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    HECW2 HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 [ Homo sapiens (human) ]

    Gene ID: 57520, updated on 5-May-2024

    Summary

    Official Symbol
    HECW2provided by HGNC
    Official Full Name
    HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2provided by HGNC
    Primary source
    HGNC:HGNC:29853
    See related
    Ensembl:ENSG00000138411 MIM:617245; AllianceGenome:HGNC:29853
    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
    NEDL2; NDHSAL
    Summary
    This gene encodes a member of a family of E3 ubiquitin ligases which plays an important role in the proliferation, migration and differentiation of neural crest cells as a regulator of glial cell line-derived neurotrophic factor (GDNF)/Ret signaling. This gene also plays an important role in angiogenesis through stabilization of endothelial cell-to-cell junctions as a regulator of angiomotin-like 1 stability. The encoded protein contains an N-terminal calcium/lipid-binding (C2) domain involved in membrane targeting, two-four WW domains responsible for cellular localization and substrate recognition, and a C-terminal homologous with E6-associated protein C-terminus (HECT) catalytic domain. Naturally occurring mutations in this gene are associated with neurodevelopmental delay, hypotonia, and epilepsy. The decreased expression of this gene in the aganglionic colon is associated with Hirschsprung's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]
    Expression
    Broad expression in spleen (RPKM 4.0), placenta (RPKM 3.5) and 19 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See HECW2 in Genome Data Viewer
    Location:
    2q32.3
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (196194072..196593554, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (196678133..197077648, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (197058796..197458278, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene dynein axonemal heavy chain 7 Neighboring gene glutathione S-transferase alpha 5 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16890 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16891 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16892 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:196961660-196962248 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16893 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16894 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16895 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:196977894-196978422 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:197023734-197024234 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16896 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12202 Neighboring gene uncharacterized LOC101927454 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12203 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16897 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16898 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16899 Neighboring gene small nucleolar RNA U13 Neighboring gene serine/threonine kinase 17b Neighboring gene MPRA-validated peak4000 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16900 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:197124217-197125416 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16901 Neighboring gene HECW2 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:197183033-197183534 Neighboring gene RNA, 7SL, cytoplasmic 820, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16902 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16903 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16904 Neighboring gene Sharpr-MPRA regulatory region 6737 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:197269708-197269898 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16905 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16906 Neighboring gene uncharacterized LOC105373822 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16907 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16908 Neighboring gene uncharacterized LOC105373821 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16909 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12204 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12205 Neighboring gene uncharacterized LOC105373823 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16910 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16911 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:197504225-197504762 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:197504763-197505300 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:197517516-197518164 Neighboring gene small Cajal body-specific RNA 16 Neighboring gene coiled-coil domain containing 150

    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?

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • DKFZp686M17164

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Process Evidence Code Pubs
    involved_in negative regulation of sodium ion transmembrane transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of dendrite morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in regulation of mitotic metaphase/anaphase transition IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in mitotic spindle IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    E3 ubiquitin-protein ligase HECW2
    Names
    HECT-type E3 ubiquitin transferase HECW2
    NEDD4-like E3 ubiquitin-protein ligase 2
    NEDD4-related E3 ubiquitin ligase NEDL2
    NP_001291769.1
    NP_001335697.1
    NP_065811.1
    XP_006712709.1
    XP_006712711.1
    XP_024308788.1
    XP_024308789.1
    XP_047301150.1
    XP_047301151.1
    XP_047301152.1
    XP_047301153.1
    XP_047301154.1
    XP_054199152.1
    XP_054199153.1
    XP_054199154.1
    XP_054199155.1
    XP_054199156.1
    XP_054199157.1
    XP_054199158.1
    XP_054199159.1
    XP_054199160.1

    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_053156.2 RefSeqGene

      Range
      5000..404482
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001304840.3NP_001291769.1  E3 ubiquitin-protein ligase HECW2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC020571, AC074090
      UniProtKB/TrEMBL
      A0A2C9F2N4
      Conserved Domains (4) summary
      pfam06390
      Location:108275
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
      smart00119
      Location:8841213
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
      cd00078
      Location:8601214
      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 ...
      pfam00397
      Location:453482
      WW; WW domain
    2. NM_001348768.2NP_001335697.1  E3 ubiquitin-protein ligase HECW2 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate exon in the 5' UTR, compared to variant 1. Both variants 1 and 3 encode the same isoform (1).
      Source sequence(s)
      AC020571, AC068544, AC074090
      Consensus CDS
      CCDS33354.1
      UniProtKB/Swiss-Prot
      B8ZZB4, Q17RT5, Q68DF8, Q9NPS9, Q9P2P5
      Related
      ENSP00000495418.1, ENST00000644978.2
      Conserved Domains (8) summary
      pfam06390
      Location:464631
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
      cd08691
      Location:185321
      C2_NEDL1-like; C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1)
      smart00456
      Location:9871018
      WW; Domain with 2 conserved Trp (W) residues
      PHA03169
      Location:584794
      PHA03169; hypothetical protein; Provisional
      cd00078
      Location:12161570
      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 ...
      pfam00397
      Location:809838
      WW; WW domain
      pfam16562
      Location:45162
      HECW_N; N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2
      pfam18436
      Location:915981
      HECW1_helix; Helical box domain of E3 ubiquitin-protein ligase HECW1
    3. NM_020760.4NP_065811.1  E3 ubiquitin-protein ligase HECW2 isoform 1

      See identical proteins and their annotated locations for NP_065811.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Both variants 1 and 3 encode the same isoform (1).
      Source sequence(s)
      AC020571, AC068544, AC074090
      Consensus CDS
      CCDS33354.1
      UniProtKB/Swiss-Prot
      B8ZZB4, Q17RT5, Q68DF8, Q9NPS9, Q9P2P5
      Related
      ENSP00000260983.2, ENST00000260983.8
      Conserved Domains (8) summary
      pfam06390
      Location:464631
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
      cd08691
      Location:185321
      C2_NEDL1-like; C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1)
      smart00456
      Location:9871018
      WW; Domain with 2 conserved Trp (W) residues
      PHA03169
      Location:584794
      PHA03169; hypothetical protein; Provisional
      cd00078
      Location:12161570
      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 ...
      pfam00397
      Location:809838
      WW; WW domain
      pfam16562
      Location:45162
      HECW_N; N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2
      pfam18436
      Location:915981
      HECW1_helix; Helical box domain of E3 ubiquitin-protein ligase HECW1

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      196194072..196593554 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006712646.4XP_006712709.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
      Conserved Domains (6) summary
      pfam06390
      Location:471638
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
      cd08691
      Location:185321
      C2_NEDL1-like; C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1)
      PHA03169
      Location:591801
      PHA03169; hypothetical protein; Provisional
      cd00078
      Location:12231577
      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 ...
      pfam00397
      Location:816845
      WW; WW domain
      pfam16562
      Location:45164
      HECW_N; N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2
    2. XM_047445197.1XP_047301153.1  E3 ubiquitin-protein ligase HECW2 isoform X2

      UniProtKB/Swiss-Prot
      B8ZZB4, Q17RT5, Q68DF8, Q9NPS9, Q9P2P5
    3. XM_024453020.2XP_024308788.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
      Related
      ENSP00000495504.1, ENST00000644030.1
      Conserved Domains (6) summary
      pfam06390
      Location:471638
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
      cd08691
      Location:185321
      C2_NEDL1-like; C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1)
      PHA03169
      Location:591801
      PHA03169; hypothetical protein; Provisional
      cd00078
      Location:12231577
      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 ...
      pfam00397
      Location:816845
      WW; WW domain
      pfam16562
      Location:45164
      HECW_N; N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2
    4. XM_024453021.2XP_024308789.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
      Conserved Domains (6) summary
      pfam06390
      Location:471638
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
      cd08691
      Location:185321
      C2_NEDL1-like; C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1)
      PHA03169
      Location:591801
      PHA03169; hypothetical protein; Provisional
      cd00078
      Location:12231577
      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 ...
      pfam00397
      Location:816845
      WW; WW domain
      pfam16562
      Location:45164
      HECW_N; N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2
    5. XM_047445198.1XP_047301154.1  E3 ubiquitin-protein ligase HECW2 isoform X2

      UniProtKB/Swiss-Prot
      B8ZZB4, Q17RT5, Q68DF8, Q9NPS9, Q9P2P5
    6. XM_047445195.1XP_047301151.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
    7. XM_047445196.1XP_047301152.1  E3 ubiquitin-protein ligase HECW2 isoform X2

      UniProtKB/Swiss-Prot
      B8ZZB4, Q17RT5, Q68DF8, Q9NPS9, Q9P2P5
    8. XM_047445194.1XP_047301150.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
    9. XM_006712648.5XP_006712711.1  E3 ubiquitin-protein ligase HECW2 isoform X3

      Conserved Domains (7) summary
      pfam06390
      Location:340507
      NESP55; Neuroendocrine-specific golgi protein P55 (NESP55)
      cd08691
      Location:54190
      C2_NEDL1-like; C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1)
      smart00119
      Location:11161445
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
      cd00078
      Location:10921446
      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 ...
      pfam00397
      Location:685714
      WW; WW domain
      pfam12446
      Location:556651
      DUF3682; Protein of unknown function (DUF3682)
      pfam16562
      Location:133
      HECW_N; N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      196678133..197077648 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343177.1XP_054199152.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
    2. XM_054343184.1XP_054199159.1  E3 ubiquitin-protein ligase HECW2 isoform X2

      UniProtKB/Swiss-Prot
      B8ZZB4, Q17RT5, Q68DF8, Q9NPS9, Q9P2P5
    3. XM_054343179.1XP_054199154.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
    4. XM_054343178.1XP_054199153.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
    5. XM_054343183.1XP_054199158.1  E3 ubiquitin-protein ligase HECW2 isoform X2

      UniProtKB/Swiss-Prot
      B8ZZB4, Q17RT5, Q68DF8, Q9NPS9, Q9P2P5
    6. XM_054343181.1XP_054199156.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
    7. XM_054343180.1XP_054199155.1  E3 ubiquitin-protein ligase HECW2 isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6F3
    8. XM_054343182.1XP_054199157.1  E3 ubiquitin-protein ligase HECW2 isoform X2

      UniProtKB/Swiss-Prot
      B8ZZB4, Q17RT5, Q68DF8, Q9NPS9, Q9P2P5
    9. XM_054343185.1XP_054199160.1  E3 ubiquitin-protein ligase HECW2 isoform X3