Seroatlas · Human Serome Atlas

ITCH

E3 ubiquitin-protein ligase Itchy homolog

Also known as: AIP4, ITCH_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: Q96J02
Gene: ITCH
Ensembl: ENSG00000078747
Chromosome: 20
Canonical length: 903 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Nucleoplasm,Vesicles

OverviewNCBI Gene

This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses. Mutations in this gene are a cause of syndromic multisystem autoimmune disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

Canonical amino-acid sequenceUniProt

903 residues, UniProt reviewed canonical sequence.

>Q96J02|ITCH
     1  MSDSGSQLGS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ SKKTEKCNNT
    61  NSPKWKQPLT VIVTPVSKLH FRVWSHQTLK SDVLLGTAAL DIYETLKSNN MKLEEVVVTL
   121  QLGGDKEPTE TIGDLSICLD GLQLESEVVT NGETTCSENG VSLCLPRLEC NSAISAHCNL
   181  CLPGLSDSPI SASRVAGFTG ASQNDDGSRS KDETRVSTNG SDDPEDAGAG ENRRVSGNNS
   241  PSLSNGGFKP SRPPRPSRPP PPTPRRPASV NGSPSATSES DGSSTGSLPP TNTNTNTSEG
   301  ATSGLIIPLT ISGGSGPRPL NPVTQAPLPP GWEQRVDQHG RVYYVDHVEK RTTWDRPEPL
   361  PPGWERRVDN MGRIYYVDHF TRTTTWQRPT LESVRNYEQW QLQRSQLQGA MQQFNQRFIY
   421  GNQDLFATSQ SKEFDPLGPL PPGWEKRTDS NGRVYFVNHN TRITQWEDPR SQGQLNEKPL
   481  PEGWEMRFTV DGIPYFVDHN RRTTTYIDPR TGKSALDNGP QIAYVRDFKA KVQYFRFWCQ
   541  QLAMPQHIKI TVTRKTLFED SFQQIMSFSP QDLRRRLWVI FPGEEGLDYG GVAREWFFLL
   601  SHEVLNPMYC LFEYAGKDNY CLQINPASYI NPDHLKYFRF IGRFIAMALF HGKFIDTGFS
   661  LPFYKRILNK PVGLKDLESI DPEFYNSLIW VKENNIEECD LEMYFSVDKE ILGEIKSHDL
   721  KPNGGNILVT EENKEEYIRM VAEWRLSRGV EEQTQAFFEG FNEILPQQYL QYFDAKELEV
   781  LLCGMQEIDL NDWQRHAIYR HYARTSKQIM WFWQFVKEID NEKRMRLLQF VTGTCRLPVG
   841  GFADLMGSNG PQKFCIEKVG KENWLPRSHT CFNRLDLPPY KSYEQLKEKL LFAIEETEGF
   901  GQE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ITCH 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: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.37
Highest tissue expression: 38 nTPM

Expression across tissuesHPA

Tissue

liver: 38 nTPM
esophagus: 23 nTPM
testis: 20 nTPM
bone marrow: 18 nTPM
spinal cord: 18 nTPM
skeletal muscle: 16 nTPM

Single-cell type

oligodendrocytes: 361 nCPM
choroid plexus epithelial cells: 286 nCPM
proximal tubule cells: 258 nCPM
distal convoluted tubule cells: 226 nCPM
renal connecting tubule cells: 220 nCPM
podocytes: 211 nCPM

Immune cell

neutrophil: 13 nTPM
plasmacytoid DC: 12 nTPM
memory B-cell: 9.9 nTPM
MAIT T-cell: 8.8 nTPM
gdT-cell: 8.3 nTPM
naive B-cell: 6.9 nTPM

Brain region

white matter: 102 nTPM
basal ganglia: 71 nTPM
thalamus: 62 nTPM
medulla oblongata: 61 nTPM
midbrain: 60 nTPM
cerebellum: 58 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ITCH.

Disease | AllUniProt

Conditions ITCH is implicated in, by any mechanism.

Autoimmune disease, multisystem, with facial dysmorphism (ADMFD) MIM:613385

Disease | GeneticClinVar

20 pathogenic / likely-pathogenic of 550 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Syndromic multisystem autoimmune disease due to ITCH deficiency

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): 0.22
gnomAD pLI: 1
gnomAD missense Z: 3.58
DepMap mean gene effect: -0.05
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 13% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ITCH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

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

ITCH is annotated at the cell surface, where native ITCH is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

Mutations in this gene are a cause of syndromic multisystem autoimmune disease.

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