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ITIH2 inter-alpha-trypsin inhibitor heavy chain 2 [ Homo sapiens (human) ]

Gene ID: 3698, updated on 5-Mar-2024

Summary

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Official Symbol
ITIH2provided by HGNC
Official Full Name
inter-alpha-trypsin inhibitor heavy chain 2provided by HGNC
Primary source
HGNC:HGNC:6167
See related
Ensembl:ENSG00000151655 MIM:146640; AllianceGenome:HGNC:6167
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
H2P; SHAP; ITI-HC2
Summary
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 MIM 176870) and a variable number of heavy chains (Salier et al., 1987 [PubMed 2446322]; Himmelfarb et al., 2004 [PubMed 14744536]).[supplied by OMIM, Nov 2009]
Expression
Restricted expression toward liver (RPKM 486.6) See more
Orthologs
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Genomic context

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See ITIH2 in Genome Data Viewer
Location:
10p14
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (7703316..7749520)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (7703948..7750283)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (7745279..7791483)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376391 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:7583451-7584310 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:7593195-7594096 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:7594097-7594998 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 5 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:7677530-7678369 Neighboring gene Sharpr-MPRA regulatory region 2566 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:7809082-7809283 Neighboring gene Kin17 DNA and RNA binding protein Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2981 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:7830681-7831224 Neighboring gene uncharacterized LOC105376392 Neighboring gene ATP synthase F1 subunit gamma

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
  • 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. [Covalent complex of hyaluronan and serum-derived protein, SHAP is a functional molecule involved in inflammation: finding, structure, formation mechanism, and function of the complex]. Kimata K. Seikagaku, 2010 Feb. PMID 20297716
  2. Role of serum-derived hyaluronan-associated protein-hyaluronan complex in ovarian cancer. Obayashi Y, et al. Oncol Rep, 2008 May. PMID 18425383
  3. Hyaluronan (HA) and serum-derived hyaluronan-associated protein (SHAP)-HA complex as predictive markers of cervical ripening in premature labor. Kishida T, et al. Connect Tissue Res, 2008. PMID 18382897
  4. The crystal structure of IgE Fc reveals an asymmetrically bent conformation. Wan T, et al. Nat Immunol, 2002 Jul. PMID 12068291
  5. Gene expression of the two heavy chains and one light chain forming the inter-alpha-trypsin-inhibitor in human tissues. Mizushima S, et al. Biol Pharm Bull, 1998 Feb. PMID 9514613

See all (63) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Both IalphaI and the HC-hyaluronan complex are substrates for the extracellular matrix proteases ADAMTS-5 and matrix metalloprotease (MMP) -3, -7, and -13.
    Title: Matrix-degrading protease ADAMTS-5 cleaves inter-α-inhibitor and releases active heavy chain 2 in synovial fluids from arthritic patients.
  2. Data suggest that Mg2+ or Mn2+ (but not Ca2+) induce a conformational change in inter-alpha-inhibitor (ITIH1 and ITIH2) and a bikunin/chondroitin sulfate-dependent increase in thermodynamic stability; bikunin binds adjacent to the two heavy chains.
    Title: The Compact and Biologically Relevant Structure of Inter-α-inhibitor Is Maintained by the Chondroitin Sulfate Chain and Divalent Cations.
  3. Human inter-alpha-inhibitor is a substrate for factor XIIIa and tissue transglutaminase.
    Title: Human inter-α-inhibitor is a substrate for factor XIIIa and tissue transglutaminase.
  4. It forms complex with hyaluronan and the comlex is a functional molecule involved in inflammation.
    Title: [Covalent complex of hyaluronan and serum-derived protein, SHAP is a functional molecule involved in inflammation: finding, structure, formation mechanism, and function of the complex].
  5. Observational study of gene-disease association. (HuGE Navigator)
    Title: A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
  6. serum-derived hyaluronan-associated protein-hyaluronan complex has a role in progression of ovarian cancer
    Title: Role of serum-derived hyaluronan-associated protein-hyaluronan complex in ovarian cancer.
  7. Increased levels of SHAP-HA complex in sera are possible predictive markers for cervical ripening in premature labor.
    Title: Hyaluronan (HA) and serum-derived hyaluronan-associated protein (SHAP)-HA complex as predictive markers of cervical ripening in premature labor.
  8. TSG-6 acts as cofactor and catalyst in the production of IalphaI heavy chain x hyaluronan complexes
    Title: Characterization of complexes formed between TSG-6 and inter-alpha-inhibitor that act as intermediates in the covalent transfer of heavy chains onto hyaluronan.
  9. Leukocytes infiltrated to the synovium were strongly positive for hyaluronic acid, SHAP, and CD44 on their surfaces, suggesting a role for the adhesion-enhancing effect of SHAP in inflammation.
    Title: SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum.
Submit: New GeneRIF Correction

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
Genetic variants and environmental factors associated with hormonal markers of ovarian reserve in Caucasian and African American women.
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

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase inhibitor activity TAS
Traceable Author Statement
more info
 PubMed 
enables hyaluronic acid binding IDA
Inferred from Direct Assay
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 hyaluronan metabolic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in blood microparticle HDA PubMed 
colocalizes_with collagen-containing extracellular matrix HDA PubMed 
located_in collagen-containing extracellular matrix HDA PubMed 
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
inter-alpha-trypsin inhibitor heavy chain H2
Names
ITI heavy chain H2
inter-alpha (globulin) inhibitor H2
inter-alpha (globulin) inhibitor, H2 polypeptide
inter-alpha-inhibitor heavy chain 2
inter-alpha-trypsin inhibitor complex component II
serum-derived hyaluronan-associated protein

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.

mRNA and Protein(s)

  1. NM_002216.3 → NP_002207.2  inter-alpha-trypsin inhibitor heavy chain H2 precursor

    See identical proteins and their annotated locations for NP_002207.2

    Status: VALIDATED

    Source sequence(s)
    AA406494, AL158044, BG617651, CB154170, X07173
    Consensus CDS
    CCDS31141.1
    UniProtKB/Swiss-Prot
    P19823, Q14659, Q15484, Q5T986
    UniProtKB/TrEMBL
    A2RTY6
    Related
    ENSP00000351190.4, ENST00000358415.9
    Conserved Domains (4) summary
    smart00609
    Location:56 → 185
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:307 → 488
    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:80 → 629
    marine_srt_targ; marine proteobacterial sortase target protein
    pfam06668
    Location:736 → 921
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    7703316..7749520
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    7703948..7750283
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P19823.2 GenPept UniProtKB/Swiss-Prot:P19823

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