Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4)
The protein contains 930 amino acids for an estimated molecular weight of 103357 Da.
Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
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.
This protein is annotated as membranous in Gene Ontology.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs13072536 | |
| empty | |
| dbSNP:rs2276814 | |
| dbSNP:rs4687657 | |
| dbSNP:rs2256734 | |
| dbSNP:rs2535621 |
No binding partner found
Biological Process
Acute-phase response
Hyaluronan metabolic process
Platelet degranulation
Response to cytokine
The reference OMIM entry for this protein is 600564
Inter-alpha-trypsin inhibitor, heavy chain 4; itih4
Inter-alpha-trypsin inhibitor, heavy chain-like, 1; itihl1
Inter-alpha-trypsin inhibitor, heavy chain-related protein; ihrp
Plasma kallikrein-sensitive glycoprotein 120; pk120
DESCRIPTION
The inter-alpha-trypsin inhibitors (ITI) are a family of structurally related plasma serine protease inhibitors involved in extracellular matrix stabilization and in prevention of tumor metastasis. The ITI family contains multiple proteins made up of a light chain (see 176870) and a variable number of heavy chains (Salier et al., 1987; Himmelfarb et al., 2004).CLONING
Nishimura et al. (1995) identified a 120-kD kallikrein-3 (KLK3; 176820)-sensitive glycoprotein (ITIH4) from human plasma. The glycoprotein, designated PK120 by them, circulates in the plasma at a concentration of 80 micrograms per milliliter and is cleaved by KLK3 into smaller fragments. The authors obtained partial amino acid sequence of purified PK120 from which degenerate PCR primers were designed. They obtained an RT-PCR product from human liver poly(A)+ RNA and used it to screen a human liver cDNA library. Their PK120 cDNA of 3,058 bp codes for a putative 28-amino acid signal sequence followed by a mature protein of 902 residues, 211 of which were confirmed by protein sequencing. Northern blots identified a strong 3.3-kb and a fainter 4-kb transcript in liver. The sequence shared similarity to the inter-alpha-trypsin inhibitor (ITI) superfamily. Saguchi et al. (1995) reported the sequence of a cDNA for a glycoprotein found in plasma that they designated 'inter-alpha-trypsin inhibitor family heavy chain-related protein' (IHRP). Based on partial amino acid sequence, the authors designed PCR primers, which were used to screen liver cDNA. The products were then used to screen liver cDNA libraries. The complete IHRP cDNA encodes a 930-residue protein. The N-terminal 28 amino acids corresponded to a signal peptide required for secretion. The first two-thirds of the predicted protein showed significant sequence similarity to the ITI heavy chains H1 (ITIH1; 147270) (52%), H2 (ITIH2; 146640) (49%), and H3 (ITIH3; 146650) (57%). Northern blot analysis demonstrated IHRP expression only in liver.GENE FUNCTION
Nishimura et al. (1995) speculated that the products of PK120 proteolysis may bind to hyaluronic acid, a major component of the extracellular matrix.MAPPING
Tobe et al. (1995) reported fluorescence in situ hybridization studies using a 2.5-kb cDNA fragment as a probe and indicating that the ITIHL1 gene is located in chromosome region 3p21-p14, where the ITIH1 and ITIH3 genes are located. This result, together with significant homology between the nucleotide sequences of ITIHL1 and the other 2 genes, supports the conclusion that ITIHL1 is a member of an evolutionarily related gene family of ITI heavy chains. Jean et al. (1997) mapped the human ITIH4 gene to 3p21.2-p14.1 by in situ hybridization. They mapped the mouse Itih4 gene to chromosome 14 by interspecific backcross analysis. In both human and mouse, the ITIH4 gene maps near the ITIH1 and ITIH3 genes. Diarra-Mehrpour et al. (1998) reported that the 3 ITIH genes are arranged ITIH1--ITIH3--ITIH4 in a cluster that spans 45 kb. The ITIH4 gene is transcribed in the opposite orientation from the others. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 600564 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).