HECW2

Protein identityUniProt · HPA

UniProt accession

Q9P2P5

Gene

HECW2

Ensembl

ENSG00000138411

Chromosome

2

Canonical length

1572 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

1572 residues, UniProt reviewed canonical sequence.

>Q9P2P5|HECW2
     1  MASSAREHLL FVRRRNPQMR YTLSPENLQS LAAQSSMPEN MTLQRANSDT DLVTSESRSS
    61  LTASMYEYTL GQAQNLIIFW DIKEEVDPSD WIGLYHIDEN SPANFWDSKN RGVTGTQKGQ
   121  IVWRIEPGPY FMEPEIKICF KYYHGISGAL RATTPCITVK NPAVMMGAEG MEGGASGNLH
   181  SRKLVSFTLS DLRAVGLKKG MFFNPDPYLK MSIQPGKKSS FPTCAHHGQE RRSTIISNTT
   241  NPIWHREKYS FFALLTDVLE IEIKDKFAKS RPIIKRFLGK LTIPVQRLLE RQAIGDQMLS
   301  YNLGRRLPAD HVSGYLQFKV EVTSSVHEDA SPEAVGTILG VNSVNGDLGS PSDDEDMPGS
   361  HHDSQVCSNG PVSEDSAADG TPKHSFRTSS TLEIDTEELT STSSRTSPPR GRQDSLNDYL
   421  DAIEHNGHSR PGTATCSERS MGASPKLRSS FPTDTRLNAM LHIDSDEEDH EFQQDLGYPS
   481  SLEEEGGLIM FSRASRADDG SLTSQTKLED NPVENEEAST HEAASFEDKP ENLPELAESS
   541  LPAGPAPEEG EGGPEPQPSA DQGSAELCGS QEVDQPTSGA DTGTSDASGG SRRAVSETES
   601  LDQGSEPSQV SSETEPSDPA RTESVSEAST RPEGESDLEC ADSSCNESVT TQLSSVDTRC
   661  SSLESARFPE TPAFSSQEEE DGACAAEPTS SGPAEGSQES VCTAGSLPVV QVPSGEDEGP
   721  GAESATVPDQ EELGEVWQRR GSLEGAAAAA ESPPQEEGSA GEAQGTCEGA TAQEEGATGG
   781  SQANGHQPLR SLPSVRQDVS RYQRVDEALP PNWEARIDSH GRIFYVDHVN RTTTWQRPTA
   841  PPAPQVLQRS NSIQQMEQLN RRYQSIRRTM TNERPEENTN AIDGAGEEAD FHQASADFRR
   901  ENILPHSTSR SRITLLLQSP PVKFLISPEF FTVLHSNPSA YRMFTNNTCL KHMITKVRRD
   961  THHFERYQHN RDLVGFLNMF ANKQLELPRG WEMKHDHQGK AFFVDHNSRT TTFIDPRLPL
  1021  QSSRPTSALV HRQHLTRQRS HSAGEVGEDS RHAGPPVLPR PSSTFNTVSR PQYQDMVPVA
  1081  YNDKIVAFLR QPNIFEILQE RQPDLTRNHS LREKIQFIRT EGTPGLVRLS SDADLVMLLS
  1141  LFEEEIMSYV PPHALLHPSY CQSPRGSPVS SPQNSPGTQR ANARAPAPYK RDFEAKLRNF
  1201  YRKLETKGYG QGPGKLKLII RRDHLLEDAF NQIMGYSRKD LQRNKLYVTF VGEEGLDYSG
  1261  PSREFFFLVS RELFNPYYGL FEYSANDTYT VQISPMSAFV DNHHEWFRFS GRILGLALIH
  1321  QYLLDAFFTR PFYKALLRIL CDLSDLEYLD EEFHQSLQWM KDNDIHDILD LTFTVNEEVF
  1381  GQITERELKP GGANIPVTEK NKKEYIERMV KWRIERGVVQ QTESLVRGFY EVVDARLVSV
  1441  FDARELELVI AGTAEIDLSD WRNNTEYRGG YHDNHIVIRW FWAAVERFNN EQRLRLLQFV
  1501  TGTSSIPYEG FASLRGSNGP RRFCVEKWGK ITALPRAHTC FNRLDLPPYP SFSMLYEKLL
  1561  TAVEETSTFG LE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HECW2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

7.6 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HECW2.

Disease | AllUniProt

Conditions HECW2 is implicated in, by any mechanism.

• Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL) MIM:617268

Disease | GeneticClinVar

38 pathogenic / likely-pathogenic of 556 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with hypotonia, seizures, and absent language
• Inborn genetic diseases
• HECW2-related disorder
• Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
• Abnormality of the nervous system

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.26

gnomAD pLI

1

gnomAD missense Z

3.31

DepMap mean gene effect

-0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• protein ubiquitination
• regulation of dendrite morphogenesis
• regulation of mitotic metaphase/anaphase transition
• ubiquitin-dependent protein catabolic process

Molecular functions

• ubiquitin protein ligase activity

Cellular components

• cytoplasm
• mitotic spindle

Protein domainsUniProt · Pfam · InterPro

• C2 domain
• HECT domain
• WW domain
• E3 ubiquitin-protein ligase HECW1/2, N-terminal
• C2 domain superfamily
• HECT, E3 ligase catalytic domain
• WW domain superfamily
• E3 ubiquitin-protein ligase HECW, C2 domain
• E3 ubiquitin-protein ligase HECW1, helical box domain
• E3 ubiquitin-protein ligase
• C2 domain
• WW domain
• HECT-domain (ubiquitin-transferase)
• N-terminal domain of E3 ubiquitin-protein ligase HECW1 and 2
• Helical box domain of E3 ubiquitin-protein ligase HECW1

KeywordsUniProt

• Coiled coil
• Cytoplasm
• Cytoskeleton
• Phosphoprotein
• Repeat
• Transferase
• Ubl conjugation
• Ubl conjugation pathway

InteractionsUniProt · HPA

Protein binding partners of HECW2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FZR1
• TP73