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Q9P2P5 (HECW2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase HECW2

EC=6.3.2.-
Alternative name(s):
HECT, C2 and WW domain-containing protein 2
NEDD4-like E3 ubiquitin-protein ligase 2
Gene names
Name:HECW2
Synonyms:KIAA1301, NEDL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1572 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73. Ref.5

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with TP73. Ref.5

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Predominantly expressed in adult brain, lung and heart. Ref.5

Sequence similarities

Contains 1 C2 domain.

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.

Contains 2 WW domains.

Sequence caution

The sequence BAA92539.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
Repeat
   Molecular functionLigase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processprotein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleus

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionubiquitin-protein ligase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9P2P5-1)

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.
Isoform 2 (identifier: Q9P2P5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-356: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15721572E3 ubiquitin-protein ligase HECW2
PRO_0000277667

Regions

Domain172 – 282111C2
Domain807 – 84034WW 1
Domain985 – 101834WW 2
Domain1237 – 1572336HECT
Region737 – 1068332Interaction with TP73
Coiled coil847 – 87428 Potential

Sites

Active site15401Glycyl thioester intermediate By similarity

Natural variations

Alternative sequence1 – 356356Missing in isoform 2.
VSP_023077

Experimental info

Sequence conflict10741Q → H in CAH18262. Ref.2

Secondary structure

................. 1572
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 20, 2007. Version 2.
Checksum: DCFF0146ADFAF8BE

FASTA1,572175,769
        10         20         30         40         50         60 
MASSAREHLL FVRRRNPQMR YTLSPENLQS LAAQSSMPEN MTLQRANSDT DLVTSESRSS 

        70         80         90        100        110        120 
LTASMYEYTL GQAQNLIIFW DIKEEVDPSD WIGLYHIDEN SPANFWDSKN RGVTGTQKGQ 

       130        140        150        160        170        180 
IVWRIEPGPY FMEPEIKICF KYYHGISGAL RATTPCITVK NPAVMMGAEG MEGGASGNLH 

       190        200        210        220        230        240 
SRKLVSFTLS DLRAVGLKKG MFFNPDPYLK MSIQPGKKSS FPTCAHHGQE RRSTIISNTT 

       250        260        270        280        290        300 
NPIWHREKYS FFALLTDVLE IEIKDKFAKS RPIIKRFLGK LTIPVQRLLE RQAIGDQMLS 

       310        320        330        340        350        360 
YNLGRRLPAD HVSGYLQFKV EVTSSVHEDA SPEAVGTILG VNSVNGDLGS PSDDEDMPGS 

       370        380        390        400        410        420 
HHDSQVCSNG PVSEDSAADG TPKHSFRTSS TLEIDTEELT STSSRTSPPR GRQDSLNDYL 

       430        440        450        460        470        480 
DAIEHNGHSR PGTATCSERS MGASPKLRSS FPTDTRLNAM LHIDSDEEDH EFQQDLGYPS 

       490        500        510        520        530        540 
SLEEEGGLIM FSRASRADDG SLTSQTKLED NPVENEEAST HEAASFEDKP ENLPELAESS 

       550        560        570        580        590        600 
LPAGPAPEEG EGGPEPQPSA DQGSAELCGS QEVDQPTSGA DTGTSDASGG SRRAVSETES 

       610        620        630        640        650        660 
LDQGSEPSQV SSETEPSDPA RTESVSEAST RPEGESDLEC ADSSCNESVT TQLSSVDTRC 

       670        680        690        700        710        720 
SSLESARFPE TPAFSSQEEE DGACAAEPTS SGPAEGSQES VCTAGSLPVV QVPSGEDEGP 

       730        740        750        760        770        780 
GAESATVPDQ EELGEVWQRR GSLEGAAAAA ESPPQEEGSA GEAQGTCEGA TAQEEGATGG 

       790        800        810        820        830        840 
SQANGHQPLR SLPSVRQDVS RYQRVDEALP PNWEARIDSH GRIFYVDHVN RTTTWQRPTA 

       850        860        870        880        890        900 
PPAPQVLQRS NSIQQMEQLN RRYQSIRRTM TNERPEENTN AIDGAGEEAD FHQASADFRR 

       910        920        930        940        950        960 
ENILPHSTSR SRITLLLQSP PVKFLISPEF FTVLHSNPSA YRMFTNNTCL KHMITKVRRD 

       970        980        990       1000       1010       1020 
THHFERYQHN RDLVGFLNMF ANKQLELPRG WEMKHDHQGK AFFVDHNSRT TTFIDPRLPL 

      1030       1040       1050       1060       1070       1080 
QSSRPTSALV HRQHLTRQRS HSAGEVGEDS RHAGPPVLPR PSSTFNTVSR PQYQDMVPVA 

      1090       1100       1110       1120       1130       1140 
YNDKIVAFLR QPNIFEILQE RQPDLTRNHS LREKIQFIRT EGTPGLVRLS SDADLVMLLS 

      1150       1160       1170       1180       1190       1200 
LFEEEIMSYV PPHALLHPSY CQSPRGSPVS SPQNSPGTQR ANARAPAPYK RDFEAKLRNF 

      1210       1220       1230       1240       1250       1260 
YRKLETKGYG QGPGKLKLII RRDHLLEDAF NQIMGYSRKD LQRNKLYVTF VGEEGLDYSG 

      1270       1280       1290       1300       1310       1320 
PSREFFFLVS RELFNPYYGL FEYSANDTYT VQISPMSAFV DNHHEWFRFS GRILGLALIH 

      1330       1340       1350       1360       1370       1380 
QYLLDAFFTR PFYKALLRIL CDLSDLEYLD EEFHQSLQWM KDNDIHDILD LTFTVNEEVF 

      1390       1400       1410       1420       1430       1440 
GQITERELKP GGANIPVTEK NKKEYIERMV KWRIERGVVQ QTESLVRGFY EVVDARLVSV 

      1450       1460       1470       1480       1490       1500 
FDARELELVI AGTAEIDLSD WRNNTEYRGG YHDNHIVIRW FWAAVERFNN EQRLRLLQFV 

      1510       1520       1530       1540       1550       1560 
TGTSSIPYEG FASLRGSNGP RRFCVEKWGK ITALPRAHTC FNRLDLPPYP SFSMLYEKLL 

      1570 
TAVEETSTFG LE 

« Hide

Isoform 2 [UniParc].

Checksum: 51B974BF1F83D6D1
Show »

FASTA1,216135,905

References

« Hide 'large scale' references
[1]"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."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1352-1572 (ISOFORM 1).
Tissue: Uterus.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Heart and Lung.
[5]"A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances its transcriptional activity."
Miyazaki K., Ozaki T., Kato C., Hanamoto T., Fujita T., Irino S., Watanabe K., Nakagawa T., Nakagawara A.
Biochem. Biophys. Res. Commun. 308:106-113(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TP73, TISSUE SPECIFICITY.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB037722 mRNA. Translation: BAA92539.1. Different initiation.
AL390186 mRNA. Translation: CAB99103.1.
CR749424 mRNA. Translation: CAH18262.1.
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.
PIRT51886.
RefSeqNP_065811.1. NM_020760.1.
UniGeneHs.654742.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LFENMR-A43-162[»]
ProteinModelPortalQ9P2P5.
SMRQ9P2P5. Positions 57-162, 189-290, 806-898, 915-1022, 1168-1569.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121581. 284 interactions.
IntActQ9P2P5. 1 interaction.
MINTMINT-2820726.
STRING9606.ENSP00000260983.

PTM databases

PhosphoSiteQ9P2P5.

Polymorphism databases

DMDM126215718.

Proteomic databases

PaxDbQ9P2P5.
PeptideAtlasQ9P2P5.
PRIDEQ9P2P5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260983; ENSP00000260983; ENSG00000138411. [Q9P2P5-1]
ENST00000409111; ENSP00000386775; ENSG00000138411. [Q9P2P5-2]
GeneID57520.
KEGGhsa:57520.
UCSCuc002utl.1. human. [Q9P2P5-1]

Organism-specific databases

CTD57520.
GeneCardsGC02M197064.
HGNCHGNC:29853. HECW2.
HPAHPA034609.
HPA044858.
neXtProtNX_Q9P2P5.
PharmGKBPA134925001.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5021.
HOGENOMHOG000069940.
HOVERGENHBG057414.
InParanoidQ9P2P5.
KOK12168.
OMAPTDTRLS.
OrthoDBEOG7BKCTS.
PhylomeDBQ9P2P5.
TreeFamTF313938.

Enzyme and pathway databases

SignaLinkQ9P2P5.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9P2P5.
BgeeQ9P2P5.
CleanExHS_HECW2.
GenevestigatorQ9P2P5.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000008. C2_dom.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view]
PfamPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]
SMARTSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 2 hits.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 2 hits.
SSF56204. SSF56204. 1 hit.
PROSITEPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHECW2. human.
GenomeRNAi57520.
NextBio63895.
PROQ9P2P5.

Entry information

Entry nameHECW2_HUMAN
AccessionPrimary (citable) accession number: Q9P2P5
Secondary accession number(s): B8ZZB4 expand/collapse secondary AC list , Q17RT5, Q68DF8, Q9NPS9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: April 16, 2014
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM