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    ITIH5 inter-alpha-trypsin inhibitor heavy chain 5 [ Homo sapiens (human) ]

    Gene ID: 80760, updated on 28-Oct-2024

    Summary

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    Official Symbol
    ITIH5provided by HGNC
    Official Full Name
    inter-alpha-trypsin inhibitor heavy chain 5provided by HGNC
    Primary source
    HGNC:HGNC:21449
    See related
    Ensembl:ENSG00000123243 MIM:609783; AllianceGenome:HGNC:21449
    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
    ITI-HC5; PP14776
    Summary
    This gene encodes a heavy chain component of one of the inter-alpha-trypsin inhibitor (ITI) family members. ITI proteins are involved in extracellular matrix stabilization and in the prevention of tumor metastasis. They are also structurally related plasma serine protease inhibitors and are composed of a light chain and varying numbers of heavy chains. This family member is thought to function as a tumor suppressor in breast and thyroid cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]
    Expression
    Broad expression in fat (RPKM 49.7), placenta (RPKM 32.8) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ITIH5 in Genome Data Viewer
    Location:
    10p14
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (7559270..7666966, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (7560192..7667778, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (7601232..7708929, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376390 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:7580314-7581513 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 OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:7677530-7678369 Neighboring gene Sharpr-MPRA regulatory region 2566 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 2 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

    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. Genome-wide in vivo RNAi screen identifies ITIH5 as a metastasis suppressor in pancreatic cancer. Sasaki K, et al. Clin Exp Metastasis, 2017 Apr. PMID 28289921, Free PMC Article
    2. Epigenetic inactivation of ITIH5 promotes bladder cancer progression and predicts early relapse of pT1 high-grade urothelial tumours. Rose M, et al. Carcinogenesis, 2014 Mar. PMID 24265292
    3. Decreased ITIH5 expression is associated with poor prognosis in primary gastric cancer. Mai C, et al. Med Oncol, 2014 Jul. PMID 24913813
    4. Epigenetic inactivation of the novel candidate tumor suppressor gene ITIH5 in colon cancer predicts unfavorable overall survival in the CpG island methylator phenotype. Kloten V, et al. Epigenetics, 2014 Sep. PMID 25093535, Free PMC Article
    5. Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is overexpressed in inflammatory skin diseases and affects epidermal morphology in constitutive knockout mice and murine 3D skin models. Huth S, et al. Exp Dermatol, 2015 Sep. PMID 25809190

    See all (39) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ITIH5 as a multifaceted player in pancreatic cancer suppression, impairing tyrosine kinase signaling, cell adhesion and migration.
      Title: ITIH5 as a multifaceted player in pancreatic cancer suppression, impairing tyrosine kinase signaling, cell adhesion and migration.
    2. The ECM Modulator ITIH5 Affects Cell Adhesion, Motility and Chemotherapeutic Response of Basal/Squamous-Like (BASQ) Bladder Cancer Cells.
      Title: The ECM Modulator ITIH5 Affects Cell Adhesion, Motility and Chemotherapeutic Response of Basal/Squamous-Like (BASQ) Bladder Cancer Cells.
    3. ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4.
      Title: ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4.
    4. Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment.
      Title: Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment.
    5. Inter-alpha-Trypsin Inhibitor Heavy Chain 5 (ITIH5) Is a Natural Stabilizer of Hyaluronan That Modulates Biological Processes in the Skin.
      Title: Inter-α-Trypsin Inhibitor Heavy Chain 5 (ITIH5) Is a Natural Stabilizer of Hyaluronan That Modulates Biological Processes in the Skin.
    6. Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5.
      Title: Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5.
    7. The results demonstrated that the MIR31HG-miR-31-ITIH5-PIK3CG pathway plays a role in the pathogenesis of Hirschsprung disease.
      Title: Aberrant expression of LncRNA-MIR31HG regulates cell migration and proliferation by affecting miR-31 and miR-31* in Hirschsprung's disease.
    8. ITIH5 may represent a novel modulator of TGF-beta superfamily signaling.
      Title: ITIH5 induces a shift in TGF-β superfamily signaling involving Endoglin and reduces risk for breast cancer metastasis and tumor death.
    9. Results provide evidence that ITIH5 triggers a reprogramming of breast cancer cells through global epigenetic changes effecting DAPK1. ITIH5 may represent an ECM modulator in epithelial breast tissue mediating suppression of tumor initiating cancer cell characteristics which are thought being responsible for the metastasis of breast cancer.
      Title: ITIH5 mediates epigenetic reprogramming of breast cancer cells.
    10. Low ITIH5 expression is associated with liver metastasis in pancreatic cancer.
      Title: Genome-wide in vivo RNAi screen identifies ITIH5 as a metastasis suppressor in pancreatic cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    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

    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

    Clone Names

    • MGC10848, DKFZp686F0145

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    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
    		  
    involved_in negative regulation of peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in collagen-containing extracellular matrix HDA PubMed 
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    inter-alpha-trypsin inhibitor heavy chain H5
    Names
    ITI heavy chain H5
    inter-alpha (globulin) inhibitor H5
    inter-alpha-trypsin inhibitor heavy chain family member 5

    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_047199.1 RefSeqGene

      Range
      5033..112729
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001001851.3 → NP_001001851.1  inter-alpha-trypsin inhibitor heavy chain H5 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001001851.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks several 3' exons and has an alternate 3' exon, compared to variant 1. The encoded isoform (3) has an alternate and shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AK027375, AK027831, AL355374, BC004282, DA246953
      UniProtKB/TrEMBL
      G5E9D8
      Related
      ENSP00000380332.2, ENST00000397145.6
      Conserved Domains (2) summary
      cd01461
      Location:292 → 473
      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 ...
      pfam08487
      Location:51 → 157
      VIT; Vault protein inter-alpha-trypsin domain

    2. NM_030569.7 → NP_085046.5  inter-alpha-trypsin inhibitor heavy chain H5 isoform 1 precursor

      See identical proteins and their annotated locations for NP_085046.5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL355374, AL833203, AY238437, BQ183379, DA246953, KF570249
      Consensus CDS
      CCDS31139.2
      UniProtKB/Swiss-Prot
      Q5T664, Q5T665, Q5T666, Q6AI60, Q6UXB7, Q86UX2, Q8TF48, Q8WYV2, Q96K70
      UniProtKB/TrEMBL
      C9J2H1
      Related
      ENSP00000380333.3, ENST00000397146.7
      Conserved Domains (3) summary
      cd01461
      Location:292 → 473
      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:716 → 909
      ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus
      pfam08487
      Location:51 → 157
      VIT; Vault protein inter-alpha-trypsin domain

    3. NM_032817.6 → NP_116206.4  inter-alpha-trypsin inhibitor heavy chain H5 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks several 5' exons and has an alternate 5' exon, compared to variant 1. The encoded isoform (2) has an alternate and shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AL355374, BC004282, BQ183379, DA833541, DB079183, KF570249
      Consensus CDS
      CCDS31140.2
      UniProtKB/TrEMBL
      A0A096LP62
      Related
      ENSP00000485414.1, ENST00000613909.4
      Conserved Domains (2) summary
      cd01461
      Location:78 → 259
      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:502 → 695
      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
      7559270..7666966 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011519713.4 → XP_011518015.1  inter-alpha-trypsin inhibitor heavy chain H5 isoform X1

      UniProtKB/Swiss-Prot
      Q5T664, Q5T665, Q5T666, Q6AI60, Q6UXB7, Q86UX2, Q8TF48, Q8WYV2, Q96K70
      Conserved Domains (3) summary
      cd01461
      Location:292 → 498
      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:741 → 934
      ITI_HC_C; Inter-alpha-trypsin inhibitor heavy chain C-terminus
      pfam08487
      Location:51 → 157
      VIT; Vault protein inter-alpha-trypsin domain

    2. XM_011519714.4 → XP_011518016.1  inter-alpha-trypsin inhibitor heavy chain H5 isoform X2

      Conserved Domains (2) summary
      cd01461
      Location:292 → 498
      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 ...
      pfam08487
      Location:51 → 157
      VIT; Vault protein inter-alpha-trypsin domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      7560192..7667778 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054366839.1 → XP_054222814.1  inter-alpha-trypsin inhibitor heavy chain H5 isoform X1

    2. XM_054366840.1 → XP_054222815.1  inter-alpha-trypsin inhibitor heavy chain H5 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q86UX2.2 GenPept UniProtKB/Swiss-Prot:Q86UX2

    Gene LinkOut

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