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., 20... See more...

Aliases for ITIH2 Gene

Aliases for ITIH2 Gene

  • Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 2 3 5
  • Inter-Alpha-Trypsin Inhibitor Complex Component II 3 4
  • Inter-Alpha (Globulin) Inhibitor, H2 Polypeptide 2 3
  • Inter-Alpha-Trypsin Inhibitor Heavy Chain H2 3 4
  • Serum-Derived Hyaluronan-Associated Protein 3 4
  • Inter-Alpha-Inhibitor Heavy Chain 2 3 4
  • ITI Heavy Chain H2 3 4
  • ITI-HC2 3 4
  • SHAP 3 4
  • H2P 2 3
  • Inter-Alpha (Globulin) Inhibitor H2 3
  • IGHEP2 4
  • ITIH2 5

External Ids for ITIH2 Gene

Previous GeneCards Identifiers for ITIH2 Gene

  • GC10P007689
  • GC10P007895
  • GC10P007749
  • GC10P007785

Summaries for ITIH2 Gene

Entrez Gene Summary for ITIH2 Gene

  • 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]

GeneCards Summary for ITIH2 Gene

ITIH2 (Inter-Alpha-Trypsin Inhibitor Heavy Chain 2) is a Protein Coding gene. Among its related pathways are Cell adhesion_Cell-matrix glycoconjugates. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity and endopeptidase inhibitor activity. An important paralog of this gene is ITIH3.

UniProtKB/Swiss-Prot Summary for ITIH2 Gene

  • May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.

Gene Wiki entry for ITIH2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ITIH2 Gene

Genomics for ITIH2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ITIH2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J007703 Promoter 1 EPDnew 250.7 +0.0 22 0.1 CEBPA YY1 FOXA2 SMAD4 ZNF511 SAP130 ETV4 TEAD3 KAT7 CREM ITIH2 lnc-KIN-1 KIN
GH10J007701 Enhancer 0.4 FANTOM5 250.7 -1.8 -1773 0.1 CHD4 HNF4A SP1 HNF4G ITIH2 HSALNG0076022 ITIH5
GH10J007786 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 7 +85.2 85220 4.7 ZNF207 MYC KLF9 POLR2A ZSCAN16 BRCA1 NFIC YY1 KLF11 SMAD5 KIN ATP5F1C HSALNG0076029 ITIH2 lnc-KIN-5 MN309149 TAF3
GH10J007796 Enhancer 0.8 Ensembl ENCODE 16.9 +94.6 94607 2.3 JUND HOMEZ FOSL2 ZBTB33 EGR1 BHLHE40 DPF2 ARID1B SMARCE1 ATF3 MN309149 ITIH2 lnc-KIN-5 ATP5F1C TAF3
GH10J007854 Enhancer 0.9 FANTOM5 Ensembl ENCODE 13.5 +152.6 152585 5.8 BHLHE40 YY1 ZBTB40 NR2F6 MEIS2 HNF1A ZNF384 PKNOX1 ZNF629 SP1 ATP5F1C ITIH2 KIN HSALNG0076032 piR-34822-034 TAF3 GATA3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ITIH2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ITIH2

Top Transcription factor binding sites by QIAGEN in the ITIH2 gene promoter:
  • FOXJ2
  • FOXJ2 (long isoform)
  • HFH-3
  • MyoD
  • MZF-1
  • Olf-1
  • PPAR-gamma1
  • PPAR-gamma2
  • RSRFC4
  • STAT5A

Genomic Locations for ITIH2 Gene

Latest Assembly
chr10:7,703,316-7,749,520
(GRCh38/hg38)
Size:
46,205 bases
Orientation:
Plus strand

Previous Assembly
chr10:7,745,279-7,791,483
(GRCh37/hg19 by Entrez Gene)
Size:
46,205 bases
Orientation:
Plus strand

chr10:7,745,232-7,791,483
(GRCh37/hg19 by Ensembl)
Size:
46,252 bases
Orientation:
Plus strand

Genomic View for ITIH2 Gene

Genes around ITIH2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ITIH2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ITIH2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ITIH2 Gene

Proteins for ITIH2 Gene

  • Protein details for ITIH2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P19823-ITIH2_HUMAN
    Recommended name:
    Inter-alpha-trypsin inhibitor heavy chain H2
    Protein Accession:
    P19823
    Secondary Accessions:
    • Q14659
    • Q15484
    • Q5T986

    Protein attributes for ITIH2 Gene

    Size:
    946 amino acids
    Molecular mass:
    106463 Da
    Quaternary structure:
    • I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (H1, H2 or H3) and one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of H1, H2 and bikunin, inter-alpha-like inhibitor (I-alpha-LI) of H2 and bikunin, and pre-alpha-inhibitor (P-alpha-I) of H3 and bikunin.
    SequenceCaution:
    • Sequence=CAA30160.1; Type=Frameshift; Evidence={ECO:0000305};

neXtProt entry for ITIH2 Gene

Post-translational modifications for ITIH2 Gene

  • Heavy chains are linked to bikunin via chondroitin 4-sulfate esterified to the alpha-carboxyl of the C-terminal aspartate after propeptide cleavage.
  • N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.
  • Phosphorylated by FAM20C in the extracellular medium.
  • Glycosylation at Asn118, Asn445, Thr601, Thr666, Ser673, Thr675, Thr691, and Asn715
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ITIH2_HUMAN (285)

Other Protein References for ITIH2 Gene

No data available for DME Specific Peptides for ITIH2 Gene

Domains & Families for ITIH2 Gene

Gene Families for ITIH2 Gene

Protein Domains for ITIH2 Gene

InterPro:
Blocks:
  • Von Willebrand factor type A domain signature
  • Inter-alpha-trypsin inhibitor heavy chain, C-terminal
  • Vault protein inter-alpha-trypsin

Suggested Antigen Peptide Sequences for ITIH2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ75038, highly similar to Homo sapiens inter-alpha (globulin) inhibitor H2 (ITIH2), mRNA (A2RTY6_HUMAN)
  • Inter-alpha (Globulin) inhibitor H2, isoform CRA_a (D3DRR6_HUMAN)
  • Serum-derived hyaluronan-associated protein (ITIH2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P19823

UniProtKB/Swiss-Prot:

ITIH2_HUMAN :
  • Belongs to the ITIH family.
Family:
  • Belongs to the ITIH family.
genes like me logo Genes that share domains with ITIH2: view

Function for ITIH2 Gene

Molecular function for ITIH2 Gene

UniProtKB/Swiss-Prot Function:
May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.
GENATLAS Biochemistry:
trypsin inhibitor,inter-alpha- (protein HC),heavy chain 2

Phenotypes From GWAS Catalog for ITIH2 Gene

Gene Ontology (GO) - Molecular Function for ITIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004866 endopeptidase inhibitor activity TAS 2476436
GO:0004867 serine-type endopeptidase inhibitor activity IEA --
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with ITIH2: view
genes like me logo Genes that share phenotypes with ITIH2: view

Animal Models for research

  • Taconic Biosciences Mouse Models for ITIH2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ITIH2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for ITIH2 Gene

Localization for ITIH2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ITIH2 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ITIH2 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 4
golgi apparatus 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1
peroxisome 0
lysosome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ITIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA,NAS 14718574
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0062023 colocalizes_with collagen-containing extracellular matrix HDA 28327460
GO:0070062 extracellular exosome HDA 20458337
GO:0072562 blood microparticle HDA 22516433
genes like me logo Genes that share ontologies with ITIH2: view

Pathways & Interactions for ITIH2 Gene

PathCards logo

SuperPathways for ITIH2 Gene

SuperPathway Contained pathways
1 Cell adhesion_Cell-matrix glycoconjugates
-
genes like me logo Genes that share pathways with ITIH2: view

Pathways by source for ITIH2 Gene

1 GeneGo (Thomson Reuters) pathway for ITIH2 Gene
  • Cell adhesion_Cell-matrix glycoconjugates

Gene Ontology (GO) - Biological Process for ITIH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0030212 hyaluronan metabolic process IEA --
GO:0043687 post-translational protein modification TAS --
GO:0044267 cellular protein metabolic process TAS --
genes like me logo Genes that share ontologies with ITIH2: view

No data available for SIGNOR curated interactions for ITIH2 Gene

Drugs & Compounds for ITIH2 Gene

(5) Drugs for ITIH2 Gene - From: DrugBank

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma Target 276
Zinc Approved, Investigational Pharma Target 1706
zinc acetate Approved, Investigational Pharma Target 0
Zinc chloride Approved, Investigational Pharma Target, binder 0
Zinc sulfate, unspecified form Approved, Experimental Pharma Target, binder 0
genes like me logo Genes that share compounds with ITIH2: view

Transcripts for ITIH2 Gene

mRNA/cDNA for ITIH2 Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ITIH2

Alternative Splicing Database (ASD) splice patterns (SP) for ITIH2 Gene

No ASD Table

Relevant External Links for ITIH2 Gene

GeneLoc Exon Structure for
ITIH2

Expression for ITIH2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ITIH2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ITIH2 Gene

This gene is overexpressed in Liver (x50.2).

Protein differential expression in normal tissues from HIPED for ITIH2 Gene

This gene is overexpressed in Serum (27.4), Plasma (13.2), and Synovial fluid (9.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ITIH2 Gene



Protein tissue co-expression partners for ITIH2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ITIH2

SOURCE GeneReport for Unigene cluster for ITIH2 Gene:

Hs.75285

mRNA Expression by UniProt/SwissProt for ITIH2 Gene:

P19823-ITIH2_HUMAN
Tissue specificity: Plasma.

Evidence on tissue expression from TISSUES for ITIH2 Gene

  • Liver(4.9)
  • Bone marrow(4.1)
  • Heart(2.7)
  • Nervous system(2.6)
  • Intestine(2.1)
genes like me logo Genes that share expression patterns with ITIH2: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ITIH2 Gene

Orthologs for ITIH2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ITIH2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ITIH2 30
  • 96 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia ITIH2 29 30
  • 85.2 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ITIH2 29 30
  • 85.13 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Itih2 29 16 30
  • 82.52 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 82 (a)
OneToMany
-- 30
  • 78 (a)
OneToMany
-- 30
  • 73 (a)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia ITIH2 30
  • 75 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ITIH2 29 30
  • 68.97 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ITIH2 30
  • 61 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia itih2 29
  • 63.13 (n)
Str.15358 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.5099 29
Zebrafish
(Danio rerio)
Actinopterygii itih2 30
  • 52 (a)
OneToOne
Dr.852 29
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2708 29
Species where no ortholog for ITIH2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ITIH2 Gene

ENSEMBL:
Gene Tree for ITIH2 (if available)
TreeFam:
Gene Tree for ITIH2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ITIH2: view image
Alliance of Genome Resources:
Additional Orthologs for ITIH2

Paralogs for ITIH2 Gene

Paralogs for ITIH2 Gene

(5) SIMAP similar genes for ITIH2 Gene using alignment to 5 proteins:

  • ITIH2_HUMAN
  • A2RTY6_HUMAN
  • D3DRR6_HUMAN
  • Q5T985_HUMAN
  • Q5T987_HUMAN
genes like me logo Genes that share paralogs with ITIH2: view

Variants for ITIH2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ITIH2 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
rs3740217 -- p.Pro674Ala
rs7075296 -- p.Asn263Ser
rs7084817 -- p.Leu569Val

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ITIH2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for ITIH2 Gene

Variant ID Type Subtype PubMed ID
esv1496692 CNV insertion 17803354
esv1652715 CNV deletion 17803354
esv2606150 CNV deletion 19546169
esv2670009 CNV deletion 23128226
esv2732373 CNV deletion 23290073
esv2732384 CNV deletion 23290073
esv3622276 CNV loss 21293372
esv3891752 CNV gain 25118596
nsv1038131 CNV gain 25217958
nsv1069015 CNV deletion 25765185
nsv549933 CNV gain 21841781
nsv957606 CNV deletion 24416366

Variation tolerance for ITIH2 Gene

Residual Variation Intolerance Score: 63.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.01; 74.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ITIH2 Gene

Human Gene Mutation Database (HGMD)
ITIH2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ITIH2
Leiden Open Variation Database (LOVD)
ITIH2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ITIH2 Gene

Disorders for ITIH2 Gene

Additional Disease Information for ITIH2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform

No disorders were found for ITIH2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for ITIH2 Gene

Publications for ITIH2 Gene

  1. A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the inter alpha-trypsin inhibitor. (PMID: 7504674) Huang L … Kimata K (The Journal of biological chemistry 1993) 3 4 22
  2. A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. (PMID: 16385451) Grupe A … Goate A (American journal of human genetics 2006) 3 40
  3. SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. (PMID: 16702221) Zhuo L … Kimata K (The Journal of biological chemistry 2006) 3 22
  4. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. (PMID: 16335952) Liu T … Smith RD (Journal of proteome research 2005) 3 4
  5. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. (PMID: 12754519) Zhang H … Aebersold R (Nature biotechnology 2003) 3 4

Products for ITIH2 Gene

Sources for ITIH2 Gene