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	microRNA	TRANSFAC	miRecords
RepTar	miRNAMap	RAID2
Protein-protein Interaction
IID	iRefIndex	PINA	HINT
Mentha
Protein 3D Structure
PDB	MMDB
Post-translational Modifications (PTMs)
CPLM	dbPAF	PhosphositePlus	dbPTM
Phospho.ELM	UniProt	PHOSIDA
Protein Expression/Proteomics
GPMDB

Status

Reviewed

Details

Family	Domain	References (PMIDs)
E3 activity/HECT	HECT	20170897; 16931910

Classification

Family	E-value	Score	Start	End
E3 activity/HECT	5.40e-136	454.5	531	863

Active Site

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

Domain Profile

E3 activity/HECT

   S: 2    ksdlkkrlevefvgEegldlgGvtreflallskelqnpdlglflysendketlqpnpdsglknpehlklFeflGrllgkalqdgrlldl 90
           ++dl++rl+v f gEegld+gGv+re+++lls+e+ np+++lf+y  +d+++lq+np+s++ np+hlk+F+f+Gr++++al++g+++d+
   Q: 531  PQDLRRRLWVIFPGEEGLDYGGVAREWFFLLSHEVLNPMYCLFEYAGKDNYCLQINPASYI-NPDHLKYFRFIGRFIAMALFHGKFIDT 618
           689*********************************************************9.89************************* PP
   S: 91   plsksfyklllgkklsledleevdpelykslkeikenaesdieelgldltfsvseeilgetkeeeLkpgGenipVtneNkeeYvklvve 179
            +s +fyk++l+k++ l+dle++dpe+y+sl ++ken   +iee+gl++ fsv++eilge+k+++Lkp+G ni Vt+eNkeeY++ v+e
   Q: 619  GFSLPFYKRILNKPVGLKDLESIDPEFYNSLIWVKEN---NIEECGLEMYFSVDKEILGEIKSHDLKPNGGNILVTEENKEEYIRMVAE 704
           ***********************************99...9************************************************ PP
   S: 180  yrlkegikeqveafreGfneviplellslFteeelellicGeeeidvedlkketkykggytedspaiqwFwevleefsseerkafLqFv 268
           +rl +g++eq++af eGfne++p++ l++F+++ele+l+cG++eid++d+++++ y++ yt++s++i wFw++++e+++e+r ++LqFv
   Q: 705  WRLSRGVEEQTQAFFEGFNEILPQQYLQYFDAKELEVLLCGMQEIDLNDWQRHAIYRH-YTRTSKQIMWFWQFVKEIDNEKRMRLLQFV 792
           ********************************************************99.****************************** PP
   S: 269  TgssrlPlgGfaelk....prlfvirkdasddrlPssnTCfnyLkLPeYsskeilkekLlyAieetkgFel 335
           Tg++rlP+gGfa+l+    p++f+i+k +++++lP+s+TCfn+L+LP+Y+s+e+lkekLl+Aieet+gF++
   Q: 793  TGTCRLPVGGFADLMgsngPQKFCIEKVGKENWLPRSHTCFNRLDLPPYKSYEQLKEKLLFAIEETEGFGQ 863
           *********************************************************************96 PP

Organism

Mus musculus

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 (By similarity). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (By similarity). Regulates the transcriptional activity of several transcription factors involved in immune response. Critical regulator of T-helper (TH2) cytokine development through its ability to induce JUNB ubiquitination and degradation. Ubiquitinates SNX9 (By similarity). Ubiquitinates CXCR4 and HGS/HRS and regulates sorting of CXCR4 to the degradative pathway (By similarity). 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 (By similarity). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (PubMed:25632008). Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP (By similarity). 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 (By similarity).

Protein Sequence
(Fasta)

MSDSGPQLDS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ SKKTEKCNNT 60
NSPKWKQPLT VIVTPTSKLC FRVWSHQTLK SDVLLGTAGL DIYETLKSNN MKLEEVVMTL 120

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Nucleotide Sequence
(Fasta)

AGTCGCTGTA GTCGGGGCTC GGGACCGGCT GCCATCTTAG CGGAGGGACT GAGGAGTCGT 60
CGCCGCCCCG AGTCCCGGTA AACACGCGCA GGCAGACTGG GGTCATTTCT GTGGCTTGGA 120

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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-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
IPR024928--E3_ub_ligase_SMURF1
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:0005737--C:cytoplasm
GO:0031410--C:cytoplasmic vesicle
GO:0005829--C:cytosol
GO:0070062--C:extracellular exosome
GO:0016020--C:membrane
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0005886--C:plasma membrane
GO:0000151--C:ubiquitin ligase complex
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:0004842--F:ubiquitin-protein transferase activity
GO:0006915--P:apoptotic process
GO:0051607--P:defense response to virus
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:0007219--P:Notch 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:0000209--P:protein polyubiquitination
GO:0016567--P:protein ubiquitination
GO:0042787--P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0090085--P:regulation of protein deubiquitination
GO:0006511--P:ubiquitin-dependent protein catabolic process

KEGG

mmu:16396

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-002302	Ailuropoda melanoleuca	95.18	0.00e+00	1575.00
IUUC-Apl-003752	Anas platyrhynchos	84.87	0.00e+00	1456.00
IUUC-Aca-005338	Anolis carolinensis	82.21	0.00e+00	1432.00
IUUC-Ago-007742	Ashbya gossypii	48.71	4.00e-162	565.00
IUUC-Ame-010601	Astyanax mexicanus	87.90	0.00e+00	1120.00
IUUC-Bta-012782	Bos taurus	95.14	0.00e+00	1568.00
IUUC-Cja-018899	Callithrix jacchus	91.69	0.00e+00	1554.00
IUUC-Cfa-020648	Canis familiaris	94.02	0.00e+00	1540.00
IUUC-Cpo-022073	Cavia porcellus	95.37	0.00e+00	1613.00
IUUC-Csa-023252	Chlorocebus sabaeus	94.56	0.00e+00	1601.00
IUUC-Cho-024695	Choloepus hoffmanni	87.96	0.00e+00	1566.00
IUUC-Dre-028809	Danio rerio	88.30	0.00e+00	1116.00
IUUC-Dno-029884	Dasypus novemcinctus	94.33	0.00e+00	1610.00
IUUC-Eca-033793	Equus caballus	95.49	0.00e+00	1595.00
IUUC-Eeu-034716	Erinaceus europaeus	93.01	0.00e+00	888.00
IUUC-Fca-035605	Felis catus	95.29	0.00e+00	1604.00
IUUC-Fal-037126	Ficedula albicollis	95.91	0.00e+00	1207.00
IUUC-Gmo-038596	Gadus morhua	80.96	0.00e+00	1009.00
IUUC-Gga-040832	Gallus gallus	83.88	0.00e+00	1466.00
IUUC-Gac-041658	Gasterosteus aculeatus	87.16	0.00e+00	1127.00
IUUC-Ggo-044535	Gorilla gorilla	92.01	0.00e+00	1572.00
IUUC-Hsa-046564	Homo sapiens	90.94	0.00e+00	1591.00
IUUC-Itr-048918	Ictidomys tridecemlineatus	94.44	0.00e+00	1557.00
IUUC-Kpa-049273	Komagataella pastoris	49.05	5.00e-163	568.00
IUUC-Lch-050454	Latimeria chalumnae	92.47	0.00e+00	1168.00
IUUC-Loc-052647	Lepisosteus oculatus	74.15	0.00e+00	1348.00
IUUC-Laf-054383	Loxodonta africana	95.72	0.00e+00	1615.00
IUUC-Mcc-055532	Macaca mulatta	94.56	0.00e+00	1603.00
IUUC-Mga-059661	Meleagris gallopavo	83.77	0.00e+00	1454.00
IUUC-Mmr-061135	Microcebus murinus	95.37	0.00e+00	1644.00
IUUC-Mdo-062505	Monodelphis domestica	87.25	0.00e+00	1504.00
IUUC-Mpu-066203	Mustela putorius furo	95.29	0.00e+00	1576.00
IUUC-Mlu-067837	Myotis lucifugus	95.14	0.00e+00	1593.00
IUUC-Nle-069244	Nomascus leucogenys	95.14	0.00e+00	1591.00
IUUC-Opr-070585	Ochotona princeps	89.28	0.00e+00	1549.00
IUUC-Ont-071798	Oreochromis niloticus	87.93	0.00e+00	1141.00
IUUC-Ocu-074298	Oryctolagus cuniculus	95.83	0.00e+00	1615.00
IUUC-Ola-086526	Oryzias latipes	70.47	0.00e+00	1305.00
IUUC-Oga-088167	Otolemur garnettii	88.45	0.00e+00	1471.00
IUUC-Oar-090316	Ovis aries	78.78	0.00e+00	1177.00
IUUC-Ptr-090819	Pan troglodytes	90.27	0.00e+00	1554.00
IUUC-Pan-092454	Papio anubis	94.56	0.00e+00	1603.00
IUUC-Psi-093319	Pelodiscus sinensis	83.18	0.00e+00	1417.00
IUUC-Pfo-096937	Poecilia formosa	89.21	0.00e+00	1131.00
IUUC-Pab-097580	Pongo abelii	84.20	0.00e+00	1432.00
IUUC-Pca-100923	Procavia capensis	77.66	0.00e+00	1324.00
IUUC-Pva-103209	Pteropus vampyrus	94.10	0.00e+00	1541.00
IUUC-Rno-104924	Rattus norvegicus	98.50	0.00e+00	1654.00
IUUC-Sha-107175	Sarcophilus harrisii	88.53	0.00e+00	1504.00
IUUC-Sja-107941	Schizosaccharomyces japonicus	45.67	2.00e-159	556.00
IUUC-Sar-113761	Sorex araneus	84.68	0.00e+00	1463.00
IUUC-Tgu-116632	Taeniopygia guttata	80.91	0.00e+00	1334.00
IUUC-Tru-118442	Takifugu rubripes	88.93	0.00e+00	1121.00
IUUC-Tsy-119198	Tarsius syrichta	89.00	0.00e+00	1485.00
IUUC-Tni-120168	Tetraodon nigroviridis	86.52	0.00e+00	1058.00
IUUC-Tbe-127756	Tupaia belangeri	76.13	0.00e+00	1266.00
IUUC-Ttr-128504	Tursiops truncatus	89.13	0.00e+00	1149.00
IUUC-Vpa-130103	Vicugna pacos	80.68	0.00e+00	1367.00
IUUC-Xtr-132885	Xenopus tropicalis	75.74	0.00e+00	1366.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence