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

    Gene ID: 23327, updated on 10-Dec-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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See NEDD4L in Genome Data Viewer
    Location:
    18q21.31
    Exon count:
    43
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (58044226..58401540)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (58244126..58602300)
    RS_2024_09 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

    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

    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 import across plasma membrane 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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in neuromuscular junction development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in neuron projection development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein ubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in receptor catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in receptor internalization IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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 regulation of synapse organization IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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 apical plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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_2024_08

    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

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    3. XM_047437407.1XP_047293363.1  E3 ubiquitin-protein ligase NEDD4-like isoform X14

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    4. XM_047437408.1XP_047293364.1  E3 ubiquitin-protein ligase NEDD4-like isoform X16

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    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

      UniProtKB/TrEMBL
      A0A6Q8PG51
    8. XM_047437418.1XP_047293374.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    9. XM_047437420.1XP_047293376.1  E3 ubiquitin-protein ligase NEDD4-like isoform X23

      UniProtKB/TrEMBL
      B7Z2P9
    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

      UniProtKB/TrEMBL
      B7Z6K0
    12. XM_047437417.1XP_047293373.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    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

      UniProtKB/TrEMBL
      B7Z2P9
    16. XM_047437404.1XP_047293360.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    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

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    19. XM_047437410.1XP_047293366.1  E3 ubiquitin-protein ligase NEDD4-like isoform X19

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    20. XM_047437403.1XP_047293359.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    21. XM_047437405.1XP_047293361.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

      UniProtKB/TrEMBL
      B7Z2P9
      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

      UniProtKB/TrEMBL
      B7Z6K0
    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

      UniProtKB/TrEMBL
      B7Z2P9
    26. XM_047437413.1XP_047293369.1  E3 ubiquitin-protein ligase NEDD4-like isoform X21

      UniProtKB/TrEMBL
      K7ERN1
    27. XM_047437412.1XP_047293368.1  E3 ubiquitin-protein ligase NEDD4-like isoform X20

      UniProtKB/TrEMBL
      B7Z2P9
    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

      UniProtKB/TrEMBL
      B7Z6K0
    32. XM_047437416.1XP_047293372.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

      UniProtKB/TrEMBL
      B7Z6K0
    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

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    2. XM_054318398.1XP_054174373.1  E3 ubiquitin-protein ligase NEDD4-like isoform X13

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    3. XM_054318399.1XP_054174374.1  E3 ubiquitin-protein ligase NEDD4-like isoform X14

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    4. XM_054318401.1XP_054174376.1  E3 ubiquitin-protein ligase NEDD4-like isoform X16

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    5. XM_054318400.1XP_054174375.1  E3 ubiquitin-protein ligase NEDD4-like isoform X15

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    6. XM_054318403.1XP_054174378.1  E3 ubiquitin-protein ligase NEDD4-like isoform X18

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    7. XM_054318418.1XP_054174393.1  E3 ubiquitin-protein ligase NEDD4-like isoform X24

      UniProtKB/TrEMBL
      A0A6Q8PG51
    8. XM_054318412.1XP_054174387.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    9. XM_054318416.1XP_054174391.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

      UniProtKB/TrEMBL
      B7Z2P9
    10. XM_054318417.1XP_054174392.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

      UniProtKB/TrEMBL
      B7Z2P9
    11. XM_054318415.1XP_054174390.1  E3 ubiquitin-protein ligase NEDD4-like isoform X23

      UniProtKB/TrEMBL
      B7Z2P9
    12. XM_054318413.1XP_054174388.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    13. XM_054318414.1XP_054174389.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    14. XM_054318390.1XP_054174365.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    15. XM_054318393.1XP_054174368.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    16. XM_054318397.1XP_054174372.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

      UniProtKB/TrEMBL
      B7Z2P9
    17. XM_054318391.1XP_054174366.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

      UniProtKB/TrEMBL
      B7Z2P9
    18. XM_054318402.1XP_054174377.1  E3 ubiquitin-protein ligase NEDD4-like isoform X17

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    19. XM_054318404.1XP_054174379.1  E3 ubiquitin-protein ligase NEDD4-like isoform X19

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    20. XM_054318392.1XP_054174367.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    21. XM_054318396.1XP_054174371.1  E3 ubiquitin-protein ligase NEDD4-like isoform X10

      UniProtKB/TrEMBL
      B7Z2P9
    22. XM_054318410.1XP_054174385.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

      UniProtKB/TrEMBL
      B7Z6K0
    23. XM_054318409.1XP_054174384.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

      UniProtKB/TrEMBL
      B7Z6K0
    24. XM_054318395.1XP_054174370.1  E3 ubiquitin-protein ligase NEDD4-like isoform X12

      UniProtKB/TrEMBL
      A0A6Q8PFI7
    25. XM_054318405.1XP_054174380.1  E3 ubiquitin-protein ligase NEDD4-like isoform X20

      UniProtKB/TrEMBL
      B7Z2P9
    26. XM_054318407.1XP_054174382.1  E3 ubiquitin-protein ligase NEDD4-like isoform X21

      UniProtKB/TrEMBL
      K7ERN1
    27. XM_054318406.1XP_054174381.1  E3 ubiquitin-protein ligase NEDD4-like isoform X20

      UniProtKB/TrEMBL
      B7Z2P9
    28. XM_054318408.1XP_054174383.1  E3 ubiquitin-protein ligase NEDD4-like isoform X22

      UniProtKB/TrEMBL
      B7Z6K0
    29. XM_054318411.1XP_054174386.1  E3 ubiquitin-protein ligase NEDD4-like isoform X9

      UniProtKB/TrEMBL
      B7Z6K0
    30. XM_054318419.1XP_054174394.1  E3 ubiquitin-protein ligase NEDD4-like isoform X21

      UniProtKB/TrEMBL
      K7ERN1
    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