iUUCD 2.0 - integrated annotations for ubiquitin and ubiquitin-like conjugation database

Protein
Gene
Annotation
Details
Classification
Domain Profile
Function
Protein Sequence
Nucleotide Sequence
Keyword
GO
Orthology
TOP

Basic Information

Integrated Annotations

Tag

Content

iUUCD ID

IUUC-Hsa-046564

UUCD1 version

UUC-HoS-00306

Ensembl Protein ID

ENSP00000262650.5

UniProt Accession

Q96J02; A6NEW4; B4E234; E1P5P3; F5H217; O43584; Q5QP37; Q5TEL0; Q96F66; Q9BY75; Q9H451; Q9H4U5; ITCH_HUMAN

Genbank Protein ID

AAK39399.1; BAB39389.1; BAG64996.1; BAG37647.1; CAI21458.1; CAI21458.1; CAI17959.1; CAI17959.1; CAI17960.1; CAI17960.1; CAI21459.1; CAI21459.1; EAW76272.1; EAW76274.1; EAW76276.1; AAH06848.1; AAH11571.1; AAC04845.1

Protein Name

E3 ubiquitin-protein ligase Itchy homolog; Atrophin-1-interacting protein 4; HECT-type E3 ubiquitin transferase Itchy homolog; NFE2-associated polypeptide 1

Genbank Nucleotide ID

AF095745; AB056663; AK304090; AK315212; AL109923; AL356299; AL356299; AL109923; AL356299; AL109923; AL109923; AL356299; CH471077; CH471077; CH471077; BC006848; BC011571; AF038564

Gene Name

ITCH

Ensembl Information

Ensembl Gene ID	Ensembl Transcript ID	Ensembl Protein ID
ENSG00000078747.13	ENST00000374864.8	ENSP00000363998.4
ENSG00000078747.13	ENST00000262650.10	ENSP00000262650.5

Annotation

Cancer Mutation
TCGA	ICGC	COSMIC	CGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEO	ArrayExpress	TCGA	ICGC
COSMIC	THPA	HPM
DNA & RNA Element
UTRdb	AREsite	circRNADb	CircNet
miRTarBase	microRNA	TRANSFAC	miRWalk
miRecords	RepTar	miRNAMap	SomamiR
miRcode	RAID2
Protein-protein Interaction
IID	iRefIndex	PINA	HINT
Mentha	InWeb_IM
Protein 3D Structure
PDB	MMDB
Disease-associated Information
ClinVar	GWASdb	OMIM
Drug and target
TTD	Manually
Post-translational Modifications (PTMs)
CPLM	dbPAF	PhosphositePlus	dbPTM
HPRD	Phospho.ELM	UniProt	PHOSIDA
BioGRID	mUbiSiDa
DNA Methylation
TCGA	ICGC	COSMIC
Protein Expression/Proteomics
THPA	HPM	GPMDB

Status

Reviewed

Details

Family	Domain	References (PMIDs)
E3 activity/HECT	HECT	20650893; 18310276; 15013426; 19592251; 19580544; 19478092; 19433584; 19352540; 16387660; 19340001; 20300110; 19339247; 18278048; 17110928; 16087662; 16055720; 15946939; 20068034; 20818436; 18334649; 18922894; 15703212; 15082780; 21383157; 21212414; 21107885; 24550385

Classification

Family	E-value	Score	Start	End
E3 activity/HECT	2.20e-135	453.1	570	902

Active Site

Position(s)	Description	Evidence
871	Glycyl thioester intermediate	{ECO:0000255\|PROSITE-ProRule:PRU00104}

Domain Profile

E3 activity/HECT

   S: 2    ksdlkkrlevefvgEegldlgGvtreflallskelqnpdlglflysendketlqpnpdsglknpehlklFeflGrllgkalqdgrlldlpls 93
           ++dl++rl+v f gEegld+gGv+re+++lls+e+ np+++lf+y  +d+++lq+np+s++ np+hlk+F+f+Gr++++al++g+++d+ +s
   Q: 570  PQDLRRRLWVIFPGEEGLDYGGVAREWFFLLSHEVLNPMYCLFEYAGKDNYCLQINPASYI-NPDHLKYFRFIGRFIAMALFHGKFIDTGFS 660
           689*********************************************************9.89**************************** PP
   S: 94   ksfyklllgkklsledleevdpelykslkeikenaesdieelgldltfsvseeilgetkeeeLkpgGenipVtneNkeeYvklvveyrlkeg 185
            +fyk++l+k++ l+dle++dpe+y+sl ++ken   +iee++l++ fsv++eilge+k+++Lkp+G ni Vt+eNkeeY++ v+e+rl +g
   Q: 661  LPFYKRILNKPVGLKDLESIDPEFYNSLIWVKEN---NIEECDLEMYFSVDKEILGEIKSHDLKPNGGNILVTEENKEEYIRMVAEWRLSRG 749
           ********************************99...9****************************************************** PP
   S: 186  ikeqveafreGfneviplellslFteeelellicGeeeidvedlkketkykggytedspaiqwFwevleefsseerkafLqFvTgssrlPlg 277
           ++eq++af eGfne++p++ l++F+++ele+l+cG++eid++d+++++ y++ y ++s++i wFw++++e+++e+r ++LqFvTg++rlP+g
   Q: 750  VEEQTQAFFEGFNEILPQQYLQYFDAKELEVLLCGMQEIDLNDWQRHAIYRH-YARTSKQIMWFWQFVKEIDNEKRMRLLQFVTGTCRLPVG 840
           **************************************************99.*************************************** PP
   S: 278  Gfaelk....prlfvirkdasddrlPssnTCfnyLkLPeYsskeilkekLlyAieetkgFel 335
           Gfa+l+    p++f+i+k +++++lP+s+TCfn+L+LP+Y+s+e+lkekLl+Aieet+gF++
   Q: 841  GFADLMgsngPQKFCIEKVGKENWLPRSHTCFNRLDLPPYKSYEQLKEKLLFAIEETEGFGQ 902
           ************************************************************96 PP

Organism

Homo sapiens

Functional Description
(View)

Functional Description

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. 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. 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).

Protein Sequence
(Fasta)

MSDSGSQLGS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ SKKTEKCNNT 60
NSPKWKQPLT VIVTPVSKLH FRVWSHQTLK SDVLLGTAAL DIYETLKSNN MKLEEVVVTL 120

It may take some time, please wait.

Nucleotide Sequence
(Fasta)

GCGCTCAGGC GCCTGCGCTT TAGCTGCTAA CTCGCTCTAG TAGCTGTGGT CGGGGCTCGG 60
GACCGGCTGC CATCTTAGTC TAGGGACTGA GGAGTCGCCG CCGCCCCGAG TCCCGGTAAA 120

It may take some time, please wait.

Sequence Source

Ensembl

Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0025--Alternative splicing
KW-0051--Antiviral defense
KW-0053--Apoptosis
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0903--Direct protein sequencing
KW-0945--Host-virus interaction
KW-0391--Immunity
KW-0399--Innate immunity
KW-0472--Membrane
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-1185--Reference proteome
KW-0677--Repeat
KW-0808--Transferase
KW-0832--Ubl conjugation
KW-0833--Ubl conjugation pathway

Interpro

IPR000008--C2_dom
IPR000569--HECT_dom
IPR001202--WW_dom

PROSITE

PS50004--C2
PS50237--HECT
PS01159--WW_DOMAIN_1
PS50020--WW_DOMAIN_2

Pfam

PF00168--C2
PF00632--HECT
PF00397--WW

SMART

SM00239--C2
SM00119--HECTc
SM00456--WW

Gene Ontology

GO:0005938--C:cell cortex
GO:0031410--C:cytoplasmic vesicle
GO:0005829--C:cytosol
GO:0070062--C:extracellular exosome
GO:0016020--C:membrane
GO:0005654--C:nucleoplasm
GO:0005886--C:plasma membrane
GO:0045236--F:CXCR chemokine receptor binding
GO:0016874--F:ligase activity
GO:0043021--F:ribonucleoprotein complex binding
GO:0061630--F:ubiquitin protein ligase activity
GO:0019787--F:ubiquitin-like protein transferase activity
GO:0004842--F:ubiquitin-protein transferase activity
GO:0006915--P:apoptotic process
GO:0051607--P:defense response to virus
GO:0006954--P:inflammatory response
GO:0045087--P:innate immune response
GO:0046642--P:negative regulation of alpha-beta T cell proliferation
GO:0043066--P:negative regulation of apoptotic process
GO:0050687--P:negative regulation of defense response to virus
GO:0046329--P:negative regulation of JNK cascade
GO:0032088--P:negative regulation of NF-kappaB transcription factor activity
GO:0032480--P:negative regulation of type I interferon production
GO:0007219--P:Notch signaling pathway
GO:0070423--P:nucleotide-binding oligomerization domain containing signaling pathway
GO:0045732--P:positive regulation of protein catabolic process
GO:0002669--P:positive regulation of T cell anergy
GO:0035519--P:protein K29-linked ubiquitination
GO:0070936--P:protein K48-linked ubiquitination
GO:0070534--P:protein K63-linked ubiquitination
GO:0016567--P:protein ubiquitination
GO:0042787--P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0001558--P:regulation of cell growth
GO:0090085--P:regulation of protein deubiquitination
GO:0006511--P:ubiquitin-dependent protein catabolic process
GO:0046718--P:viral entry into host cell

KEGG

hsa:83737

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-002302	Ailuropoda melanoleuca	92.80	0.00e+00	1605.00
IUUC-Apl-003752	Anas platyrhynchos	79.85	0.00e+00	1438.00
IUUC-Aca-005338	Anolis carolinensis	77.79	0.00e+00	1412.00
IUUC-Ago-007742	Ashbya gossypii	48.88	1.00e-162	567.00
IUUC-Ame-010601	Astyanax mexicanus	88.07	0.00e+00	1125.00
IUUC-Bta-012782	Bos taurus	92.47	0.00e+00	1572.00
IUUC-Cja-018899	Callithrix jacchus	97.41	0.00e+00	1668.00
IUUC-Cfa-020648	Canis familiaris	91.59	0.00e+00	1570.00
IUUC-Cpo-022073	Cavia porcellus	93.47	0.00e+00	1630.00
IUUC-Csa-023252	Chlorocebus sabaeus	93.80	0.00e+00	1642.00
IUUC-Cho-024695	Choloepus hoffmanni	90.37	0.00e+00	1630.00
IUUC-Dre-028451	Danio rerio	72.78	0.00e+00	1290.00
IUUC-Dno-029884	Dasypus novemcinctus	92.58	0.00e+00	1655.00
IUUC-Eca-033793	Equus caballus	93.24	0.00e+00	1632.00
IUUC-Eeu-034716	Erinaceus europaeus	92.79	0.00e+00	887.00
IUUC-Fca-035605	Felis catus	92.58	0.00e+00	1633.00
IUUC-Fal-037126	Ficedula albicollis	79.85	0.00e+00	1433.00
IUUC-Gmo-038596	Gadus morhua	80.72	0.00e+00	1014.00
IUUC-Gga-040832	Gallus gallus	80.48	0.00e+00	1449.00
IUUC-Gac-041658	Gasterosteus aculeatus	86.82	0.00e+00	1123.00
IUUC-Ggo-044535	Gorilla gorilla	91.69	0.00e+00	1617.00
IUUC-Itr-048918	Ictidomys tridecemlineatus	92.14	0.00e+00	1559.00
IUUC-Kpa-049273	Komagataella pastoris	49.23	1.00e-163	570.00
IUUC-Lch-050454	Latimeria chalumnae	73.64	0.00e+00	1374.00
IUUC-Loc-052647	Lepisosteus oculatus	75.36	0.00e+00	1389.00
IUUC-Laf-054383	Loxodonta africana	93.58	0.00e+00	1636.00
IUUC-Mcc-055532	Macaca mulatta	94.02	0.00e+00	1643.00
IUUC-Mga-059661	Meleagris gallopavo	80.37	0.00e+00	1440.00
IUUC-Mmr-061135	Microcebus murinus	93.47	0.00e+00	1658.00
IUUC-Mdo-062505	Monodelphis domestica	83.48	0.00e+00	1487.00
IUUC-Mmu-063375	Mus musculus	91.27	0.00e+00	1579.00
IUUC-Mpu-066203	Mustela putorius furo	93.14	0.00e+00	1609.00
IUUC-Mlu-067837	Myotis lucifugus	92.69	0.00e+00	1627.00
IUUC-Nle-069244	Nomascus leucogenys	93.26	0.00e+00	1624.00
IUUC-Opr-070585	Ochotona princeps	91.14	0.00e+00	1592.00
IUUC-Ont-071822	Oreochromis niloticus	73.05	0.00e+00	1338.00
IUUC-Oan-073679	Ornithorhynchus anatinus	67.07	0.00e+00	989.00
IUUC-Ocu-074298	Oryctolagus cuniculus	93.26	0.00e+00	1618.00
IUUC-Ola-086526	Oryzias latipes	68.44	0.00e+00	1306.00
IUUC-Oga-088167	Otolemur garnettii	87.32	0.00e+00	1514.00
IUUC-Oar-090316	Ovis aries	76.94	0.00e+00	1182.00
IUUC-Ptr-090819	Pan troglodytes	98.78	0.00e+00	1718.00
IUUC-Pan-092454	Papio anubis	94.02	0.00e+00	1643.00
IUUC-Psi-093319	Pelodiscus sinensis	78.07	0.00e+00	1406.00
IUUC-Pfo-096937	Poecilia formosa	89.38	0.00e+00	1136.00
IUUC-Pab-097580	Pongo abelii	92.14	0.00e+00	1587.00
IUUC-Pca-100923	Procavia capensis	75.64	0.00e+00	1346.00
IUUC-Pva-103209	Pteropus vampyrus	91.69	0.00e+00	1574.00
IUUC-Rno-104924	Rattus norvegicus	91.05	0.00e+00	1589.00
IUUC-Sha-107175	Sarcophilus harrisii	84.81	0.00e+00	1490.00
IUUC-Sja-107941	Schizosaccharomyces japonicus	44.96	1.00e-160	560.00
IUUC-Sar-113761	Sorex araneus	86.92	0.00e+00	1501.00
IUUC-Tgu-116632	Taeniopygia guttata	76.97	0.00e+00	1315.00
IUUC-Tru-118442	Takifugu rubripes	89.27	0.00e+00	1128.00
IUUC-Tsy-119198	Tarsius syrichta	86.71	0.00e+00	1518.00
IUUC-Tni-120168	Tetraodon nigroviridis	86.88	0.00e+00	1063.00
IUUC-Tbe-127756	Tupaia belangeri	78.29	0.00e+00	1322.00
IUUC-Ttr-128504	Tursiops truncatus	84.69	0.00e+00	1150.00
IUUC-Vpa-130103	Vicugna pacos	82.74	0.00e+00	1407.00
IUUC-Xtr-132885	Xenopus tropicalis	77.04	0.00e+00	1406.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence