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UniProtKB - Q9P2P5 (HECW2_HUMAN)

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Protein

E3 ubiquitin-protein ligase HECW2

Gene

HECW2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).2 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1540Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9P2P5
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase HECW2 (EC:2.3.2.26)
Alternative name(s):
HECT, C2 and WW domain-containing protein 2
HECT-type E3 ubiquitin transferase HECW2
NEDD4-like E3 ubiquitin-protein ligase 2
Gene namesi
Name:HECW2
Synonyms:KIAA1301, NEDL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000138411.10
HGNCiHGNC:29853 HECW2
MIMi617245 gene
neXtProtiNX_Q9P2P5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:617268
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0779051191R → Q in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854416EnsemblClinVar.1
Natural variantiVAR_0779061193F → V in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854422EnsemblClinVar.1
Natural variantiVAR_0779071330R → W in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854417EnsemblClinVar.1
Natural variantiVAR_0779081445E → G in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854424EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi57520
MalaCardsiHECW2
MIMi617268 phenotype
OpenTargetsiENSG00000138411
PharmGKBiPA134925001

Polymorphism and mutation databases

BioMutaiHECW2
DMDMi126215718

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002776671 – 1572E3 ubiquitin-protein ligase HECW2Add BLAST1572

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei48PhosphoserineCombined sources1
Modified residuei852PhosphoserineCombined sources1
Modified residuei909PhosphoserineCombined sources1
Modified residuei1175PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9P2P5
MaxQBiQ9P2P5
PaxDbiQ9P2P5
PeptideAtlasiQ9P2P5
PRIDEiQ9P2P5

PTM databases

iPTMnetiQ9P2P5
PhosphoSitePlusiQ9P2P5

Expressioni

Tissue specificityi

Predominantly expressed in adult brain, lung and heart.1 Publication

Gene expression databases

BgeeiENSG00000138411
CleanExiHS_HECW2
ExpressionAtlasiQ9P2P5 baseline and differential
GenevisibleiQ9P2P5 HS

Organism-specific databases

HPAiHPA034609

Interactioni

Subunit structurei

Interacts with TP73 (PubMed:12890487). Interacts with FZR1 (PubMed:24163370).2 Publications

Protein-protein interaction databases

BioGridi121581, 301 interactors
IntActiQ9P2P5, 1 interactor
MINTiQ9P2P5
STRINGi9606.ENSP00000260983

Structurei

Secondary structure

11572
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi60 – 64Combined sources5
Beta strandi66 – 69Combined sources4
Beta strandi76 – 81Combined sources6
Beta strandi91 – 96Combined sources6
Beta strandi117 – 123Combined sources7
Beta strandi133 – 144Combined sources12
Turni145 – 148Combined sources4
Beta strandi149 – 153Combined sources5
Beta strandi157 – 160Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LFENMR-A43-162[»]
ProteinModelPortaliQ9P2P5
SMRiQ9P2P5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini172 – 282C2PROSITE-ProRule annotationAdd BLAST111
Domaini807 – 840WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini985 – 1018WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini1237 – 1572HECTPROSITE-ProRule annotationAdd BLAST336

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni737 – 1068Interaction with TP731 PublicationAdd BLAST332

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili847 – 874Sequence analysisAdd BLAST28

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000069940
HOVERGENiHBG057414
InParanoidiQ9P2P5
KOiK12168
OMAiYHIDENS
OrthoDBiEOG091G0A54
PhylomeDBiQ9P2P5
TreeFamiTF313938

Family and domain databases

CDDicd08691 C2_NEDL1-like, 1 hit
cd00078 HECTc, 1 hit
cd00201 WW, 2 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR037795 C2_HECW
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR032348 HECW_N
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF00632 HECT, 1 hit
PF16562 HECW_N, 1 hit
PF00397 WW, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 2 hits
SUPFAMiSSF51045 SSF51045, 2 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 2 hits
PS50020 WW_DOMAIN_2, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9P2P5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASSAREHLL FVRRRNPQMR YTLSPENLQS LAAQSSMPEN MTLQRANSDT 
        60         70         80         90        100
DLVTSESRSS LTASMYEYTL GQAQNLIIFW DIKEEVDPSD WIGLYHIDEN 
       110        120        130        140        150
SPANFWDSKN RGVTGTQKGQ IVWRIEPGPY FMEPEIKICF KYYHGISGAL 
       160        170        180        190        200
RATTPCITVK NPAVMMGAEG MEGGASGNLH SRKLVSFTLS DLRAVGLKKG 
       210        220        230        240        250
MFFNPDPYLK MSIQPGKKSS FPTCAHHGQE RRSTIISNTT NPIWHREKYS 
       260        270        280        290        300
FFALLTDVLE IEIKDKFAKS RPIIKRFLGK LTIPVQRLLE RQAIGDQMLS 
       310        320        330        340        350
YNLGRRLPAD HVSGYLQFKV EVTSSVHEDA SPEAVGTILG VNSVNGDLGS 
       360        370        380        390        400
PSDDEDMPGS HHDSQVCSNG PVSEDSAADG TPKHSFRTSS TLEIDTEELT 
       410        420        430        440        450
STSSRTSPPR GRQDSLNDYL DAIEHNGHSR PGTATCSERS MGASPKLRSS 
       460        470        480        490        500
FPTDTRLNAM LHIDSDEEDH EFQQDLGYPS SLEEEGGLIM FSRASRADDG 
       510        520        530        540        550
SLTSQTKLED NPVENEEAST HEAASFEDKP ENLPELAESS LPAGPAPEEG 
       560        570        580        590        600
EGGPEPQPSA DQGSAELCGS QEVDQPTSGA DTGTSDASGG SRRAVSETES 
       610        620        630        640        650
LDQGSEPSQV SSETEPSDPA RTESVSEAST RPEGESDLEC ADSSCNESVT 
       660        670        680        690        700
TQLSSVDTRC SSLESARFPE TPAFSSQEEE DGACAAEPTS SGPAEGSQES 
       710        720        730        740        750
VCTAGSLPVV QVPSGEDEGP GAESATVPDQ EELGEVWQRR GSLEGAAAAA 
       760        770        780        790        800
ESPPQEEGSA GEAQGTCEGA TAQEEGATGG SQANGHQPLR SLPSVRQDVS 
       810        820        830        840        850
RYQRVDEALP PNWEARIDSH GRIFYVDHVN RTTTWQRPTA PPAPQVLQRS 
       860        870        880        890        900
NSIQQMEQLN RRYQSIRRTM TNERPEENTN AIDGAGEEAD FHQASADFRR 
       910        920        930        940        950
ENILPHSTSR SRITLLLQSP PVKFLISPEF FTVLHSNPSA YRMFTNNTCL 
       960        970        980        990       1000
KHMITKVRRD THHFERYQHN RDLVGFLNMF ANKQLELPRG WEMKHDHQGK 
      1010       1020       1030       1040       1050
AFFVDHNSRT TTFIDPRLPL QSSRPTSALV HRQHLTRQRS HSAGEVGEDS 
      1060       1070       1080       1090       1100
RHAGPPVLPR PSSTFNTVSR PQYQDMVPVA YNDKIVAFLR QPNIFEILQE 
      1110       1120       1130       1140       1150
RQPDLTRNHS LREKIQFIRT EGTPGLVRLS SDADLVMLLS LFEEEIMSYV 
      1160       1170       1180       1190       1200
PPHALLHPSY CQSPRGSPVS SPQNSPGTQR ANARAPAPYK RDFEAKLRNF 
      1210       1220       1230       1240       1250
YRKLETKGYG QGPGKLKLII RRDHLLEDAF NQIMGYSRKD LQRNKLYVTF 
      1260       1270       1280       1290       1300
VGEEGLDYSG PSREFFFLVS RELFNPYYGL FEYSANDTYT VQISPMSAFV 
      1310       1320       1330       1340       1350
DNHHEWFRFS GRILGLALIH QYLLDAFFTR PFYKALLRIL CDLSDLEYLD 
      1360       1370       1380       1390       1400
EEFHQSLQWM KDNDIHDILD LTFTVNEEVF GQITERELKP GGANIPVTEK 
      1410       1420       1430       1440       1450
NKKEYIERMV KWRIERGVVQ QTESLVRGFY EVVDARLVSV FDARELELVI 
      1460       1470       1480       1490       1500
AGTAEIDLSD WRNNTEYRGG YHDNHIVIRW FWAAVERFNN EQRLRLLQFV 
      1510       1520       1530       1540       1550
TGTSSIPYEG FASLRGSNGP RRFCVEKWGK ITALPRAHTC FNRLDLPPYP 
      1560       1570 
SFSMLYEKLL TAVEETSTFG LE
Length:1,572
Mass (Da):175,769
Last modified:February 20, 2007 - v2
Checksum:iDCFF0146ADFAF8BE
GO
Isoform 2 (identifier: Q9P2P5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-131: Missing.
     191-213: DLRAVGLKKGMFFNPDPYLKMSI → ARKEEQFPHLCPPRAGETVYYHQ
     214-1572: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:82
Mass (Da):9,041
Checksum:i954974F23D7CB9F5
GO

Sequence cautioni

The sequence BAA92539 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAH18262 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1074Q → H in CAH18262 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0779051191R → Q in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854416EnsemblClinVar.1
Natural variantiVAR_0779061193F → V in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854422EnsemblClinVar.1
Natural variantiVAR_0779071330R → W in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854417EnsemblClinVar.1
Natural variantiVAR_0779081445E → G in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854424EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0591061 – 131Missing in isoform 2. 1 PublicationAdd BLAST131
Alternative sequenceiVSP_059107191 – 213DLRAV…LKMSI → ARKEEQFPHLCPPRAGETVY YHQ in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_059108214 – 1572Missing in isoform 2. 1 PublicationAdd BLAST1359

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037722 mRNA Translation: BAA92539.1 Different initiation.
AL390186 mRNA Translation: CAB99103.1
CR749424 mRNA Translation: CAH18262.1 Sequence problems.
AC020571 Genomic DNA No translation available.
AC068544 Genomic DNA No translation available.
AC073905 Genomic DNA No translation available.
AC074090 Genomic DNA No translation available.
AC093379 Genomic DNA No translation available.
BC117194 mRNA Translation: AAI17195.1
BC117198 mRNA Translation: AAI17199.1
CCDSiCCDS33354.1 [Q9P2P5-1]
PIRiT51886
RefSeqiNP_065811.1, NM_020760.2 [Q9P2P5-1]
XP_016860052.1, XM_017004563.1 [Q9P2P5-1]
UniGeneiHs.633212
Hs.654742

Genome annotation databases

EnsembliENST00000260983; ENSP00000260983; ENSG00000138411 [Q9P2P5-1]
GeneIDi57520
KEGGihsa:57520
UCSCiuc002utl.2 human [Q9P2P5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHECW2_HUMAN
AccessioniPrimary (citable) accession number: Q9P2P5
Secondary accession number(s): B8ZZB4
, Q17RT5, Q68DF8, Q9NPS9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: April 25, 2018
This is version 138 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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