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Itih4 inter alpha-trypsin inhibitor, heavy chain 4 [ Mus musculus (house mouse) ]

Gene ID: 16427, updated on 5-Mar-2024

Summary

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Official Symbol
Itih4provided by MGI
Official Full Name
inter alpha-trypsin inhibitor, heavy chain 4provided by MGI
Primary source
MGI:MGI:109536
See related
Ensembl:ENSMUSG00000021922 AllianceGenome:MGI:109536
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
Itih-4; PK-120; ITI-HC4
Summary
This gene encodes a member of the inter-alpha trypsin inhibitor (IaI) family of plasma serine protease inhibitors with diverse functions as anti-apoptotic and matrix stabilizing molecules during development. This gene is predominantly expressed in the liver and the encoded protein was found to be a plasma kallikrein-sensitive glycoprotein. This gene is located in a cluster of related inter alpha trypsin inhibitor genes on chromosome 14. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
Expression
Biased expression in liver adult (RPKM 412.1), liver E18 (RPKM 232.0) and 2 other tissues See more
Orthologs
human all
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Genomic context

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Location:
14 B; 14 19.09 cM
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 14 NC_000080.7 (30608433..30623943)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 14 NC_000080.6 (30886476..30901986)

Chromosome 14 - NC_000080.7Genomic Context describing neighboring genes Neighboring gene STIM activating enhancer Neighboring gene musculoskeletal, embryonic nuclear protein 1 Neighboring gene inter-alpha trypsin inhibitor, heavy chain 3 Neighboring gene inter-alpha trypsin inhibitor, heavy chain 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Conformational changes in inter-α-trypsin inhibitor heavy chain 4 activate its tumor-specific activity in mice with B16 melanoma. Kormosh NG, et al. Mol Med Rep, 2015 Sep. PMID 26094694
  2. Identification of mouse itih-4 encoding a glycoprotein with two EF-hand motifs from early embryonic liver. Cai T, et al. Biochim Biophys Acta, 1998 May 29. PMID 9602042
  3. Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer's Disease Model. Shi X, et al. J Alzheimers Dis, 2019. PMID 30958362
  4. Inter-α-inhibitor deficiency in the mouse is associated with alterations in anxiety-like behavior, exploration and social approach. Goulding DR, et al. Genes Brain Behav, 2019 Jan. PMID 29987918, Free PMC Article
  5. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Tang Y, et al. Proc Natl Acad Sci U S A, 2008 Feb 19. PMID 18263735, Free PMC Article

See all (28) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Role of inter-alpha-trypsin inhibitor heavy chain 4 and its citrullinated form in experimental arthritis murine models.
    Title: Role of inter-alpha-trypsin inhibitor heavy chain 4 and its citrullinated form in experimental arthritis murine models.
  2. Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer's Disease Model.
    Title: Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer's Disease Model.
  3. Tumor-free mice and mice with B16 melanoma have differential proteolytic fragments of serum ITIH4.
    Title: Conformational changes in inter-α-trypsin inhibitor heavy chain 4 activate its tumor-specific activity in mice with B16 melanoma.
  4. role in liver development and regeneration
    Title: Itih-4, a serine protease inhibitor regulated in interleukin-6-dependent liver formation: role in liver development and regeneration.
Submit: New GeneRIF Correction

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Targeted (4)  1 citation
  • Endonuclease-mediated (4) 

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 MGI

Function Evidence Code Pubs
NOT enables calcium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
NOT enables hyaluronic acid binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables peptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
  
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
acts_upstream_of_or_within acute-phase response IEA
Inferred from Electronic Annotation
more info
  
involved_in hyaluronan metabolic process IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within 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 cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular region IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular space ISO
Inferred from Sequence Orthology
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
inter alpha-trypsin inhibitor, heavy chain 4
Names
ITI heavy chain H4
inter-alpha-inhibitor heavy chain 4

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_001159299.2 → NP_001152771.1  inter alpha-trypsin inhibitor, heavy chain 4 isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This difference results in a protein (isoform 2) that is 1 amino acid shorter than isoform 1.
    Source sequence(s)
    AK050270, BB809402, BY788238
    Consensus CDS
    CCDS49433.1
    UniProtKB/TrEMBL
    E9PVD2
    Related
    ENSMUSP00000077580.6, ENSMUST00000078490.14
    Conserved Domains (3) summary
    smart00609
    Location:19 → 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

  2. NM_001289632.1 → NP_001276561.1  inter alpha-trypsin inhibitor, heavy chain 4 isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an in-frame exon in the 3' coding region, compared to variant 1. This difference results in a shorter protein (isoform 3), compared to isoform 1.
    Source sequence(s)
    AK050270, BB809402, BY788238
    Consensus CDS
    CCDS70558.1
    UniProtKB/TrEMBL
    E9Q5L2
    Related
    ENSMUSP00000125920.2, ENSMUST00000168782.4
    Conserved Domains (3) summary
    smart00609
    Location:19 → 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

  3. NM_001289633.1 → NP_001276562.1  inter alpha-trypsin inhibitor, heavy chain 4 isoform 4 precursor

    See identical proteins and their annotated locations for NP_001276562.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice site and lacks an in-frame exon in the 3' coding region, compared to variant 1. This difference results in a shorter protein (isoform 4), compared to isoform 1.
    Source sequence(s)
    AK004893, BB809402, BY788238
    Consensus CDS
    CCDS79286.1
    UniProtKB/TrEMBL
    A0A2K6EDJ7
    Related
    ENSMUSP00000006703.8, ENSMUST00000006703.15
    Conserved Domains (3) summary
    smart00609
    Location:19 → 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

  4. NM_018746.4 → NP_061216.2  inter alpha-trypsin inhibitor, heavy chain 4 isoform 1 precursor

    See identical proteins and their annotated locations for NP_061216.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AK050270, BB809402, BY788238
    Consensus CDS
    CCDS26901.1
    UniProtKB/Swiss-Prot
    A6X935, O54882, Q505P8, Q8C7G9, Q8C7K5, Q91W60, Q9DBK8
    Related
    ENSMUSP00000112798.4, ENSMUST00000120269.11
    Conserved Domains (3) summary
    smart00609
    Location:19 → 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

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000080.7 Reference GRCm39 C57BL/6J

    Range
    30608433..30623943
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
A6X935.2 GenPept UniProtKB/Swiss-Prot:A6X935

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