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-046479

UUCD1 version

UUC-HoS-00073

Ensembl Protein ID

ENSP00000424827.1

UniProt Accession

P46934; A1KY35; A6ND72; A7MD29; B4E2R7; B7ZM59; B7ZM60; B9EGN5; D6RF89; NEDD4_HUMAN

Genbank Protein ID

BAA07655.1; BAG65229.1; AAT52215.1; EAW77495.1; AAI36606.1; AAI44285.1; AAI44286.1; AAI52453.1; AAI52563.1

Protein Name

E3 ubiquitin-protein ligase NEDD4; Cell proliferation-inducing gene 53 protein; HECT-type E3 ubiquitin transferase NEDD4; Neural precursor cell expressed developmentally down-regulated protein 4

Genbank Nucleotide ID

D42055; AK304394; AY550969; AL832063; BC136605; BC144284; BC144285; BC152452; BC152562

Gene Name

NEDD4; KIAA0093; NEDD4-1; PIG53

Ensembl Information

Ensembl Gene ID	Ensembl Transcript ID	Ensembl Protein ID
ENSG00000069869.15	ENST00000508871.5	ENSP00000422455.1
ENSG00000069869.15	ENST00000503468.5	ENSP00000426051.1
ENSG00000069869.15	ENST00000338963.6	ENSP00000345530.2
ENSG00000069869.15	ENST00000508342.5	ENSP00000424827.1
ENSG00000069869.15	ENST00000435532.7	ENSP00000410613.3
ENSG00000069869.15	ENST00000506154.1	ENSP00000422705.1
ENSG00000069869.15	ENST00000502612.5	ENSP00000424471.1
ENSG00000069869.15	ENST00000507063.1	ENSP00000421047.1

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
UTRdb	AREsite	circBase	circRNADb
CircNet	miRTarBase	microRNA	TRANSFAC
miRWalk	RepTar	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	UniProt	BioGRID	mUbiSiDa
DNA Methylation
MethyCancer	TCGA	ICGC	COSMIC
Protein Expression/Proteomics
THPA	HPM	GPMDB

Status

Reviewed

Details

Family	Domain	References (PMIDs)
E3 activity/HECT	HECT	19808888; 20086093; 19953087; 15013426; 19193720; 18286479; 12907674; 19125695; 17592138; 17137798; 15060076; 19864419; 20855896; 17996703; 21338354; 21320486; 21212261; 20159449; 18772139; 19787053; 19797085; 19054764; 11598133; 15703212; 15082780; 20559325; 15581898; 26006083

Classification

Family	E-value	Score	Start	End
E3 activity/HECT	7.80e-135	451.3	987	1316

Active Site

Position(s)	Description	Evidence
1286	Glycyl thioester intermediate	{ECO:0000255\|PROSITE-ProRule:PRU00104}

Domain Profile

E3 activity/HECT

   S: 4    dlkkrlevefvgEegldlgGvtreflallskelqnpdlglflysendketlqpnpdsglknpehlklFeflGrllgkalqdgrlldlpls 93
            lk+rl++ef gE+gld+gGv+re+++l+ske++np++glf+ys++d++tlq+np+sgl+n++hl++F+f+Gr+ g+a+++g+lld ++ 
   Q: 987  FLKARLWIEFDGEKGLDYGGVAREWFFLISKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFKFIGRVAGMAVYHGKLLDGFFI 1076
           5899************************************************************************************** PP
   S: 94   ksfyklllgkklsledleevdpelykslkeikenaesdieelgldltfsvseeilgetkeeeLkpgGenipVtneNkeeYvklvveyrlk 183
           ++fyk++l+k+++l+d+e+vd+e+y+sl +i+en   d +e  ldl+f ++ee++g+t+++eLk gG++i Vtn+Nk+eY+ lv+++r+ 
   Q: 1077 RPFYKMMLHKPITLHDMESVDSEYYNSLRWILEN---DPTE--LDLRFIIDEELFGQTHQHELKNGGSEIVVTNKNKKEYIYLVIQWRFV 1161
           ********************************99...6666..7********************************************** PP
   S: 184  egikeqveafreGfneviplellslFteeelellicGeeeidvedlkketkykggytedspaiqwFwevleefsseerkafLqFvTgssr 273
           ++i++q++af+eGf e+ip++l+++F+e+elell+cG  ++dv+d++++tkyk+gy++++++iqwFw+++ +++se+r ++LqFvTg+sr
   Q: 1162 NRIQKQMAAFKEGFFELIPQDLIKIFDENELELLMCGLGDVDVNDWREHTKYKNGYSANHQVIQWFWKAVLMMDSEKRIRLLQFVTGTSR 1251
           ****************************************************************************************** PP
   S: 274  lPlgGfaelk....prlfvirkdasddrlPssnTCfnyLkLPeYsskeilkekLlyAieetkgFe 334
           +P++Gfael     p++f++++++++++lP+++TCfn+L+LP+Y+s e+l +kL++Aie+t+gF+
   Q: 1252 VPMNGFAELYgsngPQSFTVEQWGTPEKLPRAHTCFNRLDLPPYESFEELWDKLQMAIENTQGFD 1316
           ****************************************************************8 PP

Organism

Homo sapiens

Functional Description
(View)

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. Specifically ubiquitinates 'Lys-63' in target proteins (PubMed:23644597). Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Promotes ubiquitination of RAPGEF2. According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD. Involved in the budding of many viruses. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2. Involved in the ubiquitination of ebola virus VP40 protein and this ubiquitination plays a role in facilitating viral budding. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046).

Protein Sequence
(Fasta)

MAQSLRLHFA ARRSNTYPLS ETSGDDLDSH VHMCFKRPTR ISTSNVVQMK LTPRQTALAP 60
LIKENVQSQE RSSVPSSENV NKKSSCLQIS LQPTRYSGYL QSSNVLADSD DASFTCILKD 120

It may take some time, please wait.

Nucleotide Sequence
(Fasta)

GGCCTTTTCC CGCCGCGCTG CCGGGTGCCG CTAGTGCCCG CTCGCCGCGG GAGGCGCTGC 60
TGTCGCTGAG GGAGCGCCTC CTCCTCTTCC TCCAACTCTT CCCCGCCTCC TCCCGCTTCT 120

It may take some time, please wait.

Sequence Source

Ensembl

Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0025--Alternative splicing
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0945--Host-virus interaction
KW-0472--Membrane
KW-0524--Neurogenesis
KW-0597--Phosphoprotein
KW-0621--Polymorphism
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

PS50237--HECT
PS01159--WW_DOMAIN_1
PS50020--WW_DOMAIN_2

Pfam

PF00632--HECT
PF00397--WW

SMART

SM00119--HECTc
SM00456--WW

Gene Ontology

GO:0016327--C:apicolateral plasma membrane
GO:0005938--C:cell cortex
GO:0000785--C:chromatin
GO:0005737--C:cytoplasm
GO:0005829--C:cytosol
GO:0043197--C:dendritic spine
GO:0070062--C:extracellular exosome
GO:0005794--C:Golgi apparatus
GO:0048471--C:perinuclear region of cytoplasm
GO:0005886--C:plasma membrane
GO:0000151--C:ubiquitin ligase complex
GO:0031698--F:beta-2 adrenergic receptor binding
GO:0050815--F:phosphoserine binding
GO:0050816--F:phosphothreonine binding
GO:0070064--F:proline-rich region binding
GO:0019904--F:protein domain specific binding
GO:0070063--F:RNA polymerase binding
GO:0019871--F:sodium channel inhibitor activity
GO:0043130--F:ubiquitin binding
GO:0061630--F:ubiquitin protein ligase activity
GO:0002250--P:adaptive immune response
GO:0048514--P:blood vessel morphogenesis
GO:0034644--P:cellular response to UV
GO:0044111--P:development involved in symbiotic interaction
GO:0003197--P:endocardial cushion development
GO:0042921--P:glucocorticoid receptor signaling pathway
GO:0007041--P:lysosomal transport
GO:2000650--P:negative regulation of sodium ion transmembrane transporter activity
GO:0010766--P:negative regulation of sodium ion transport
GO:0010768--P:negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage
GO:0030948--P:negative regulation of vascular endothelial growth factor receptor signaling pathway
GO:0007528--P:neuromuscular junction development
GO:0031175--P:neuron projection development
GO:0003151--P:outflow tract morphogenesis
GO:0046824--P:positive regulation of nucleocytoplasmic transport
GO:0014068--P:positive regulation of phosphatidylinositol 3-kinase signaling
GO:0045732--P:positive regulation of protein catabolic process
GO:0050847--P:progesterone receptor signaling pathway
GO:0070534--P:protein K63-linked ubiquitination
GO:0006513--P:protein monoubiquitination
GO:0006622--P:protein targeting to lysosome
GO:0016567--P:protein ubiquitination
GO:0042787--P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0032801--P:receptor catabolic process
GO:0031623--P:receptor internalization
GO:0048814--P:regulation of dendrite morphogenesis
GO:0034765--P:regulation of ion transmembrane transport
GO:0016241--P:regulation of macroautophagy
GO:0042391--P:regulation of membrane potential
GO:1901016--P:regulation of potassium ion transmembrane transporter activity
GO:0050807--P:regulation of synapse organization
GO:0051592--P:response to calcium ion
GO:0042110--P:T cell activation
GO:0019089--P:transmission of virus
GO:0043162--P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

KEGG

hsa:4734

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-001201	Ailuropoda melanoleuca	91.31	0.00e+00	2370.00
IUUC-Apl-003886	Anas platyrhynchos	75.61	0.00e+00	1273.00
IUUC-Ame-011138	Astyanax mexicanus	83.75	0.00e+00	853.00
IUUC-Bta-012453	Bos taurus	89.55	0.00e+00	2308.00
IUUC-Cja-019034	Callithrix jacchus	96.52	0.00e+00	1445.00
IUUC-Cfa-020258	Canis familiaris	91.76	0.00e+00	2310.00
IUUC-Cpo-021648	Cavia porcellus	91.03	0.00e+00	1481.00
IUUC-Csa-023334	Chlorocebus sabaeus	98.88	0.00e+00	1529.00
IUUC-Cho-024672	Choloepus hoffmanni	83.53	0.00e+00	721.00
IUUC-Cin-025157	Ciona intestinalis	55.58	0.00e+00	877.00
IUUC-Dno-029159	Dasypus novemcinctus	90.61	0.00e+00	1339.00
IUUC-Dor-030729	Dipodomys ordii	80.00	0.00e+00	1045.00
IUUC-Dme-032166	Drosophila melanogaster	67.99	0.00e+00	714.00
IUUC-Ete-032409	Echinops telfairi	86.77	0.00e+00	1201.00
IUUC-Eca-033441	Equus caballus	95.77	0.00e+00	1459.00
IUUC-Eeu-034546	Erinaceus europaeus	75.19	0.00e+00	1193.00
IUUC-Fca-036384	Felis catus	91.62	0.00e+00	2357.00
IUUC-Fal-037547	Ficedula albicollis	80.89	0.00e+00	1306.00
IUUC-Gmo-039679	Gadus morhua	67.04	0.00e+00	1090.00
IUUC-Gga-040524	Gallus gallus	82.01	0.00e+00	1313.00
IUUC-Itr-048383	Ictidomys tridecemlineatus	83.67	0.00e+00	1224.00
IUUC-Lch-050445	Latimeria chalumnae	60.21	0.00e+00	1470.00
IUUC-Loc-052645	Lepisosteus oculatus	73.04	0.00e+00	1194.00
IUUC-Laf-053638	Loxodonta africana	84.06	0.00e+00	1368.00
IUUC-Mcc-055585	Macaca mulatta	97.88	0.00e+00	2458.00
IUUC-Meu-056897	Macropus eugenii	95.47	3.00e-171	596.00
IUUC-Mga-059362	Meleagris gallopavo	75.20	0.00e+00	1282.00
IUUC-Mvi-060395	Microbotryum violaceum	53.31	6.00e-150	525.00
IUUC-Mmr-061061	Microcebus murinus	93.33	0.00e+00	2394.00
IUUC-Mmu-063318	Mus musculus	80.20	0.00e+00	1282.00
IUUC-Mpu-066567	Mustela putorius furo	95.17	0.00e+00	1548.00
IUUC-Mlu-068148	Myotis lucifugus	88.52	0.00e+00	2276.00
IUUC-Nle-069225	Nomascus leucogenys	98.10	0.00e+00	2487.00
IUUC-Oan-073019	Ornithorhynchus anatinus	85.84	0.00e+00	1395.00
IUUC-Ocu-074409	Oryctolagus cuniculus	89.02	0.00e+00	2266.00
IUUC-Oga-088241	Otolemur garnettii	87.90	0.00e+00	2164.00
IUUC-Oar-089797	Ovis aries	95.52	0.00e+00	1525.00
IUUC-Ptr-091629	Pan troglodytes	97.86	0.00e+00	1421.00
IUUC-Psi-093618	Pelodiscus sinensis	68.13	0.00e+00	1630.00
IUUC-Pab-098394	Pongo abelii	99.13	0.00e+00	1548.00
IUUC-Pca-100568	Procavia capensis	78.44	0.00e+00	1152.00
IUUC-Rno-106095	Rattus norvegicus	80.20	0.00e+00	1287.00
IUUC-Sha-107370	Sarcophilus harrisii	67.77	0.00e+00	1770.00
IUUC-Sja-107786	Schizosaccharomyces japonicus	50.63	7.00e-157	548.00
IUUC-Tgu-117474	Taeniopygia guttata	81.27	0.00e+00	1315.00
IUUC-Tru-117675	Takifugu rubripes	64.49	0.00e+00	1068.00
IUUC-Tbe-127408	Tupaia belangeri	87.13	0.00e+00	1176.00
IUUC-Ttr-128437	Tursiops truncatus	85.53	0.00e+00	1201.00
IUUC-Vpa-130503	Vicugna pacos	89.15	0.00e+00	1312.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence