HECW2

HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 is a protein that in humans is encoded by the HECW2 gene.[5]

HECW2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LFE
Identifiers
Aliases	HECW2, NEDL2, HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2, NDHSAL
External IDs	OMIM: 617245 MGI: 2685817 HomoloGene: 66192 GeneCards: HECW2
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q32.3 Start 196,189,099 bp[1] End 196,593,684 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 C1.1 Start 53,806,876 bp[2] End 54,195,168 bp[2]
Gene ontology Molecular function • transferase activity • ubiquitin-protein transferase activity • GO:0001948 protein binding • GO:1904264, GO:1904822, GO:0090622, GO:0090302 ubiquitin protein ligase activity Cellular component • mitotic spindle • spindle • cytoskeleton • cytoplasm Biological process • protein ubiquitination • regulation of mitotic metaphase/anaphase transition • proteasome-mediated ubiquitin-dependent protein catabolic process • protein polyubiquitination • ubiquitin-dependent protein catabolic process • positive regulation of protein catabolic process • regulation of dendrite morphogenesis • negative regulation of sodium ion transmembrane transporter activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	57520	329152
Ensembl	ENSG00000138411	ENSMUSG00000042807
UniProt	Q9P2P5	Q6I6G8
RefSeq (mRNA)	NM_001304840 NM_020760 NM_001348768	NM_001001883 NM_172655
RefSeq (protein)	NP_001291769 NP_065811 NP_001335697	NP_001001883 NP_766243
Location (UCSC)	Chr 2: 196.19 – 196.59 Mb	Chr 1: 53.81 – 54.2 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Model organisms

Model organisms have been used in the study of HECW2 function. A conditional knockout mouse line called Hecw2^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12]

Hecw2 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[7][12]
Insulin	Normal
Homozygous viability at P14	Abnormal
Recessive lethal study	Abnormal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

Clinical significance

Mutations in the HECW2 gene have been associated to epilepsy and intellectual disability. These mutations affect one copy of the HECW2 gene and are believed to change the function of the HECW2 protein.[13]

References

1. GRCh38: Ensembl release 89: ENSG00000138411 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000042807 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2". Retrieved 2014-10-24.
6. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
7. "International Mouse Phenotyping Consortium".
8. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
9. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
10. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
11. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
12. "Infection and Immunity Immunophenotyping (3i) Consortium".
13. Halvardson J, Zhao JJ, Zaghlool A, Wentzel C, Georgii-Hemming P, Månsson E, Ederth Sävmarker H, Brandberg G, Soussi Zander C, Thuresson AC, Feuk L (2016). "Mutations in HECW2 are associated with intellectual disability and epilepsy". Journal of Medical Genetics. 53: 697–704. doi:10.1136/jmedgenet-2016-103814. PMC 5099177. PMID 27334371.

Further reading

• Miyazaki K, Ozaki T, Kato C, Hanamoto T, Fujita T, Irino S, Watanabe K, Nakagawa T, Nakagawara A (Aug 2003). "A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances its transcriptional activity". Biochemical and Biophysical Research Communications. 308 (1): 106–13. doi:10.1016/s0006-291x(03)01347-0. PMID 12890487.
• Cui Y, He S, Xing C, Lu K, Wang J, Xing G, Meng A, Jia S, He F, Zhang L (Jul 2011). "SCFFBXL¹⁵ regulates BMP signalling by directing the degradation of HECT-type ubiquitin ligase Smurf1". The EMBO Journal. 30 (13): 2675–89. doi:10.1038/emboj.2011.155. PMC 3155294. PMID 21572392.