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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-045968
UUCD1 version UUC-HoS-00316
Ensembl Protein ID ENSP00000383199.2
UniProt Accession Q96PU5; O43165; Q3LSM7; Q7Z5F1; Q7Z5F2; Q7Z5N3; Q8N5A7; Q8WUU9; Q9BW58; Q9H2W4; Q9NT88; NED4L_HUMAN
Genbank Protein ID AAG43524.1; AAM46208.1; AAP75706.1; AAM76728.1; AAM76729.1; AAM76730.1; BAB69424.1; ABA10330.1; EAW63065.1; AAH00621.2; AAH19345.1; AAH32597.1; BAA23711.1; CAB70754.1
Protein Name E3 ubiquitin-protein ligase NEDD4-like; HECT-type E3 ubiquitin transferase NED4L; NEDD4.2; Nedd4-2
Genbank Nucleotide ID AF210730; AF385931; AY312514; AY112983; AY112984; AY112985; AB071179; DQ181796; AC015988; BC000621; BC019345; BC032597; AB007899; AL137469
Gene Name NEDD4L; KIAA0439; NEDL3
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000049759.17 ENST00000356462.10 ENSP00000348847.5
ENSG00000049759.17 ENST00000400345.7 ENSP00000383199.2
ENSG00000049759.17 ENST00000589054.5 ENSP00000465669.1
ENSG00000049759.17 ENST00000617539.1 ENSP00000479462.1
ENSG00000049759.17 ENST00000382850.8 ENSP00000372301.3
ENSG00000049759.17 ENST00000256830.13 ENSP00000256830.8
ENSG00000049759.17 ENST00000357895.9 ENSP00000350569.4
ENSG00000049759.17 ENST00000586263.5 ENSP00000468546.1
ENSG00000049759.17 ENST00000635997.1 ENSP00000490696.1
ENSG00000049759.17 ENST00000587881.1 ENSP00000468332.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICTHPAHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
miRWalkRepTarSomamiRmiRcode
RAID2LncRNADisease
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Protein 3D Structure
PDBMMDB
Disease-associated Information
ClinVarGWASdbOMIM
Post-translational Modifications (PTMs)
CPLMdbPAFPhosSNPPhosphositePlus
dbPTMHPRDPhospho.ELMUniProt
PHOSIDABioGRIDmUbiSiDa
DNA Methylation
TCGAICGCCOSMIC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
E3 activity/HECT HECT 19953087; 18577513; 18792916; 19617352; 18805448; 19473961; 19364400; 15576372; 20843805; 20504882; 21212261; 19615332; 17609522; 17322297; 21463633
Classification
Family E-value Score Start End
E3 activity/HECT 1.10e-134 450.8 641 972
Active Site
Position(s) Description Evidence
942 Glycyl thioester intermediate N/A
Domain Profile

   E3 activity/HECT
   S: 2    ksdlkkrlevefvgEegldlgGvtreflallskelqnpdlglflysendketlqpnpdsglknpehlklFeflGrllgkalqdgrlldlpls 93
           ++ lk+rl++ef+ E+gld+gGv+re+++llske++np++glf+ys++d++tlq+np+sgl+n++hl++F+f+Gr+ g+a+++g+lld ++ 
   Q: 641  PDVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFTFIGRVAGLAVFHGKLLDGFFI 732
           57899*************************************************************************************** PP
   S: 94   ksfyklllgkklsledleevdpelykslkeikenaesdieelgldltfsvseeilgetkeeeLkpgGenipVtneNkeeYvklvveyrlkeg 185
           ++fyk++lgk+++l+d+e+vd+e+y+slk+i+en   d +e  ldl+f+++ee++g+t++++Lkp+G++i+VtneNk+eY++lv+++r+ ++
   Q: 733  RPFYKMMLGKQITLNDMESVDSEYYNSLKWILEN---DPTE--LDLMFCIDEENFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNR 819
           ********************************99...6666..7************************************************ PP
   S: 186  ikeqveafreGfneviplellslFteeelellicGeeeidvedlkketkykggytedspaiqwFwevleefsseerkafLqFvTgssrlPlg 277
           +++q++af eGf+e++p++l+++F+e+elell+cG  ++dv+d++++  yk+gy +++p+iqwFw+++  +++e+r ++LqFvTg+sr+P++
   Q: 820  VQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMN 911
           ******************************************************************************************** PP
   S: 278  Gfaelk....prlfvirkdasddrlPssnTCfnyLkLPeYsskeilkekLlyAieetkgFe 334
           Gfael     p+lf+i++++s+++lP+++TCfn+L+LP+Y++ e l+ekLl+A+e+++gFe
   Q: 912  GFAELYgsngPQLFTIEQWGSPEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 972
           ************************************************************8 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     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. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, KCNH2, EAAT1 or CLC5 (PubMed:26363003). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961).
 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. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, KCNH2, EAAT1 or CLC5 (PubMed:26363003). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961).
Protein Sequence
(Fasta)
MATGLGEPVY GLSEDEGESR ILRVKVVSGI DLAKKDIFGA SDPYVKLSLY VADENRELAL 60
VQTKTIKKTL NPKWNEEFYF RVNPSNHRLL FEVFDENRLT RDDFLGQVDV PLSHLPTEDP 120
It may take some time, please wait.

Protein Fasta Sequence


>IUUC-Hsa-045968|E3,HECT|Homo sapiens
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Nucleotide Sequence
(Fasta)
GCGCCGCCGC CGCGCGCAGT GAGAGGCGCC GGGGCTGCCG CCCGGTGCTC GGCGCGCTCT 60
CGGGAGCCGC CCGCCCGCTG GTCCCGCAGC CTTCCGGGAG GAAGCGGTGC CGGCAGCGTC 120
It may take some time, please wait.

Nucleotide Fasta Sequence


>IUUC-Hsa-045968|E3,HECT|Homo sapiens
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0025--Alternative splicing
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0221--Differentiation
KW-0903--Direct protein sequencing
KW-0967--Endosome
KW-0333--Golgi apparatus
KW-0945--Host-virus interaction
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

PS50004--C2
PS50237--HECT
PS01159--WW_DOMAIN_1
PS50020--WW_DOMAIN_2
Pfam

PF00168--C2
PF00632--HECT
PF00397--WW
PRINTS

PR00360--C2DOMAIN
SMART

SM00239--C2
SM00119--HECTc
SM00456--WW
Gene Ontology

GO:0005829--C:cytosol
GO:0070062--C:extracellular exosome
GO:0005794--C:Golgi apparatus
GO:0005622--C:intracellular
GO:0005771--C:multivesicular body
GO:0005654--C:nucleoplasm
GO:0044325--F:ion channel binding
GO:0019870--F:potassium channel inhibitor activity
GO:0015459--F:potassium channel regulator activity
GO:0019871--F:sodium channel inhibitor activity
GO:0017080--F:sodium channel regulator activity
GO:0004842--F:ubiquitin-protein transferase activity
GO:0006883--P:cellular sodium ion homeostasis
GO:0007588--P:excretion
GO:0034220--P:ion transmembrane transport
GO:1901380--P:negative regulation of potassium ion transmembrane transport
GO:1901017--P:negative regulation of potassium ion transmembrane transporter activity
GO:2000009--P:negative regulation of protein localization to cell surface
GO:1902306--P:negative regulation of sodium ion transmembrane transport
GO:2000650--P:negative regulation of sodium ion transmembrane transporter activity
GO:0000122--P:negative regulation of transcription from RNA polymerase II promoter
GO:2001288--P:positive regulation of caveolin-mediated endocytosis
GO:1903861--P:positive regulation of dendrite extension
GO:0045807--P:positive regulation of endocytosis
GO:0045732--P:positive regulation of protein catabolic process
GO:0043161--P:proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0070936--P:protein K48-linked ubiquitination
GO:0006513--P:protein monoubiquitination
GO:0000209--P:protein polyubiquitination
GO:0016567--P:protein ubiquitination
GO:0042787--P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0034765--P:regulation of ion transmembrane transport
GO:0003254--P:regulation of membrane depolarization
GO:0042391--P:regulation of membrane potential
GO:0060306--P:regulation of membrane repolarization
GO:1901016--P:regulation of potassium ion transmembrane transporter activity
GO:0042176--P:regulation of protein catabolic process
GO:0010038--P:response to metal ion
GO:0006814--P:sodium ion transport
GO:0086005--P:ventricular cardiac muscle cell action potential
GO:0019058--P:viral life cycle
GO:0030104--P:water homeostasis
KEGG hsa:23327
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-001314 Ailuropoda melanoleuca 95.86 0.00e+00 1701.00
IUUC-Apl-003893 Anas platyrhynchos 94.37 0.00e+00 1712.00
IUUC-Aca-004744 Anolis carolinensis 90.88 0.00e+00 1668.00
IUUC-Acl-008273 Aspergillus clavatus 49.26 7.00e-164 571.00
IUUC-Afl-008713 Aspergillus flavus 49.01 2.00e-161 562.00
IUUC-Afu-009103 Aspergillus fumigatus 49.02 1.00e-163 570.00
IUUC-Ani-009259 Aspergillus nidulans 48.53 4.00e-162 565.00
IUUC-Ang-009738 Aspergillus niger 49.33 3.00e-162 565.00
IUUC-Aor-010053 Aspergillus oryzae 58.05 2.00e-101 362.00
IUUC-Ate-010529 Aspergillus terreus 49.42 1.00e-164 573.00
IUUC-Ame-010810 Astyanax mexicanus 71.77 0.00e+00 1251.00
IUUC-Bgr-012148 Blumeria graminis 47.91 3.00e-154 538.00
IUUC-Bta-012679 Bos taurus 97.95 0.00e+00 1605.00
IUUC-Bci-013785 Botrytis cinerea 47.99 4.00e-156 545.00
IUUC-Cel-018564 Caenorhabditis elegans 52.84 0.00e+00 634.00
IUUC-Cja-018732 Callithrix jacchus 99.39 0.00e+00 1858.00
IUUC-Cfa-021226 Canis familiaris 97.71 0.00e+00 1800.00
IUUC-Cpo-021671 Cavia porcellus 96.46 0.00e+00 1758.00
IUUC-Csa-023344 Chlorocebus sabaeus 97.89 0.00e+00 1844.00
IUUC-Cho-024832 Choloepus hoffmanni 100.00 0.00e+00 743.00
IUUC-Csv-026098 Ciona savignyi 59.04 0.00e+00 654.00
IUUC-Cgl-026642 Colletotrichum gloeosporioides 48.34 3.00e-155 542.00
IUUC-Cne-026849 Cryptococcus neoformans 47.53 5.00e-159 555.00
IUUC-Dre-027770 Danio rerio 78.52 0.00e+00 1442.00
IUUC-Dno-029466 Dasypus novemcinctus 98.26 0.00e+00 1846.00
IUUC-Dor-030138 Dipodomys ordii 92.51 0.00e+00 1643.00
IUUC-Dse-031241 Dothistroma septosporum 47.70 4.00e-160 558.00
IUUC-Ete-033145 Echinops telfairi 89.17 0.00e+00 1290.00
IUUC-Eca-033445 Equus caballus 98.40 0.00e+00 1600.00
IUUC-Eeu-035247 Erinaceus europaeus 89.11 0.00e+00 1499.00
IUUC-Fca-035489 Felis catus 94.91 0.00e+00 1541.00
IUUC-Fal-037604 Ficedula albicollis 91.48 0.00e+00 1721.00
IUUC-Fox-037774 Fusarium oxysporum 48.76 8.00e-159 554.00
IUUC-Fso-038393 Fusarium solani 47.41 6.00e-154 538.00
IUUC-Gmo-039674 Gadus morhua 76.88 0.00e+00 1399.00
IUUC-Ggr-040107 Gaeumannomyces graminis 47.75 5.00e-156 545.00
IUUC-Gga-040703 Gallus gallus 93.54 0.00e+00 1768.00
IUUC-Gac-042020 Gasterosteus aculeatus 80.20 0.00e+00 1441.00
IUUC-Ggo-045332 Gorilla gorilla 97.65 0.00e+00 1753.00
IUUC-Lch-050443 Latimeria chalumnae 86.70 0.00e+00 1444.00
IUUC-Loc-052662 Lepisosteus oculatus 80.42 0.00e+00 1459.00
IUUC-Laf-053850 Loxodonta africana 96.88 0.00e+00 1796.00
IUUC-Mcc-055821 Macaca mulatta 99.58 0.00e+00 1819.00
IUUC-Meu-056712 Macropus eugenii 82.28 0.00e+00 785.00
IUUC-Mor-057097 Magnaporthe oryzae 47.75 1.00e-156 546.00
IUUC-Mpo-057442 Magnaporthe poae 52.16 2.00e-145 510.00
IUUC-Mla-058996 Melampsora laricipopulina 53.94 7.00e-150 525.00
IUUC-Mmr-060798 Microcebus murinus 94.59 0.00e+00 1685.00
IUUC-Mdo-062173 Monodelphis domestica 95.67 0.00e+00 1841.00
IUUC-Mmu-064136 Mus musculus 97.34 0.00e+00 1805.00
IUUC-Mpu-066765 Mustela putorius furo 98.33 0.00e+00 1784.00
IUUC-Mlu-067565 Myotis lucifugus 95.45 0.00e+00 1576.00
IUUC-Nfi-068427 Neosartorya fischeri 49.02 4.00e-164 572.00
IUUC-Ncr-068918 Neurospora crassa 47.40 2.00e-157 550.00
IUUC-Nle-069070 Nomascus leucogenys 96.00 0.00e+00 1759.00
IUUC-Opr-071044 Ochotona princeps 96.12 0.00e+00 1198.00
IUUC-Ont-072044 Oreochromis niloticus 78.35 0.00e+00 1475.00
IUUC-Oan-073032 Ornithorhynchus anatinus 92.99 0.00e+00 1445.00
IUUC-Ocu-074160 Oryctolagus cuniculus 95.21 0.00e+00 1736.00
IUUC-Ola-087467 Oryzias latipes 79.96 0.00e+00 1462.00
IUUC-Oga-088460 Otolemur garnettii 93.39 0.00e+00 1575.00
IUUC-Oar-090198 Ovis aries 97.71 0.00e+00 1766.00
IUUC-Ptr-090939 Pan troglodytes 100.00 0.00e+00 1856.00
IUUC-Pan-092284 Papio anubis 99.69 0.00e+00 1855.00
IUUC-Psi-093645 Pelodiscus sinensis 94.26 0.00e+00 1765.00
IUUC-Pma-094364 Petromyzon marinus 82.67 0.00e+00 863.00
IUUC-Pno-095118 Phaeosphaeria nodorum 48.32 7.00e-165 574.00
IUUC-Pfo-097145 Poecilia formosa 62.19 0.00e+00 1129.00
IUUC-Pab-098088 Pongo abelii 99.59 0.00e+00 1828.00
IUUC-Pca-100714 Procavia capensis 76.07 0.00e+00 1321.00
IUUC-Pva-102354 Pteropus vampyrus 95.93 0.00e+00 1695.00
IUUC-Pgr-103620 Puccinia graminis 53.53 3.00e-148 519.00
IUUC-Ptt-103806 Puccinia triticina 53.38 6.00e-123 435.00
IUUC-Pte-104016 Pyrenophora teres 49.00 2.00e-162 566.00
IUUC-Pyt-104550 Pyrenophora triticirepentis 49.00 2.00e-162 566.00
IUUC-Rno-105318 Rattus norvegicus 96.57 0.00e+00 1758.00
IUUC-Sce-106289 Saccharomyces cerevisiae 49.25 5.00e-164 571.00
IUUC-Sha-107482 Sarcophilus harrisii 96.82 0.00e+00 1632.00
IUUC-Ssl-108514 Sclerotinia sclerotiorum 48.49 1.00e-157 550.00
IUUC-Ssc-115950 Sus scrofa 70.23 0.00e+00 1180.00
IUUC-Tgu-117130 Taeniopygia guttata 94.47 0.00e+00 1749.00
IUUC-Tru-118610 Takifugu rubripes 80.33 0.00e+00 1485.00
IUUC-Tsy-119492 Tarsius syrichta 92.36 0.00e+00 1653.00
IUUC-Tni-120113 Tetraodon nigroviridis 74.90 0.00e+00 1360.00
IUUC-Tre-122203 Trichoderma reesei 46.86 2.00e-152 532.00
IUUC-Tvi-122595 Trichoderma virens 47.27 2.00e-154 540.00
IUUC-Tbe-127441 Tupaia belangeri 90.60 0.00e+00 795.00
IUUC-Ttr-128235 Tursiops truncatus 87.79 0.00e+00 1515.00
IUUC-Vda-129753 Verticillium dahliae 47.85 5.00e-157 548.00
IUUC-Xtr-132859 Xenopus tropicalis 89.74 0.00e+00 1666.00
IUUC-Xma-133797 Xiphophorus maculatus 81.21 0.00e+00 1479.00
IUUC-Yli-134668 Yarrowia lipolytica 46.58 2.00e-162 566.00
Created Date 25-Jun-2017

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