Heparin cofactor 2 (SERPIND1)
The protein contains 499 amino acids for an estimated molecular weight of 57071 Da.
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 inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.', 'Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs5905 | |
| dbSNP:rs165867 | |
| dbSNP:rs34324685 | |
| dbSNP:rs11542069 | |
| THPH10 | |
| dbSNP:rs1042435 | |
| dbSNP:rs5904 | |
| THPH10 | |
| THPH10 |
No binding partner found
Biological Process
Blood coagulation
Cellular protein metabolic process
Chemotaxis
Negative regulation of endopeptidase activity
Post-translational protein modification
Cellular Component
Endoplasmic reticulum lumen
Extracellular exosome
Extracellular region
Extracellular space
The reference OMIM entry for this protein is 142360
Heparin cofactor ii; hcf2
Leuserpin 2; ls2
Serpind1
DESCRIPTION
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).CLONING
From a human liver cDNA library, Ragg (1986) isolated a novel member of the protease inhibitor family. The inhibitor, named leuserpin-2, has 48 amino acids and contains a leucine residue at its putative reactive center. It shows about 25% to 28% homology to 3 human members of the plasma protease inhibitor family: antithrombin III (AT3; 107300), alpha-1-antitrypsin (PI; 107400), and alpha-1-antichymotrypsin (AACT; 107280). Comparison with published partial amino acid sequences suggested that LS2 is closely related or identical to heparin cofactor II. Blinder et al. (1988) isolated an apparently full-length cDNA for HCF II from a human liver cDNA library.GENE STRUCTURE
Herzog et al. (1991) determined that the HCF2 gene contains 5 exons.MAPPING
By blot hybridization of a probe to DNA isolated from sorted human chromosomes, Blinder et al. (1988) mapped the HCF2 gene to chromosome 22. By use of rodent-human somatic cell hybrids carrying only parts of human chromosome 22 and by study of a chronic myelogenous leukemia cell line, Herzog et al. (1991) localized the HCF2 gene to chromosome 22q11, proximal to the breakpoint cluster region (151410).GENE FUNCTION
Aihara et al. (2004) measured plasma HCF II activity, HDL cholesterol level, and carotid artery plaque thickness in 306 Japanese individuals over 40 (mean age, 68.9 years) and observed that HCF II activity decreased with age. Multiple regression analysis revealed that plasma HCF II activity and HDL cholesterol level were independently associated with decreased plaque thickness and that the antiatherogenic contribution of HCF II activity was stronger than that of HDL cholesterol.MOLECULAR GENETICS
Using crossed immunolectrophoresis, Andersson et al. (1987) were the first to demonstrate molecular heterogeneity of the HCF II molecule, the so-called 'Oslo variant,' in affected members of 2 Norwegian families with HCF II deficiency (612356). Their findings were consistent with an autosomal dominant pattern of inheritance; affected individuals had half the normal amount of normal HCF II and were presumed heterozygotes. Using PCR, Blinder et al. (1989) amplified DNA fragments encoding the N-terminal 220 amino acids of HCF II from a patient with the Oslo variant. They identified a point mutation resulting in an arg189-to-his (R189H; 142360.0001) substitution in 1 allele. Blinder et al. (1989) created the same mutation in the cDNA of native HCF II by oligonucleotide-directed mutagenesis and expressed it in E. coli. The recombinant cofactor reacted with thrombin in the presence of heparin, but not dermatan sulfate, confirming that the R189H mutation is responsible for the functional abnormality in HCF II Oslo.ANIMAL MODEL
Vicente et al. (2007) reported that Hcf2 -/- mice are born at the expected mendelian frequency and that they appear normal and are fertile. However, Vicente et al. (2007) found that Hcf2 -/- mice were more sensitive than wildtype mice to neointima formation following mechanical dilation of the common carotid artery. Dermatan sulfate administered intravenously within 48 hours of injury inhibited neointima formation in wildtype mice, but it had no effect in Hcf2 -/- mice. In addition, Hcf2 deletion increased the size of diet-i ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for SERPIND1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 142360 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed