ITCH

Functionⁱ

Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:14602072, PubMed:17028573, PubMed:16387660, PubMed:18718448, PubMed:18718449, PubMed:11046148, PubMed:19592251, PubMed:19116316, PubMed:19881509, PubMed:20491914, PubMed:20392206, PubMed:20068034, PubMed:23146885, PubMed:24790097, PubMed:25631046). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965, PubMed:19881509). Involved in the control of inflammatory signaling pathways (PubMed:19131965). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (PubMed:19131965). Promotes the association of the complex after TNF stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (PubMed:19592251). Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation (PubMed:16387660). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (PubMed:19881509). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (PubMed:19881509). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (PubMed:23146885). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (PubMed:23146885). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:14602072, PubMed:23146885). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:17028573, PubMed:18628966, PubMed:23886940). Ubiquitinates SNX9 (PubMed:20491914). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (By similarity). Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP (PubMed:20068034). Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Inhibits the replication of influenza A virus (IAV) via ubiquitination of IAV matrix protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1 proteasomal degradation (PubMed:30328013).By similarity18 Publications

Catalytic activityⁱ

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.
15 Publications
Manual assertion based on experiment inⁱ
- Ref.11
  "The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4."
  Marchese A., Raiborg C., Santini F., Keen J.H., Stenmark H., Benovic J.L.
  Dev. Cell 5:709-722(2003) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, INTERACTION WITH HGS, MUTAGENESIS OF CYS-871.
- Ref.13
  "Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains."
  Chastagner P., Israel A., Brou C.
  EMBO Rep. 7:1147-1153(2006) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH DTX1, UBIQUITINATION OF DTX1.
- Ref.14
  "Negative regulation of the E3 ubiquitin ligase itch via Fyn-mediated tyrosine phosphorylation."
  Yang C., Zhou W., Jeon M.S., Demydenko D., Harada Y., Zhou H., Liu Y.C.
  Mol. Cell 21:135-141(2006) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH JUNB AND FYN, PHOSPHORYLATION AT TYR-420, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF TYR-343; TYR-420 AND TYR-455.
- Ref.15
  "Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination."
  Lee T.-L., Shyu Y.-C., Hsu T.-Y., Shen C.-K.J.
  Biochem. Biophys. Res. Commun. 375:326-330(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH NFE2.
- Ref.16
  "Itch self-polyubiquitylation occurs through lysine-63 linkages."
  Scialpi F., Malatesta M., Peschiaroli A., Rossi M., Melino G., Bernassola F.
  Biochem. Pharmacol. 76:1515-1521(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AUTOUBIQUITINATION, IDENTIFICATION BY MASS SPECTROMETRY.
- Ref.18
  "AIP4/Itch regulates Notch receptor degradation in the absence of ligand."
  Chastagner P., Israel A., Brou C.
  PLoS ONE 3:E2735-E2735(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, UBIQUITINATION OF NOTCH1.
- Ref.21
  "ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways."
  Tao M., Scacheri P.C., Marinis J.M., Harhaj E.W., Matesic L.E., Abbott D.W.
  Curr. Biol. 19:1255-1263(2009) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, UBIQUITINATION OF RIPK2.
- Ref.23
  "The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction."
  Bhandari D., Robia S.L., Marchese A.
  Mol. Biol. Cell 20:1324-1339(2009) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH CXCR4, UBIQUITINATION.
- Ref.24
  "PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4."
  You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z., Jiang Z.
  Nat. Immunol. 10:1300-1308(2009) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, UBIQUITINATION OF MAVS, INTERACTION WITH PCBP2, MUTAGENESIS OF CYS-871.
- Ref.26
  "The E3 ubiquitin ligase Itch regulates sorting nexin 9 through an unconventional substrate recognition domain."
  Baumann C., Lindholm C.K., Rimoldi D., Levy F.
  FEBS J. 277:2803-2814(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH SNX9 AND SNX18, UBIQUITINATION OF SNX9.
- Ref.27
  "The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid."
  Azakir B.A., Desrochers G., Angers A.
  FEBS J. 277:1319-1330(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH P15 BID, UBIQUITINATION OF P15 BID.
- Ref.28
  "The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation."
  Zhang P., Wang C., Gao K., Wang D., Mao J., An J., Xu C., Wu D., Yu H., Liu J.O., Yu L.
  J. Biol. Chem. 285:8869-8879(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH TXNIP, UBIQUITINATION OF TXNIP.
- Ref.33
  "Phosphatidylinositol 4-kinase IIalpha function at endosomes is regulated by the ubiquitin ligase Itch."
  Mossinger J., Wieffer M., Krause E., Freund C., Gerth F., Krauss M., Haucke V.
  EMBO Rep. 13:1087-1094(2012) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, INTERACTION WITH PI4K2A, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF CYS-871.
- Ref.37
  "The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein-coupled receptor CXCR4."
  Holleman J., Marchese A.
  Mol. Biol. Cell 25:1892-1904(2014) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, INTERACTION WITH DTX3L, IDENTIFICATION IN A COMPLEX WITH DTX3L; STAM AND HGS, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-871.
- Ref.38
  "Nedd4 family interacting protein 1 (Ndfip1) is required for ubiquitination and nuclear trafficking of BRCA1-associated ATM activator 1 (BRAT1) during the DNA damage response."
  Low L.H., Chow Y.L., Li Y., Goh C.P., Putz U., Silke J., Ouchi T., Howitt J., Tan S.S.
  J. Biol. Chem. 290:7141-7150(2015) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION IN UBIQUITINATION OF BRAT1, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY.
EC:2.3.2.26

Activity regulationⁱ

Activated by NDFIP1- and NDFIP2-binding (PubMed:25631046). Activated by PI4K2A-binding (PubMed:23146885). Inhibited by DTX3L-binding (PubMed:24790097). Inhibited by N4BP1 binding (By similarity).By similarity3 Publications

Pathwayⁱ: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.15 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Active siteⁱ	871	Glycyl thioester intermediatePROSITE-ProRule annotation		1

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Transferase
Biological process	Antiviral defense, Apoptosis, Host-virus interaction, Immunity, Innate immunity, Ubl conjugation pathway

Enzyme and pathway databases

BRENDAⁱ	6.3.2.19, 2681
PathwayCommonsⁱ	Q96J02
Reactomeⁱ	R-HSA-1253288, Downregulation of ERBB4 signaling R-HSA-168638, NOD1/2 Signaling Pathway R-HSA-2122948, Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-5610780, Degradation of GLI1 by the proteasome R-HSA-5632684, Hedgehog 'on' state R-HSA-8939236, RUNX1 regulates transcription of genes involved in differentiation of HSCs R-HSA-936440, Negative regulators of DDX58/IFIH1 signaling R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkⁱ	Q96J02
SIGNORⁱ	Q96J02
UniPathwayⁱ	UPA00143

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: E3 ubiquitin-protein ligase Itchy homolog (EC:2.3.2.267 Publications) Short name: Itch Alternative name(s): Atrophin-1-interacting protein 4 Short name: AIP4 HECT-type E3 ubiquitin transferase Itchy homolog NFE2-associated polypeptide 1 Short name: NAPP1
Gene namesⁱ	Name:ITCH
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 20

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:13890, ITCH
MIMⁱ	606409, gene
neXtProtⁱ	NX_Q96J02
VEuPathDBⁱ	HostDB:ENSG00000078747.12

Keywords - Cellular componentⁱ

Cell membrane, Cytoplasm, Endosome, Membrane, Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Autoimmune disease, multisystem, with facial dysmorphism (ADMFD)1 Publication

The disease is caused by variants affecting the gene represented in this entry.

Disease descriptionA disorder characterized by organomegaly, failure to thrive, developmental delay, dysmorphic features and autoimmune inflammatory cell infiltration of the lungs, liver and gut.

Related information in OMIM

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	343	Y → F: No effect on phosphorylation on T-cell stimulation nor in the presence of FYN. 1 Publication	1
Mutagenesisⁱ	420	Y → F: Greatly reduced phosphorylation on T-cell stimulation and in the presence of FYN. Increased ITCH-mediated Ub conjugation and degradation of JUNB. 1 Publication	1
Mutagenesisⁱ	455	Y → F: No effect on phosphorylation on T-cell stimulation nor in the presence of FYN. 1 Publication	1
Mutagenesisⁱ	871	C → A: Loss of ubiquitin protein ligase activity. Results in altered endosomal sorting and reduced degradation of CXCR4. Unable to inhibit MAVS-induced activation of INFB. 5 Publications	1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	83737
MalaCards human disease database More...MalaCardsⁱ	ITCH
MIMⁱ	613385, phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000078747
Orphanetⁱ	228426, Syndromic multisystem autoimmune disease due to Itch deficiency
PharmGKBⁱ	PA29934

Miscellaneous databases

Pharosⁱ	Q96J02, Tbio

Pharosⁱ

Q96J02, Tbio

Chemistry databases

ChEMBLⁱ	CHEMBL4295925

ChEMBLⁱ

CHEMBL4295925

Genetic variation databases

BioMutaⁱ	ITCH
DMDMⁱ	37537897

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		RemovedCombined sources
ChainⁱPRO_0000120317	2 – 903	E3 ubiquitin-protein ligase Itchy homologAdd BLAST		902

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	2	N-acetylserineCombined sources	1
Modified residueⁱ	240	Phosphoserine; by MAPK8By similarity	1
Modified residueⁱ	263	Phosphothreonine; by MAPK8By similarity	1
Modified residueⁱ	273	Phosphoserine; by MAPK8By similarity	1
Modified residueⁱ	385	Phosphothreonine; by SGK31 Publication	1
Modified residueⁱ	420	Phosphotyrosine; by FYN1 Publication	1
Modified residueⁱ	450	Phosphoserine; by SGK31 Publication	1

Post-translational modificationⁱ

On T-cell activation, phosphorylation by the JNK cascade on serine and threonine residues surrounding the PRR domain accelerates the ubiquitination and degradation of JUN and JUNB. The increased ITCH catalytic activity due to phosphorylation by JNK1 may occur due to a conformational change disrupting the interaction between the PRR/WW motifs domain and the HECT domain and, thus exposing the HECT domain (By similarity). Phosphorylation by FYN reduces interaction with JUNB and negatively controls JUN ubiquitination and degradation.By similarity4 Publications

Monoubiquitinated (PubMed:19116316). Autopolyubiquitinated with 'Lys-63' linkages which does not lead to protein degradation (PubMed:18718449, PubMed:23146885, PubMed:24790097).4 Publications

Keywords - PTMⁱ

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	Q96J02
jPOSTⁱ	Q96J02
MassIVEⁱ	Q96J02
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q96J02
PaxDbⁱ	Q96J02
PeptideAtlas More...PeptideAtlasⁱ	Q96J02
PRIDEⁱ	Q96J02
ProteomicsDBⁱ	25826 76882 [Q96J02-1] 76883 [Q96J02-2]

PTM databases

iPTMnetⁱ	Q96J02
PhosphoSitePlusⁱ	Q96J02

Expressionⁱ

Tissue specificityⁱ

Widely expressed.

Gene expression databases

Bgeeⁱ	ENSG00000078747, Expressed in sperm and 232 other tissues
ExpressionAtlasⁱ	Q96J02, baseline and differential
Genevisibleⁱ	Q96J02, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000078747, Low tissue specificity

HPAⁱ

ENSG00000078747, Low tissue specificity

Interactionⁱ

Subunit structureⁱ

Monomer.

Interacts (via WW domains) with OCNL (By similarity).

Interacts (via WW domains) with NOTCH1 (By similarity).

Interacts (via WW domains) with JUN (By similarity).

Interacts with JUNB; the interaction promotes ITCH-mediated ubiquitination and degradation of JUNB (PubMed:16387660).

Interacts with FYN; the interaction phosphorylates ITCH on Tyr-420 decreasing binding of JUNB (PubMed:16387660).

Interacts (via WW domain 2) with N4BP1; the interaction inhibits the E3 ubiquitin-protein ligase activity (By similarity).

Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (By similarity).

Interacts with ARHGEF7 (PubMed:17652093).

Interacts with RNF11 (PubMed:14559117, PubMed:19131965).

Interacts (via the WW 1 domain) with NFE2 (via the PXY motif 1); the interaction promotes 'Lys-63'-linked ubiquitination of NFE2, retains it in the cytoplasm and prevents its transactivation activity (PubMed:11318614, PubMed:18718448).

Interacts (via WW domains) with CXCR4 (via C-terminus); the interaction depends on CXCR4 phosphorylation (PubMed:19116316).

Found in a complex with E3 ligase DTX3L and ESCRT-0 components HGS and STAM (PubMed:24790097).

Interacts with DTX3L (via C-terminus); the interaction is increased upon CXCL12 stimulation and inhibits ITCH catalytic activity (the interaction is direct) (PubMed:24790097).

Interacts with HGS (PubMed:14602072).

Interacts (via WW domains) with PCBP2 within a complex containing ITCH, MAVS and PCBP2 (PubMed:19881509).

Interacts (via WW domains) with TXNIP (via C-terminus) (PubMed:20068034).

Interacts with p15 BID (PubMed:20392206).

Interacts with ERBB4 (PubMed:20858735).

Interacts with DTX1 (PubMed:17028573).

Interacts with SPART (PubMed:19580544).

Interacts with SNX9 and SNX18 (PubMed:20491914).

Interacts (via its WW domains) with ATN1 (PubMed:9647693).

Interacts (via WW domains) with SGK3 (PubMed:16888620).

Interacts with CBLC (PubMed:12226085).

Interacts with OTUD7B (PubMed:22179831).

Interacts (via WW domain 1,2 and 3) with PI4K2A; the interaction inhibits PI4K2A catalytic activity and promotes ITCH catalytic activity (PubMed:23146885).

Interacts with ARRDC4 (PubMed:23236378).

Part of a complex containing ITCH, NDFIP1 and MAP3K7 (By similarity).

Interacts with UBE2L3; the interaction is mediated by NDFIP1 (PubMed:25632008).

Interacts with MAPK8/JNK1 (By similarity).

Interacts (via WW domains) with ARRDC1 (via PPxY motifs); the interaction is direct and participates in the recruitment of the ubiquitin-protein ligase ITCH to the NOTCH1 receptor (PubMed:21191027, PubMed:23886940).

Interacts (via WW domains) with ARRDC2 (PubMed:21191027).

Interacts (via WW domains) with ARRDC3 (PubMed:21191027, PubMed:23886940).

By similarity25 Publications

(Microbial infection) Interacts with Epstein-Barr virus LMP2A.

1 Publication

(Microbial infection) Interacts with Human cytomegalovirus (HCMV) protein UL42; this interaction induces ubiquitination and degradation of ITCH.

2 Publications

(Microbial infection) Interacts with herpesvirus 1 (HHV-1) UL56 protein; this interaction induces ubiquitination and probably degradation of ITCH.

1 Publication

(Microbial infection) Interacts with herpesvirus 2 (HHV-2) UL56 protein.

1 Publication

(Microbial infection) Interacts with varicella-zoster virus (VZV) Orf0 protein.

1 Publication

(Microbial infection) Interacts with herpesvirus 6A (HHV-6A) U24 protein.

1 Publication

(Microbial infection) Interacts with ebola virus protein VP40; this interaction is required for efficient viral egress from the infected cell.

1 Publication

(Microbial infection) Interacts with influenza A virus matrix protein 1.

1 Publication

Binary interactionsⁱ

Hide details

Q96J02

With	#Exp.	IntAct
ARRDC3 [Q96B67]	3	EBI-1564678,EBI-2875665
CYLD [Q9NQC7]	3	EBI-1564678,EBI-2117940
GLI1 [P08151]	4	EBI-1564678,EBI-308084
N4BP1 [O75113]	3	EBI-1564678,EBI-5278391
PI4K2A [Q9BTU6]	5	EBI-1564678,EBI-3239392
RNF11 [Q9Y3C5]	2	EBI-1564678,EBI-396669
SGK3 [Q96BR1]	5	EBI-1564678,EBI-2801236
SNX9 [Q9Y5X1]	7	EBI-1564678,EBI-77848
TP53BP2 [Q13625]	2	EBI-1564678,EBI-77642
TP63 [Q9H3D4]	2	EBI-1564678,EBI-2337775
TP73 [O15350]	3	EBI-1564678,EBI-389606
TP73 - isoform Alpha [O15350-1]	5	EBI-1564678,EBI-389619
TP73 - isoform dN-Alpha [O15350-8]	2	EBI-1564678,EBI-5651259
LMP2 [P13285] from Epstein-Barr virus (strain B95-8).	3	EBI-1564678,EBI-7181113
Numb - isoform 2 [Q9QZS3-2] from Mus musculus.	2	EBI-1564678,EBI-3896014

Isoform 2 [Q96J02-2]

With	#Exp.	IntAct
CYLD [Q9NQC7]	2	EBI-6672198,EBI-2117940
ERBB4 [Q15303]	3	EBI-6672198,EBI-80371
ERBB4 - isoform JM-A CYT-2 [Q15303-3]	2	EBI-6672198,EBI-15692884
JPH3 [Q8WXH2]	3	EBI-6672198,EBI-1055254

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	123747, 250 interactors
CORUMⁱ	Q96J02
Database of interacting proteins More...DIPⁱ	DIP-29849N
ELMⁱ	Q96J02
IntActⁱ	Q96J02, 61 interactors
Molecular INTeraction database More...MINTⁱ	Q96J02
STRINGⁱ	9606.ENSP00000480499

Miscellaneous databases

RNActⁱ	Q96J02, protein

RNActⁱ

Q96J02, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	18 – 29	Combined sources	12
Beta strandⁱ	41 – 47	Combined sources	7
Beta strandⁱ	50 – 53	Combined sources	4
Beta strandⁱ	64 – 73	Combined sources	10
Beta strandⁱ	78 – 85	Combined sources	8
Beta strandⁱ	88 – 90	Combined sources	3
Beta strandⁱ	93 – 101	Combined sources	9
Helixⁱ	102 – 108	Combined sources	7
Turnⁱ	109 – 111	Combined sources	3
Beta strandⁱ	112 – 126	Combined sources	15
Beta strandⁱ	130 – 143	Combined sources	14
Beta strandⁱ	332 – 336	Combined sources	5
Beta strandⁱ	342 – 346	Combined sources	5
Turnⁱ	347 – 349	Combined sources	3
Beta strandⁱ	352 – 355	Combined sources	4
Beta strandⁱ	365 – 368	Combined sources	4
Beta strandⁱ	374 – 377	Combined sources	4
Beta strandⁱ	379 – 381	Combined sources	3
Beta strandⁱ	444 – 448	Combined sources	5
Beta strandⁱ	454 – 458	Combined sources	5
Turnⁱ	459 – 462	Combined sources	4
Beta strandⁱ	463 – 467	Combined sources	5
Helixⁱ	469 – 471	Combined sources	3
Beta strandⁱ	484 – 488	Combined sources	5
Beta strandⁱ	494 – 498	Combined sources	5
Turnⁱ	499 – 502	Combined sources	4
Beta strandⁱ	503 – 507	Combined sources	5
Turnⁱ	509 – 511	Combined sources	3
Helixⁱ	528 – 539	Combined sources	12
Turnⁱ	540 – 542	Combined sources	3
Beta strandⁱ	545 – 551	Combined sources	7
Beta strandⁱ	554 – 556	Combined sources	3
Helixⁱ	557 – 567	Combined sources	11
Helixⁱ	572 – 574	Combined sources	3
Beta strandⁱ	575 – 580	Combined sources	6
Helixⁱ	589 – 603	Combined sources	15
Turnⁱ	607 – 609	Combined sources	3
Beta strandⁱ	611 – 614	Combined sources	4
Beta strandⁱ	621 – 624	Combined sources	4
Helixⁱ	626 – 630	Combined sources	5
Helixⁱ	634 – 650	Combined sources	17
Helixⁱ	661 – 667	Combined sources	7
Helixⁱ	675 – 677	Combined sources	3
Turnⁱ	678 – 680	Combined sources	3
Helixⁱ	682 – 692	Combined sources	11
Helixⁱ	696 – 699	Combined sources	4
Beta strandⁱ	704 – 709	Combined sources	6
Beta strandⁱ	716 – 721	Combined sources	6
Helixⁱ	724 – 726	Combined sources	3
Turnⁱ	731 – 733	Combined sources	3
Helixⁱ	735 – 747	Combined sources	13
Helixⁱ	751 – 764	Combined sources	14
Helixⁱ	767 – 770	Combined sources	4
Helixⁱ	775 – 783	Combined sources	9
Helixⁱ	790 – 795	Combined sources	6
Beta strandⁱ	798 – 801	Combined sources	4
Helixⁱ	807 – 818	Combined sources	12
Helixⁱ	821 – 832	Combined sources	12
Helixⁱ	842 – 844	Combined sources	3
Beta strandⁱ	848 – 851	Combined sources	4
Beta strandⁱ	855 – 858	Combined sources	4
Beta strandⁱ	867 – 869	Combined sources	3
Helixⁱ	870 – 872	Combined sources	3
Beta strandⁱ	874 – 877	Combined sources	4
Helixⁱ	883 – 895	Combined sources	13

Show more details

3D structure databases

SMRⁱ	Q96J02
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q96J02

EvolutionaryTraceⁱ

Q96J02

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	1 – 115	C2PROSITE-ProRule annotationAdd BLAST	115
Domainⁱ	326 – 359	WW 1PROSITE-ProRule annotationAdd BLAST	34
Domainⁱ	358 – 391	WW 2PROSITE-ProRule annotationAdd BLAST	34
Domainⁱ	438 – 471	WW 3PROSITE-ProRule annotationAdd BLAST	34
Domainⁱ	478 – 511	WW 4PROSITE-ProRule annotationAdd BLAST	34
Domainⁱ	569 – 903	HECTPROSITE-ProRule annotationAdd BLAST	335

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	395 – 471	Required for interaction with FYN1 PublicationAdd BLAST		77
Regionⁱ	574 – 583	MAP kinase docking siteBy similarity		10

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	252 – 267	Arg/Pro-rich (PRR domain)Add BLAST		16

Domainⁱ

The WW domains mediate interaction with PPxY motif-containing proteins.1 Publication

Keywords - Domainⁱ

Repeat

Phylogenomic databases

eggNOGⁱ	KOG0940, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000157014
HOGENOMⁱ	CLU_002173_0_1_1
InParanoidⁱ	Q96J02
OMAⁱ	RQIVWFW
Database of Orthologous Groups More...OrthoDBⁱ	167687at2759
PhylomeDBⁱ	Q96J02
TreeFamⁱ	TF323658

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00078, HECTc, 1 hit cd00201, WW, 4 hits
Gene3Dⁱ	2.60.40.150, 1 hit
IDEALⁱ	IID00178
InterProⁱ	View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR024928, E3_ub_ligase_SMURF1 IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR001202, WW_dom IPR036020, WW_dom_sf
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF00397, WW, 4 hits
PIRSFⁱ	PIRSF001569, E3_ub_ligase_SMURF1, 1 hit
SMARTⁱ	View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 4 hits
SUPFAMⁱ	SSF51045, SSF51045, 4 hits SSF56204, SSF56204, 1 hit
PROSITEⁱ	View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 4 hits PS50020, WW_DOMAIN_2, 4 hits

Sequences (3+)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 3 described isoforms and 8 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: Q96J02-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the canonicalⁱ sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSDSGSQLGS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ 
        60         70         80         90        100
SKKTEKCNNT NSPKWKQPLT VIVTPVSKLH FRVWSHQTLK SDVLLGTAAL 
       110        120        130        140        150
DIYETLKSNN MKLEEVVVTL QLGGDKEPTE TIGDLSICLD GLQLESEVVT 
       160        170        180        190        200
NGETTCSENG VSLCLPRLEC NSAISAHCNL CLPGLSDSPI SASRVAGFTG 
       210        220        230        240        250
ASQNDDGSRS KDETRVSTNG SDDPEDAGAG ENRRVSGNNS PSLSNGGFKP 
       260        270        280        290        300
SRPPRPSRPP PPTPRRPASV NGSPSATSES DGSSTGSLPP TNTNTNTSEG 
       310        320        330        340        350
ATSGLIIPLT ISGGSGPRPL NPVTQAPLPP GWEQRVDQHG RVYYVDHVEK 
       360        370        380        390        400
RTTWDRPEPL PPGWERRVDN MGRIYYVDHF TRTTTWQRPT LESVRNYEQW 
       410        420        430        440        450
QLQRSQLQGA MQQFNQRFIY GNQDLFATSQ SKEFDPLGPL PPGWEKRTDS 
       460        470        480        490        500
NGRVYFVNHN TRITQWEDPR SQGQLNEKPL PEGWEMRFTV DGIPYFVDHN 
       510        520        530        540        550
RRTTTYIDPR TGKSALDNGP QIAYVRDFKA KVQYFRFWCQ QLAMPQHIKI 
       560        570        580        590        600
TVTRKTLFED SFQQIMSFSP QDLRRRLWVI FPGEEGLDYG GVAREWFFLL 
       610        620        630        640        650
SHEVLNPMYC LFEYAGKDNY CLQINPASYI NPDHLKYFRF IGRFIAMALF 
       660        670        680        690        700
HGKFIDTGFS LPFYKRILNK PVGLKDLESI DPEFYNSLIW VKENNIEECD 
       710        720        730        740        750
LEMYFSVDKE ILGEIKSHDL KPNGGNILVT EENKEEYIRM VAEWRLSRGV 
       760        770        780        790        800
EEQTQAFFEG FNEILPQQYL QYFDAKELEV LLCGMQEIDL NDWQRHAIYR 
       810        820        830        840        850
HYARTSKQIM WFWQFVKEID NEKRMRLLQF VTGTCRLPVG GFADLMGSNG 
       860        870        880        890        900
PQKFCIEKVG KENWLPRSHT CFNRLDLPPY KSYEQLKEKL LFAIEETEGF 

GQE

Length:903

Mass (Da):102,803

Last modified:October 3, 2003 - v2

Checksum:ⁱ6777A2043C7B67BC

GO

Isoform 2 (identifier: Q96J02-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
159-200: NGVSLCLPRLECNSAISAHCNLCLPGLSDSPISASRVAGFTG → S

« Hide

        10         20         30         40         50
MSDSGSQLGS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ 
        60         70         80         90        100
SKKTEKCNNT NSPKWKQPLT VIVTPVSKLH FRVWSHQTLK SDVLLGTAAL 
       110        120        130        140        150
DIYETLKSNN MKLEEVVVTL QLGGDKEPTE TIGDLSICLD GLQLESEVVT 
       160        170        180        190        200
NGETTCSESA SQNDDGSRSK DETRVSTNGS DDPEDAGAGE NRRVSGNNSP 
       210        220        230        240        250
SLSNGGFKPS RPPRPSRPPP PTPRRPASVN GSPSATSESD GSSTGSLPPT 
       260        270        280        290        300
NTNTNTSEGA TSGLIIPLTI SGGSGPRPLN PVTQAPLPPG WEQRVDQHGR 
       310        320        330        340        350
VYYVDHVEKR TTWDRPEPLP PGWERRVDNM GRIYYVDHFT RTTTWQRPTL 
       360        370        380        390        400
ESVRNYEQWQ LQRSQLQGAM QQFNQRFIYG NQDLFATSQS KEFDPLGPLP 
       410        420        430        440        450
PGWEKRTDSN GRVYFVNHNT RITQWEDPRS QGQLNEKPLP EGWEMRFTVD 
       460        470        480        490        500
GIPYFVDHNR RTTTYIDPRT GKSALDNGPQ IAYVRDFKAK VQYFRFWCQQ 
       510        520        530        540        550
LAMPQHIKIT VTRKTLFEDS FQQIMSFSPQ DLRRRLWVIF PGEEGLDYGG 
       560        570        580        590        600
VAREWFFLLS HEVLNPMYCL FEYAGKDNYC LQINPASYIN PDHLKYFRFI 
       610        620        630        640        650
GRFIAMALFH GKFIDTGFSL PFYKRILNKP VGLKDLESID PEFYNSLIWV 
       660        670        680        690        700
KENNIEECDL EMYFSVDKEI LGEIKSHDLK PNGGNILVTE ENKEEYIRMV 
       710        720        730        740        750
AEWRLSRGVE EQTQAFFEGF NEILPQQYLQ YFDAKELEVL LCGMQEIDLN 
       760        770        780        790        800
DWQRHAIYRH YARTSKQIMW FWQFVKEIDN EKRMRLLQFV TGTCRLPVGG 
       810        820        830        840        850
FADLMGSNGP QKFCIEKVGK ENWLPRSHTC FNRLDLPPYK SYEQLKEKLL 
       860 
FAIEETEGFG QE

Show »

Length:862

Mass (Da):98,676

Checksum:ⁱA3D960E7F4DBF9D3

GO

Isoform 3 (identifier: Q96J02-3) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-110: Missing.
159-200: NGVSLCLPRLECNSAISAHCNLCLPGLSDSPISASRVAGFTG → S

« Hide

        10         20         30         40         50
MKLEEVVVTL QLGGDKEPTE TIGDLSICLD GLQLESEVVT NGETTCSESA 
        60         70         80         90        100
SQNDDGSRSK DETRVSTNGS DDPEDAGAGE NRRVSGNNSP SLSNGGFKPS 
       110        120        130        140        150
RPPRPSRPPP PTPRRPASVN GSPSATSESD GSSTGSLPPT NTNTNTSEGA 
       160        170        180        190        200
TSGLIIPLTI SGGSGPRPLN PVTQAPLPPG WEQRVDQHGR VYYVDHVEKR 
       210        220        230        240        250
TTWDRPEPLP PGWERRVDNM GRIYYVDHFT RTTTWQRPTL ESVRNYEQWQ 
       260        270        280        290        300
LQRSQLQGAM QQFNQRFIYG NQDLFATSQS KEFDPLGPLP PGWEKRTDSN 
       310        320        330        340        350
GRVYFVNHNT RITQWEDPRS QGQLNEKPLP EGWEMRFTVD GIPYFVDHNR 
       360        370        380        390        400
RTTTYIDPRT GKSALDNGPQ IAYVRDFKAK VQYFRFWCQQ LAMPQHIKIT 
       410        420        430        440        450
VTRKTLFEDS FQQIMSFSPQ DLRRRLWVIF PGEEGLDYGG VAREWFFLLS 
       460        470        480        490        500
HEVLNPMYCL FEYAGKDNYC LQINPASYIN PDHLKYFRFI GRFIAMALFH 
       510        520        530        540        550
GKFIDTGFSL PFYKRILNKP VGLKDLESID PEFYNSLIWV KENNIEECDL 
       560        570        580        590        600
EMYFSVDKEI LGEIKSHDLK PNGGNILVTE ENKEEYIRMV AEWRLSRGVE 
       610        620        630        640        650
EQTQAFFEGF NEILPQQYLQ YFDAKELEVL LCGMQEIDLN DWQRHAIYRH 
       660        670        680        690        700
YARTSKQIMW FWQFVKEIDN EKRMRLLQFV TGTCRLPVGG FADLMGSNGP 
       710        720        730        740        750
QKFCIEKVGK ENWLPRSHTC FNRLDLPPYK SYEQLKEKLL FAIEETEGFG 

QE

Show »

Length:752

Mass (Da):86,498

Checksum:ⁱB08AB68B285391F8

GO

Computationally mapped potential isoform sequencesⁱ

There are 8 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

A0A590UJQ1	A0A590UJQ1_HUMAN	E3 ubiquitin-protein ligase E3 ubiquitin-protein ligase, EC 2.3.2.26	ITCH	900	Annotation score:
A0A590UJW8	A0A590UJW8_HUMAN	E3 ubiquitin-protein ligase E3 ubiquitin-protein ligase, EC 2.3.2.26	ITCH	830	Annotation score:
A0A590UK44	A0A590UK44_HUMAN	E3 ubiquitin-protein ligase E3 ubiquitin-protein ligase, EC 2.3.2.26	ITCH	779	Annotation score:
A0A590UK95	A0A590UK95_HUMAN	HECT-type E3 ubiquitin transferase HECT-type E3 ubiquitin transferase, EC 2.3.2.26	ITCH	553	Annotation score:
A0A1W2PNZ8	A0A1W2PNZ8_HUMAN	E3 ubiquitin-protein ligase Itchy h... E3 ubiquitin-protein ligase Itchy homolog	ITCH	37	Annotation score:
A0A590UJ55	A0A590UJ55_HUMAN	E3 ubiquitin-protein ligase Itchy h... E3 ubiquitin-protein ligase Itchy homolog	ITCH	73	Annotation score:
A0A1W2PR79	A0A1W2PR79_HUMAN	E3 ubiquitin-protein ligase Itchy h... E3 ubiquitin-protein ligase Itchy homolog	ITCH	158	Annotation score:
A0A590UIY0	A0A590UIY0_HUMAN	E3 ubiquitin-protein ligase Itchy h... E3 ubiquitin-protein ligase Itchy homolog	ITCH	91	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	297	T → I in BAG64996 (PubMed:14702039).Curated		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_044732	1 – 110	Missing in isoform 3. 1 PublicationAdd BLAST		110
Alternative sequenceⁱVSP_008451	159 – 200	NGVSL…AGFTG → S in isoform 2 and isoform 3. 5 PublicationsAdd BLAST		42

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF095745 mRNA Translation: AAK39399.1 AB056663 mRNA Translation: BAB39389.1 AK304090 mRNA Translation: BAG64996.1 AK315212 mRNA Translation: BAG37647.1 AL109923 Genomic DNA No translation available. AL356299 Genomic DNA No translation available. CH471077 Genomic DNA Translation: EAW76272.1 CH471077 Genomic DNA Translation: EAW76274.1 CH471077 Genomic DNA Translation: EAW76276.1 BC006848 mRNA Translation: AAH06848.1 BC011571 mRNA Translation: AAH11571.1 AF038564 mRNA Translation: AAC04845.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS13234.1 [Q96J02-2] CCDS58768.1 [Q96J02-1] CCDS58769.1 [Q96J02-3]
NCBI Reference Sequences More...RefSeqⁱ	NP_001244066.1, NM_001257137.2 [Q96J02-1] NP_001244067.1, NM_001257138.2 [Q96J02-3] NP_001311126.1, NM_001324197.1 [Q96J02-1] NP_001311127.1, NM_001324198.1 [Q96J02-2] NP_113671.3, NM_031483.6 [Q96J02-2] XP_016883578.1, XM_017028089.1 [Q96J02-1] XP_016883580.1, XM_017028091.1 [Q96J02-3]

Genome annotation databases

Ensemblⁱ	ENST00000262650; ENSP00000262650; ENSG00000078747 [Q96J02-1] ENST00000374864; ENSP00000363998; ENSG00000078747 [Q96J02-2] ENST00000535650; ENSP00000445608; ENSG00000078747 [Q96J02-3] ENST00000665346; ENSP00000499786; ENSG00000078747 [Q96J02-1]
GeneIDⁱ	83737
KEGGⁱ	hsa:83737
UCSC genome browser More...UCSCⁱ	uc002xak.3, human [Q96J02-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q96J02-2	HECT-type E3 ubiquitin transferase		HUMAN		553	UniRef100_A0A590UK95
E3 ubiquitin-protein ligase		PANTR		862
E3 ubiquitin-protein ligase		PANPA		862
E3 ubiquitin-protein ligase		PANTR		862
Q96J02-3	E3 ubiquitin-protein ligase		PANTR		902	UniRef100_A0A2J8JYF3
E3 ubiquitin-protein ligase Itchy homolog (Fragment)		HUMAN		73
E3 ubiquitin-protein ligase		PANTR		752

Protein	Similar proteins		Species	Score	Length	Source
Q96J02	E3 ubiquitin-protein ligase		GORGO		903	UniRef90_Q96J02
E3 ubiquitin-protein ligase		PANPA		870
E3 ubiquitin-protein ligase		Bison bison bison		862
+1
Q96J02-2	E3 ubiquitin-protein ligase		CHLSB		862	UniRef90_A0A0D9RI42
E3 ubiquitin-protein ligase		MACMU		918
E3 ubiquitin-protein ligase		CERAT		862
E3 ubiquitin-protein ligase		PAPAN		862
E3 ubiquitin-protein ligase		MACFA		862
+51
Q96J02-3	Dynein light chain roadblock-type 1	)	MOUSE		96	UniRef90_P62627
Dynein light chain roadblock-type 1		BOVIN		96
Dynein light chain roadblock-type 1		RAT		96
HECT-type E3 ubiquitin transferase		wild yak		1123
Dynein light chain roadblock		Enhydra lutris kenyoni		96
+60

Protein	Similar proteins		Species	Score	Length	Source
Q96J02	Dynein light chain roadblock-type 1	)	MOUSE		96	UniRef50_Q96J02
Dynein light chain roadblock-type 1		BOVIN		96
Dynein light chain roadblock-type 1		RAT		96
E3 ubiquitin-protein ligase		GORGO		903
E3 ubiquitin-protein ligase		PANPA		870
+139
Q96J02-2	NEDD4-like E3 ubiquitin-protein ligase WWP1		MOUSE		918	UniRef50_Q8BZZ3
E3 ubiquitin-protein ligase		PERMB		919
E3 ubiquitin-protein ligase		CRIGR		919
E3 ubiquitin-protein ligase		MESAU		919
E3 ubiquitin-protein ligase		RAT		918
+777

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF095745 mRNA Translation: AAK39399.1 AB056663 mRNA Translation: BAB39389.1 AK304090 mRNA Translation: BAG64996.1 AK315212 mRNA Translation: BAG37647.1 AL109923 Genomic DNA No translation available. AL356299 Genomic DNA No translation available. CH471077 Genomic DNA Translation: EAW76272.1 CH471077 Genomic DNA Translation: EAW76274.1 CH471077 Genomic DNA Translation: EAW76276.1 BC006848 mRNA Translation: AAH06848.1 BC011571 mRNA Translation: AAH11571.1 AF038564 mRNA Translation: AAC04845.1
CCDSⁱ	CCDS13234.1 [Q96J02-2] CCDS58768.1 [Q96J02-1] CCDS58769.1 [Q96J02-3]
RefSeqⁱ	NP_001244066.1, NM_001257137.2 [Q96J02-1] NP_001244067.1, NM_001257138.2 [Q96J02-3] NP_001311126.1, NM_001324197.1 [Q96J02-1] NP_001311127.1, NM_001324198.1 [Q96J02-2] NP_113671.3, NM_031483.6 [Q96J02-2] XP_016883578.1, XM_017028089.1 [Q96J02-1] XP_016883580.1, XM_017028091.1 [Q96J02-3]

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2DMV	NMR	-	A	328-357	[»]
	2KYK	NMR	-	A	359-392	[»]
	2NQ3	X-ray	1.80	A	1-155	[»]
	2P4R	X-ray	2.00	T	246-270	[»]
	2YSF	NMR	-	A	480-512	[»]
	3TUG	X-ray	2.27	A	524-903	[»]
	4ROF	X-ray	2.03	A/B	436-474	[»]
	5C7M	X-ray	3.03	A	524-899	[»]
	5CQ2	X-ray	1.40	A	433-521	[»]
	5DWS	X-ray	1.65	A/C/E/G	436-474	[»]
	5DZD	X-ray	1.57	A/B	475-514	[»]
	5SXP	X-ray	1.65	F/G	249-269	[»]
SMRⁱ	Q96J02
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	123747, 250 interactors
CORUMⁱ	Q96J02
DIPⁱ	DIP-29849N
ELMⁱ	Q96J02
IntActⁱ	Q96J02, 61 interactors
MINTⁱ	Q96J02
STRINGⁱ	9606.ENSP00000480499

Chemistry databases

ChEMBLⁱ	CHEMBL4295925

ChEMBLⁱ

CHEMBL4295925

PTM databases

iPTMnetⁱ	Q96J02
PhosphoSitePlusⁱ	Q96J02

Genetic variation databases

BioMutaⁱ	ITCH
DMDMⁱ	37537897

Proteomic databases

EPDⁱ	Q96J02
jPOSTⁱ	Q96J02
MassIVEⁱ	Q96J02
MaxQBⁱ	Q96J02
PaxDbⁱ	Q96J02
PeptideAtlasⁱ	Q96J02
PRIDEⁱ	Q96J02
ProteomicsDBⁱ	25826 76882 [Q96J02-1] 76883 [Q96J02-2]

Protocols and materials databases

Antibodypediaⁱ	10897, 308 antibodies
The CPTC Antibody Portal More...CPTCⁱ	Q96J02, 3 antibodies

Genome annotation databases

Ensemblⁱ	ENST00000262650; ENSP00000262650; ENSG00000078747 [Q96J02-1] ENST00000374864; ENSP00000363998; ENSG00000078747 [Q96J02-2] ENST00000535650; ENSP00000445608; ENSG00000078747 [Q96J02-3] ENST00000665346; ENSP00000499786; ENSG00000078747 [Q96J02-1]
GeneIDⁱ	83737
KEGGⁱ	hsa:83737
UCSCⁱ	uc002xak.3, human [Q96J02-1]

Organism-specific databases

CTDⁱ	83737
DisGeNETⁱ	83737
GeneCardsⁱ	ITCH
HGNCⁱ	HGNC:13890, ITCH
HPAⁱ	ENSG00000078747, Low tissue specificity
MalaCardsⁱ	ITCH
MIMⁱ	606409, gene 613385, phenotype
neXtProtⁱ	NX_Q96J02
OpenTargetsⁱ	ENSG00000078747
Orphanetⁱ	228426, Syndromic multisystem autoimmune disease due to Itch deficiency
PharmGKBⁱ	PA29934
VEuPathDBⁱ	HostDB:ENSG00000078747.12
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0940, Eukaryota
GeneTreeⁱ	ENSGT00940000157014
HOGENOMⁱ	CLU_002173_0_1_1
InParanoidⁱ	Q96J02
OMAⁱ	RQIVWFW
OrthoDBⁱ	167687at2759
PhylomeDBⁱ	Q96J02
TreeFamⁱ	TF323658

Enzyme and pathway databases

UniPathwayⁱ	UPA00143
BRENDAⁱ	6.3.2.19, 2681
PathwayCommonsⁱ	Q96J02
Reactomeⁱ	R-HSA-1253288, Downregulation of ERBB4 signaling R-HSA-168638, NOD1/2 Signaling Pathway R-HSA-2122948, Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-5610780, Degradation of GLI1 by the proteasome R-HSA-5632684, Hedgehog 'on' state R-HSA-8939236, RUNX1 regulates transcription of genes involved in differentiation of HSCs R-HSA-936440, Negative regulators of DDX58/IFIH1 signaling R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkⁱ	Q96J02
SIGNORⁱ	Q96J02

Miscellaneous databases

BioGRID-ORCSⁱ	83737, 8 hits in 1004 CRISPR screens
ChiTaRSⁱ	ITCH, human
EvolutionaryTraceⁱ	Q96J02
GenomeRNAiⁱ	83737
Pharosⁱ	Q96J02, Tbio
Protein Ontology More...PROⁱ	PR:Q96J02
RNActⁱ	Q96J02, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000078747, Expressed in sperm and 232 other tissues
ExpressionAtlasⁱ	Q96J02, baseline and differential
Genevisibleⁱ	Q96J02, HS

Family and domain databases

CDDⁱ	cd00078, HECTc, 1 hit cd00201, WW, 4 hits
Gene3Dⁱ	2.60.40.150, 1 hit
IDEALⁱ	IID00178
InterProⁱ	View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR024928, E3_ub_ligase_SMURF1 IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR001202, WW_dom IPR036020, WW_dom_sf
Pfamⁱ	View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF00397, WW, 4 hits
PIRSFⁱ	PIRSF001569, E3_ub_ligase_SMURF1, 1 hit
SMARTⁱ	View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 4 hits
SUPFAMⁱ	SSF51045, SSF51045, 4 hits SSF56204, SSF56204, 1 hit
PROSITEⁱ	View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 4 hits PS50020, WW_DOMAIN_2, 4 hits
ProtoNetⁱ	Search...
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	ITCH_HUMAN
Accessionⁱ	Q96J02Primary (citable) accession number: Q96J02 Secondary accession number(s): A6NEW4 Q9H4U5
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
	Last sequence update:	October 3, 2003
	Last modified:	April 7, 2021
	This is version 195 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Direct protein sequencing, Reference proteome

Documents

Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PATHWAY comments
Index of metabolic and biosynthesis pathways
PDB cross-references
Index of Protein Data Bank (PDB) cross-references

UniProtKB

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UniRef

Proteomes

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Supporting data

UniProtKB - Q96J02 (ITCH_HUMAN)

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E3 ubiquitin-protein ligase Itchy homolog

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Cytoplasm and Cytosol

Plasma membrane

Endosome

Nucleus

Cytosol

Endosome

Extracellular region or secreted

Nucleus

Plasma Membrane

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Miscellaneous databases

Chemistry databases

Genetic variation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Q96J02

Isoform 2 [Q96J02-2]

GO - Molecular functioni

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Compositional bias

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Genetic variation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

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Functionⁱ

Catalytic activityⁱ

Pathwayⁱ: protein ubiquitination

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ