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NEDD4L NEDD4 like E3 ubiquitin protein ligase [ Homo sapiens (human) ]

Gene ID: 23327, updated on 5-May-2024

Summary

Official Symbol
NEDD4Lprovided by HGNC
Official Full Name
NEDD4 like E3 ubiquitin protein ligaseprovided by HGNC
Primary source
HGNC:HGNC:7728
See related
Ensembl:ENSG00000049759 MIM:606384; AllianceGenome:HGNC:7728
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
RSP5; PVNH7; NEDD4-2; NEDD4.2; hNEDD4-2
Summary
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]
Expression
Broad expression in prostate (RPKM 13.1), kidney (RPKM 13.0) and 25 other tissues See more
Orthologs
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Genomic context

See NEDD4L in Genome Data Viewer
Location:
18q21.31
Exon count:
43
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (58044226..58401540)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (58244126..58602300)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (55711458..56068772)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1897 Neighboring gene Sharpr-MPRA regulatory region 3246 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13381 Neighboring gene CRISPRi-validated cis-regulatory element chr18.1280 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9482 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9483 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 30 Neighboring gene NANOG hESC enhancer GRCh37_chr18:55747705-55748297 Neighboring gene Sharpr-MPRA regulatory region 539 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13382 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13383 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:55793171-55793670 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:55838061-55838872 Neighboring gene uncharacterized LOC105372143 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:55862243-55862765 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:55862766-55863287 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13384 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:55890569-55891162 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13385 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13386 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:55914788-55915293 Neighboring gene ReSE screen-validated silencer GRCh37_chr18:55977766-55977988 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr18:55982687-55983886 Neighboring gene Sharpr-MPRA regulatory region 8690 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13387 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:56045193-56045729 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:56045730-56046265 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:56059391-56059890 Neighboring gene MIR122 host gene Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:56160423-56160924 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:56160925-56161424 Neighboring gene microRNA 3591 Neighboring gene microRNA 122 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr18:56178733-56179504 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr18:56179505-56180274 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13388 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9486 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13389 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13390 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr18:56202574-56203773 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13395 Neighboring gene alpha kinase 2 Neighboring gene uncharacterized LOC105372145 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13396 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13397

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Periventricular nodular heterotopia 7
MedGen: C4310669 OMIM: 617201 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide association study of caffeine-related sleep disturbance: confirmation of a role for a common variant in the adenosine receptor.
EBI GWAS Catalog
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
EBI GWAS Catalog
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
EBI GWAS Catalog
Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).
EBI GWAS Catalog
Genome-wide meta-analysis identifies new susceptibility loci for migraine.
EBI GWAS Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 replication is enhanced by CIT expression, which is dependent on NEDD4L expression as shown through siRNA knockdown of NEDD4L PubMed

Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag Angiomotin (AMOT) stimulates NEDD4L-dependent release of HIV-1 Gag delta PTAP/YP in a does-dependent manner in 293T cells PubMed
gag Angiomotin (AMOT), AMOT-like protein 1, and AMOT-like protein 2 bind directly and specifically to NEDD4L and HIV-1 Gag-delta p6 in protein pull-down experiments PubMed
gag The residual C2 domain (residues 1-31) of NEDD4-2s confers the ability to associate with HIV-1 Gag and to rescue HIV-1delta(PTAPP) budding PubMed
gag Targeting of the catalytic HECT domain (residues 598-952) of NEDD4-2s to HIV-1 Gag via CypA is sufficient to rescue HIV-1 budding defects PubMed
Vpr vpr HIV-1 Vpr is identified to have a physical interaction with neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
nucleocapsid gag Mutations in the basic residues of the nucleocapsid domain of Gag cause severe defects in HIV-1 release, and overexpression of Nedd4.2 rescues NC mutant release defects PubMed
p6 gag The residual C2-domain (amino acids 1-31) in NEDD4L is essential for the rescue of p6 late-domain mutants PubMed
gag NEDD4L-mediated stimulation of virus budding is dependent upon the ubiquitin ligase activity of NEDD4L and requires only the minimal HIV-1 Gag assembly regions and TSG101 PubMed
gag Overexpression of the HECT ubiquitin E3 ligase, NEDD4L/NEDD4-2 stimulates the release of HIV-1 constructs that lack TSG101- and ALIX-binding late domains in p6 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Clone Names

  • FLJ33870, KIAA0439

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables potassium channel inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
enables potassium channel regulator activity IDA
Inferred from Direct Assay
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables sodium channel inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
 
enables sodium channel inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
enables sodium channel regulator activity IDA
Inferred from Direct Assay
more info
PubMed 
enables transmembrane transporter binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
 
enables ubiquitin-protein transferase activity NAS
Non-traceable Author Statement
more info
PubMed 
enables ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
involved_in cell differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in monoatomic ion transmembrane transport TAS
Traceable Author Statement
more info
 
involved_in negative regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of potassium ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of protein localization to cell surface IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of sodium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of sodium ion transmembrane transporter activity IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in negative regulation of sodium ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of caveolin-mediated endocytosis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of dendrite extension IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of protein catabolic process IEA
Inferred from Electronic Annotation
more info
 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein monoubiquitination IEA
Inferred from Electronic Annotation
more info
 
involved_in protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of dendrite morphogenesis IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in regulation of membrane depolarization IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of membrane potential IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of membrane repolarization IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of monoatomic ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of potassium ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of protein stability IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of sodium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
involved_in ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in ventricular cardiac muscle cell action potential ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IEA
Inferred from Electronic Annotation
more info
 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in cytosol TAS
Traceable Author Statement
more info
 
located_in extracellular exosome HDA PubMed 
located_in multivesicular body IEA
Inferred from Electronic Annotation
more info
 
located_in nucleoplasm TAS
Traceable Author Statement
more info
 
colocalizes_with plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
E3 ubiquitin-protein ligase NEDD4-like
Names
HECT-type E3 ubiquitin transferase NED4L
neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase
ubiquitin-protein ligase Rsp5
NP_001138436.1
NP_001138437.1
NP_001138438.1
NP_001138439.1
NP_001138440.1
NP_001138441.1
NP_001138442.1
NP_001138443.1
NP_001230889.1
NP_056092.2
XP_005266715.3
XP_005266717.3
XP_005266720.3
XP_006722484.3
XP_006722487.3
XP_006722488.3
XP_006722489.1
XP_006722491.1
XP_006722493.1
XP_011524189.1
XP_016881165.2
XP_016881166.2
XP_016881167.1
XP_016881168.1
XP_016881170.1
XP_024306897.1
XP_024306899.1
XP_024306902.1
XP_024306903.1
XP_024306904.1
XP_047293358.1
XP_047293359.1
XP_047293360.1
XP_047293361.1
XP_047293362.1
XP_047293363.1
XP_047293364.1
XP_047293365.1
XP_047293366.1
XP_047293367.1
XP_047293368.1
XP_047293369.1
XP_047293370.1
XP_047293371.1
XP_047293372.1
XP_047293373.1
XP_047293374.1
XP_047293375.1
XP_047293376.1
XP_047293377.1
XP_054174357.1
XP_054174358.1
XP_054174359.1
XP_054174360.1
XP_054174361.1
XP_054174362.1
XP_054174363.1
XP_054174364.1
XP_054174365.1
XP_054174366.1
XP_054174367.1
XP_054174368.1
XP_054174369.1
XP_054174370.1
XP_054174371.1
XP_054174372.1
XP_054174373.1
XP_054174374.1
XP_054174375.1
XP_054174376.1
XP_054174377.1
XP_054174378.1
XP_054174379.1
XP_054174380.1
XP_054174381.1
XP_054174382.1
XP_054174383.1
XP_054174384.1
XP_054174385.1
XP_054174386.1
XP_054174387.1
XP_054174388.1
XP_054174389.1
XP_054174390.1
XP_054174391.1
XP_054174392.1
XP_054174393.1
XP_054174394.1

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029954.1 RefSeqGene

    Range
    4849..362162
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001144964.1NP_001138436.1  E3 ubiquitin-protein ligase NEDD4-like isoform 2

    See identical proteins and their annotated locations for NP_001138436.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (b) uses an alternate first exon, compared to variant j, which results in the use of a downstream in-frame start codon. The encoded protein (isoform 2) has a shorter N-terminus that lacks a C2 domain, compared to isoform 1. Variant b is also known as NEDD4-2C7. Variants a, b, and f encode the same isoform (2).
    Source sequence(s)
    AC090236, AF070601, AF385931, BC019345, BP260852, DA759940, DB317092
    Consensus CDS
    CCDS45875.1
    UniProtKB/TrEMBL
    B7Z6K0
    Related
    ENSP00000411947.1, ENST00000456986.5
    Conserved Domains (5) summary
    smart00456
    Location:428460
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:521850
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    PHA03247
    Location:198381
    PHA03247; large tegument protein UL36; Provisional
    pfam00397
    Location:266295
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  2. NM_001144965.2NP_001138437.1  E3 ubiquitin-protein ligase NEDD4-like isoform 2

    See identical proteins and their annotated locations for NP_001138437.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (f) uses an alternate first exon, compared to variant j, which results in the use of a downstream in-frame start codon. The encoded protein (isoform 2) has a shorter N-terminus that lacks a C2 domain, compared to isoform 1. Variants a, b, and f encode the same isoform (2).
    Source sequence(s)
    AC090236, AC107896, AY112983, BC032597
    Consensus CDS
    CCDS45875.1
    UniProtKB/TrEMBL
    B7Z6K0
    Conserved Domains (5) summary
    smart00456
    Location:428460
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:521850
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    PHA03247
    Location:198381
    PHA03247; large tegument protein UL36; Provisional
    pfam00397
    Location:266295
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  3. NM_001144966.3NP_001138438.1  E3 ubiquitin-protein ligase NEDD4-like isoform 2

    See identical proteins and their annotated locations for NP_001138438.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (a) uses an alternate first exon, compared to variant j, which results in the use of a downstream in-frame start codon. The encoded protein (isoform 2) has a shorter N-terminus that lacks a C2 domain, compared to isoform 1. Variant a is also known as NEDD4-2A. Variants a, b, and f encode the same isoform (2).
    Source sequence(s)
    AC090236, AF210730, AK300444, DC381911
    Consensus CDS
    CCDS45875.1
    UniProtKB/TrEMBL
    B7Z6K0
    Related
    ENSP00000389406.1, ENST00000431212.6
    Conserved Domains (5) summary
    smart00456
    Location:428460
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:521850
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    PHA03247
    Location:198381
    PHA03247; large tegument protein UL36; Provisional
    pfam00397
    Location:266295
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  4. NM_001144967.3NP_001138439.1  E3 ubiquitin-protein ligase NEDD4-like isoform 1

    See identical proteins and their annotated locations for NP_001138439.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (j) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC090236, AC107896, AY312514, BQ215431
    Consensus CDS
    CCDS45872.1
    UniProtKB/Swiss-Prot
    O43165, Q3LSM7, Q7Z5F1, Q7Z5F2, Q7Z5N3, Q8N5A7, Q8WUU9, Q96PU5, Q9BW58, Q9H2W4, Q9NT88
    UniProtKB/TrEMBL
    A0A6Q8PFI7
    Related
    ENSP00000383199.2, ENST00000400345.8
    Conserved Domains (5) summary
    cd04033
    Location:21153
    C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)
    smart00456
    Location:549581
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:642971
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    PHA03247
    Location:319502
    PHA03247; large tegument protein UL36; Provisional
    pfam00397
    Location:387416
    WW; WW domain
  5. NM_001144968.2NP_001138440.1  E3 ubiquitin-protein ligase NEDD4-like isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (g) uses an alternate first exon, compared to variant j, which results in the use of a different start codon and a protein (isoform 4) with a shorter and distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    AC090236, AC107896, AY112984, BC032597
    Consensus CDS
    CCDS45874.1
    UniProtKB/TrEMBL
    A0A6Q8PFI7
    Related
    ENSP00000350569.4, ENST00000357895.9
    Conserved Domains (6) summary
    cd04033
    Location:13145
    C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)
    smart00456
    Location:541573
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:634963
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00201
    Location:492522
    WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
    pfam00397
    Location:379408
    WW; WW domain
    cl26464
    Location:311494
    Atrophin-1; Atrophin-1 family
  6. NM_001144969.2NP_001138441.1  E3 ubiquitin-protein ligase NEDD4-like isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (h) uses an alternate first exon and lacks a downstream in-frame exon, compared to variant j, which results in the use of a different start codon and a protein (isoform 5) with a shorter and distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    AC090236, AC107896, AF070601, AY112985, BP260852, DA759940, DB317092, DQ181796
    Consensus CDS
    CCDS59323.1
    UniProtKB/TrEMBL
    A0A6Q8PFI7
    Related
    ENSP00000468546.1, ENST00000586263.5
    Conserved Domains (5) summary
    cd04033
    Location:13145
    C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)
    smart00456
    Location:521553
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:614943
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00201
    Location:472502
    WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
    pfam00397
    Location:359388
    WW; WW domain
  7. NM_001144970.3NP_001138442.1  E3 ubiquitin-protein ligase NEDD4-like isoform 6

    See identical proteins and their annotated locations for NP_001138442.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (c) uses an alternate first exon and lacks a downstream in-frame exon, compared to variant j. These differences result in the use of a downstream in-frame start codon and a protein (isoform 6) with a shorter N-terminus, compared to isoform 1. Variant c is also known as NEDD4-2B. Variants c and k encode the same isoform (6).
    Source sequence(s)
    AB007899, AC090236, AK294963, BC000621, DA819220
    Consensus CDS
    CCDS45876.1
    UniProtKB/TrEMBL
    B7Z2P9
    Related
    ENSP00000405440.1, ENST00000456173.6
    Conserved Domains (4) summary
    smart00456
    Location:408440
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:501830
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    pfam00397
    Location:246275
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  8. NM_001144971.2NP_001138443.1  E3 ubiquitin-protein ligase NEDD4-like isoform 6

    See identical proteins and their annotated locations for NP_001138443.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (k) uses two alternate exons in its 5' end and lacks a downstream in-frame exon, compared to variant j. These differences result in the use of a downstream in-frame start codon and a protein (isoform 6) with a shorter N-terminus, compared to isoform 1. Variants c and k encode the same isoform (6).
    Source sequence(s)
    AC090236, AC107896, AF070601, BP260852, DA759940, DB317092, DQ181796
    Consensus CDS
    CCDS45876.1
    UniProtKB/TrEMBL
    B7Z2P9
    Related
    ENSP00000393395.1, ENST00000435432.6
    Conserved Domains (4) summary
    smart00456
    Location:408440
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:501830
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    pfam00397
    Location:246275
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  9. NM_001243960.2NP_001230889.1  E3 ubiquitin-protein ligase NEDD4-like isoform 7

    See identical proteins and their annotated locations for NP_001230889.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (i) lacks two consecutive exons in the coding region, but maintains the reading frame, compared to variant j. The encoded isoform (7) is shorter than isoform 1.
    Source sequence(s)
    AC090236, AC107896, BC032597
    Consensus CDS
    CCDS58632.1
    UniProtKB/TrEMBL
    A0A6Q8PFI7
    Related
    ENSP00000348847.5, ENST00000356462.10
    Conserved Domains (5) summary
    cd04033
    Location:21153
    C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)
    smart00456
    Location:485517
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:578907
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00201
    Location:436466
    WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
    pfam00397
    Location:198224
    WW; WW domain
  10. NM_015277.6NP_056092.2  E3 ubiquitin-protein ligase NEDD4-like isoform 3

    See identical proteins and their annotated locations for NP_056092.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (d) lacks an in-frame exon, compared to variant j, resulting in a shorter protein (isoform 3), compared to isoform 1. Variant d is also known as NEDD4-2C6 and NEDL3.
    Source sequence(s)
    AB071179, AC090236, AC107896, BC000621
    Consensus CDS
    CCDS45873.1
    UniProtKB/TrEMBL
    A0A6Q8PFI7
    Related
    ENSP00000372301.3, ENST00000382850.8
    Conserved Domains (4) summary
    cd04033
    Location:21153
    C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)
    smart00456
    Location:529561
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:622951
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    pfam00397
    Location:367396
    WW; WW domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

    Range
    58044226..58401540
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006722426.5XP_006722489.1  E3 ubiquitin-protein ligase NEDD4-like isoform X11

    UniProtKB/TrEMBL
    A0A6Q8PFI7
    Conserved Domains (6) summary
    cd04033
    Location:21179
    C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)
    smart00456
    Location:575625
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:6861015
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00078
    Location:6621016
    HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
    cd00201
    Location:526556
    WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
    pfam00397
    Location:413442
    WW; WW domain
  2. XM_047437406.1XP_047293362.1  E3 ubiquitin-protein ligase NEDD4-like isoform X13

  3. XM_047437407.1XP_047293363.1  E3 ubiquitin-protein ligase NEDD4-like isoform X14

  4. XM_047437408.1XP_047293364.1  E3 ubiquitin-protein ligase NEDD4-like isoform X16

  5. XM_006722428.5XP_006722491.1  E3 ubiquitin-protein ligase NEDD4-like isoform X15

    UniProtKB/TrEMBL
    A0A6Q8PFI7
    Conserved Domains (6) summary
    cd04033
    Location:21153
    C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)
    smart00456
    Location:549599
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:660989
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00078
    Location:636990
    HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
    cd00201
    Location:500530
    WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
    pfam00397
    Location:387416
    WW; WW domain
  6. XM_017025678.3XP_016881167.1  E3 ubiquitin-protein ligase NEDD4-like isoform X18

    UniProtKB/TrEMBL
    A0A6Q8PFI7
  7. XM_047437421.1XP_047293377.1  E3 ubiquitin-protein ligase NEDD4-like isoform X24

  8. XM_047437418.1XP_047293374.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  9. XM_047437420.1XP_047293376.1  E3 ubiquitin-protein ligase NEDD4-like isoform X23

  10. XM_024451135.2XP_024306903.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

    UniProtKB/TrEMBL
    B7Z2P9
    Related
    ENSP00000502688.1, ENST00000675801.1
    Conserved Domains (4) summary
    smart00456
    Location:408440
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:501830
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    pfam00397
    Location:246275
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  11. XM_047437419.1XP_047293375.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  12. XM_047437417.1XP_047293373.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  13. XM_024451136.2XP_024306904.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

    UniProtKB/TrEMBL
    B7Z2P9
    Conserved Domains (4) summary
    smart00456
    Location:408440
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:501830
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    pfam00397
    Location:246275
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  14. XM_024451129.2XP_024306897.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

    UniProtKB/TrEMBL
    B7Z6K0
    Conserved Domains (5) summary
    smart00456
    Location:428460
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:521850
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    PHA03247
    Location:198381
    PHA03247; large tegument protein UL36; Provisional
    pfam00397
    Location:266295
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  15. XM_047437402.1XP_047293358.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

  16. XM_047437404.1XP_047293360.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  17. XM_024451131.2XP_024306899.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

    UniProtKB/TrEMBL
    B7Z2P9
    Conserved Domains (4) summary
    smart00456
    Location:408440
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:501830
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    pfam00397
    Location:246275
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  18. XM_047437409.1XP_047293365.1  E3 ubiquitin-protein ligase NEDD4-like isoform X17

  19. XM_047437410.1XP_047293366.1  E3 ubiquitin-protein ligase NEDD4-like isoform X19

  20. XM_047437403.1XP_047293359.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  21. XM_047437405.1XP_047293361.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

    Related
    ENSP00000502428.1, ENST00000675502.1
  22. XM_024451134.2XP_024306902.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

    UniProtKB/TrEMBL
    B7Z6K0
    Conserved Domains (6) summary
    smart00456
    Location:428478
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:539868
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00201
    Location:379409
    WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
    pfam00397
    Location:266295
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
    cl26464
    Location:198381
    Atrophin-1; Atrophin-1 family
  23. XM_047437414.1XP_047293370.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

  24. XM_011525887.4XP_011524189.1  E3 ubiquitin-protein ligase NEDD4-like isoform X12

    UniProtKB/TrEMBL
    A0A6Q8PFI7
    Conserved Domains (6) summary
    cd04033
    Location:13171
    C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)
    smart00456
    Location:567617
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:6781007
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00078
    Location:6541008
    HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
    cd00201
    Location:518548
    WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
    pfam00397
    Location:405434
    WW; WW domain
  25. XM_047437411.1XP_047293367.1  E3 ubiquitin-protein ligase NEDD4-like isoform X20

  26. XM_047437413.1XP_047293369.1  E3 ubiquitin-protein ligase NEDD4-like isoform X21

  27. XM_047437412.1XP_047293368.1  E3 ubiquitin-protein ligase NEDD4-like isoform X20

  28. XM_006722430.5XP_006722493.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

    UniProtKB/TrEMBL
    B7Z6K0
    Conserved Domains (6) summary
    smart00456
    Location:428478
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:539868
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00201
    Location:379409
    WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
    pfam00397
    Location:266295
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
    cl26464
    Location:198381
    Atrophin-1; Atrophin-1 family
  29. XM_017025679.3XP_016881168.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

    UniProtKB/TrEMBL
    B7Z6K0
    Conserved Domains (5) summary
    smart00456
    Location:428460
    WW; Domain with 2 conserved Trp (W) residues
    smart00119
    Location:521850
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    PHA03247
    Location:198381
    PHA03247; large tegument protein UL36; Provisional
    pfam00397
    Location:266295
    WW; WW domain
    cl14603
    Location:132
    C2; C2 domain
  30. XM_017025681.3XP_016881170.1  E3 ubiquitin-protein ligase NEDD4-like isoform X21

    UniProtKB/TrEMBL
    K7ERN1
    Related
    ENSP00000468332.1, ENST00000587881.1
  31. XM_047437415.1XP_047293371.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

  32. XM_047437416.1XP_047293372.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

  33. XM_005266658.5XP_005266715.3  E3 ubiquitin-protein ligase NEDD4-like isoform X1

  34. XM_005266660.5XP_005266717.3  E3 ubiquitin-protein ligase NEDD4-like isoform X2

    UniProtKB/TrEMBL
    A0A1B0GVY1
    Related
    ENSP00000490696.1, ENST00000635997.1
  35. XM_006722421.5XP_006722484.3  E3 ubiquitin-protein ligase NEDD4-like isoform X3

  36. XM_005266663.5XP_005266720.3  E3 ubiquitin-protein ligase NEDD4-like isoform X4

  37. XM_017025676.2XP_016881165.2  E3 ubiquitin-protein ligase NEDD4-like isoform X5

  38. XM_017025677.2XP_016881166.2  E3 ubiquitin-protein ligase NEDD4-like isoform X6

  39. XM_006722424.4XP_006722487.3  E3 ubiquitin-protein ligase NEDD4-like isoform X7

  40. XM_006722425.4XP_006722488.3  E3 ubiquitin-protein ligase NEDD4-like isoform X8

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060942.1 Alternate T2T-CHM13v2.0

    Range
    58244126..58602300
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054318394.1XP_054174369.1  E3 ubiquitin-protein ligase NEDD4-like isoform X11

  2. XM_054318398.1XP_054174373.1  E3 ubiquitin-protein ligase NEDD4-like isoform X13

  3. XM_054318399.1XP_054174374.1  E3 ubiquitin-protein ligase NEDD4-like isoform X14

  4. XM_054318401.1XP_054174376.1  E3 ubiquitin-protein ligase NEDD4-like isoform X16

  5. XM_054318400.1XP_054174375.1  E3 ubiquitin-protein ligase NEDD4-like isoform X15

  6. XM_054318403.1XP_054174378.1  E3 ubiquitin-protein ligase NEDD4-like isoform X18

  7. XM_054318418.1XP_054174393.1  E3 ubiquitin-protein ligase NEDD4-like isoform X24

  8. XM_054318412.1XP_054174387.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  9. XM_054318416.1XP_054174391.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

  10. XM_054318417.1XP_054174392.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

  11. XM_054318415.1XP_054174390.1  E3 ubiquitin-protein ligase NEDD4-like isoform X23

  12. XM_054318413.1XP_054174388.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  13. XM_054318414.1XP_054174389.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  14. XM_054318390.1XP_054174365.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  15. XM_054318393.1XP_054174368.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  16. XM_054318397.1XP_054174372.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

  17. XM_054318391.1XP_054174366.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

  18. XM_054318402.1XP_054174377.1  E3 ubiquitin-protein ligase NEDD4-like isoform X17

  19. XM_054318404.1XP_054174379.1  E3 ubiquitin-protein ligase NEDD4-like isoform X19

  20. XM_054318392.1XP_054174367.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  21. XM_054318396.1XP_054174371.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

  22. XM_054318410.1XP_054174385.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

  23. XM_054318409.1XP_054174384.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

  24. XM_054318395.1XP_054174370.1  E3 ubiquitin-protein ligase NEDD4-like isoform X12

  25. XM_054318405.1XP_054174380.1  E3 ubiquitin-protein ligase NEDD4-like isoform X20

  26. XM_054318407.1XP_054174382.1  E3 ubiquitin-protein ligase NEDD4-like isoform X21

  27. XM_054318406.1XP_054174381.1  E3 ubiquitin-protein ligase NEDD4-like isoform X20

  28. XM_054318408.1XP_054174383.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

  29. XM_054318411.1XP_054174386.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

  30. XM_054318419.1XP_054174394.1  E3 ubiquitin-protein ligase NEDD4-like isoform X21

  31. XM_054318382.1XP_054174357.1  E3 ubiquitin-protein ligase NEDD4-like isoform X1

  32. XM_054318383.1XP_054174358.1  E3 ubiquitin-protein ligase NEDD4-like isoform X2

    UniProtKB/TrEMBL
    A0A1B0GVY1
  33. XM_054318384.1XP_054174359.1  E3 ubiquitin-protein ligase NEDD4-like isoform X3

  34. XM_054318385.1XP_054174360.1  E3 ubiquitin-protein ligase NEDD4-like isoform X4

  35. XM_054318386.1XP_054174361.1  E3 ubiquitin-protein ligase NEDD4-like isoform X5

  36. XM_054318387.1XP_054174362.1  E3 ubiquitin-protein ligase NEDD4-like isoform X6

  37. XM_054318388.1XP_054174363.1  E3 ubiquitin-protein ligase NEDD4-like isoform X7

  38. XM_054318389.1XP_054174364.1  E3 ubiquitin-protein ligase NEDD4-like isoform X8