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

Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEO	ArrayExpress	GXD
DNA & RNA Element
AREsite	miRTarBase	microRNA	TRANSFAC
RepTar	RAID2
Protein-protein Interaction
IID	iRefIndex	PINA	HINT
Mentha
Protein 3D Structure
PDB	MMDB
Post-translational Modifications (PTMs)
CPLM	dbPAF	PhosphositePlus	dbPTM
PHOSIDA
Protein Expression/Proteomics
GPMDB

Status

Unreviewed

Classification

Family	E-Value	Score	Start	End
DUB/OTU	1.60e-38	133.4	93	262
UBD/ZnF/ZnF_A20	2.80e-24	85.9	742	775

Active Site

Position(s)	Description	Evidence
100	N/A	{ECO:0000250}
103	Nucleophile	ECO:0000250}
256	Proton acceptor	ECO:0000250}

Domain Profile

DUB/OTU

   S: 2    lilktkgDGnCLlrAvsqsllgvfddds.lsdalveaLreltseyl....qkesdffsefieek........edekefcqklvepe... 74
           ++lkt+gDGnCL++A+ q+++gv+d+d+ l++al ++L+e+ ++++    q es + +ef+e++        +de++++ k+++ +   
   Q: 93   VALKTNGDGNCLMHAACQYMWGVQDTDLvLRKALCSTLKETDTRNFkfrwQLESLKSQEFVETGlcydtrnwNDEWDNLVKMASADtpa 181
           789**********************************************9**********************************99665 PP
   S: 75   akg.......eeihifaLaqiLsrpiivvdvdsles..........kvggillpllfpeek.lkkpivLlYrsgHYdaLva 137
           a++       eeihif+L++iL+rpiiv+++++l+s          kvggi+lpl++p+++ +++pivL+Y+s H+ +Lv+
   Q: 182  ARSglqynslEEIHIFVLSNILRRPIIVISDKMLRSlesgsnfaplKVGGIYLPLHWPAQEcYRYPIVLGYDSQHFVPLVT 262
           5526999************************************************************************97 PP

UBD/ZnF/ZnF_A20

   S: 2    pskllCkk.gCgfYGnpetngyCSkCyreelrrr 34
           p+k++C++ +C+++Gn+++ngyC++Cy+++++++
   Q: 742  PPKQRCRApACDHFGNAKCNGYCNECYQFKQMYG 775
           9*******************************96 PP

Organism

Mus musculus

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)

MAEQLLPQAL YLSNMRKAVK IRERTPEDIF KPTNGIIYHF KTMHRYTLEM FRTCQFCPQF 60
REIIHKALID RSVQASLESQ KKLNWCREVR KLVALKTNGD GNCLMHAACQ YMWGVQDTDL 120

It may take some time, please wait.

Nucleotide Sequence
(Fasta)

TGATTTTCTT CAGAAAAGAA GCTATAAAAA AGAACCTATT GCATTTCCAG TTCCCATCAC 60
CGCGATTTCC ACATGGATGT GACGTGGAAG GCAGCTTCCG AAATGCCCAG GTGACTCACG 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-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-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: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:0019900--F:kinase 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:0002315--P:marginal zone B cell differentiation
GO:0010507--P:negative regulation of autophagy
GO:0050869--P:negative regulation of B cell activation
GO:2000349--P:negative regulation of CD40 signaling pathway
GO:0060548--P:negative regulation of cell death
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:0002632--P:negative regulation of granuloma formation
GO:0034115--P:negative regulation of heterotypic cell-cell adhesion
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:0031397--P:negative regulation of protein ubiquitination
GO:0048662--P:negative regulation of smooth muscle cell proliferation
GO:0034140--P:negative regulation of toll-like receptor 3 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: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:0002634--P:regulation of germinal center formation
GO:0002637--P:regulation of immunoglobulin production
GO:0045088--P:regulation of innate immune response
GO:0002237--P:response to molecule of bacterial origin
GO:0032495--P:response to muramyl dipeptide
GO:0009611--P:response to wounding
GO:0072573--P:tolerance induction to lipopolysaccharide

KEGG

mmu:21929

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-001825	Ailuropoda melanoleuca	87.72	0.00e+00	1426.00
IUUC-Apl-003501	Anas platyrhynchos	65.20	0.00e+00	1027.00
IUUC-Aca-004245	Anolis carolinensis	63.81	0.00e+00	1043.00
IUUC-Ame-011789	Astyanax mexicanus	46.94	0.00e+00	696.00
IUUC-Bta-012664	Bos taurus	85.10	0.00e+00	1342.00
IUUC-Cja-019895	Callithrix jacchus	88.35	0.00e+00	1430.00
IUUC-Cfa-020754	Canis familiaris	88.23	0.00e+00	1437.00
IUUC-Cpo-021780	Cavia porcellus	86.99	0.00e+00	1408.00
IUUC-Csa-023568	Chlorocebus sabaeus	88.61	0.00e+00	1448.00
IUUC-Cho-024300	Choloepus hoffmanni	88.63	0.00e+00	644.00
IUUC-Dre-028577	Danio rerio	48.27	0.00e+00	686.00
IUUC-Dno-029382	Dasypus novemcinctus	81.52	0.00e+00	1304.00
IUUC-Dor-030874	Dipodomys ordii	86.08	0.00e+00	1374.00
IUUC-Ete-032721	Echinops telfairi	90.43	0.00e+00	795.00
IUUC-Eca-033596	Equus caballus	83.67	0.00e+00	1360.00
IUUC-Eeu-035159	Erinaceus europaeus	84.87	0.00e+00	1076.00
IUUC-Fca-035847	Felis catus	88.48	0.00e+00	1441.00
IUUC-Fal-036681	Ficedula albicollis	64.27	0.00e+00	1036.00
IUUC-Gmo-038521	Gadus morhua	58.23	2.00e-144	506.00
IUUC-Gga-040975	Gallus gallus	63.33	0.00e+00	1041.00
IUUC-Gac-042216	Gasterosteus aculeatus	61.11	1.00e-152	533.00
IUUC-Ggo-045258	Gorilla gorilla	88.10	0.00e+00	1444.00
IUUC-Hsa-046071	Homo sapiens	88.10	0.00e+00	1444.00
IUUC-Itr-048386	Ictidomys tridecemlineatus	89.62	0.00e+00	1451.00
IUUC-Lch-050326	Latimeria chalumnae	57.41	0.00e+00	915.00
IUUC-Loc-051945	Lepisosteus oculatus	45.00	1.00e-176	613.00
IUUC-Laf-053722	Loxodonta africana	85.82	0.00e+00	1390.00
IUUC-Mcc-055503	Macaca mulatta	88.35	0.00e+00	1444.00
IUUC-Meu-056481	Macropus eugenii	74.33	0.00e+00	1155.00
IUUC-Mga-059690	Meleagris gallopavo	62.60	0.00e+00	975.00
IUUC-Mmr-061233	Microcebus murinus	87.50	0.00e+00	1403.00
IUUC-Mdo-062446	Monodelphis domestica	78.92	0.00e+00	1262.00
IUUC-Mpu-066808	Mustela putorius furo	87.59	0.00e+00	1425.00
IUUC-Mlu-067339	Myotis lucifugus	86.01	0.00e+00	1392.00
IUUC-Nle-069888	Nomascus leucogenys	87.97	0.00e+00	1440.00
IUUC-Opr-070303	Ochotona princeps	86.11	0.00e+00	1402.00
IUUC-Ont-072283	Oreochromis niloticus	59.08	3.00e-147	516.00
IUUC-Oan-072925	Ornithorhynchus anatinus	76.07	0.00e+00	1221.00
IUUC-Ocu-073889	Oryctolagus cuniculus	87.29	0.00e+00	1387.00
IUUC-Ola-087417	Oryzias latipes	59.81	2.00e-148	519.00
IUUC-Oga-088708	Otolemur garnettii	84.18	0.00e+00	1317.00
IUUC-Oar-089271	Ovis aries	85.35	0.00e+00	1354.00
IUUC-Ptr-091296	Pan troglodytes	88.10	0.00e+00	1442.00
IUUC-Pan-092474	Papio anubis	88.48	0.00e+00	1447.00
IUUC-Psi-093447	Pelodiscus sinensis	67.62	0.00e+00	1090.00
IUUC-Pfo-096511	Poecilia formosa	59.56	6.00e-149	521.00
IUUC-Pab-098700	Pongo abelii	87.97	0.00e+00	1439.00
IUUC-Pca-100246	Procavia capensis	73.67	0.00e+00	1151.00
IUUC-Pva-102606	Pteropus vampyrus	76.65	9.00e-177	613.00
IUUC-Rno-105818	Rattus norvegicus	94.85	0.00e+00	1525.00
IUUC-Sha-106559	Sarcophilus harrisii	78.18	0.00e+00	1248.00
IUUC-Sit-110516	Setaria italica	41.86	3.60e-02	34.70
IUUC-Sar-113454	Sorex araneus	92.38	0.00e+00	639.00
IUUC-Ssc-116064	Sus scrofa	86.50	0.00e+00	1379.00
IUUC-Tgu-117212	Taeniopygia guttata	64.18	0.00e+00	1027.00
IUUC-Tru-118230	Takifugu rubripes	59.81	4.00e-151	528.00
IUUC-Tsy-119066	Tarsius syrichta	86.66	0.00e+00	1403.00
IUUC-Tni-119825	Tetraodon nigroviridis	47.85	0.00e+00	676.00
IUUC-Tur-126383	Triticum urartu	41.67	1.30e-02	31.20
IUUC-Tbe-127601	Tupaia belangeri	95.43	0.00e+00	664.00
IUUC-Ttr-128930	Tursiops truncatus	85.61	0.00e+00	1363.00
IUUC-Vpa-130450	Vicugna pacos	93.52	0.00e+00	787.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence