Seroatlas · Human Serome Atlas

ITIH3

Inter-alpha-trypsin inhibitor heavy chain H3

Also known as: H3P, ITIH3_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q06033
Gene: ITIH3
Ensembl: ENSG00000162267
Chromosome: 3
Canonical length: 890 aa
Protein class: Plasma proteins, Predicted secreted proteins
Secretome location: Secreted to blood

OverviewNCBI Gene

This gene encodes the heavy chain subunit of the pre-alpha-trypsin inhibitor complex. This complex may stabilize the extracellular matrix through its ability to bind hyaluronic acid. Polymorphisms of this gene may be associated with increased risk for schizophrenia and major depressive disorder. This gene is present in an inter-alpha-trypsin inhibitor family gene cluster on chromosome 3. [provided by RefSeq, Jul 2015]

Canonical amino-acid sequenceUniProt

890 residues, UniProt reviewed canonical sequence.

>Q06033|ITIH3
     1  MAFAWWPCLI LALLSSLAAS GFPRSPFRLL GKRSLPEGVA NGIEVYSTKI NSKVTSRFAH
    61  NVVTMRAVNR ADTAKEVSFD VELPKTAFIT NFTLTIDGVT YPGNVKEKEV AKKQYEKAVS
   121  QGKTAGLVKA SGRKLEKFTV SVNVAAGSKV TFELTYEELL KRHKGKYEMY LKVQPKQLVK
   181  HFEIEVDIFE PQGISMLDAE ASFITNDLLG SALTKSFSGK KGHVSFKPSL DQQRSCPTCT
   241  DSLLNGDFTI TYDVNRESPG NVQIVNGYFV HFFAPQGLPV VPKNVAFVID ISGSMAGRKL
   301  EQTKEALLRI LEDMQEEDYL NFILFSGDVS TWKEHLVQAT PENLQEARTF VKSMEDKGMT
   361  NINDGLLRGI SMLNKAREEH RIPERSTSIV IMLTDGDANV GESRPEKIQE NVRNAIGGKF
   421  PLYNLGFGNN LNYNFLENMA LENHGFARRI YEDSDADLQL QGFYEEVANP LLTGVEMEYP
   481  ENAILDLTQN TYQHFYDGSE IVVAGRLVDE DMNSFKADVK GHGATNDLTF TEEVDMKEME
   541  KALQERDYIF GNYIERLWAY LTIEQLLEKR KNAHGEEKEN LTARALDLSL KYHFVTPLTS
   601  MVVTKPEDNE DERAIADKPG EDAEATPVSP AMSYLTSYQP PQNPYYYVDG DPHFIIQIPE
   661  KDDALCFNID EAPGTVLRLI QDAVTGLTVN GQITGDKRGS PDSKTRKTYF GKLGIANAQM
   721  DFQVEVTTEK ITLWNRAVPS TFSWLDTVTV TQDGLSMMIN RKNMVVSFGD GVTFVVVLHQ
   781  VWKKHPVHRD FLGFYVVDSH RMSAQTHGLL GQFFQPFDFK VSDIRPGSDP TKPDATLVVK
   841  NHQLIVTRGS QKDYRKDASI GTKVVCWFVH NNGEGLIDGV HTDYIVPNLF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ITIH3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.27
Highest tissue expression: 798 nTPM

Expression across tissuesHPA

Tissue

liver: 798 nTPM
blood vessel: 62 nTPM
spleen: 6.3 nTPM
adipose tissue: 4.3 nTPM
cervix: 4 nTPM
testis: 3.1 nTPM

Single-cell type

hepatocytes: 954 nCPM
late spermatids: 228 nCPM
vascular smooth muscle cells: 52 nCPM
hepatic stellate cells: 45 nCPM
early spermatids: 25 nCPM
cholangiocytes: 24 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

basal ganglia: 1 nTPM
cerebral cortex: 1 nTPM
white matter: 0.5 nTPM
amygdala: 0.4 nTPM
hippocampal formation: 0.4 nTPM
medulla oblongata: 0.4 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.89
gnomAD pLI: 0
gnomAD missense Z: 0.84
DepMap mean gene effect: -0.15
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

hyaluronan metabolic process

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ITIH3 as an antibody target. Whether an autoantibody or antibody against ITIH3 could matter depends on whether native ITIH3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ITIH3 is annotated as secreted, so native ITIH3 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label ITIH3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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