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Protein

E3 ubiquitin-protein ligase Itchy homolog

Gene

ITCH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. It catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation. It is involved in the control of inflammatory signaling pathways. Is an essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of the complex after TNF stimulation. Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1. Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways. Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response. Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages. Critical regulator of T-helper (TH2) cytokine development through its ability to induce JUNB ubiquitination and degradation (By similarity). Ubiquitinates SNX9. Ubiquitinates CXCR4 and HGS/HRS and regulates sorting of CXCR4 to the degradative pathway. It is involved in the negative regulation of MAVS-dependent cellular antiviral responses. Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation. Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP. Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID. Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046).By similarity13 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.

Enzyme regulationi

Activated by NDFIP1- and NDFIP2-binding.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.5 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei871Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • CXCR chemokine receptor binding Source: UniProtKB
  • ribonucleoprotein complex 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 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
  • Notch signaling pathway Source: Reactome
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • protein K29-linked ubiquitination Source: UniProtKB
  • protein K48-linked ubiquitination Source: UniProtKB
  • protein K63-linked ubiquitination Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • regulation of cell growth Source: UniProtKB
  • regulation of protein deubiquitination Source: BHF-UCL
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
  • viral entry into host cell Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Antiviral defense, Apoptosis, Host-virus interaction, Immunity, Innate immunity, Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi6.3.2.19. 2681.
ReactomeiR-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-936440. Negative regulators of RIG-I/MDA5 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ96J02.
SIGNORiQ96J02.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase Itchy homolog (EC:2.3.2.26)
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:13890. ITCH.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleus Source: HPA
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Autoimmune disease, multisystem, with facial dysmorphism (ADMFD)1 Publication
The disease is caused by mutations 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.
See also OMIM:613385

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi343Y → F: No effect on phosphorylation on T-cell stimulation nor in the presence of FYN. 1 Publication1
Mutagenesisi420Y → F: Greatly reduced phosphorylation on T-cell stimulation and in the presence of FYN. Increased ITCH-mediated Ub conjugation and degradation of JUNB. 1 Publication1
Mutagenesisi455Y → F: No effect on phosphorylation on T-cell stimulation nor in the presence of FYN. 1 Publication1
Mutagenesisi871C → 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. 3 Publications1

Organism-specific databases

DisGeNETi83737.
MalaCardsiITCH.
MIMi613385. phenotype.
OpenTargetsiENSG00000078747.
ENSG00000283472.
Orphaneti228426. Syndromic multisystem autoimmune disease due to Itch deficiency.
PharmGKBiPA29934.

Polymorphism and mutation databases

BioMutaiITCH.
DMDMi37537897.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001203172 – 903E3 ubiquitin-protein ligase Itchy homologAdd BLAST902

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei240Phosphoserine; by MAPK8By similarity1
Modified residuei263Phosphothreonine; by MAPK8By similarity1
Modified residuei273Phosphoserine; by MAPK8By similarity1
Modified residuei385Phosphothreonine; by SGK31 Publication1
Modified residuei420Phosphotyrosine; by FYN1 Publication1
Modified residuei450Phosphoserine; by SGK31 Publication1

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
Ubiquitinated; autopolyubiquitination with 'Lys-63' linkages which does not lead to protein degradation.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96J02.
MaxQBiQ96J02.
PaxDbiQ96J02.
PeptideAtlasiQ96J02.
PRIDEiQ96J02.

PTM databases

iPTMnetiQ96J02.
PhosphoSitePlusiQ96J02.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000078747.
CleanExiHS_ITCH.
GenevisibleiQ96J02. HS.

Organism-specific databases

HPAiCAB072824.
HPA021126.
HPA049032.

Interactioni

Subunit structurei

Monomer (By similarity). Interacts (via its WW domains) with OCNL, NOTCH1 AND JUN. Interacts (via WW domain 2) with N4BP1; leading to inhibiting its E3 ubiquitin-protein ligase activity. Interacts with JUNB; the interaction promotes ITCH-mediated ubiquitination and degradation of JUNB. 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. 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. Interacts with FYN; the interaction phosphorylates ITCH on Tyr-420 decreasing binding of JUNB. Interacts (via WW domains) with CXCR4 (via C-terminus); the interaction depends on CXCR4 phosphorylation. Interacts (via WW domains) with PCBP2 within a complex containing ITCH, MAVS and PCBP2. Interacts (via WW domains) with TXNIP (via C-terminus). Interacts with p15 BID. Interacts with ERBB4, DTX1, SPG20, SNX9 and SNX18. Interacts (via its WW domains) with ATN1. Interacts with Epstein-Barr virus LMP2A. Interacts (via WW domains) with SGK3. Interacts with OTUD7B. Interacts with PI4K2A (PubMed:23146885). Interacts with ARRDC4 (PubMed:23236378).By similarity21 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BidP704442EBI-1564678,EBI-783400From a different organism.
CYLDQ9NQC73EBI-1564678,EBI-2117940
GLI1P081514EBI-1564678,EBI-308084
LMP2P132853EBI-1564678,EBI-7181113From a different organism.
NumbQ9QZS3-22EBI-1564678,EBI-3896014From a different organism.
PI4K2AQ9BTU65EBI-1564678,EBI-3239392
RNF11Q9Y3C52EBI-1564678,EBI-396669
SGK3Q96BR15EBI-1564678,EBI-2801236
SNX9Q9Y5X17EBI-1564678,EBI-77848
TP53BP2Q136252EBI-1564678,EBI-77642
TP73O15350-15EBI-1564678,EBI-389619
TP73O15350-82EBI-1564678,EBI-5651259

GO - Molecular functioni

  • CXCR chemokine receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi123747. 173 interactors.
DIPiDIP-29849N.
IntActiQ96J02. 34 interactors.
MINTiMINT-148272.
STRINGi9606.ENSP00000363998.

Structurei

Secondary structure

1903
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi18 – 29Combined sources12
Beta strandi41 – 47Combined sources7
Beta strandi50 – 53Combined sources4
Beta strandi64 – 73Combined sources10
Beta strandi78 – 85Combined sources8
Beta strandi88 – 90Combined sources3
Beta strandi93 – 101Combined sources9
Helixi102 – 108Combined sources7
Turni109 – 111Combined sources3
Beta strandi112 – 126Combined sources15
Beta strandi130 – 143Combined sources14
Beta strandi332 – 336Combined sources5
Beta strandi342 – 346Combined sources5
Turni347 – 349Combined sources3
Beta strandi352 – 355Combined sources4
Beta strandi365 – 368Combined sources4
Beta strandi374 – 377Combined sources4
Beta strandi379 – 381Combined sources3
Beta strandi444 – 448Combined sources5
Beta strandi454 – 458Combined sources5
Turni459 – 462Combined sources4
Beta strandi463 – 467Combined sources5
Helixi469 – 471Combined sources3
Beta strandi484 – 488Combined sources5
Beta strandi494 – 498Combined sources5
Turni499 – 502Combined sources4
Beta strandi503 – 507Combined sources5
Turni509 – 511Combined sources3
Helixi528 – 539Combined sources12
Turni540 – 542Combined sources3
Beta strandi545 – 551Combined sources7
Beta strandi554 – 556Combined sources3
Helixi557 – 567Combined sources11
Helixi572 – 574Combined sources3
Beta strandi575 – 580Combined sources6
Helixi589 – 603Combined sources15
Turni607 – 609Combined sources3
Beta strandi611 – 614Combined sources4
Beta strandi621 – 624Combined sources4
Helixi626 – 630Combined sources5
Helixi634 – 650Combined sources17
Helixi661 – 667Combined sources7
Helixi675 – 677Combined sources3
Turni678 – 680Combined sources3
Helixi682 – 692Combined sources11
Helixi696 – 699Combined sources4
Beta strandi704 – 709Combined sources6
Beta strandi716 – 721Combined sources6
Helixi724 – 726Combined sources3
Turni731 – 733Combined sources3
Helixi735 – 747Combined sources13
Helixi751 – 764Combined sources14
Helixi767 – 770Combined sources4
Helixi775 – 783Combined sources9
Helixi790 – 795Combined sources6
Beta strandi798 – 801Combined sources4
Helixi807 – 818Combined sources12
Helixi821 – 832Combined sources12
Helixi842 – 844Combined sources3
Beta strandi848 – 851Combined sources4
Beta strandi855 – 858Combined sources4
Beta strandi867 – 869Combined sources3
Helixi870 – 872Combined sources3
Beta strandi874 – 877Combined sources4
Helixi883 – 895Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DMVNMR-A328-357[»]
2KYKNMR-A359-392[»]
2NQ3X-ray1.80A1-155[»]
2P4RX-ray2.00T246-270[»]
2YSFNMR-A480-512[»]
3TUGX-ray2.27A524-903[»]
4ROFX-ray2.03A/B436-474[»]
5C7MX-ray3.03A524-899[»]
5CQ2X-ray1.40A433-521[»]
5DWSX-ray1.65A/C/E/G436-474[»]
5DZDX-ray1.57A/B475-514[»]
ProteinModelPortaliQ96J02.
SMRiQ96J02.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96J02.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 99C2PROSITE-ProRule annotationAdd BLAST95
Domaini326 – 359WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini358 – 391WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini438 – 471WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini478 – 511WW 4PROSITE-ProRule annotationAdd BLAST34
Domaini569 – 903HECTPROSITE-ProRule annotationAdd BLAST335

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni395 – 471Required for interaction with FYN1 PublicationAdd BLAST77
Regioni574 – 583MAP kinase docking siteBy similarity10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi252 – 267Arg/Pro-rich (PRR domain)Add BLAST16

Sequence similaritiesi

Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
Contains 4 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOVERGENiHBG004134.
InParanoidiQ96J02.
KOiK05632.
OMAiSICLDGL.
OrthoDBiEOG091G0SS8.
PhylomeDBiQ96J02.
TreeFamiTF323658.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]

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. AlignAdd to basket

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

This isoform has been chosen as the 'canonical' 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
Note: No experimental confirmation available.
Length:903
Mass (Da):102,803
Last modified:October 3, 2003 - v2
Checksum:i6777A2043C7B67BC
GO
Isoform 2 (identifier: Q96J02-2) [UniParc]FASTAAdd to basket

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

Show »
Length:862
Mass (Da):98,676
Checksum:iA3D960E7F4DBF9D3
GO
Isoform 3 (identifier: Q96J02-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:752
Mass (Da):86,498
Checksum:iB08AB68B285391F8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti297T → I in BAG64996 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0447321 – 110Missing in isoform 3. 1 PublicationAdd BLAST110
Alternative sequenceiVSP_008451159 – 200NGVSL…AGFTG → S in isoform 2 and isoform 3. 5 PublicationsAdd BLAST42

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, AL356299 Genomic DNA. Translation: CAI21458.1.
AL356299, AL109923 Genomic DNA. Translation: CAI17959.1.
AL356299, AL109923 Genomic DNA. Translation: CAI17960.1.
AL109923, AL356299 Genomic DNA. Translation: CAI21459.1.
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.
CCDSiCCDS13234.1. [Q96J02-2]
CCDS58768.1. [Q96J02-1]
CCDS58769.1. [Q96J02-3]
RefSeqiNP_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]
UniGeneiHs.632272.

Genome annotation databases

EnsembliENST00000262650; ENSP00000262650; ENSG00000078747. [Q96J02-1]
ENST00000374864; ENSP00000363998; ENSG00000078747. [Q96J02-2]
GeneIDi83737.
KEGGihsa:83737.
UCSCiuc002xak.3. human. [Q96J02-1]

Keywords - Coding sequence diversityi

Alternative splicing

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, AL356299 Genomic DNA. Translation: CAI21458.1.
AL356299, AL109923 Genomic DNA. Translation: CAI17959.1.
AL356299, AL109923 Genomic DNA. Translation: CAI17960.1.
AL109923, AL356299 Genomic DNA. Translation: CAI21459.1.
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.
CCDSiCCDS13234.1. [Q96J02-2]
CCDS58768.1. [Q96J02-1]
CCDS58769.1. [Q96J02-3]
RefSeqiNP_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]
UniGeneiHs.632272.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DMVNMR-A328-357[»]
2KYKNMR-A359-392[»]
2NQ3X-ray1.80A1-155[»]
2P4RX-ray2.00T246-270[»]
2YSFNMR-A480-512[»]
3TUGX-ray2.27A524-903[»]
4ROFX-ray2.03A/B436-474[»]
5C7MX-ray3.03A524-899[»]
5CQ2X-ray1.40A433-521[»]
5DWSX-ray1.65A/C/E/G436-474[»]
5DZDX-ray1.57A/B475-514[»]
ProteinModelPortaliQ96J02.
SMRiQ96J02.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123747. 173 interactors.
DIPiDIP-29849N.
IntActiQ96J02. 34 interactors.
MINTiMINT-148272.
STRINGi9606.ENSP00000363998.

PTM databases

iPTMnetiQ96J02.
PhosphoSitePlusiQ96J02.

Polymorphism and mutation databases

BioMutaiITCH.
DMDMi37537897.

Proteomic databases

EPDiQ96J02.
MaxQBiQ96J02.
PaxDbiQ96J02.
PeptideAtlasiQ96J02.
PRIDEiQ96J02.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262650; ENSP00000262650; ENSG00000078747. [Q96J02-1]
ENST00000374864; ENSP00000363998; ENSG00000078747. [Q96J02-2]
GeneIDi83737.
KEGGihsa:83737.
UCSCiuc002xak.3. human. [Q96J02-1]

Organism-specific databases

CTDi83737.
DisGeNETi83737.
GeneCardsiITCH.
H-InvDBHIX0015745.
HGNCiHGNC:13890. ITCH.
HPAiCAB072824.
HPA021126.
HPA049032.
MalaCardsiITCH.
MIMi606409. gene.
613385. phenotype.
neXtProtiNX_Q96J02.
OpenTargetsiENSG00000078747.
ENSG00000283472.
Orphaneti228426. Syndromic multisystem autoimmune disease due to Itch deficiency.
PharmGKBiPA29934.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOVERGENiHBG004134.
InParanoidiQ96J02.
KOiK05632.
OMAiSICLDGL.
OrthoDBiEOG091G0SS8.
PhylomeDBiQ96J02.
TreeFamiTF323658.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 2681.
ReactomeiR-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-936440. Negative regulators of RIG-I/MDA5 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ96J02.
SIGNORiQ96J02.

Miscellaneous databases

ChiTaRSiITCH. human.
EvolutionaryTraceiQ96J02.
GenomeRNAii83737.
PROiQ96J02.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000078747.
CleanExiHS_ITCH.
GenevisibleiQ96J02. HS.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiITCH_HUMAN
AccessioniPrimary (citable) accession number: Q96J02
Secondary accession number(s): A6NEW4
, B4E234, E1P5P3, F5H217, O43584, Q5QP37, Q5TEL0, Q96F66, Q9BY75, Q9H451, Q9H4U5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: November 30, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.