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-046071

UUCD1 version

UUC-HoS-00059

Ensembl Protein ID

ENSP00000237289.4

UniProt Accession

P21580; B2R767; E1P588; Q2HIX9; Q5VXQ7; Q9NSR6; TNAP3_HUMAN

Genbank Protein ID

AAA51550.1; BAG35714.1; AAO61093.1; CAH72937.1; EAW47925.1; EAW47926.1; AAI13872.1; AAI14481.1; CAB75664.1

Protein Name

Tumor necrosis factor alpha-induced protein 3; OTU domain-containing protein 7C; Putative DNA-binding protein A20; Zinc finger protein A20; A20p50; A20p37

Genbank Nucleotide ID

M59465; AK312862; AY248754; AL357060; CH471051; CH471051; BC113871; BC114480; AL157444

Gene Name

TNFAIP3; OTUD7C; A20

Ensembl Information

Ensembl Gene ID	Ensembl Transcript ID	Ensembl Protein ID
ENSG00000118503.14	ENST00000237289.8	ENSP00000237289.4
ENSG00000118503.14	ENST00000619035.4	ENSP00000478438.1
ENSG00000118503.14	ENST00000615468.4	ENSP00000479556.1
ENSG00000118503.14	ENST00000621150.3	ENSP00000484332.2
ENSG00000118503.14	ENST00000620204.3	ENSP00000481454.1
ENSG00000118503.14	ENST00000614035.4	ENSP00000481122.2

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	circBase	circRNADb
CircNet	miRTarBase	microRNA	TRANSFAC
miRWalk	TargetScan	RepTar	SomamiR
miRcode	RAID2	LncRNADisease
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
Post-translational Modifications (PTMs)
CPLM	dbPAF	PhosphositePlus	dbPTM
HPRD	Phospho.ELM	UniProt	PHOSIDA
BioGRID	mUbiSiDa
DNA Methylation
MethyCancer	TCGA	ICGC	COSMIC
Protein Expression/Proteomics
THPA	HPM	GPMDB

Status

Reviewed

Details

Family	Domain	References (PMIDs)
E3 activity/A20	A20	19380636
DUB/OTU	OTU	19380636
UBD/ZnF/ZnF_A20	ZnF_A20	23032186

Classification

Family	E-value	Score	Start	End
DUB/OTU	2.00e-40	140.1	93	262
UBD/ZnF/ZnF_A20	4.90e-25	88.8	756	790

Active Site

Position(s)	Description	Evidence
100	N/A	{ECO:0000250}
103	Nucleophile	{ECO:0000269\|PubMed:18164316}
256	Proton acceptor	{ECO:0000305\|PubMed:18164316}

Domain Profile

DUB/OTU

   S: 2    lilktkgDGnCLlrAvsqsllgvfddds.lsdalveaLreltseyl....qkesdffsefieek........edekefcqklvepe...ak. 76
           ++lkt+gDGnCL++A+sq+++gv+d+d+ l++al+++L+e+ ++++    q es + +ef+e++        +de++++ k+++++   a+ 
   Q: 93   VALKTNGDGNCLMHATSQYMWGVQDTDLvLRKALFSTLKETDTRNFkfrwQLESLKSQEFVETGlcydtrnwNDEWDNLIKMASTDtpmARs 184
           789**********************************************9**********************************99766664 PP
   S: 77   g......eeihifaLaqiLsrpiivvdvdsles..........kvggillpllfpeek.lkkpivLlYrsgHYdaLva 137
           g      eeihif+L++iL+rpiiv+++++l+s          kvggi+lpl++p+++ +++pivL+Y+s+H+ +Lv+
   Q: 185  GlqynslEEIHIFVLCNILRRPIIVISDKMLRSlesgsnfaplKVGGIYLPLHWPAQEcYRYPIVLGYDSHHFVPLVT 262
           4999999*********************************************************************97 PP

UBD/ZnF/ZnF_A20

   S: 1    dpskllCkk.gCgfYGnpetngyCSkCyreelrrr 34
           dp+k++C++ +C+++Gn+++ngyC++C++++++++
   Q: 756  DPPKQRCRApACDHFGNAKCNGYCNECFQFKQMYG 790
           8********************************96 PP

Organism

Homo sapiens

Functional Description
(View)

Functional Description

Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, 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 NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of proinflammatory cytokines and IFN beta in LPS-tolerized macrophages.

Protein Sequence
(Fasta)

MAEQVLPQAL YLSNMRKAVK IRERTPEDIF KPTNGIIHHF KTMHRYTLEM FRTCQFCPQF 60
REIIHKALID RNIQATLESQ KKLNWCREVR KLVALKTNGD GNCLMHATSQ YMWGVQDTDL 120

It may take some time, please wait.

Nucleotide Sequence
(Fasta)

CTTTGGAAAG TCCCGTGGAA ATCCCCGGGC CTACAACCCG CATACAACTG AAACGGGGCA 60
AAGCAGACTG CGCAGTCTGC AGTCTTCGTG GCGGGCCAAG CGAGCTTGGA GCCCGCGGGG 120

It may take some time, please wait.

Sequence Source

Ensembl

Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0053--Apoptosis
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0225--Disease mutation
KW-0238--DNA-binding
KW-0378--Hydrolase
KW-0395--Inflammatory response
KW-0436--Ligase
KW-0458--Lysosome
KW-0479--Metal-binding
KW-0511--Multifunctional enzyme
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-0645--Protease
KW-1185--Reference proteome
KW-0677--Repeat
KW-0788--Thiol protease
KW-0833--Ubl conjugation pathway
KW-0862--Zinc
KW-0863--Zinc-finger

Interpro

IPR033478--A20
IPR003323--OTU_dom
IPR002653--Znf_A20

PROSITE

PS50802--OTU
PS51036--ZF_A20

Pfam

PF02338--OTU
PF01754--zf-A20

SMART

SM00259--ZnF_A20

Gene Ontology

GO:0005737--C:cytoplasm
GO:0005829--C:cytosol
GO:0070062--C:extracellular exosome
GO:0005764--C:lysosome
GO:0005634--C:nucleus
GO:0003677--F:DNA binding
GO:0042802--F:identical protein binding
GO:0070530--F:K63-linked polyubiquitin binding
GO:0016874--F:ligase activity
GO:0061578--F:Lys63-specific deubiquitinase activity
GO:0002020--F:protease binding
GO:0043621--F:protein self-association
GO:0004843--F:thiol-dependent ubiquitin-specific protease activity
GO:0043130--F:ubiquitin binding
GO:0004842--F:ubiquitin-protein transferase activity
GO:0008270--F:zinc ion binding
GO:0006915--P:apoptotic process
GO:0001922--P:B-1 B cell homeostasis
GO:0070301--P:cellular response to hydrogen peroxide
GO:0071222--P:cellular response to lipopolysaccharide
GO:0072666--P:establishment of protein localization to vacuole
GO:0006954--P:inflammatory response
GO:0050869--P:negative regulation of B cell activation
GO:0045779--P:negative regulation of bone resorption
GO:2000349--P:negative regulation of CD40 signaling pathway
GO:0002677--P:negative regulation of chronic inflammatory response
GO:0045736--P:negative regulation of cyclin-dependent protein serine/threonine kinase activity
GO:2000352--P:negative regulation of endothelial cell apoptotic process
GO:1902042--P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:0043124--P:negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0050728--P:negative regulation of inflammatory response
GO:0045824--P:negative regulation of innate immune response
GO:0032691--P:negative regulation of interleukin-1 beta production
GO:0032703--P:negative regulation of interleukin-2 production
GO:0032715--P:negative regulation of interleukin-6 production
GO:0032088--P:negative regulation of NF-kappaB transcription factor activity
GO:0070429--P:negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
GO:0070433--P:negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0090291--P:negative regulation of osteoclast proliferation
GO:0031397--P:negative regulation of protein ubiquitination
GO:0048662--P:negative regulation of smooth muscle cell proliferation
GO:0034136--P:negative regulation of toll-like receptor 2 signaling pathway
GO:0034140--P:negative regulation of toll-like receptor 3 signaling pathway
GO:0034144--P:negative regulation of toll-like receptor 4 signaling pathway
GO:0034148--P:negative regulation of toll-like receptor 5 signaling pathway
GO:0032720--P:negative regulation of tumor necrosis factor production
GO:0032480--P:negative regulation of type I interferon production
GO:0070423--P:nucleotide-binding oligomerization domain containing signaling pathway
GO:1903364--P:positive regulation of cellular protein catabolic process
GO:2000347--P:positive regulation of hepatocyte proliferation
GO:0045732--P:positive regulation of protein catabolic process
GO:0016579--P:protein deubiquitination
GO:0071947--P:protein deubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0035871--P:protein K11-linked deubiquitination
GO:0071108--P:protein K48-linked deubiquitination
GO:0070936--P:protein K48-linked ubiquitination
GO:0070536--P:protein K63-linked deubiquitination
GO:0051259--P:protein oligomerization
GO:0050691--P:regulation of defense response to virus by host
GO:0002634--P:regulation of germinal center formation
GO:0050727--P:regulation of inflammatory response
GO:0010803--P:regulation of tumor necrosis factor-mediated signaling pathway
GO:0061043--P:regulation of vascular wound healing
GO:0002237--P:response to molecule of bacterial origin
GO:0032495--P:response to muramyl dipeptide
GO:0072573--P:tolerance induction to lipopolysaccharide

KEGG

hsa:7128

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-001825	Ailuropoda melanoleuca	90.76	0.00e+00	1495.00
IUUC-Apl-003501	Anas platyrhynchos	66.08	0.00e+00	1039.00
IUUC-Aca-004245	Anolis carolinensis	64.43	0.00e+00	1060.00
IUUC-Ame-011789	Astyanax mexicanus	45.63	0.00e+00	693.00
IUUC-Bta-012664	Bos taurus	85.57	0.00e+00	1366.00
IUUC-Cja-019895	Callithrix jacchus	96.84	0.00e+00	1571.00
IUUC-Cfa-020754	Canis familiaris	90.25	0.00e+00	1498.00
IUUC-Cpo-021780	Cavia porcellus	89.65	0.00e+00	1466.00
IUUC-Csa-023568	Chlorocebus sabaeus	98.48	0.00e+00	1610.00
IUUC-Cho-024300	Choloepus hoffmanni	90.38	0.00e+00	653.00
IUUC-Dre-028577	Danio rerio	48.20	0.00e+00	682.00
IUUC-Dno-029382	Dasypus novemcinctus	84.43	0.00e+00	1352.00
IUUC-Dor-030874	Dipodomys ordii	86.58	0.00e+00	1409.00
IUUC-Ete-032721	Echinops telfairi	91.63	0.00e+00	803.00
IUUC-Eca-033596	Equus caballus	87.34	0.00e+00	1408.00
IUUC-Eeu-035159	Erinaceus europaeus	88.22	0.00e+00	1135.00
IUUC-Fca-035847	Felis catus	91.27	0.00e+00	1502.00
IUUC-Fal-036681	Ficedula albicollis	64.89	0.00e+00	1046.00
IUUC-Gmo-038521	Gadus morhua	58.82	3.00e-146	512.00
IUUC-Gga-040975	Gallus gallus	64.68	0.00e+00	1055.00
IUUC-Gac-042216	Gasterosteus aculeatus	61.02	5.00e-153	535.00
IUUC-Ggo-045258	Gorilla gorilla	99.24	0.00e+00	1623.00
IUUC-Itr-048386	Ictidomys tridecemlineatus	92.41	0.00e+00	1506.00
IUUC-Lch-050326	Latimeria chalumnae	57.09	0.00e+00	914.00
IUUC-Loc-051945	Lepisosteus oculatus	45.47	7.00e-175	607.00
IUUC-Laf-053722	Loxodonta africana	89.62	0.00e+00	1446.00
IUUC-Mcc-055503	Macaca mulatta	98.23	0.00e+00	1605.00
IUUC-Meu-056481	Macropus eugenii	76.09	0.00e+00	1199.00
IUUC-Mga-059690	Meleagris gallopavo	62.85	0.00e+00	972.00
IUUC-Mmr-061233	Microcebus murinus	91.41	0.00e+00	1467.00
IUUC-Mdo-062446	Monodelphis domestica	81.05	0.00e+00	1313.00
IUUC-Mmu-063436	Mus musculus	88.10	0.00e+00	1410.00
IUUC-Mpu-066808	Mustela putorius furo	90.89	0.00e+00	1495.00
IUUC-Mlu-067339	Myotis lucifugus	89.62	0.00e+00	1446.00
IUUC-Nle-069888	Nomascus leucogenys	99.11	0.00e+00	1618.00
IUUC-Opr-070303	Ochotona princeps	89.66	0.00e+00	1449.00
IUUC-Ont-072283	Oreochromis niloticus	58.94	3.00e-147	515.00
IUUC-Oan-072925	Ornithorhynchus anatinus	76.57	0.00e+00	1245.00
IUUC-Ocu-073889	Oryctolagus cuniculus	90.01	0.00e+00	1431.00
IUUC-Oni-082742	Oryza nivara	28.57	2.20e-01	32.70
IUUC-Oru-085223	Oryza rufipogon	28.57	2.10e-01	32.70
IUUC-Ola-087417	Oryzias latipes	59.18	2.00e-147	516.00
IUUC-Oga-088708	Otolemur garnettii	88.61	0.00e+00	1402.00
IUUC-Oar-089271	Ovis aries	85.82	0.00e+00	1380.00
IUUC-Ptr-091296	Pan troglodytes	99.75	0.00e+00	1630.00
IUUC-Pan-092474	Papio anubis	98.35	0.00e+00	1607.00
IUUC-Psi-093447	Pelodiscus sinensis	69.10	0.00e+00	1118.00
IUUC-Pfo-096511	Poecilia formosa	59.42	5.00e-149	521.00
IUUC-Pab-098700	Pongo abelii	98.99	0.00e+00	1615.00
IUUC-Pca-100246	Procavia capensis	76.08	0.00e+00	1194.00
IUUC-Pva-102606	Pteropus vampyrus	79.19	0.00e+00	627.00
IUUC-Rno-105818	Rattus norvegicus	87.86	0.00e+00	1441.00
IUUC-Sha-106559	Sarcophilus harrisii	79.42	0.00e+00	1283.00
IUUC-Sit-110516	Setaria italica	42.86	9.40e-02	33.10
IUUC-Sar-113454	Sorex araneus	93.90	0.00e+00	648.00
IUUC-Ssc-116064	Sus scrofa	88.86	0.00e+00	1422.00
IUUC-Tgu-117212	Taeniopygia guttata	64.68	0.00e+00	1037.00
IUUC-Tru-118230	Takifugu rubripes	60.39	3.00e-152	532.00
IUUC-Tsy-119066	Tarsius syrichta	89.87	0.00e+00	1479.00
IUUC-Tni-119825	Tetraodon nigroviridis	46.63	0.00e+00	680.00
IUUC-Tvi-122358	Trichoderma virens	35.59	8.70e-02	31.60
IUUC-Tur-126383	Triticum urartu	50.00	8.00e-03	31.60
IUUC-Tbe-127601	Tupaia belangeri	96.95	0.00e+00	675.00
IUUC-Ttr-128930	Tursiops truncatus	86.96	0.00e+00	1408.00
IUUC-Vpa-130450	Vicugna pacos	94.51	0.00e+00	799.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence