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

Ensembl Gene ID	Ensembl Transcript ID	Ensembl Protein ID
ENSG00000083799.17	ENST00000569418.5	ENSP00000457576.1
ENSG00000083799.17	ENST00000311559.13	ENSP00000308928.9
ENSG00000083799.17	ENST00000566206.5	ENSP00000462134.1
ENSG00000083799.17	ENST00000568704.2	ENSP00000456488.2
ENSG00000083799.17	ENST00000562884.1	ENSP00000463197.1
ENSG00000083799.17	ENST00000566024.1	ENSP00000458507.1

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
AREsite	circBase	circRNADb	CircNet
miRTarBase	microRNA	TRANSFAC	miRWalk
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
Post-translational Modifications (PTMs)
CPLM	dbPAF	PhosphositePlus	dbPTM
HPRD	Phospho.ELM	UniProt	BioGRID
DNA Methylation
TCGA	ICGC	COSMIC
Protein Expression/Proteomics
THPA	HPM	GPMDB

Status

Reviewed

Details

Family	Domain	References (PMIDs)
DUB/USP	USP	17981138; 18313383; 15933713

Classification

Family	E-value	Score	Start	End
DUB/USP	3.60e-24	87.2	593	949

Active Site

Position(s)	Description	Evidence
601	Nucleophile	ECO:0000255\|PROSITE-ProRule:PRU10092, ECO:0000269\|PubMed:18313383}
871	Proton acceptor	{ECO:0000305\|PubMed:18313383}

Domain Profile

DUB/USP

   S: 2    GlkNlgNtCYmNSvLQcLsnipelrelllekkkeklneenpkepkgellkslqklfeelw.kskkkavsprellkalkkeaeefsgyeqqDa 92
           G++ + N+CY++S+L cL++++++ + +l + kek + e ++e+++ l +++ + ++     + +k ++ r++l+++++++    ++e++D 
   Q: 593  GIQGHYNSCYLDSTLFCLFAFSSVLDTVLLRPKEKNDVEYYSETQELLRTEIVNPLRIYGyVCATKIMKLRKILEKVEAASGF--TSEEKDP 682
           999***************************99999999999999999999****999887899**************988875..899**** PP
   S: 93   qEflaflldqleeelkkeknkpkeeeeeedkselsdeaeekkkkknkslisdlFqgqlksq.ik...clecdnvs.sreepfldlslpvpgk 179
           +Efl++l++++ +       k ++  ++ +++   ++  ek++k +  +i++l+++++ ++ +k    ++c  ++  r+ + ++l  ++  +
   Q: 683  EEFLNILFHHILRVE--PLLKIRSAGQKVQDCYFYQIFMEKNEKVGVPTIQQLLEWSFINSnLKfaeAPSCLIIQmPRFGKDFKLFKKIFPS 772
           *************99..88999999999999**************************9854144444799****99**************99 PP
   S: 180  eetkkeslqdcLesftkeeelegenk.yycekckkkqeaekklklkklPe....vLilhLkRfsfseeqksrekinkkvefpleL...dlsp 263
            e    +++d+Le+  ++++++g  + y+c++c+++ + +   k+k++++      +lh kR   +       +  + v++p+ L   d ++
   Q: 773  LEL---NITDLLEDTPRQCRICGGLAmYECRECYDDPDISAG-KIKQFCKtcntQVHLHPKRL--N-------HKYNPVSLPKDLpdwDWRH 851
           998...***************987655********9984433.55555553334688999999..2.......3356788886651114444 PP
   S: 264  fctspeekqkekkkYeLiavvvHsGslssGHYvayvknekgk..WllfdD.............skVtevke.eevleetg............ 327
            c+        +++ eL+av++ +      HYva+vk  k++  Wl fd               +Vt+++e  e l+++             
   Q: 852  GCIP-------CQNMELFAVLCIET----SHYVAFVKYGKDDsaWLFFDSmadrdggqngfniPQVTPCPEvGEYLKMSLedlhsldsrriq 932
           4554.......99*********999....9********777788*****9999*******99999999976678888776899999999999 PP
   S: 328  .......staYvlfYkr 337
                  ++aY+++Y++
   Q: 933  gcarrllCDAYMCMYQS 949
           999************85 PP

Organism

Homo sapiens

Functional Description
(View)

Deubiquitinase that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Has endodeubiquitinase activity. Plays an important role in the regulation of pathways leading to NF-kappa-B activation (PubMed:12917689, PubMed:12917691). Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation (PubMed:12917690). Negative regulator of Wnt signaling (PubMed:20227366). Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules (PubMed:19893491). Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis (PubMed:18222923, PubMed:20194890). Required for normal cell cycle progress and normal cytokinesis (PubMed:17495026, PubMed:19893491). Inhibits nuclear translocation of NF-kappa-B. Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation (PubMed:18636086). Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells. Negatively regulates TNFRSF11A signaling and osteoclastogenesis (By similarity). Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (By similarity). Also able to remove linear ('Met-1'-linked) polyubiquitin chains to regulate innate immunity: recruited to the LUBAC complex and, together with OTULIN, restricts linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (PubMed:26670046, PubMed:26997266).

Protein Sequence
(Fasta)

MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI QDRSVGHSRI 60
PSAKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL LAITNCEERF SLFKNRNRLS 120

It may take some time, please wait.

Nucleotide Sequence
(Fasta)

GTGCGGTTCG GAGGCGGGGC AGGTGGGGGC GGGCCCAGGT AGCAGGTTTG GCTGCGCGGG 60
GGCCGCGCGT CGGAGGTAAA TACTAGGGCG GTGGGTGTGG GGAGCCGGGG CCGGCCCGGG 120

It may take some time, please wait.

Sequence Source

Ensembl

Keyword

KW-0002--3D-structure
KW-0025--Alternative splicing
KW-0131--Cell cycle
KW-1003--Cell membrane
KW-0966--Cell projection
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0206--Cytoskeleton
KW-0225--Disease mutation
KW-0378--Hydrolase
KW-0391--Immunity
KW-0399--Innate immunity
KW-0472--Membrane
KW-0479--Metal-binding
KW-0493--Microtubule
KW-0597--Phosphoprotein
KW-0645--Protease
KW-1185--Reference proteome
KW-0677--Repeat
KW-0788--Thiol protease
KW-0043--Tumor suppressor
KW-0833--Ubl conjugation pathway
KW-0879--Wnt signaling pathway
KW-0862--Zinc

Interpro

IPR000938--CAP-Gly_domain
IPR001394--Peptidase_C19_UCH
IPR018200--USP_CS
IPR028889--USP_dom

PROSITE

PS00845--CAP_GLY_1
PS50245--CAP_GLY_2
PS00972--USP_1
PS50235--USP_3

Pfam

PF01302--CAP_GLY
PF00443--UCH

SMART

SM01052--CAP_GLY

Gene Ontology

GO:0005813--C:centrosome
GO:0036064--C:ciliary basal body
GO:0097542--C:ciliary tip
GO:0005829--C:cytosol
GO:0031234--C:extrinsic component of cytoplasmic side of plasma membrane
GO:0005874--C:microtubule
GO:0048471--C:perinuclear region of cytoplasm
GO:0005819--C:spindle
GO:1990380--F:Lys48-specific deubiquitinase activity
GO:0061578--F:Lys63-specific deubiquitinase activity
GO:0070064--F:proline-rich region binding
GO:0019901--F:protein kinase binding
GO:0004843--F:thiol-dependent ubiquitin-specific protease activity
GO:0036459--F:thiol-dependent ubiquitinyl hydrolase activity
GO:0008270--F:zinc ion binding
GO:0043369--P:CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
GO:0007049--P:cell cycle
GO:0048872--P:homeostasis of number of cells
GO:0045087--P:innate immune response
GO:0070266--P:necroptotic process
GO:0090090--P:negative regulation of canonical Wnt signaling pathway
GO:0042347--P:negative regulation of NF-kappaB import into nucleus
GO:0032088--P:negative regulation of NF-kappaB transcription factor activity
GO:0045581--P:negative regulation of T cell differentiation
GO:0032480--P:negative regulation of type I interferon production
GO:0070423--P:nucleotide-binding oligomerization domain containing signaling pathway
GO:1903829--P:positive regulation of cellular protein localization
GO:2001238--P:positive regulation of extrinsic apoptotic signaling pathway
GO:0045582--P:positive regulation of T cell differentiation
GO:0050862--P:positive regulation of T cell receptor signaling pathway
GO:0016579--P:protein deubiquitination
GO:0070536--P:protein K63-linked deubiquitination
GO:1990108--P:protein linear deubiquitination
GO:0045577--P:regulation of B cell differentiation
GO:1902017--P:regulation of cilium assembly
GO:2001242--P:regulation of intrinsic apoptotic signaling pathway
GO:0070507--P:regulation of microtubule cytoskeleton organization
GO:0007346--P:regulation of mitotic cell cycle
GO:0043393--P:regulation of protein binding
GO:0010803--P:regulation of tumor necrosis factor-mediated signaling pathway
GO:1901026--P:ripoptosome assembly involved in necroptotic process
GO:0006511--P:ubiquitin-dependent protein catabolic process
GO:0016055--P:Wnt signaling pathway

KEGG

hsa:1540

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-001298	Ailuropoda melanoleuca	96.97	0.00e+00	1924.00
IUUC-Apl-003356	Anas platyrhynchos	87.25	0.00e+00	1693.00
IUUC-Aca-004402	Anolis carolinensis	80.89	0.00e+00	1518.00
IUUC-Ame-011581	Astyanax mexicanus	67.85	0.00e+00	1224.00
IUUC-Bta-012359	Bos taurus	96.55	0.00e+00	1898.00
IUUC-Cel-018528	Caenorhabditis elegans	34.72	3.00e-55	211.00
IUUC-Cja-018797	Callithrix jacchus	98.85	0.00e+00	1961.00
IUUC-Cfa-020264	Canis familiaris	96.86	0.00e+00	1912.00
IUUC-Cpo-022057	Cavia porcellus	96.13	0.00e+00	1905.00
IUUC-Csa-023093	Chlorocebus sabaeus	99.16	0.00e+00	1956.00
IUUC-Cho-024486	Choloepus hoffmanni	83.11	6.00e-180	624.00
IUUC-Cin-025179	Ciona intestinalis	43.89	1.00e-115	410.00
IUUC-Dre-028233	Danio rerio	67.25	0.00e+00	1259.00
IUUC-Dno-029496	Dasypus novemcinctus	95.82	0.00e+00	1894.00
IUUC-Dor-030919	Dipodomys ordii	90.38	0.00e+00	1763.00
IUUC-Dme-032159	Drosophila melanogaster	45.68	1.00e-124	440.00
IUUC-Ete-032734	Echinops telfairi	90.06	0.00e+00	1771.00
IUUC-Eca-033350	Equus caballus	96.76	0.00e+00	1912.00
IUUC-Eeu-034566	Erinaceus europaeus	98.39	1.00e-114	407.00
IUUC-Fca-035632	Felis catus	95.74	0.00e+00	1331.00
IUUC-Fal-037313	Ficedula albicollis	82.24	0.00e+00	1575.00
IUUC-Gmo-039239	Gadus morhua	67.15	0.00e+00	1205.00
IUUC-Gga-040668	Gallus gallus	87.57	0.00e+00	1693.00
IUUC-Gac-042630	Gasterosteus aculeatus	67.43	0.00e+00	1196.00
IUUC-Ggo-044462	Gorilla gorilla	99.90	0.00e+00	1975.00
IUUC-Itr-048894	Ictidomys tridecemlineatus	93.55	0.00e+00	835.00
IUUC-Lch-050303	Latimeria chalumnae	70.64	0.00e+00	1312.00
IUUC-Loc-052190	Lepisosteus oculatus	69.71	0.00e+00	1274.00
IUUC-Laf-054480	Loxodonta africana	92.48	0.00e+00	761.00
IUUC-Mcc-055849	Macaca mulatta	99.48	0.00e+00	1968.00
IUUC-Meu-056755	Macropus eugenii	82.77	0.00e+00	880.00
IUUC-Mga-059561	Meleagris gallopavo	87.08	0.00e+00	1683.00
IUUC-Mmr-060942	Microcebus murinus	97.49	0.00e+00	1912.00
IUUC-Mdo-062618	Monodelphis domestica	92.99	0.00e+00	1855.00
IUUC-Mmu-063843	Mus musculus	94.77	0.00e+00	1827.00
IUUC-Mpu-066919	Mustela putorius furo	96.76	0.00e+00	1913.00
IUUC-Mlu-066983	Myotis lucifugus	90.27	0.00e+00	1766.00
IUUC-Nle-069893	Nomascus leucogenys	99.79	0.00e+00	1974.00
IUUC-Opr-071181	Ochotona princeps	87.49	0.00e+00	1592.00
IUUC-Ont-071697	Oreochromis niloticus	66.60	0.00e+00	1188.00
IUUC-Oan-073658	Ornithorhynchus anatinus	90.59	0.00e+00	1783.00
IUUC-Ocu-074954	Oryctolagus cuniculus	96.65	0.00e+00	1910.00
IUUC-Ola-086523	Oryzias latipes	66.12	0.00e+00	1181.00
IUUC-Oga-089003	Otolemur garnettii	97.38	0.00e+00	1924.00
IUUC-Oar-090376	Ovis aries	96.56	0.00e+00	1911.00
IUUC-Ptr-090520	Pan troglodytes	98.12	0.00e+00	1927.00
IUUC-Pan-092281	Papio anubis	99.16	0.00e+00	1956.00
IUUC-Psi-093047	Pelodiscus sinensis	88.63	0.00e+00	1618.00
IUUC-Pma-094575	Petromyzon marinus	55.50	9.00e-67	246.00
IUUC-Pfo-096358	Poecilia formosa	66.33	0.00e+00	1137.00
IUUC-Pab-097740	Pongo abelii	99.16	0.00e+00	1963.00
IUUC-Pca-100461	Procavia capensis	86.26	0.00e+00	1534.00
IUUC-Pva-102134	Pteropus vampyrus	85.77	0.00e+00	1675.00
IUUC-Rno-105807	Rattus norvegicus	92.78	0.00e+00	1781.00
IUUC-Sha-107236	Sarcophilus harrisii	93.50	0.00e+00	1794.00
IUUC-Sar-113366	Sorex araneus	98.44	0.00e+00	938.00
IUUC-Tgu-117201	Taeniopygia guttata	84.25	0.00e+00	1617.00
IUUC-Tru-117953	Takifugu rubripes	67.95	0.00e+00	1186.00
IUUC-Tsy-119610	Tarsius syrichta	95.08	0.00e+00	1877.00
IUUC-Tni-120743	Tetraodon nigroviridis	40.85	3.00e-166	579.00
IUUC-Tbe-128155	Tupaia belangeri	78.40	0.00e+00	754.00
IUUC-Ttr-128942	Tursiops truncatus	91.63	0.00e+00	1795.00
IUUC-Vpa-130281	Vicugna pacos	85.98	0.00e+00	1657.00
IUUC-Xtr-132627	Xenopus tropicalis	76.32	0.00e+00	1404.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence