UniProtKB - Q96J02 (ITCH_HUMAN)
E3 ubiquitin-protein ligase Itchy homolog
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 PublicationsCatalytic 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 EC:2.3.2.26
Activity regulationi
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.15 PublicationsView 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
- arrestin family protein binding Source: UniProtKB
- CXCR chemokine receptor binding Source: UniProtKB
- ligase activity Source: Ensembl
- ribonucleoprotein complex binding Source: UniProtKB
- ubiquitin-like protein ligase binding Source: UniProtKB
- ubiquitin-like protein transferase activity Source: Reactome
- ubiquitin protein ligase activity Source: MGI
- ubiquitin-protein transferase activity Source: UniProtKB
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- defense response to virus Source: UniProtKB-KW
- inflammatory response Source: UniProtKB
- innate immune response Source: UniProtKB-KW
- negative regulation of alpha-beta T cell proliferation Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of defense response to virus Source: UniProtKB
- negative regulation of JNK cascade Source: BHF-UCL
- negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
- negative regulation of type I interferon production Source: Reactome
- nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
- positive regulation of protein catabolic process Source: GO_Central
- positive regulation of receptor catabolic process Source: UniProtKB
- positive regulation of T cell anergy Source: Ensembl
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: ARUK-UCL
- protein autoubiquitination Source: UniProtKB
- protein K29-linked ubiquitination Source: UniProtKB
- protein K48-linked ubiquitination Source: UniProtKB
- protein K63-linked ubiquitination Source: UniProtKB
- protein polyubiquitination Source: GO_Central
- protein ubiquitination Source: UniProtKB
- regulation of cell growth Source: UniProtKB
- regulation of hematopoietic stem cell differentiation Source: Reactome
- regulation of protein deubiquitination Source: BHF-UCL
- ubiquitin-dependent protein catabolic process Source: MGI
- viral entry into host cell Source: UniProtKB
Keywordsi
Molecular function | Transferase |
Biological process | Antiviral defense, Apoptosis, Host-virus interaction, Immunity, Innate immunity, Ubl conjugation pathway |
Enzyme and pathway databases
BRENDAi | 2.3.2.26, 2681 2.3.2.B8, 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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:13890, ITCH |
MIMi | 606409, gene |
neXtProti | NX_Q96J02 |
VEuPathDBi | HostDB:ENSG00000078747 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Endosome
- Early endosome membrane 3 Publications; Peripheral membrane protein 3 Publications; Cytoplasmic side 3 Publications
- Endosome membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
Plasma membrane
- Cell membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Note: May be recruited to exosomes by NDFIP1 (PubMed:18819914). Localizes to plasma membrane upon CXCL12 stimulation where it co-localizes with CXCL4 (PubMed:14602072). Localization to early endosomes is increased upon CXCL12 stimulation where it co-localizes with DTX3L and CXCL4 (PubMed:24790097).3 Publications
Cytosol
- cytosol Source: Reactome
Endosome
- early endosome membrane Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cell cortex Source: Ensembl
- cytoplasm Source: GO_Central
- cytoplasmic vesicle Source: ARUK-UCL
- intracellular membrane-bounded organelle Source: HPA
- membrane Source: UniProtKB
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Endosome, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Autoimmune disease, multisystem, with facial dysmorphism (ADMFD)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | 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
DisGeNETi | 83737 |
MalaCardsi | ITCH |
MIMi | 613385, phenotype |
OpenTargetsi | ENSG00000078747 |
Orphaneti | 228426, Syndromic multisystem autoimmune disease due to Itch deficiency |
PharmGKBi | PA29934 |
Miscellaneous databases
Pharosi | Q96J02, Tbio |
Chemistry databases
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 | Graphical view | 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
Keywords - PTMi
Acetylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q96J02 |
jPOSTi | Q96J02 |
MassIVEi | Q96J02 |
MaxQBi | Q96J02 |
PaxDbi | Q96J02 |
PeptideAtlasi | Q96J02 |
PRIDEi | Q96J02 |
ProteomicsDBi | 25826 76882 [Q96J02-1] 76883 [Q96J02-2] |
PTM databases
GlyGeni | Q96J02, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q96J02 |
PhosphoSitePlusi | Q96J02 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000078747, Expressed in sperm and 232 other tissues |
ExpressionAtlasi | Q96J02, baseline and differential |
Genevisiblei | Q96J02, HS |
Organism-specific databases
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).
Interacts directly with LDLRAD3; this interaction promotes ITCH auto-ubiquitination leading to its degradation (PubMed:26854353).
By similarity26 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 PublicationBinary interactionsi
Q96J02
Isoform 2 [Q96J02-2]
GO - Molecular functioni
- arrestin family protein binding Source: UniProtKB
- CXCR chemokine receptor binding Source: UniProtKB
- ubiquitin-like protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 123747, 281 interactors |
CORUMi | Q96J02 |
DIPi | DIP-29849N |
ELMi | Q96J02 |
IntActi | Q96J02, 65 interactors |
MINTi | Q96J02 |
STRINGi | 9606.ENSP00000480499 |
Miscellaneous databases
RNActi | Q96J02, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q96J02 |
SMRi | Q96J02 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96J02 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | 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 | 197 – 301 | DisorderedSequence analysisAdd BLAST | 105 | |
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 | 206 – 230 | Basic and acidic residuesSequence analysisAdd BLAST | 25 | |
Compositional biasi | 233 – 247 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 252 – 268 | Pro residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 269 – 301 | Polar residuesSequence analysisAdd BLAST | 33 |
Domaini
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0940, Eukaryota |
GeneTreei | ENSGT00940000157014 |
HOGENOMi | CLU_002173_0_1_1 |
InParanoidi | Q96J02 |
OMAi | DDWVIVP |
OrthoDBi | 167687at2759 |
PhylomeDBi | Q96J02 |
TreeFami | TF323658 |
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 | SSF49562, SSF49562, 1 hit 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 |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A590UJQ1 | A0A590UJQ1_HUMAN | E3 ubiquitin-protein ligase | ITCH | 900 | Annotation score: | ||
A0A590UJW8 | A0A590UJW8_HUMAN | E3 ubiquitin-protein ligase | ITCH | 830 | Annotation score: | ||
A0A590UK44 | A0A590UK44_HUMAN | E3 ubiquitin-protein ligase | ITCH | 779 | Annotation score: | ||
A0A590UK95 | A0A590UK95_HUMAN | HECT-type E3 ubiquitin transferase | ITCH | 553 | Annotation score: | ||
A0A1W2PNZ8 | A0A1W2PNZ8_HUMAN | E3 ubiquitin-protein ligase Itchy h... | ITCH | 37 | Annotation score: | ||
A0A590UJ55 | A0A590UJ55_HUMAN | E3 ubiquitin-protein ligase Itchy h... | ITCH | 73 | Annotation score: | ||
A0A1W2PR79 | A0A1W2PR79_HUMAN | E3 ubiquitin-protein ligase Itchy h... | ITCH | 158 | Annotation score: | ||
A0A590UIY0 | A0A590UIY0_HUMAN | E3 ubiquitin-protein ligase Itchy h... | 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 |
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] |
Genome annotation databases
Ensembli | ENST00000262650.10; ENSP00000262650.5; ENSG00000078747.16 ENST00000374864.10; ENSP00000363998.4; ENSG00000078747.16 [Q96J02-2] ENST00000535650.7; ENSP00000445608.1; ENSG00000078747.16 [Q96J02-3] ENST00000665346.1; ENSP00000499786.1; ENSG00000078747.16 |
GeneIDi | 83737 |
KEGGi | hsa:83737 |
MANE-Selecti | ENST00000374864.10; ENSP00000363998.4; NM_031483.7; NP_113671.3 [Q96J02-2] |
UCSCi | uc002xak.3, human [Q96J02-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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: PDBei RCSB PDBi 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 | [»] | |
AlphaFoldDBi | Q96J02 | |||||
SMRi | Q96J02 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 123747, 281 interactors |
CORUMi | Q96J02 |
DIPi | DIP-29849N |
ELMi | Q96J02 |
IntActi | Q96J02, 65 interactors |
MINTi | Q96J02 |
STRINGi | 9606.ENSP00000480499 |
Chemistry databases
ChEMBLi | CHEMBL4295925 |
PTM databases
GlyGeni | Q96J02, 1 site, 1 O-linked glycan (1 site) |
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, 324 antibodies from 42 providers |
CPTCi | Q96J02, 3 antibodies |
DNASUi | 83737 |
Genome annotation databases
Ensembli | ENST00000262650.10; ENSP00000262650.5; ENSG00000078747.16 ENST00000374864.10; ENSP00000363998.4; ENSG00000078747.16 [Q96J02-2] ENST00000535650.7; ENSP00000445608.1; ENSG00000078747.16 [Q96J02-3] ENST00000665346.1; ENSP00000499786.1; ENSG00000078747.16 |
GeneIDi | 83737 |
KEGGi | hsa:83737 |
MANE-Selecti | ENST00000374864.10; ENSP00000363998.4; NM_031483.7; NP_113671.3 [Q96J02-2] |
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 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0940, Eukaryota |
GeneTreei | ENSGT00940000157014 |
HOGENOMi | CLU_002173_0_1_1 |
InParanoidi | Q96J02 |
OMAi | DDWVIVP |
OrthoDBi | 167687at2759 |
PhylomeDBi | Q96J02 |
TreeFami | TF323658 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
BRENDAi | 2.3.2.26, 2681 2.3.2.B8, 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, 18 hits in 1130 CRISPR screens |
ChiTaRSi | ITCH, human |
EvolutionaryTracei | Q96J02 |
GenomeRNAii | 83737 |
Pharosi | Q96J02, Tbio |
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 | SSF49562, SSF49562, 1 hit 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 |
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: | May 25, 2022 | |
This is version 199 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 proteomeDocuments
- 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