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ITIH1 inter-alpha-trypsin inhibitor heavy chain 1 [ Homo sapiens (human) ]

Gene ID: 3697, updated on 14-Nov-2024

Summary

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Official Symbol
ITIH1provided by HGNC
Official Full Name
inter-alpha-trypsin inhibitor heavy chain 1provided by HGNC
Primary source
HGNC:HGNC:6166
See related
Ensembl:ENSG00000055957 MIM:147270; AllianceGenome:HGNC:6166
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
H1P; ITIH; SHAP; IATIH; IGHEP1; ITI-HC1
Summary
This gene encodes a member of the inter-alpha-trypsin inhibitor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the heavy chain of the inter-alpha-trypsin inhibitor complex, which is secreted by hepatocytes into the blood. The heavy chain also interacts with hyaluronan, and this interaction may play a role in ovulation and fertilization, and has been implicated in multiple inflammatory diseases. This gene is present in a gene cluster on chromosome 3. [provided by RefSeq, Nov 2015]
Expression
Restricted expression toward liver (RPKM 383.5) See more
Orthologs
mouse all
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Genomic context

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See ITIH1 in Genome Data Viewer
Location:
3p21.1
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (52777599..52792068)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (52810510..52824977)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (52811615..52826084)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene NIMA related kinase 4 Neighboring gene adenylate kinase 3 pseudogene Neighboring gene AKTIP pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:52804733-52805250 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:52812248-52813447 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19948 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 inter-alpha-trypsin inhibitor heavy chain 4 Neighboring gene ITIH4 antisense RNA 1

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. Human inter-alpha-trypsin inhibitor: full-length cDNA sequence of the heavy chain H1. Diarra-Mehrpour M, et al. Biochim Biophys Acta, 1992 Aug 17. PMID 1380832
  2. Molecular basis of inter-alpha-trypsin inhibitor heavy chain H1 (ITIH1) polymorphism. Ding M, et al. Hum Genet, 1995 Apr. PMID 7535743
  3. Evidence for the covalent binding of SHAP, heavy chains of inter-alpha-trypsin inhibitor, to hyaluronan. Zhao M, et al. J Biol Chem, 1995 Nov 3. PMID 7592891
  4. Disulphide bonds assignment in the inter-alpha-inhibitor heavy chains--structural and functional implications. Flahaut C, et al. Eur J Biochem, 1998 Jul 1. PMID 9692908
  5. Isolation and characterization of the human inter-alpha-trypsin inhibitor heavy-chain H1 gene. Bost F, et al. Eur J Biochem, 1993 Dec 1. PMID 7505744

See all (64) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Lysine demethylase 5C epigenetically reduces transcription of ITIH1 that results in augmented progression of liver hepatocellular carcinoma.
    Title: Lysine demethylase 5C epigenetically reduces transcription of ITIH1 that results in augmented progression of liver hepatocellular carcinoma.
  2. Pan-cancer analysis identifies ITIH1 as a novel prognostic indicator for hepatocellular carcinoma.
    Title: Pan-cancer analysis identifies ITIH1 as a novel prognostic indicator for hepatocellular carcinoma.
  3. 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.
  4. Furthermore, thrombin treatment of the inflammatory matrix leads to dissolution of HC-HA cable structures and abolishes leukocyte adhesion. These data establish a novel mechanism whereby thrombin cleavage of HC1 regulates the adhesive properties of an inflammatory HA matrix.
    Title: Thrombin Cleavage of Inter-α-inhibitor Heavy Chain 1 Regulates Leukocyte Binding to an Inflammatory Hyaluronan Matrix.
  5. 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.
  6. The results of this study revealed that the shared genetic risk factors of both schizophrenia and major depressive disorder exist in ITIH family genes in the Han Chinese population.
    Title: ITIH family genes confer risk to schizophrenia and major depressive disorder in the Han Chinese population.
  7. Data indicate that TSG-6-mediated cross-linking of hyaluronan (HA) films is impaired in the presence of inter-alpha-inhibitor (IalphaI) and that this effect suppresses the TSG-6-mediated enhancement of HA binding to CD44-positive cells.
    Title: Inter-α-inhibitor impairs TSG-6-induced hyaluronan cross-linking.
  8. 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.
  9. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
    Title: Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population.
  10. Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
    Title: Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry.
Submit: New GeneRIF Correction See all GeneRIFs (13)

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
Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
EBI GWAS Catalog
Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
EBI GWAS Catalog
Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry.
EBI GWAS Catalog
GWAS meta analysis identifies TSNARE1 as a novel Schizophrenia / Bipolar susceptibility locus.
EBI GWAS Catalog
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
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

Clone Names

  • MGC126415

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calcium ion binding TAS
Traceable Author Statement
more info
 PubMed 
enables carbohydrate binding EXP
Inferred from Experiment
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 
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 

General protein information

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Preferred Names
inter-alpha-trypsin inhibitor heavy chain H1
Names
ITI heavy chain H1
inter-alpha (globulin) inhibitor, H1 polypeptide
inter-alpha-inhibitor heavy chain 1
inter-alpha-trypsin inhibitor complex component III
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.

Genomic

  1. NG_016005.1 RefSeqGene

    Range
    5008..19471
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001166434.3 → NP_001159906.1  inter-alpha-trypsin inhibitor heavy chain H1 isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform a.
    Source sequence(s)
    AA897466, AC006254, AK292750, AK298455, DB188130, M18192
    UniProtKB/TrEMBL
    B7Z8B6
    Related
    ENST00000628722.2
    Conserved Domains (3) summary
    cd01461
    Location:147 → 328
    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 ...
    pfam06668
    Location:564 → 750
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus
    cl02699
    Location:1 → 24
    VIT; Vault protein inter-alpha-trypsin domain

  2. NM_001166435.2 → NP_001159907.1  inter-alpha-trypsin inhibitor heavy chain H1 isoform c

    See identical proteins and their annotated locations for NP_001159907.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (c) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform a. Both variants 3 and 4 ncode isoform c.
    Source sequence(s)
    AA897466, AC006254, AK303156
    Consensus CDS
    CCDS54595.1
    UniProtKB/TrEMBL
    B7Z8B6
    Related
    ENSP00000443847.1, ENST00000537050.5
    Conserved Domains (2) summary
    cd01461
    Location:1 → 182
    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 ...
    pfam06668
    Location:418 → 604
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  3. NM_001166436.2 → NP_001159908.1  inter-alpha-trypsin inhibitor heavy chain H1 isoform c

    See identical proteins and their annotated locations for NP_001159908.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (c) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform a. Both variants 3 and 4 encode isoform c.
    Source sequence(s)
    AA897466, AC006254, AK303110
    Consensus CDS
    CCDS54595.1
    UniProtKB/TrEMBL
    B7Z8B6
    Conserved Domains (2) summary
    cd01461
    Location:1 → 182
    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 ...
    pfam06668
    Location:418 → 604
    ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus

  4. NM_002215.4 → NP_002206.2  inter-alpha-trypsin inhibitor heavy chain H1 isoform a preproprotein

    See identical proteins and their annotated locations for NP_002206.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AA897466, BC069464
    Consensus CDS
    CCDS2864.1
    UniProtKB/Swiss-Prot
    A8K9N5, B2RAH9, B7Z558, B7Z8C0, F5H165, F5H7Y8, P19827, P78455, Q01746, Q562G1
    Related
    ENSP00000273283.2, ENST00000273283.7
    Conserved Domains (4) summary
    smart00609
    Location:37 → 166
    VIT; Vault protein Inter-alpha-Trypsin domain
    cd01461
    Location:289 → 470
    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:58 → 608
    marine_srt_targ; marine proteobacterial sortase target protein
    pfam06668
    Location:706 → 892
    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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    52777599..52792068
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    52810510..52824977
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P19827.3 GenPept UniProtKB/Swiss-Prot:P19827

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