117601 (Hs), ENSMUSG00000026715 (Mm), ENSRNOG00000002783 (Rn)
Entrez Gene 462 (Hs), 11905 (Mm), 304917 (Rn)
Human Protein Atlas ENSG00000117601 (Hs)
KEGG Gene hsa:462 (Hs), mmu:11905 (Mm), rno:304917 (Rn)
OMIM 107300 (Hs)
Orphanet ORPHA118609 (Hs)
Pharos P01008 (Hs)
RefSeq Nucleotide NM_000488 (Hs), NM_080844 (Mm), NM_001012027 (Rn)
RefSeq Protein NP_000479 (Hs), NP_543120 (Mm), NP_001012027 (Rn)
UniProtKB P01008 (Hs), P32261 (Mm)
Wikipedia SERPINC1 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
heparin Small molecule or natural product Approved drug Primary target of this compound 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 Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure 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 Small molecule or natural product Approved drug Primary target of this compound Hs Activation - - 5
⤷ [5]
Description: Catalyses the inactivation of coagulation proteases by activated antithrombin-III
danaparoid Small molecule or natural product Approved drug Primary target of this compound Hs Activation - - 1,6
⤷ [1,6]
Description: Catalyses the inactivation of coagulation proteases by activated antithrombin-III
enoxaparin Small molecule or natural product Approved drug Primary target of this compound Hs Activation - - 2
⤷ [2]
Description: Catalyses the inactivation of coagulation proteases by activated antithrombin-III
tinzaparin Small molecule or natural product Approved drug Primary target of this compound 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
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.
Clinically-Relevant Mutations and Pathophysiology Click here for help
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

Show »

1. Cziraky MJ, Spinler SA. (1993) Low-molecular-weight heparins for the treatment of deep-vein thrombosis. Clin Pharm, 12 (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. Drugs, 48 (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. Talanta, 105: 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. Haemostasis, 16 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. Blood, 99 (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 Pharmacokinet, 41 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 Drugs, 11 (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