Format

Send to:

Choose Destination

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

Gene ID: 57520, updated on 15-Apr-2019

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
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

Genomic context

See HECW2 in Genome Data Viewer
Location:
2q32.3
Exon count:
32
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 2 NC_000002.12 (196194370..196593692, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (197063971..197458416, 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 uncharacterized LOC101927454 Neighboring gene serine/threonine kinase 17b Neighboring gene HECW2 antisense RNA 1 Neighboring gene RNA, 7SL, cytoplasmic 820, pseudogene Neighboring gene uncharacterized LOC105373822 Neighboring gene uncharacterized LOC105373821 Neighboring gene uncharacterized LOC105373823 Neighboring gene uncharacterized LOC100130452 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 FunctionsWhat's a GeneRIF?

Pathways from BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystem (from REACTOME)
    Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystemIntracellular foreign or aberrant host proteins are cleaved into peptide fragments of a precise size, such that they can be loaded on to class I MHC molecules and presented externally to cytotoxic T ...
  • Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
    Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp686M17164

Gene Ontology Provided by GOA

Function Evidence Code Pubs
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
negative regulation of sodium ion transmembrane transporter activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
proteasome-mediated ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein polyubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of dendrite morphogenesis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of mitotic metaphase/anaphase transition IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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

NCBI Reference Sequences (RefSeq)

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_053156.1 RefSeqGene

    Range
    5001..404323
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001304840.2NP_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)
    AB037722, AC020571, AC074090, AL390186, CR749424, R41900
    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
    Related
    ENSP00000495418.1, ENST00000644978.2
    Conserved Domains (6) 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)
    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:45164
    HECW_N; N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2
  3. NM_020760.3NP_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)
    AB037722, AC020571, AC068544, AL390186, BC117194, R41900
    Consensus CDS
    CCDS33354.1
    UniProtKB/Swiss-Prot
    Q9P2P5
    Related
    ENSP00000260983.2, ENST00000260983.8
    Conserved Domains (6) 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)
    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:45164
    HECW_N; N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

    Range
    196194370..196593692 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006712646.3XP_006712709.1  E3 ubiquitin-protein ligase HECW2 isoform X1

    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_024453020.1XP_024308788.1  E3 ubiquitin-protein ligase HECW2 isoform X1

    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
  3. XM_024453021.1XP_024308789.1  E3 ubiquitin-protein ligase HECW2 isoform X1

    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_006712648.4XP_006712711.1  E3 ubiquitin-protein ligase HECW2 isoform X2

    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
Support Center