• Gene id: 83737

Gene Summary

• Gene Symbol: ITCH   Gene   UCSC   Ensembl
• Aliases: ADMFD, AIF4, AIP4, NAPP1
• Gene name: itchy E3 ubiquitin protein ligase
• Alternate names: E3 ubiquitin-protein ligase Itchy homolog, HECT-type E3 ubiquitin transferase Itchy homolog, NFE2-associated polypeptide 1, atrophin-1 interacting protein 4, itchy E3 ubiquitin protein ligase homolog,
• Gene location: 20q11.22 (657652: 673577)     Exons: 8     NC_000018.10
• Gene summary(Entrez): 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
• OMIM: 606409

Protein Summary

• Protein general information: Q96J02  
  • Name: E3 ubiquitin protein ligase Itchy homolog (Itch) (EC 2.3.2.26) (Atrophin 1 interacting protein 4) (AIP4) (HECT type E3 ubiquitin transferase Itchy homolog) (NFE2 associated polypeptide 1) (NAPP1)
  • Length: 903  
  • Mass: 102803
  • Tissue specificity: Widely expressed.
• Sequence:

  MSDSGSQLGSMGSLTMKSQLQITVISAKLKENKKNWFGPSPYVEVTVDGQSKKTEKCNNTNSPKWKQPLTVIVTP
  VSKLHFRVWSHQTLKSDVLLGTAALDIYETLKSNNMKLEEVVVTLQLGGDKEPTETIGDLSICLDGLQLESEVVT
  NGETTCSENGVSLCLPRLECNSAISAHCNLCLPGLSDSPISASRVAGFTGASQNDDGSRSKDETRVSTNGSDDPE
  DAGAGENRRVSGNNSPSLSNGGFKPSRPPRPSRPPPPTPRRPASVNGSPSATSESDGSSTGSLPPTNTNTNTSEG
  ATSGLIIPLTISGGSGPRPLNPVTQAPLPPGWEQRVDQHGRVYYVDHVEKRTTWDRPEPLPPGWERRVDNMGRIY
  YVDHFTRTTTWQRPTLESVRNYEQWQLQRSQLQGAMQQFNQRFIYGNQDLFATSQSKEFDPLGPLPPGWEKRTDS
  NGRVYFVNHNTRITQWEDPRSQGQLNEKPLPEGWEMRFTVDGIPYFVDHNRRTTTYIDPRTGKSALDNGPQIAYV
  RDFKAKVQYFRFWCQQLAMPQHIKITVTRKTLFEDSFQQIMSFSPQDLRRRLWVIFPGEEGLDYGGVAREWFFLL
  SHEVLNPMYCLFEYAGKDNYCLQINPASYINPDHLKYFRFIGRFIAMALFHGKFIDTGFSLPFYKRILNKPVGLK
  DLESIDPEFYNSLIWVKENNIEECDLEMYFSVDKEILGEIKSHDLKPNGGNILVTEENKEEYIRMVAEWRLSRGV
  EEQTQAFFEGFNEILPQQYLQYFDAKELEVLLCGMQEIDLNDWQRHAIYRHYARTSKQIMWFWQFVKEIDNEKRM
  RLLQFVTGTCRLPVGGFADLMGSNGPQKFCIEKVGKENWLPRSHTCFNRLDLPPYKSYEQLKEKLLFAIEETEGF
  GQE

• Structural information:
  • Protein Domains: (1..11-)
    (/note="C2-)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00041-)
    (326..35-)
    (/note="WW-1)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00224-)
    (358..39-)
    (/note="WW-2)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00224-)
    (438-)
  • Interpro: IPR000008  IPR035892  IPR024928  IPR000569  IPR035983   IPR001202  IPR036020  
  • Prosite: PS50004 PS50237 PS01159 PS50020
  • CDD: cd00078 cd00201
  • PDB: 2DMV 2KYK 2NQ3 2P4R 2YSF 3TUG 4ROF 5C7M 5CQ2 5DWS 5DZD 5SXP
  • PDBsum: 2DMV 2KYK 2NQ3 2P4R 2YSF 3TUG 4ROF 5C7M 5CQ2 5DWS 5DZD 5SXP
  • DIP: 29849
  • STRING: ENSP00000480499
• Other Databases: GeneCards:  ITCH  Malacards:  ITCH

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0006511	ubiquitin-dependent protein catabolic process	IMP	biological process
GO:0000209	protein polyubiquitination	IBA	biological process
GO:0005737	cytoplasm	IBA	cellular component
GO:0016567	protein ubiquitination	IBA	biological process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	IBA	biological process
GO:0006511	ubiquitin-dependent protein catabolic process	IBA	biological process
GO:0035519	protein K29-linked ubiquitination	IBA	biological process
GO:0045732	positive regulation of protein catabolic process	IBA	biological process
GO:0061630	ubiquitin protein ligase activity	IBA	molecular function
GO:0070534	protein K63-linked ubiquitination	IBA	biological process
GO:0070936	protein K48-linked ubiquitination	IBA	biological process
GO:0070936	protein K48-linked ubiquitination	IDA	biological process
GO:0070534	protein K63-linked ubiquitination	IDA	biological process
GO:0070534	protein K63-linked ubiquitination	IDA	biological process
GO:0035519	protein K29-linked ubiquitination	IDA	biological process
GO:0035519	protein K29-linked ubiquitination	IDA	biological process
GO:0004842	ubiquitin-protein transferase activity	IDA	molecular function
GO:0016567	protein ubiquitination	IDA	biological process
GO:0016567	protein ubiquitination	IDA	biological process
GO:0005886	plasma membrane	IDA	cellular component
GO:0050687	negative regulation of defense response to virus	IMP	biological process
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:1990763	arrestin family protein binding	IPI	molecular function
GO:1990763	arrestin family protein binding	IPI	molecular function
GO:0045236	CXCR chemokine receptor binding	IPI	molecular function
GO:0043021	ribonucleoprotein complex binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0004842	ubiquitin-protein transferase activity	IEA	molecular function
GO:0006511	ubiquitin-dependent protein catabolic process	IEA	biological process
GO:0061630	ubiquitin protein ligase activity	IEA	molecular function
GO:0005768	endosome	IEA	cellular component
GO:0045087	innate immune response	IEA	biological process
GO:0051607	defense response to virus	IEA	biological process
GO:0016740	transferase activity	IEA	molecular function
GO:0002376	immune system process	IEA	biological process
GO:0005886	plasma membrane	IEA	cellular component
GO:0016020	membrane	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0016032	viral process	IEA	biological process
GO:0006915	apoptotic process	IEA	biological process
GO:0061630	ubiquitin protein ligase activity	IDA	molecular function
GO:0006511	ubiquitin-dependent protein catabolic process	IDA	biological process
GO:0032480	negative regulation of type I interferon production	TAS	biological process
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0007219	Notch signaling pathway	TAS	biological process
GO:0061630	ubiquitin protein ligase activity	TAS	molecular function
GO:0061630	ubiquitin protein ligase activity	TAS	molecular function
GO:0061630	ubiquitin protein ligase activity	TAS	molecular function
GO:0061630	ubiquitin protein ligase activity	TAS	molecular function
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway	TAS	biological process
GO:1902036	regulation of hematopoietic stem cell differentiation	TAS	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0032088	negative regulation of NF-kappaB transcription factor activity	ISS	biological process
GO:0046329	negative regulation of JNK cascade	ISS	biological process
GO:0090085	regulation of protein deubiquitination	ISS	biological process
GO:0031901	early endosome membrane	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0010008	endosome membrane	IEA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0043231	intracellular membrane-bounded organelle	IDA	cellular component
GO:0016567	protein ubiquitination	IEA	biological process
GO:0005769	early endosome	IDA	colocalizes with
GO:0032991	protein-containing complex	IDA	cellular component
GO:0016020	membrane	HDA	cellular component
GO:0006954	inflammatory response	NAS	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0004842	ubiquitin-protein transferase activity	NAS	molecular function
GO:0046718	viral entry into host cell	TAS	biological process
GO:0070062	extracellular exosome	HDA	cellular component
GO:0006511	ubiquitin-dependent protein catabolic process	NAS	biological process
GO:0001558	regulation of cell growth	NAS	biological process
GO:0051865	protein autoubiquitination	IMP	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0004842	ubiquitin-protein transferase activity	IMP	molecular function
GO:0016567	protein ubiquitination	IMP	biological process
GO:0044389	ubiquitin-like protein ligase binding	IPI	molecular function
GO:2000646	positive regulation of receptor catabolic process	IMP	biological process

KEGG pathways

Pathway id	Pathway name
hsa04144	Endocytosis
hsa04120	Ubiquitin mediated proteolysis
hsa04932	Non-alcoholic fatty liver disease
hsa04668	TNF signaling pathway

Diseases

Associated diseases	References
Syndromic multisystem autoimmune disease	KEGG:H01232
Syndromic multisystem autoimmune disease	KEGG:H01232
Aberrant CpGs in Low Motility Sperm	MIK: 21674046
Cryptorchidism	MIK: 28606200
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
17327269	Teratozoospermia			19 (6 controls, 13 cases)	Male infertility	GSE6872 analyzed by GEO2R (cutoff 1.5 fold)
21674046	Aberrant CpGs in Low Motility Sperm			18	Male infertility	GSE26881
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq