UniProtKB - Q96PU5 (NED4L_HUMAN)
E3 ubiquitin-protein ligase NEDD4-like
NEDD4L
Functioni
E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair (PubMed:31959741, PubMed:33608556, PubMed:20064473).
Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation (PubMed:15496141).
Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels (PubMed:28820317, PubMed:31959741).
Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338).
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).
Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338).
Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3 (PubMed:33608556).
By similarity13 PublicationsCatalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication EC:2.3.2.26
- [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine.1 Publication EC:2.3.2.36
Activity regulationi
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 942 | Glycyl thioester intermediatePROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- potassium channel inhibitor activity Source: BHF-UCL
- potassium channel regulator activity Source: BHF-UCL
- sodium channel inhibitor activity Source: BHF-UCL
- sodium channel regulator activity Source: UniProtKB
- transmembrane transporter binding Source: BHF-UCL
- ubiquitin protein ligase activity Source: GO_Central
- ubiquitin-protein transferase activity Source: Reactome
GO - Biological processi
- cell differentiation Source: UniProtKB-KW
- ion transmembrane transport Source: Reactome
- negative regulation of potassium ion transmembrane transport Source: BHF-UCL
- negative regulation of potassium ion transmembrane transporter activity Source: BHF-UCL
- negative regulation of protein localization to cell surface Source: BHF-UCL
- negative regulation of sodium ion transmembrane transport Source: BHF-UCL
- negative regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
- positive regulation of caveolin-mediated endocytosis Source: BHF-UCL
- positive regulation of dendrite extension Source: UniProtKB
- positive regulation of protein catabolic process Source: GO_Central
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: BHF-UCL
- protein K48-linked ubiquitination Source: BHF-UCL
- protein polyubiquitination Source: GO_Central
- protein ubiquitination Source: UniProtKB
- regulation of dendrite morphogenesis Source: GO_Central
- regulation of ion transmembrane transport Source: BHF-UCL
- regulation of membrane depolarization Source: BHF-UCL
- regulation of membrane potential Source: BHF-UCL
- regulation of membrane repolarization Source: BHF-UCL
- regulation of potassium ion transmembrane transporter activity Source: BHF-UCL
- regulation of protein stability Source: UniProtKB
- regulation of sodium ion transmembrane transport Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: BHF-UCL
- ventricular cardiac muscle cell action potential Source: BHF-UCL
Keywordsi
Molecular function | Transferase |
Biological process | Differentiation, Host-virus interaction, Ubl conjugation pathway |
Enzyme and pathway databases
BRENDAi | 2.3.2.26, 2681 2.3.2.B8, 2681 |
PathwayCommonsi | Q96PU5 |
Reactomei | R-HSA-162588, Budding and maturation of HIV virion R-HSA-2173788, Downregulation of TGF-beta receptor signaling R-HSA-2173795, Downregulation of SMAD2/3:SMAD4 transcriptional activity R-HSA-2672351, Stimuli-sensing channels R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
SignaLinki | Q96PU5 |
SIGNORi | Q96PU5 |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7728, NEDD4L |
MIMi | 606384, gene |
neXtProti | NX_Q96PU5 |
VEuPathDBi | HostDB:ENSG00000049759 |
Subcellular locationi
Endosome
- multivesicular body 1 Publication
Golgi apparatus
- Golgi apparatus 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 3 Publications
Note: May be recruited to exosomes by NDFIP1.
Cytosol
- cytosol Source: Reactome
Endosome
- multivesicular body Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: UniProtKB-SubCell
Nucleus
- nucleoplasm Source: Reactome
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, Endosome, Golgi apparatusPathology & Biotechi
Involvement in diseasei
Periventricular nodular heterotopia 7 (PVNH7)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077880 | 679 | Y → C in PVNH7. 1 PublicationCorresponds to variant dbSNP:rs879255599Ensembl. | 1 | |
Natural variantiVAR_077881 | 694 | Q → H in PVNH7; increased degradation; changed function in regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs879255598Ensembl. | 1 | |
Natural variantiVAR_077882 | 893 | E → K in PVNH7; increased degradation; changed function in regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs879255597Ensembl. | 1 | |
Natural variantiVAR_077883 | 897 | R → Q in PVNH7; increased degradation; changed function in regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs879255596Ensembl. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 448 | S → A: Abolishes interaction with 1433F. 1 Publication | 1 | |
Mutagenesisi | 942 | C → S: Abolishes activity. No effect on USP36 protein levels. 2 Publications | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 23327 |
MalaCardsi | NEDD4L |
MIMi | 617201, phenotype |
OpenTargetsi | ENSG00000049759 |
Orphaneti | 98892, Periventricular nodular heterotopia |
PharmGKBi | PA31534 |
Miscellaneous databases
Pharosi | Q96PU5, Tbio |
Genetic variation databases
BioMutai | NEDD4L |
DMDMi | 73921204 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000120323 | 2 – 975 | E3 ubiquitin-protein ligase NEDD4-likeAdd BLAST | 974 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 312 | PhosphoserineCombined sources | 1 | |
Modified residuei | 318 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 342 | Phosphoserine; by WNK1 and WNK4Combined sources2 Publications | 1 | |
Modified residuei | 367 | Phosphothreonine; by SGK11 Publication | 1 | |
Modified residuei | 446 | PhosphoserineCombined sources | 1 | |
Modified residuei | 448 | Phosphoserine; by PKA and SGK1Combined sources2 Publications | 1 | |
Modified residuei | 449 | Phosphoserine; by WNK1 and WNK4Combined sources1 Publication | 1 | |
Modified residuei | 464 | PhosphoserineCombined sources | 1 | |
Modified residuei | 475 | PhosphoserineCombined sources | 1 | |
Modified residuei | 479 | PhosphoserineCombined sources | 1 | |
Modified residuei | 483 | PhosphoserineCombined sources | 1 | |
Modified residuei | 487 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q96PU5 |
jPOSTi | Q96PU5 |
MassIVEi | Q96PU5 |
MaxQBi | Q96PU5 |
PaxDbi | Q96PU5 |
PeptideAtlasi | Q96PU5 |
PRIDEi | Q96PU5 |
ProteomicsDBi | 77752 [Q96PU5-1] 77753 [Q96PU5-2] 77754 [Q96PU5-3] 77755 [Q96PU5-4] 77756 [Q96PU5-5] 77757 [Q96PU5-6] 77758 [Q96PU5-7] 77760 [Q96PU5-9] |
PTM databases
GlyGeni | Q96PU5, 2 sites, 2 O-linked glycans (2 sites) |
iPTMneti | Q96PU5 |
PhosphoSitePlusi | Q96PU5 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000049759, Expressed in forebrain and 226 other tissues |
ExpressionAtlasi | Q96PU5, baseline and differential |
Genevisiblei | Q96PU5, HS |
Organism-specific databases
HPAi | ENSG00000049759, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with UBE2E3 (By similarity).
Interacts with NDFIP1; this interaction activates the E3 ubiquitin-protein ligase (PubMed:11748237, PubMed:26363003).
Interacts with NDFIP2; this interaction activates the E3 ubiquitin-protein ligase (PubMed:26363003).
Interacts (via WW domains) with SCNN1A (PubMed:11696533, PubMed:11244092, PubMed:14556380).
Interacts (via WW domains) with SCNN1B (PubMed:11244092, PubMed:14556380).
Interacts (via WW domains) with SCNN1G (PubMed:11244092, PubMed:14556380).
Interacts (via WW domains) with SCN1A (By similarity).
Interacts (via WW domains) with SCN2A (PubMed:15548568).
Interacts (via WW domains) with SCN3A (PubMed:15548568).
Interacts (via WW domains) with SCN5A (PubMed:15217910, PubMed:15548568).
Interacts (via WW domains) with SCN8A (By similarity).
Interacts (via WW domains) with SCN9A (By similarity).
Interacts (via WW domains) with SCN10A (By similarity).
Interacts (via WW domains) with CLCN5 (PubMed:15489223).
Interacts with SMAD2 (PubMed:15496141).
Interacts with SMAD3 (PubMed:15496141).
Interacts with SMAD6 (PubMed:15496141).
Interacts with SMAD7 (PubMed:15496141). The phosphorylated form interacts with 14-3-3 proteins (PubMed:15677482).
Interacts with TNK2 (PubMed:19144635, PubMed:20086093).
Interacts with WNK1 (PubMed:20525693).
Interacts with SGK1 (PubMed:11696533, PubMed:20730100).
Interacts (via C2 domain) with NPC2 (PubMed:19664597).
Interacts with ARRDC4 (PubMed:23236378).
Interacts with KCNQ1; promotes internalization of KCNQ1 (PubMed:22024150).
Interacts (via domains WW1, 3 and 4) with USP36; the interaction inhibits ubiquitination of, at least, NTRK1, KCNQ2 and KCNQ3 by NEDD4L (PubMed:27445338).
Interacts with PRRG4 (via cytoplasmic domain) (PubMed:23873930).
Interacts with LDLRAD3; the interaction is direct (PubMed:26854353).
Interacts with UBE2D2 (PubMed:20064473).
By similarity21 Publications(Microbial infection) Interacts with Epstein-Barr virus LMP2A.
1 PublicationBinary interactionsi
Q96PU5
Isoform 2 [Q96PU5-2]
With | #Exp. | IntAct |
---|---|---|
ARRDC3 [Q96B67] | 5 | EBI-6955201,EBI-2875665 |
DAZAP2 [Q15038] | 3 | EBI-6955201,EBI-724310 |
Isoform 5 [Q96PU5-5]
With | #Exp. | IntAct |
---|---|---|
SMAD7 [O15105] | 3 | EBI-7196393,EBI-3861591 |
GO - Molecular functioni
- transmembrane transporter binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 116915, 294 interactors |
CORUMi | Q96PU5 |
DIPi | DIP-41935N |
IntActi | Q96PU5, 52 interactors |
MINTi | Q96PU5 |
STRINGi | 9606.ENSP00000383199 |
Miscellaneous databases
RNActi | Q96PU5, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q96PU5 |
BMRBi | Q96PU5 |
SMRi | Q96PU5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96PU5 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 4 – 126 | C2PROSITE-ProRule annotationAdd BLAST | 123 | |
Domaini | 193 – 226 | WW 1PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 385 – 418 | WW 2PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 497 – 530 | WW 3PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 548 – 581 | WW 4PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 640 – 974 | HECTPROSITE-ProRule annotationAdd BLAST | 335 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 178 – 202 | DisorderedSequence analysisAdd BLAST | 25 | |
Regioni | 244 – 272 | DisorderedSequence analysisAdd BLAST | 29 | |
Regioni | 285 – 312 | DisorderedSequence analysisAdd BLAST | 28 | |
Regioni | 349 – 393 | DisorderedSequence analysisAdd BLAST | 45 | |
Regioni | 424 – 496 | DisorderedSequence analysisAdd BLAST | 73 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 244 – 261 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 424 – 455 | Polar residuesSequence analysisAdd BLAST | 32 |
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0940, Eukaryota |
GeneTreei | ENSGT00940000156873 |
InParanoidi | Q96PU5 |
OMAi | PAHIAMQ |
OrthoDBi | 271539at2759 |
PhylomeDBi | Q96PU5 |
TreeFami | TF323658 |
Family and domain databases
CDDi | cd00078, HECTc, 1 hit cd00201, WW, 4 hits |
DisProti | DP02292 |
Gene3Di | 2.60.40.150, 1 hit |
IDEALi | IID00114 |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR024928, E3_ub_ligase_SMURF1 IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR001202, WW_dom IPR036020, WW_dom_sf |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF00397, WW, 4 hits |
PIRSFi | PIRSF001569, E3_ub_ligase_SMURF1, 1 hit |
PRINTSi | PR00360, C2DOMAIN |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 4 hits |
SUPFAMi | SSF49562, SSF49562, 1 hit SSF51045, SSF51045, 4 hits SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 4 hits PS50020, WW_DOMAIN_2, 4 hits |
s (8+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 8 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 8 described isoforms and 16 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MATGLGEPVY GLSEDEGESR ILRVKVVSGI DLAKKDIFGA SDPYVKLSLY
60 70 80 90 100
VADENRELAL VQTKTIKKTL NPKWNEEFYF RVNPSNHRLL FEVFDENRLT
110 120 130 140 150
RDDFLGQVDV PLSHLPTEDP TMERPYTFKD FLLRPRSHKS RVKGFLRLKM
160 170 180 190 200
AYMPKNGGQD EENSDQRDDM EHGWEVVDSN DSASQHQEEL PPPPLPPGWE
210 220 230 240 250
EKVDNLGRTY YVNHNNRTTQ WHRPSLMDVS SESDNNIRQI NQEAAHRRFR
260 270 280 290 300
SRRHISEDLE PEPSEGGDVP EPWETISEEV NIAGDSLGLA LPPPPASPGS
310 320 330 340 350
RTSPQELSEE LSRRLQITPD SNGEQFSSLI QREPSSRLRS CSVTDAVAEQ
360 370 380 390 400
GHLPPPSAPA GRARSSTVTG GEEPTPSVAY VHTTPGLPSG WEERKDAKGR
410 420 430 440 450
TYYVNHNNRT TTWTRPIMQL AEDGASGSAT NSNNHLIEPQ IRRPRSLSSP
460 470 480 490 500
TVTLSAPLEG AKDSPVRRAV KDTLSNPQSP QPSPYNSPKP QHKVTQSFLP
510 520 530 540 550
PGWEMRIAPN GRPFFIDHNT KTTTWEDPRL KFPVHMRSKT SLNPNDLGPL
560 570 580 590 600
PPGWEERIHL DGRTFYIDHN SKITQWEDPR LQNPAITGPA VPYSREFKQK
610 620 630 640 650
YDYFRKKLKK PADIPNRFEM KLHRNNIFEE SYRRIMSVKR PDVLKARLWI
660 670 680 690 700
EFESEKGLDY GGVAREWFFL LSKEMFNPYY GLFEYSATDN YTLQINPNSG
710 720 730 740 750
LCNEDHLSYF TFIGRVAGLA VFHGKLLDGF FIRPFYKMML GKQITLNDME
760 770 780 790 800
SVDSEYYNSL KWILENDPTE LDLMFCIDEE NFGQTYQVDL KPNGSEIMVT
810 820 830 840 850
NENKREYIDL VIQWRFVNRV QKQMNAFLEG FTELLPIDLI KIFDENELEL
860 870 880 890 900
LMCGLGDVDV NDWRQHSIYK NGYCPNHPVI QWFWKAVLLM DAEKRIRLLQ
910 920 930 940 950
FVTGTSRVPM NGFAELYGSN GPQLFTIEQW GSPEKLPRAH TCFNRLDLPP
960 970
YETFEDLREK LLMAVENAQG FEGVD
Computationally mapped potential isoform sequencesi
There are 16 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A6Q8PG51 | A0A6Q8PG51_HUMAN | E3 ubiquitin-protein ligase | NEDD4L | 863 | Annotation score: | ||
K7ERN1 | K7ERN1_HUMAN | HECT-type E3 ubiquitin transferase | NEDD4L | 639 | Annotation score: | ||
A0A6Q8PFI7 | A0A6Q8PFI7_HUMAN | E3 ubiquitin-protein ligase | NEDD4L | 948 | Annotation score: | ||
A0A6Q8PGP5 | A0A6Q8PGP5_HUMAN | E3 ubiquitin-protein ligase | NEDD4L | 942 | Annotation score: | ||
A0A6Q8PHJ5 | A0A6Q8PHJ5_HUMAN | E3 ubiquitin-protein ligase | NEDD4L | 930 | Annotation score: | ||
A0A1B0GVY1 | A0A1B0GVY1_HUMAN | HECT-type E3 ubiquitin transferase | NEDD4L | 1,254 | Annotation score: | ||
A0A7P0Z498 | A0A7P0Z498_HUMAN | HECT-type E3 ubiquitin transferase | NEDD4L | 618 | Annotation score: | ||
K7ENS6 | K7ENS6_HUMAN | E3 ubiquitin-protein ligase NEDD4-l... | NEDD4L | 150 | Annotation score: | ||
K7EKL1 | K7EKL1_HUMAN | E3 ubiquitin-protein ligase NEDD4-l... | NEDD4L | 106 | Annotation score: | ||
A0A6Q8PG81 | A0A6Q8PG81_HUMAN | E3 ubiquitin-protein ligase NEDD4-l... | NEDD4L | 394 | Annotation score: | ||
There are more potential isoformsShow all |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 52 | A → P in AAM76729 (PubMed:14615060).Curated | 1 | |
Sequence conflicti | 52 | A → P in AAM76730 (PubMed:14615060).Curated | 1 | |
Sequence conflicti | 188 | E → K in AAP75706 (PubMed:14556380).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023415 | 355 | P → L Impaired ability to inhibit SCNN. 1 PublicationCorresponds to variant dbSNP:rs767136811EnsemblClinVar. | 1 | |
Natural variantiVAR_023416 | 497 | S → R1 Publication | 1 | |
Natural variantiVAR_077880 | 679 | Y → C in PVNH7. 1 PublicationCorresponds to variant dbSNP:rs879255599Ensembl. | 1 | |
Natural variantiVAR_077881 | 694 | Q → H in PVNH7; increased degradation; changed function in regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs879255598Ensembl. | 1 | |
Natural variantiVAR_077882 | 893 | E → K in PVNH7; increased degradation; changed function in regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs879255597Ensembl. | 1 | |
Natural variantiVAR_077883 | 897 | R → Q in PVNH7; increased degradation; changed function in regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs879255596Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_015444 | 1 – 121 | Missing in isoform 4 and isoform 8. 4 PublicationsAdd BLAST | 121 | |
Alternative sequenceiVSP_015446 | 1 – 16 | MATGL…LSEDE → MRRLAFEQ in isoform 6 and isoform 7. 1 PublicationAdd BLAST | 16 | |
Alternative sequenceiVSP_015447 | 356 – 459 | Missing in isoform 3. 1 PublicationAdd BLAST | 104 | |
Alternative sequenceiVSP_015448 | 356 – 419 | Missing in isoform 2. 1 PublicationAdd BLAST | 64 | |
Alternative sequenceiVSP_043848 | 356 – 375 | Missing in isoform 5, isoform 6 and isoform 8. 5 PublicationsAdd BLAST | 20 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2LAJ | NMR | - | A | 496-535 | [»] | |
2LB2 | NMR | - | A | 386-420 | [»] | |
2LTY | NMR | - | A | 385-417 | [»] | |
2MPT | NMR | - | A | 496-539 | [»] | |
B | 945-957 | [»] | ||||
2NSQ | X-ray | 1.85 | A | 1-154 | [»] | |
2ONI | X-ray | 2.20 | A | 594-967 | [»] | |
3JVZ | X-ray | 3.30 | C/D | 596-975 | [»] | |
3JW0 | X-ray | 3.10 | C/D | 596-975 | [»] | |
5HPK | X-ray | 2.43 | A | 594-975 | [»] | |
6ZBT | X-ray | 1.80 | E/F/G/H | 338-347 | [»] | |
6ZC9 | X-ray | 1.90 | E/F/G/H | 444-453 | [»] | |
7LP1 | X-ray | 1.35 | A | 494-532 | [»] | |
7LP3 | X-ray | 1.61 | A/C | 193-226 | [»] | |
7LP4 | NMR | - | A | 493-539 | [»] | |
7LP5 | NMR | - | A | 493-539 | [»] | |
7NMZ | X-ray | 2.30 | C | 335-455 | [»] | |
AlphaFoldDBi | Q96PU5 | |||||
BMRBi | Q96PU5 | |||||
SMRi | Q96PU5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 116915, 294 interactors |
CORUMi | Q96PU5 |
DIPi | DIP-41935N |
IntActi | Q96PU5, 52 interactors |
MINTi | Q96PU5 |
STRINGi | 9606.ENSP00000383199 |
PTM databases
GlyGeni | Q96PU5, 2 sites, 2 O-linked glycans (2 sites) |
iPTMneti | Q96PU5 |
PhosphoSitePlusi | Q96PU5 |
Genetic variation databases
BioMutai | NEDD4L |
DMDMi | 73921204 |
Proteomic databases
EPDi | Q96PU5 |
jPOSTi | Q96PU5 |
MassIVEi | Q96PU5 |
MaxQBi | Q96PU5 |
PaxDbi | Q96PU5 |
PeptideAtlasi | Q96PU5 |
PRIDEi | Q96PU5 |
ProteomicsDBi | 77752 [Q96PU5-1] 77753 [Q96PU5-2] 77754 [Q96PU5-3] 77755 [Q96PU5-4] 77756 [Q96PU5-5] 77757 [Q96PU5-6] 77758 [Q96PU5-7] 77760 [Q96PU5-9] |
Protocols and materials databases
Antibodypediai | 5421, 259 antibodies from 33 providers |
DNASUi | 23327 |
Genome annotation databases
Organism-specific databases
CTDi | 23327 |
DisGeNETi | 23327 |
GeneCardsi | NEDD4L |
HGNCi | HGNC:7728, NEDD4L |
HPAi | ENSG00000049759, Low tissue specificity |
MalaCardsi | NEDD4L |
MIMi | 606384, gene 617201, phenotype |
neXtProti | NX_Q96PU5 |
OpenTargetsi | ENSG00000049759 |
Orphaneti | 98892, Periventricular nodular heterotopia |
PharmGKBi | PA31534 |
VEuPathDBi | HostDB:ENSG00000049759 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0940, Eukaryota |
GeneTreei | ENSGT00940000156873 |
InParanoidi | Q96PU5 |
OMAi | PAHIAMQ |
OrthoDBi | 271539at2759 |
PhylomeDBi | Q96PU5 |
TreeFami | TF323658 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
BRENDAi | 2.3.2.26, 2681 2.3.2.B8, 2681 |
PathwayCommonsi | Q96PU5 |
Reactomei | R-HSA-162588, Budding and maturation of HIV virion R-HSA-2173788, Downregulation of TGF-beta receptor signaling R-HSA-2173795, Downregulation of SMAD2/3:SMAD4 transcriptional activity R-HSA-2672351, Stimuli-sensing channels R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
SignaLinki | Q96PU5 |
SIGNORi | Q96PU5 |
Miscellaneous databases
BioGRID-ORCSi | 23327, 13 hits in 1118 CRISPR screens |
ChiTaRSi | NEDD4L, human |
EvolutionaryTracei | Q96PU5 |
GeneWikii | NEDD4L |
GenomeRNAii | 23327 |
Pharosi | Q96PU5, Tbio |
PROi | PR:Q96PU5 |
RNActi | Q96PU5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000049759, Expressed in forebrain and 226 other tissues |
ExpressionAtlasi | Q96PU5, baseline and differential |
Genevisiblei | Q96PU5, HS |
Family and domain databases
CDDi | cd00078, HECTc, 1 hit cd00201, WW, 4 hits |
DisProti | DP02292 |
Gene3Di | 2.60.40.150, 1 hit |
IDEALi | IID00114 |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR024928, E3_ub_ligase_SMURF1 IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR001202, WW_dom IPR036020, WW_dom_sf |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF00397, WW, 4 hits |
PIRSFi | PIRSF001569, E3_ub_ligase_SMURF1, 1 hit |
PRINTSi | PR00360, C2DOMAIN |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 4 hits |
SUPFAMi | SSF49562, SSF49562, 1 hit SSF51045, SSF51045, 4 hits SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 4 hits PS50020, WW_DOMAIN_2, 4 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | NED4L_HUMAN | |
Accessioni | Q96PU5Primary (citable) accession number: Q96PU5 Secondary accession number(s): O43165 Q9NT88 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 30, 2005 |
Last sequence update: | August 30, 2005 | |
Last modified: | May 25, 2022 | |
This is version 193 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 18
Human chromosome 18: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references