Seroatlas · Human Serome Atlas

NEDD4L

E3 ubiquitin-protein ligase NEDD4-like

Also known as: KIAA0439, NED4L_HUMAN, NEDD4-2, RSP5

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

Protein identityUniProt · HPA

UniProt accession: Q96PU5
Gene: NEDD4L
Ensembl: ENSG00000049759
Chromosome: 18
Canonical length: 975 aa
Protein class: Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

Canonical amino-acid sequenceUniProt

975 residues, UniProt reviewed canonical sequence.

>Q96PU5|NEDD4L
     1  MATGLGEPVY GLSEDEGESR ILRVKVVSGI DLAKKDIFGA SDPYVKLSLY VADENRELAL
    61  VQTKTIKKTL NPKWNEEFYF RVNPSNHRLL FEVFDENRLT RDDFLGQVDV PLSHLPTEDP
   121  TMERPYTFKD FLLRPRSHKS RVKGFLRLKM AYMPKNGGQD EENSDQRDDM EHGWEVVDSN
   181  DSASQHQEEL PPPPLPPGWE EKVDNLGRTY YVNHNNRTTQ WHRPSLMDVS SESDNNIRQI
   241  NQEAAHRRFR SRRHISEDLE PEPSEGGDVP EPWETISEEV NIAGDSLGLA LPPPPASPGS
   301  RTSPQELSEE LSRRLQITPD SNGEQFSSLI QREPSSRLRS CSVTDAVAEQ GHLPPPSAPA
   361  GRARSSTVTG GEEPTPSVAY VHTTPGLPSG WEERKDAKGR TYYVNHNNRT TTWTRPIMQL
   421  AEDGASGSAT NSNNHLIEPQ IRRPRSLSSP TVTLSAPLEG AKDSPVRRAV KDTLSNPQSP
   481  QPSPYNSPKP QHKVTQSFLP PGWEMRIAPN GRPFFIDHNT KTTTWEDPRL KFPVHMRSKT
   541  SLNPNDLGPL PPGWEERIHL DGRTFYIDHN SKITQWEDPR LQNPAITGPA VPYSREFKQK
   601  YDYFRKKLKK PADIPNRFEM KLHRNNIFEE SYRRIMSVKR PDVLKARLWI EFESEKGLDY
   661  GGVAREWFFL LSKEMFNPYY GLFEYSATDN YTLQINPNSG LCNEDHLSYF TFIGRVAGLA
   721  VFHGKLLDGF FIRPFYKMML GKQITLNDME SVDSEYYNSL KWILENDPTE LDLMFCIDEE
   781  NFGQTYQVDL KPNGSEIMVT NENKREYIDL VIQWRFVNRV QKQMNAFLEG FTELLPIDLI
   841  KIFDENELEL LMCGLGDVDV NDWRQHSIYK NGYCPNHPVI QWFWKAVLLM DAEKRIRLLQ
   901  FVTGTSRVPM NGFAELYGSN GPQLFTIEQW GSPEKLPRAH TCFNRLDLPP YETFEDLREK
   961  LLMAVENAQG FEGVD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NEDD4L 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: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.4
Highest tissue expression: 55 nTPM

Expression across tissuesHPA

Tissue

pancreas: 55 nTPM
prostate: 54 nTPM
kidney: 48 nTPM
stomach: 48 nTPM
lung: 43 nTPM
rectum: 40 nTPM

Single-cell type

prostatic glandular cells: 2,828 nCPM
renal collecting duct intercalated cells: 2,575 nCPM
transitional alveolar cells: 2,573 nCPM
urothelial cells: 2,504 nCPM
alveolar cells type 2: 2,267 nCPM
cone photoreceptor cells: 1,890 nCPM

Immune cell

T-reg: 5.1 nTPM
eosinophil: 1.2 nTPM
memory B-cell: 0.8 nTPM
basophil: 0.7 nTPM
memory CD4 T-cell: 0.6 nTPM
MAIT T-cell: 0.5 nTPM

Brain region

basal ganglia: 85 nTPM
hippocampal formation: 79 nTPM
cerebral cortex: 78 nTPM
cerebellum: 64 nTPM
midbrain: 52 nTPM
thalamus: 47 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NEDD4L.

Disease | AllUniProt

Conditions NEDD4L is implicated in, by any mechanism.

Periventricular nodular heterotopia 7 (PVNH7) MIM:617201

Disease | GeneticClinVar

11 pathogenic / likely-pathogenic of 1,173 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Periventricular nodular heterotopia 7
Periventricular nodular heterotopia with syndactyly, cleft palate and developmental delay
Chromosome 5Q14.3 deletion syndrome, distal
Intellectual disability

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): 0.2
gnomAD pLI: 1
gnomAD missense Z: 3.73
DepMap mean gene effect: 0.06
DepMap dependency class: selective

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 NEDD4L 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 NEDD4L as an antibody target. Whether an autoantibody or antibody against NEDD4L could matter depends on whether native NEDD4L is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NEDD4L is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label NEDD4L as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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