Free for academic non-profit institutions. Other users need a Commercial license

Aliases for ITIH4 Gene

Aliases for ITIH4 Gene

  • Inter-Alpha-Trypsin Inhibitor Heavy Chain Family Member 4 2 3 5
  • Inter-Alpha (Globulin) Inhibitor H4 (Plasma Kallikrein-Sensitive Glycoprotein) 2 3
  • Inter-Alpha-Trypsin Inhibitor Family Heavy Chain-Related Protein 3 4
  • Inter-Alpha-Inhibitor Heavy Chain 4 3 4
  • ITI Heavy Chain H4 3 4
  • ITI-HC4 3 4
  • ITIHL1 3 4
  • PK-120 3 4
  • GP120 3 4
  • PK120 3 4
  • IHRP 3 4
  • Inter-Alpha-Trypsin Inhibitor Heavy Chain Family, Member 4 2
  • Inter-Alpha-Trypsin Inhibitor, Heavy Chain-Like, 1 3
  • Inter-Alpha-Trypsin Inhibitor Heavy Chain H4 3
  • Plasma Kallikrein-Sensitive Glycoprotein 120 3
  • Plasma Kallikrein Sensitive Glycoprotein 120 4
  • Plasma Kallikrein-Sensitive Glycoprotein 2
  • H4P 3

External Ids for ITIH4 Gene

Previous HGNC Symbols for ITIH4 Gene

  • ITIHL1

Previous GeneCards Identifiers for ITIH4 Gene

  • GC03M051939
  • GC03M052098
  • GC03M052701
  • GC03M052804
  • GC03M052822
  • GC03M052846

Summaries for ITIH4 Gene

Entrez Gene Summary for ITIH4 Gene

  • The protein encoded by this gene is secreted into the blood, where it is cleaved by plasma kallikrein into two smaller forms. Expression of this gene has been detected only in liver, and it seems to be upregulated during surgical trauma. This gene is part of a cluster of similar genes on chromosome 3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

GeneCards Summary for ITIH4 Gene

ITIH4 (Inter-Alpha-Trypsin Inhibitor Heavy Chain Family Member 4) is a Protein Coding gene. Diseases associated with ITIH4 include Hypercholesterolemia, Familial and Aids Dementia Complex. Among its related pathways are Response to elevated platelet cytosolic Ca2+. 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 for ITIH4 Gene

  • Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration.

Gene Wiki entry for ITIH4 Gene

Additional gene information for ITIH4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ITIH4 Gene

Genomics for ITIH4 Gene

GeneHancer (GH) Regulatory Elements for ITIH4 Gene

Promoters and enhancers for ITIH4 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
GH03I052830 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 614.3 +0.0 12 2.2 HDAC1 PKNOX1 FOXA2 NFIB MZF1 FEZF1 RAD21 YY1 ZNF335 GLIS2 ITIH4 ITIH1 ENSG00000243696 ITIH4-AS1
GH03I052833 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE dbSUPER 48.1 -4.3 -4273 3.6 TFAP4 POLR2A HLF CEBPA CEBPB EBF1 CEBPG YY1 TEAD3 ENSG00000243696 MUSTN1 ITIH4 RFT1 ITIH1 PIR43341 TMEM110-MUSTN1 STIMATE
GH03I052890 Enhancer 1.4 FANTOM5 Ensembl ENCODE 44.9 -61.1 -61145 4.3 HDGF ATF1 FOXA2 MLX ARID4B DMAP1 IRF4 ETS1 YY1 ZNF207 ITIH4 ENSG00000243696 ITIH4-AS1 PBRM1 MUSTN1 SNORD69 ENSG00000222345 ENSG00000252787 SNORD19 SNORD19B
GH03I052896 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE 34.9 -65.8 -65810 1.9 HDGF ATF1 RB1 SIN3A ZNF335 GLIS2 ZNF366 SCRT2 ZNF143 ATF7 STIMATE TMEM110-MUSTN1 ITIH4 ITIH3 ENSG00000279144
GH03I053043 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE 32.2 -213.8 -213810 3.9 CLOCK FOXA2 ARNT SIN3A ZNF766 GLIS2 ZNF207 ZNF143 ATF7 ZNF263 SFMBT1 GC03P053048 ITIH4 RFT1 PBRM1 STIMATE SNORD19B PRKCD ITIH3 LOC105377135
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around ITIH4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ITIH4 gene promoter:

Genomic Locations for ITIH4 Gene

Genomic Locations for ITIH4 Gene
chr3:52,812,975-52,831,479
(GRCh38/hg38)
Size:
18,505 bases
Orientation:
Minus strand
chr3:52,846,991-52,865,495
(GRCh37/hg19)

Genomic View for ITIH4 Gene

Genes around ITIH4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ITIH4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ITIH4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ITIH4 Gene

Proteins for ITIH4 Gene

  • Protein details for ITIH4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14624-ITIH4_HUMAN
    Recommended name:
    Inter-alpha-trypsin inhibitor heavy chain H4
    Protein Accession:
    Q14624
    Secondary Accessions:
    • B7Z545
    • E9PGN5
    • Q15135
    • Q9P190
    • Q9UQ54

    Protein attributes for ITIH4 Gene

    Size:
    930 amino acids
    Molecular mass:
    103357 Da
    Quaternary structure:
    • Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain); this interaction protects ITIH4 against cleavage by kallikrein in vitro.
    Miscellaneous:
    • Possible biomarker for acute ischemic stroke (PubMed:19263524). Peptides derived from the proline-rich potentially active peptide (PRO_0000016542) may be biomarkers for a variety of disease states including breast cancer (PubMed:21137033).

    Alternative splice isoforms for ITIH4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ITIH4 Gene

Post-translational modifications for ITIH4 Gene

  • Cleaved by plasma kallikrein to yield 100 kDa and 35 kDa fragments, and the resulting 100 kDa fragment is further converted to a 70 kDa fragment.
  • N- and O-glycosylated. In urine, O-linked glycosylation on threonine residues in the region from Thr-719 to Thr-725 consists of core 1 or possibly core 8 glycans. Mainly Hex(HexNAc)(2), but also some Hex(3)(HexNAc)(3). N-glycosylated but not O-glycosylated in plasma.
  • Glycosylation at isoforms=2, 3, 481, posLast=207207, isoforms=2, 3, 4274, isoforms=2, 3, 4517, posLast=577577, isoforms=2, 3, 4719, posLast=720720, and isoforms=2, 3, 4722

Other Protein References for ITIH4 Gene

No data available for DME Specific Peptides for ITIH4 Gene

Domains & Families for ITIH4 Gene

Gene Families for ITIH4 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Graphical View of Domain Structure for InterPro Entry

Q14624

UniProtKB/Swiss-Prot:

ITIH4_HUMAN :
  • Belongs to the ITIH family.
Family:
  • Belongs to the ITIH family.
genes like me logo Genes that share domains with ITIH4: view

Function for ITIH4 Gene

Molecular function for ITIH4 Gene

GENATLAS Biochemistry:
trypsin inhibitor inter-alpha (protein HC),heavy chain 4
UniProtKB/Swiss-Prot Function:
Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration.
UniProtKB/Swiss-Prot Induction:
Levels increase from 1.4 to 3-fold in acute-phase processes such as in acute ischemia stroke (AIS), unstable angina and programmed surgery. In hepatocytes, induced by IL6 but not by other cytokines such as IL1B.

Phenotypes From GWAS Catalog for ITIH4 Gene

Gene Ontology (GO) - Molecular Function for ITIH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004866 endopeptidase inhibitor activity TAS 9756925
GO:0004867 serine-type endopeptidase inhibitor activity IEA --
GO:0005515 protein binding IPI 16271702
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with ITIH4: view

Phenotypes for ITIH4 Gene

MGI mutant phenotypes for ITIH4:
inferred from 1 alleles
GenomeRNAi human phenotypes for ITIH4:
genes like me logo Genes that share phenotypes with ITIH4: view

Animal Models for ITIH4 Gene

MGI Knock Outs for ITIH4:

miRNA for ITIH4 Gene

miRTarBase miRNAs that target ITIH4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ITIH4 Gene

Localization for ITIH4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ITIH4 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 ITIH4 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
golgi apparatus 2
peroxisome 1
lysosome 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ITIH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0031089 platelet dense granule lumen TAS --
GO:0070062 extracellular exosome IDA,HDA 19056867
GO:0072562 blood microparticle IDA,HDA 22516433
genes like me logo Genes that share ontologies with ITIH4: view

Pathways & Interactions for ITIH4 Gene

genes like me logo Genes that share pathways with ITIH4: view

Gene Ontology (GO) - Biological Process for ITIH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002576 platelet degranulation TAS --
GO:0006953 acute-phase response IEP 19263524
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0030212 hyaluronan metabolic process IEA --
genes like me logo Genes that share ontologies with ITIH4: view

No data available for SIGNOR curated interactions for ITIH4 Gene

Drugs & Compounds for ITIH4 Gene

(45) Drugs for ITIH4 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Zinc Approved, Investigational Pharma Target 2430

(53) Additional Compounds for ITIH4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ITIH4: view

Transcripts for ITIH4 Gene

Unigene Clusters for ITIH4 Gene

Inter-alpha-trypsin inhibitor heavy chain family, member 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ITIH4 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9a · 9b · 9c ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13 ^ 14a · 14b ^
SP1: - -
SP2: - - - -
SP3: - -
SP4: - -
SP5:
SP6:
SP7: - - - - - - - - -
SP8: - - - - - - - - - -
SP9:
SP10:
SP11: - -
SP12: -

ExUns: 15 ^ 16a · 16b ^ 17 ^ 18a · 18b ^ 19 ^ 20a · 20b ^ 21 ^ 22a · 22b · 22c · 22d · 22e ^ 23 ^ 24a · 24b ^ 25a · 25b ^ 26
SP1: - - - -
SP2: - - - - - - - - - -
SP3: - - - - - -
SP4: -
SP5: -
SP6: - - - - - -
SP7:
SP8:
SP9: - -
SP10:
SP11:
SP12:

Relevant External Links for ITIH4 Gene

GeneLoc Exon Structure for
ITIH4
ECgene alternative splicing isoforms for
ITIH4

Expression for ITIH4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ITIH4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ITIH4 Gene

This gene is overexpressed in Serum (20.3), Synovial fluid (17.2), Plasma (13.6), and Urine (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for ITIH4 Gene



Protein tissue co-expression partners for ITIH4 Gene

NURSA nuclear receptor signaling pathways regulating expression of ITIH4 Gene:

ITIH4

SOURCE GeneReport for Unigene cluster for ITIH4 Gene:

Hs.709406

mRNA Expression by UniProt/SwissProt for ITIH4 Gene:

Q14624-ITIH4_HUMAN
Tissue specificity: Liver specific.

Evidence on tissue expression from TISSUES for ITIH4 Gene

  • Liver(4.3)
  • Bone marrow(4.2)
  • Blood(3)
  • Nervous system(2.2)
  • Lymph node(2.1)
  • Spleen(2.1)
genes like me logo Genes that share expression patterns with ITIH4: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ITIH4 Gene

Orthologs for ITIH4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ITIH4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ITIH4 33 34
  • 99.26 (n)
dog
(Canis familiaris)
Mammalia ITIH4 33 34
  • 81.29 (n)
cow
(Bos Taurus)
Mammalia ITIH4 33 34
  • 80.29 (n)
mouse
(Mus musculus)
Mammalia Itih4 33 16 34
  • 74.72 (n)
rat
(Rattus norvegicus)
Mammalia Itih4 33
  • 73.83 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 34
  • 54 (a)
OneToMany
-- 34
  • 51 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia ITIH4 34
  • 52 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ITIH4 34
  • 48 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100487172 33
  • 56.47 (n)
zebrafish
(Danio rerio)
Actinopterygii zgc:112265 33
  • 52.1 (n)
ITIH4 34
  • 50 (a)
OneToOne
wufb66b03 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8594 33
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.1308 33
Species where no ortholog for ITIH4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • chicken (Gallus gallus)
  • 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)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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 ITIH4 Gene

ENSEMBL:
Gene Tree for ITIH4 (if available)
TreeFam:
Gene Tree for ITIH4 (if available)

Paralogs for ITIH4 Gene

Paralogs for ITIH4 Gene

(6) SIMAP similar genes for ITIH4 Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with ITIH4: view

Variants for ITIH4 Gene

Sequence variations from dbSNP and Humsavar for ITIH4 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs1000169200 -- 52,828,736(-) G/A intron_variant
rs1000502655 -- 52,829,918(-) A/ intron_variant
rs1000503680 -- 52,825,764(-) C/T intron_variant
rs1000659595 -- 52,820,401(-) C/T intron_variant
rs1000744390 -- 52,823,416(-) T/A intron_variant

Structural Variations from Database of Genomic Variants (DGV) for ITIH4 Gene

Variant ID Type Subtype PubMed ID
esv2762328 CNV loss 21179565
nsv1010761 CNV gain 25217958
nsv3822 CNV insertion 18451855
nsv508928 CNV insertion 20534489
nsv590308 CNV loss 21841781
nsv834698 CNV gain 17160897

Variation tolerance for ITIH4 Gene

Residual Variation Intolerance Score: 87% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.60; 86.18% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ITIH4 Gene

Human Gene Mutation Database (HGMD)
ITIH4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ITIH4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ITIH4 Gene

Disorders for ITIH4 Gene

MalaCards: The human disease database

(10) MalaCards diseases for ITIH4 Gene - From: HGMD, OMIM, GTR, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search ITIH4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ITIH4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ITIH4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ITIH4 Gene

Publications for ITIH4 Gene

  1. SNP analysis of the inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene by a fluorescence-adapted SSCP method. (PMID: 12147176) Tozaki T … Tomita M (BMC medical genetics 2002) 3 4 22 58
  2. Isolation and characterization of the human inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1). (PMID: 8797089) Saguchi K … Tomita M (Journal of biochemistry 1996) 3 4 22 58
  3. Purification and characterization of a novel glycoprotein which has significant homology to heavy chains of inter-alpha-trypsin inhibitor family from human plasma. (PMID: 7541790) Choi-Miura NH … Tomita M (Journal of biochemistry 1995) 3 4 22 58
  4. Cloning and characterization of cDNA for inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP), a novel human plasma glycoprotein. (PMID: 7775381) Saguchi K … Tomita M (Journal of biochemistry 1995) 3 4 22 58
  5. cDNA and deduced amino acid sequence of human PK-120, a plasma kallikrein-sensitive glycoprotein. (PMID: 7805892) Nishimura H … Nagasawa S (FEBS letters 1995) 2 3 4 58

Products for ITIH4 Gene

  • Addgene plasmids for ITIH4

Sources for ITIH4 Gene

Content
Loading form....