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ITIH4 inter-alpha-trypsin inhibitor heavy chain 4 [ Homo sapiens (human) ]

Gene ID: 3700, updated on 3-Nov-2024

Summary

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Official Symbol
ITIH4provided by HGNC
Official Full Name
inter-alpha-trypsin inhibitor heavy chain 4provided by HGNC
Primary source
HGNC:HGNC:6169
See related
Ensembl:ENSG00000055955 MIM:600564; AllianceGenome:HGNC:6169
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
H4P; IHRP; GP120; PK120; ITIHL1; PK-120; ITI-HC4
Summary
The protein encoded by this gene is secreted into the blood, where it is cleaved by plasma kallikrein into two smaller forms. Expression of this gene has been detected only in liver, and it seems to be upregulated during surgical trauma. This gene is part of a cluster of similar genes on chromosome 3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Expression
Restricted expression toward liver (RPKM 556.7) See more
Orthologs
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Genomic context

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See ITIH4 in Genome Data Viewer
Location:
3p21.1
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (52812962..52830672, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (52845872..52863582, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (52846978..52864688, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:52812248-52813447 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19948 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52828410-52829299 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 3 Neighboring gene uncharacterized LOC124906240 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52853641-52854629 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:52858275-52858432 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52861432-52862040 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52862041-52862648 Neighboring gene ITIH4 antisense RNA 1 Neighboring gene STIMATE-MUSTN1 readthrough Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_70612 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52873819-52874320 Neighboring gene musculoskeletal, embryonic nuclear protein 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:52878501-52879001 Neighboring gene STIM activating enhancer Neighboring gene microRNA 8064

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. cDNA and deduced amino acid sequence of human PK-120, a plasma kallikrein-sensitive glycoprotein. Nishimura H, et al. FEBS Lett, 1995 Jan 3. PMID 7805892
  2. Opposing roles of inter-α-trypsin inhibitor heavy chain 4 in recurrent pregnancy loss. Li L, et al. EBioMedicine, 2018 Nov. PMID 30348621, Free PMC Article
  3. ITI-H4, as a biomarker in the serum of recurrent pregnancy loss (RPL) patients. Kim MS, et al. Mol Biosyst, 2011 May. PMID 21331437
  4. Serological targeted analysis of an ITIH4 peptide isoform: a preterm birth biomarker and its associated SNP implications. Tan Z, et al. J Genet Genomics, 2015 Sep 20. PMID 26408095, Free PMC Article
  5. Inter-alpha-trypsin inhibitor heavy chain 4: a novel biomarker for environmental exposure to particulate air pollution in patients with chronic obstructive pulmonary disease. Lee KY, et al. Int J Chron Obstruct Pulmon Dis, 2015. PMID 25977605, Free PMC Article

See all (74) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Translatome profiling reveals Itih4 as a novel smooth muscle cell-specific gene in atherosclerosis.
    Title: Translatome profiling reveals Itih4 as a novel smooth muscle cell-specific gene in atherosclerosis.
  2. Serum interalpha-trypsin inhibitor heavy chain H4 may be an anti-inflammatory marker reflecting disease risk, activity and treatment outcome of ankylosing spondylitis.
    Title: Serum interα-trypsin inhibitor heavy chain H4 may be an anti-inflammatory marker reflecting disease risk, activity and treatment outcome of ankylosing spondylitis.
  3. Hyperglycosylated N-Linked Site 339 of gp120 Appears to Be Unique and May Contribute to CRF01_AE Transmission Among Men Who Have Sex with Men in China and Thailand.
    Title: Hyperglycosylated N-Linked Site 339 of gp120 Appears to Be Unique and May Contribute to CRF01_AE Transmission Among Men Who Have Sex with Men in China and Thailand.
  4. PGK1 modulates balance between pro- and anti-inflammatory cytokines by interacting with ITI-H4.
    Title: PGK1 modulates balance between pro- and anti-inflammatory cytokines by interacting with ITI-H4.
  5. Serum ITIH4 in coronary heart disease: a potential anti-inflammatory biomarker related to stenosis degree and risk of major adverse cardiovascular events.
    Title: Serum ITIH4 in coronary heart disease: a potential anti-inflammatory biomarker related to stenosis degree and risk of major adverse cardiovascular events.
  6. Longitudinal change of serum inter-alpha-trypsin inhibitor heavy chain H4, and its correlation with inflammation, multiorgan injury, and death risk in sepsis.
    Title: Longitudinal change of serum inter-alpha-trypsin inhibitor heavy chain H4, and its correlation with inflammation, multiorgan injury, and death risk in sepsis.
  7. Associations between KCNQ1 and ITIH4 gene polymorphisms and infant weight gain in early life.
    Title: Associations between KCNQ1 and ITIH4 gene polymorphisms and infant weight gain in early life.
  8. ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection.
    Title: ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection.
  9. ITIH4 is a novel serum biomarker for early gastric cancer diagnosis.
    Title: ITIH4 is a novel serum biomarker for early gastric cancer diagnosis.
  10. Citrullinated inter-alpha-trypsin inhibitor heavy chain 4 in arthritic joints and its potential effect in the neutrophil migration.
    Title: Citrullinated inter-alpha-trypsin inhibitor heavy chain 4 in arthritic joints and its potential effect in the neutrophil migration.
Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
EBI GWAS Catalog
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
EBI GWAS Catalog
Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
EBI GWAS Catalog
Genome-wide association study identifies five new schizophrenia loci.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: MUSTN1

Homology

Clone Names

  • DKFZp686G21125

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase inhibitor activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in acute-phase response IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in hyaluronan metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of peptidase activity IEA
Inferred from Electronic Annotation
more info
  
involved_in response to cytokine IEP
Inferred from Expression Pattern
more info
 PubMed 
Component Evidence Code Pubs
located_in blood microparticle HDA PubMed 
located_in collagen-containing extracellular matrix HDA PubMed 
located_in extracellular exosome HDA PubMed 
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in platelet dense granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
inter-alpha-trypsin inhibitor heavy chain H4
Names
ITI heavy chain H4
inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein)
inter-alpha-inhibitor heavy chain 4
inter-alpha-trypsin inhibitor family heavy chain-related protein
inter-alpha-trypsin inhibitor heavy chain family member 4
inter-alpha-trypsin inhibitor, heavy chain-like, 1
plasma kallikrein-sensitive glycoprotein 120

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_016006.2 RefSeqGene

    Range
    5030..22740
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001166449.2 → NP_001159921.1  inter-alpha-trypsin inhibitor heavy chain H4 isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame segment compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AC006254, AK298412, AW291001, BC136392
    Consensus CDS
    CCDS54596.1
    UniProtKB/TrEMBL
    B7Z544
    Related
    ENSP00000384425.1, ENST00000406595.5
    Conserved Domains (5) summary
    smart00609
    Location:21 → 148
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:271 → 452
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    TIGR03788
    Location:40 → 592
    marine_srt_targ; marine proteobacterial sortase target protein
    pfam06668
    Location:736 → 898
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus
    cl17185
    Location:703 → 730
    LPLAT; Lysophospholipid acyltransferases (LPLATs) of glycerophospholipid biosynthesis

  2. NM_002218.5 → NP_002209.2  inter-alpha-trypsin inhibitor heavy chain H4 isoform 1 precursor

    See identical proteins and their annotated locations for NP_002209.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC006254, AW291001, BC136392, BC136393
    Consensus CDS
    CCDS2865.1
    UniProtKB/Swiss-Prot
    B7Z545, E9PGN5, Q14624, Q15135, Q9P190, Q9UQ54
    UniProtKB/TrEMBL
    B2RMS9
    Related
    ENSP00000266041.4, ENST00000266041.9
    Conserved Domains (5) summary
    smart00609
    Location:21 → 148
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:271 → 452
    vWA_interalpha_trypsin_inhibitor; vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to ...
    TIGR03788
    Location:40 → 626
    marine_srt_targ; marine proteobacterial sortase target protein
    pfam06668
    Location:766 → 928
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus
    cl17185
    Location:733 → 760
    LPLAT; Lysophospholipid acyltransferases (LPLATs) of glycerophospholipid biosynthesis

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    52812962..52830672 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    52845872..52863582 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q14624.4 GenPept UniProtKB/Swiss-Prot:Q14624

Gene LinkOut

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