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

    Gene ID: 3698, updated on 27-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (7703316..7749520)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (7703948..7750283)
    RS_2024_09 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. Complementary DNA and derived amino acid sequence of the precursor of one of the three protein components of the inter-alpha-trypsin inhibitor complex. Gebhard W, et al. FEBS Lett, 1988 Feb 29. PMID 2450046
    2. Human inter-alpha-trypsin inhibitor. Isolation and characterization of heavy (H) chain cDNA clones coding for a 383 amino-acid sequence of the H chain. Salier JP, et al. Biol Chem Hoppe Seyler, 1988 May. PMID 2462430
    3. 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
    4. The crystal structure of IgE Fc reveals an asymmetrically bent conformation. Wan T, et al. Nat Immunol, 2002 Jul. PMID 12068291
    5. 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

    See all (67) 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)

    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_2024_08

    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

    Gene LinkOut

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