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Aliases for HECW2 Gene

Aliases for HECW2 Gene

  • HECT, C2 And WW Domain Containing E3 Ubiquitin Protein Ligase 2 2 3 5
  • HECT-Type E3 Ubiquitin Transferase HECW2 3 4
  • NEDD4-Like E3 Ubiquitin-Protein Ligase 2 3 4
  • NEDL2 3 4
  • HECT, C2 And WW Domain-Containing Protein 2 4
  • NEDD4-Related E3 Ubiquitin Ligase NEDL2 3
  • E3 Ubiquitin-Protein Ligase HECW2 3
  • EC 2.3.2.26 4
  • KIAA1301 4
  • EC 6.3.2 61
  • NDHSAL 3

External Ids for HECW2 Gene

Previous GeneCards Identifiers for HECW2 Gene

  • GC02M196890
  • GC02M196772
  • GC02M197064
  • GC02M188916

Summaries for HECW2 Gene

Entrez Gene Summary for HECW2 Gene

  • 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]

GeneCards Summary for HECW2 Gene

HECW2 (HECT, C2 And WW Domain Containing E3 Ubiquitin Protein Ligase 2) is a Protein Coding gene. Diseases associated with HECW2 include Neurodevelopmental Disorder With Hypotonia, Seizures, And Absent Language and Hypotonia. Among its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. GO annotations related to this gene include ligase activity and ubiquitin-protein transferase activity. An important paralog of this gene is HECW1.

UniProtKB/Swiss-Prot for HECW2 Gene

  • E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73 (PubMed:12890487). Involved in the regulation of mitotic metaphase/anaphase transition (PubMed:24163370).

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HECW2 Gene

Genomics for HECW2 Gene

Regulatory Elements for HECW2 Gene

Enhancers for HECW2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02G196600 1.5 FANTOM5 Ensembl ENCODE 10.1 -8.0 -8033 2.0 PKNOX1 SIN3A BMI1 ZBTB40 RAD21 RFX5 GATA2 RCOR1 FOS CREM CCDC150 HECW2 LOC105373823
GH02G196591 1.1 ENCODE dbSUPER 10.8 +0.8 791 2.0 FUS SIN3A ZNF48 RAD21 GLIS2 ZNF366 SP3 CEBPB ZEB2 GATAD2B HECW2 ANKRD44 GC02P196542
GH02G196582 1.1 dbSUPER 10.8 +8.1 8071 6.8 HNRNPUL1 HDGF FOXA2 PKNOX1 CREB3L1 MLX ARNT ZFP64 ARID4B SIN3A GTF3C3 NPM1P46 HECW2 LOC101927482 GC02P196542
GH02G196748 1.1 ENCODE 10.4 -155.4 -155369 0.9 PKNOX1 FOXA2 MLX ZFP64 ARID4B DMAP1 FEZF1 YY1 SLC30A9 FOS HECW2 LOC100130452 GTF3C3
GH02G196751 1 Ensembl ENCODE 10.4 -157.6 -157568 0.3 CTCF PKNOX1 FOXA2 WRNIP1 ZNF644 RAD21 YY1 ZNF143 SMC3 HOMEZ HECW2 LOC100130452 GTF3C3
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HECW2 on UCSC Golden Path with GeneCards custom track

Promoters for HECW2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000128335 691 1600 SIN3A ZNF48 RAD21 ZNF366 SP3 CEBPB ZEB2 MAFF SMARCA4 ZNF341

Genomic Location for HECW2 Gene

Chromosome:
2
Start:
196,194,370 bp from pter
End:
196,593,692 bp from pter
Size:
399,323 bases
Orientation:
Minus strand

Genomic View for HECW2 Gene

Genes around HECW2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HECW2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HECW2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HECW2 Gene

Proteins for HECW2 Gene

  • Protein details for HECW2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P2P5-HECW2_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase HECW2
    Protein Accession:
    Q9P2P5
    Secondary Accessions:
    • B8ZZB4
    • Q17RT5
    • Q68DF8
    • Q9NPS9

    Protein attributes for HECW2 Gene

    Size:
    1572 amino acids
    Molecular mass:
    175769 Da
    Quaternary structure:
    • Interacts with TP73 (PubMed:12890487). Interacts with FZR1 (PubMed:24163370).
    SequenceCaution:
    • Sequence=BAA92539.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for HECW2 Gene

    Alternative splice isoforms for HECW2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HECW2 Gene

Selected DME Specific Peptides for HECW2 Gene

Q9P2P5:
  • LYEKLLTAVEET
  • KNKKEYI
  • NPYYGLF
  • RTTTWQRPT
  • HTCFNRLDLPPY
  • RLLQFVTG

Post-translational modifications for HECW2 Gene

  • Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.
  • Ubiquitination at isoforms=183
  • Modification sites at PhosphoSitePlus

Domains & Families for HECW2 Gene

Gene Families for HECW2 Gene

Protein Domains for HECW2 Gene

Suggested Antigen Peptide Sequences for HECW2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with HECW2: view

No data available for UniProtKB/Swiss-Prot for HECW2 Gene

Function for HECW2 Gene

Molecular function for HECW2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.
UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73 (PubMed:12890487). Involved in the regulation of mitotic metaphase/anaphase transition (PubMed:24163370).

Enzyme Numbers (IUBMB) for HECW2 Gene

Gene Ontology (GO) - Molecular Function for HECW2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IEA --
GO:0005515 protein binding IPI 24163370
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with HECW2: view
genes like me logo Genes that share phenotypes with HECW2: view

Animal Models for HECW2 Gene

MGI Knock Outs for HECW2:

Animal Model Products

  • Taconic Biosciences Mouse Models for HECW2

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for HECW2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HECW2 Gene

Localization for HECW2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HECW2 Gene

Cytoplasm. Cytoplasm, cytoskeleton, spindle.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HECW2 gene
Compartment Confidence
cytoskeleton 5
mitochondrion 3
cytosol 2
golgi apparatus 2
nucleus 1

Gene Ontology (GO) - Cellular Components for HECW2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0072686 mitotic spindle IDA 24163370
genes like me logo Genes that share ontologies with HECW2: view

Pathways & Interactions for HECW2 Gene

genes like me logo Genes that share pathways with HECW2: view

UniProtKB/Swiss-Prot Q9P2P5-HECW2_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for HECW2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016567 protein ubiquitination IEA --
GO:0030071 regulation of mitotic metaphase/anaphase transition IMP 24163370
genes like me logo Genes that share ontologies with HECW2: view

No data available for SIGNOR curated interactions for HECW2 Gene

Drugs & Compounds for HECW2 Gene

No Compound Related Data Available

Transcripts for HECW2 Gene

Unigene Clusters for HECW2 Gene

HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for HECW2

Alternative Splicing Database (ASD) splice patterns (SP) for HECW2 Gene

No ASD Table

Relevant External Links for HECW2 Gene

GeneLoc Exon Structure for
HECW2
ECgene alternative splicing isoforms for
HECW2

Expression for HECW2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HECW2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HECW2 Gene

This gene is overexpressed in Lung (x4.5).

Protein differential expression in normal tissues from HIPED for HECW2 Gene

This gene is overexpressed in Serum (63.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for HECW2 Gene



NURSA nuclear receptor signaling pathways regulating expression of HECW2 Gene:

HECW2

SOURCE GeneReport for Unigene cluster for HECW2 Gene:

Hs.654742

mRNA Expression by UniProt/SwissProt for HECW2 Gene:

Q9P2P5-HECW2_HUMAN
Tissue specificity: Predominantly expressed in adult brain, lung and heart.

Evidence on tissue expression from TISSUES for HECW2 Gene

  • Nervous system(4.3)
  • Heart(4.2)
  • Liver(4.2)
  • Lung(4.2)
genes like me logo Genes that share expression patterns with HECW2: view

Primer Products

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for HECW2 Gene

Orthologs for HECW2 Gene

This gene was present in the common ancestor of animals.

Orthologs for HECW2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HECW2 34 35
  • 99.45 (n)
cow
(Bos Taurus)
Mammalia HECW2 35 34
  • 93.97 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HECW2 35
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hecw2 34 16 35
  • 89.41 (n)
rat
(Rattus norvegicus)
Mammalia Hecw2 34
  • 88.87 (n)
dog
(Canis familiaris)
Mammalia HECW2 34 35
  • 88.11 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia HECW2 35
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves HECW2 34 35
  • 78.82 (n)
lizard
(Anolis carolinensis)
Reptilia HECW2 35
  • 84 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii hecw2 34
  • 70.61 (n)
hecw2a 35
  • 69 (a)
OneToMany
HECW2 (2 of 2) 35
  • 67 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta CG42797 35
  • 41 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea hecw-1 35
  • 32 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.1682 35
  • 68 (a)
OneToMany
Species where no ortholog for HECW2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for HECW2 Gene

ENSEMBL:
Gene Tree for HECW2 (if available)
TreeFam:
Gene Tree for HECW2 (if available)

Paralogs for HECW2 Gene

Paralogs for HECW2 Gene

(9) SIMAP similar genes for HECW2 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with HECW2: view

Variants for HECW2 Gene

Sequence variations from dbSNP and Humsavar for HECW2 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
VAR_077905 Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL) [MIM:617268]
VAR_077906 Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL) [MIM:617268]
VAR_077907 Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL) [MIM:617268]
VAR_077908 Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL) [MIM:617268]
rs878854416 Pathogenic 196,242,162(-) CAAGC(A/G)GGATT reference, missense

Structural Variations from Database of Genomic Variants (DGV) for HECW2 Gene

Variant ID Type Subtype PubMed ID
esv2671294 CNV deletion 23128226
esv2721335 CNV deletion 23290073
esv3304762 CNV mobile element insertion 20981092
esv3391461 CNV insertion 20981092
esv3584263 CNV loss 25503493
esv3593885 CNV loss 21293372
esv3593886 CNV loss 21293372
esv3593887 CNV loss 21293372
esv3593889 CNV loss 21293372
esv3593890 CNV loss 21293372
esv3593891 CNV gain 21293372
esv3593892 CNV loss 21293372
nsv1005678 CNV gain 25217958
nsv1124821 CNV duplication 24896259
nsv3095 CNV insertion 18451855
nsv507058 OTHER sequence alteration 20534489
nsv834504 CNV loss 17160897
nsv999398 CNV gain 25217958

Variation tolerance for HECW2 Gene

Residual Variation Intolerance Score: 4.61% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.59; 56.24% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HECW2 Gene

Human Gene Mutation Database (HGMD)
HECW2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HECW2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HECW2 Gene

Disorders for HECW2 Gene

MalaCards: The human disease database

(2) MalaCards diseases for HECW2 Gene - From: ClinVar, Swiss-Prot, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search HECW2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HECW2_HUMAN
  • Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL) [MIM:617268]: A neurodevelopmental disorder characterized by severely delayed psychomotor development, absent speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and macrocephaly. Brain imaging show cerebral atrophy, enlarged ventricles, and white matter abnormalities. {ECO:0000269 PubMed:27389779}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for HECW2

Genetic Association Database (GAD)
HECW2
Human Genome Epidemiology (HuGE) Navigator
HECW2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HECW2
genes like me logo Genes that share disorders with HECW2: view

No data available for Genatlas for HECW2 Gene

Publications for HECW2 Gene

  1. A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances its transcriptional activity. (PMID: 12890487) Miyazaki K. … Nakagawara A. (Biochem. Biophys. Res. Commun. 2003) 2 3 4 22 64
  2. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10718198) Nagase T. … Ohara O. (DNA Res. 2000) 2 3 4 64
  3. De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia. (PMID: 27389779) Berko E.R. … Chung W.K. (J. Med. Genet. 2016) 3 4 64
  4. The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting complex/cyclosome (APC/C)-Cdh1, and its tight regulation maintains the metaphase to anaphase transition. (PMID: 24163370) Lu L. … Zhang L. (J. Biol. Chem. 2013) 3 4 64
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose J.E. … Uhl G.R. (Mol. Med. 2010) 3 46 64

Products for HECW2 Gene

  • Addgene plasmids for HECW2

Sources for HECW2 Gene

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