Human Gene ITIH4 (ENST00000266041.9) from GENCODE V44
  Description: Homo sapiens inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), transcript variant 1, mRNA. (from RefSeq NM_002218)
RefSeq Summary (NM_002218): 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].
Gencode Transcript: ENST00000266041.9
Gencode Gene: ENSG00000055955.17
Transcript (Including UTRs)
   Position: hg38 chr3:52,812,962-52,830,672 Size: 17,711 Total Exon Count: 24 Strand: -
Coding Region
   Position: hg38 chr3:52,813,421-52,830,642 Size: 17,222 Coding Exon Count: 24 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:52,812,962-52,830,672)mRNA (may differ from genome)Protein (930 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ITIH4_HUMAN
DESCRIPTION: RecName: Full=Inter-alpha-trypsin inhibitor heavy chain H4; Short=ITI heavy chain H4; Short=ITI-HC4; Short=Inter-alpha-inhibitor heavy chain 4; AltName: Full=Inter-alpha-trypsin inhibitor family heavy chain-related protein; Short=IHRP; AltName: Full=Plasma kallikrein sensitive glycoprotein 120; Short=Gp120; Short=PK-120; Contains: RecName: Full=70 kDa inter-alpha-trypsin inhibitor heavy chain H4; Contains: RecName: Full=35 kDa inter-alpha-trypsin inhibitor heavy chain H4; Flags: Precursor;
FUNCTION: May be involved in acute phase reactions.
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Liver specific.
INDUCTION: Levels increase significantly in the sera of patients after different surgical trauma.
PTM: 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.
PTM: Appears to be both N- and O-glycosylated. The O-linked polysaccharides on Ser-696, Thr-701 and Ser-702 are probably the mucin type linked to GalNAc. O-linked glycosylations in the region AA 719-725 consist of core 1 or possibly core 8 glycans.
SIMILARITY: Belongs to the ITIH family.
SIMILARITY: Contains 1 VIT domain.
SIMILARITY: Contains 1 VWFA domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: ITIH4
Diseases sorted by gene-association score: hypercholesterolemia, familial* (208), aids dementia complex (19), acquired immunodeficiency syndrome (19), human immunodeficiency virus infectious disease (11), retinitis pigmentosa 70 (11), primary immunodeficiency disease (8), syphilitic meningitis (8), viral infectious disease (8), toxic encephalopathy (4), encephalitis (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 0.45 RPKM in Liver
Total median expression: 0.55 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -4.9030-0.163 Picture PostScript Text
3' UTR -157.50459-0.343 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR010600 - ITI_HC_C
IPR013694 - VIT
IPR002035 - VWF_A

Pfam Domains:
PF06668 - Inter-alpha-trypsin inhibitor heavy chain C-terminus
PF08487 - Vault protein inter-alpha-trypsin domain
PF00092 - von Willebrand factor type A domain

ModBase Predicted Comparative 3D Structure on Q14624
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004866 endopeptidase inhibitor activity
GO:0004867 serine-type endopeptidase inhibitor activity
GO:0005515 protein binding
GO:0030414 peptidase inhibitor activity

Biological Process:
GO:0002576 platelet degranulation
GO:0006953 acute-phase response
GO:0010466 negative regulation of peptidase activity
GO:0010951 negative regulation of endopeptidase activity
GO:0030212 hyaluronan metabolic process
GO:0034097 response to cytokine

Cellular Component:
GO:0005576 extracellular region
GO:0031089 platelet dense granule lumen
GO:0070062 extracellular exosome
GO:0072562 blood microparticle


-  Descriptions from all associated GenBank mRNAs
  AB209388 - Homo sapiens mRNA for inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein) variant protein.
BC136392 - Homo sapiens inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein), mRNA (cDNA clone MGC:168002 IMAGE:9020379), complete cds.
BC136393 - Homo sapiens inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein), mRNA (cDNA clone MGC:168003 IMAGE:9020380), complete cds.
AF119856 - Homo sapiens PRO1851 mRNA, complete cds.
AK298407 - Homo sapiens cDNA FLJ51742 complete cds, highly similar to Inter-alpha-trypsin inhibitor heavy chain H4 precursor.
D38595 - Homo sapiens mRNA for inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP), complete cds.
CR749404 - Homo sapiens mRNA; cDNA DKFZp686G21125 (from clone DKFZp686G21125).
BX647322 - Homo sapiens mRNA; cDNA DKFZp779B0415 (from clone DKFZp779B0415).
D38535 - Homo sapiens mRNA for PK-120, complete cds.
AK298412 - Homo sapiens cDNA FLJ60068 complete cds, highly similar to Inter-alpha-trypsin inhibitor heavy chain H4 precursor.
AK298429 - Homo sapiens cDNA FLJ60767 complete cds, highly similar to Inter-alpha-trypsin inhibitor heavy chain H4 precursor.
AK303769 - Homo sapiens cDNA FLJ53871 complete cds, highly similar to Inter-alpha-trypsin inhibitor heavy chain H4 precursor.
AK309031 - Homo sapiens cDNA, FLJ99072.
AK310752 - Homo sapiens cDNA, FLJ17794.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q14624 (Reactome details) participates in the following event(s):

R-HSA-481009 Exocytosis of platelet dense granule content
R-HSA-114608 Platelet degranulation
R-HSA-76005 Response to elevated platelet cytosolic Ca2+
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-109582 Hemostasis

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000266041.1, ENST00000266041.2, ENST00000266041.3, ENST00000266041.4, ENST00000266041.5, ENST00000266041.6, ENST00000266041.7, ENST00000266041.8, IHRP, ITIH4_HUMAN, ITIHL1, NM_002218, PK120, PRO1851, Q14624, Q15135, Q9P190, Q9UQ54, uc003dfz.1, uc003dfz.2, uc003dfz.3, uc003dfz.4, uc003dfz.5
UCSC ID: ENST00000266041.9
RefSeq Accession: NM_002218
Protein: Q14624 (aka ITIH4_HUMAN)
CCDS: CCDS2865.1, CCDS54596.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.