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

Summary

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

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_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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

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

G62028 (e-PCR)
- UniSTS:139117

STS-X69532 (e-PCR)
- UniSTS:74095

G44326 (e-PCR)
- UniSTS:95115

SHGC-11985 (e-PCR)
- UniSTS:23187

GDB:303926 (e-PCR)
- UniSTS:156400

SHGC-77008 (e-PCR)
- UniSTS:28656

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
involved_in negative regulation of peptidase activity	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in blood microparticle	HDA more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular exosome	HDA more info	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

NG_016005.1 RefSeqGene

Range

5008..19471

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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