Seroatlas · Human Serome Atlas

NEDD4

E3 ubiquitin-protein ligase NEDD4

Also known as: KIAA0093, MGC176705, NEDD4_HUMAN, NEDD4-1, RPF1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P46934
Gene
NEDD4
Ensembl
ENSG00000069869
Chromosome
15
Canonical length
1319 aa
Protein class
Enzymes, Metabolic proteins, Predicted intracellular proteins, Transporters
Subcellular location
Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

1319 residues, UniProt reviewed canonical sequence.

>P46934|NEDD4
     1  MAQSLRLHFA ARRSNTYPLS ETSGDDLDSH VHMCFKRPTR ISTSNVVQMK LTPRQTALAP
    61  LIKENVQSQE RSSVPSSENV NKKSSCLQIS LQPTRYSGYL QSSNVLADSD DASFTCILKD
   121  GIYSSAVVDN ELNAVNDGHL VSSPAICSGS LSNFSTSDNG SYSSNGSDFG SCASITSGGS
   181  YTNSVISDSS SYTFPPSDDT FLGGNLPSDS TSNRSVPNRN TTPCEIFSRS TSTDPFVQDD
   241  LEHGLEIMKL PVSRNTKIPL KRYSSLVIFP RSPSTTRPTS PTSLCTLLSK GSYQTSHQFI
   301  ISPSEIAHNE DGTSAKGFLS TAVNGLRLSK TICTPGEVRD IRPLHRKGSL QKKIVLSNNT
   361  PRQTVCEKSS EGYSCVSVHF TQRKAATLDC ETTNGDCKPE MSEIKLNSDS EYIKLMHRTS
   421  ACLPSSQNVD CQININGELE RPHSQMNKNH GILRRSISLG GAYPNISCLS SLKHNCSKGG
   481  PSQLLIKFAS GNEGKVDNLS RDSNRDCTNE LSNSCKTRDD FLGQVDVPLY PLPTENPRLE
   541  RPYTFKDFVL HPRSHKSRVK GYLRLKMTYL PKTSGSEDDN AEQAEELEPG WVVLDQPDAA
   601  CHLQQQQEPS PLPPGWEERQ DILGRTYYVN HESRRTQWKR PTPQDNLTDA ENGNIQLQAQ
   661  RAFTTRRQIS EETESVDNRE SSENWEIIRE DEATMYSNQA FPSPPPSSNL DVPTHLAEEL
   721  NARLTIFGNS AVSQPASSSN HSSRRGSLQA YTFEEQPTLP VLLPTSSGLP PGWEEKQDER
   781  GRSYYVDHNS RTTTWTKPTV QATVETSQLT SSQSSAGPQS QASTSDSGQQ VTQPSEIEQG
   841  FLPKGWEVRH APNGRPFFID HNTKTTTWED PRLKIPAHLR GKTSLDTSND LGPLPPGWEE
   901  RTHTDGRIFY INHNIKRTQW EDPRLENVAI TGPAVPYSRD YKRKYEFFRR KLKKQNDIPN
   961  KFEMKLRRAT VLEDSYRRIM GVKRADFLKA RLWIEFDGEK GLDYGGVARE WFFLISKEMF
  1021  NPYYGLFEYS ATDNYTLQIN PNSGLCNEDH LSYFKFIGRV AGMAVYHGKL LDGFFIRPFY
  1081  KMMLHKPITL HDMESVDSEY YNSLRWILEN DPTELDLRFI IDEELFGQTH QHELKNGGSE
  1141  IVVTNKNKKE YIYLVIQWRF VNRIQKQMAA FKEGFFELIP QDLIKIFDEN ELELLMCGLG
  1201  DVDVNDWREH TKYKNGYSAN HQVIQWFWKA VLMMDSEKRI RLLQFVTGTS RVPMNGFAEL
  1261  YGSNGPQSFT VEQWGTPEKL PRAHTCFNRL DLPPYESFEE LWDKLQMAIE NTQGFDGVD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NEDD4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.51
Highest tissue expression
63 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 63 nTPM
  • tongue: 54 nTPM
  • liver: 26 nTPM
  • placenta: 15 nTPM
  • skin: 8.6 nTPM
  • blood vessel: 7.7 nTPM

Single-cell type

  • myonuclei: 525 nCPM
  • enterocytes: 266 nCPM
  • neutrophil progenitors: 220 nCPM
  • hematopoietic stem cells: 180 nCPM
  • cytotrophoblasts: 178 nCPM
  • vascular endothelial cells: 168 nCPM

Immune cell

  • intermediate monocyte: 0.4 nTPM
  • MAIT T-cell: 0.3 nTPM
  • memory CD4 T-cell: 0.2 nTPM
  • naive CD4 T-cell: 0.2 nTPM
  • naive CD8 T-cell: 0.2 nTPM
  • neutrophil: 0.2 nTPM

Brain region

  • hypothalamus: 5.4 nTPM
  • medulla oblongata: 5.1 nTPM
  • white matter: 4.9 nTPM
  • thalamus: 4.2 nTPM
  • pons: 4.1 nTPM
  • spinal cord: 3.9 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.63
gnomAD pLI
0
gnomAD missense Z
0.23
DepMap mean gene effect
0.02
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of NEDD4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads NEDD4 as an antibody target. Whether an autoantibody or antibody against NEDD4 could matter depends on whether native NEDD4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NEDD4 is annotated at the cell surface, where native NEDD4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label NEDD4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/NEDD4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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