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Q9P2P5

- HECW2_HUMAN

UniProt

Q9P2P5 - HECW2_HUMAN

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Protein

E3 ubiquitin-protein ligase HECW2

Gene

HECW2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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 TP73.1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei1540 – 15401Glycyl thioester intermediatePROSITE-ProRule annotation

GO - Molecular functioni

  1. ligase activity Source: UniProtKB-KW
  2. ubiquitin-protein transferase activity Source: RefGenome

GO - Biological processi

  1. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

SignaLinkiQ9P2P5.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:HECW2
Synonyms:KIAA1301, NEDL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:29853. HECW2.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. cytoplasm Source: RefGenome
  2. nucleus Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134925001.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 15721572E3 ubiquitin-protein ligase HECW2PRO_0000277667Add
BLAST

Proteomic databases

MaxQBiQ9P2P5.
PaxDbiQ9P2P5.
PeptideAtlasiQ9P2P5.
PRIDEiQ9P2P5.

PTM databases

PhosphoSiteiQ9P2P5.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ9P2P5.
CleanExiHS_HECW2.
ExpressionAtlasiQ9P2P5. baseline and differential.
GenevestigatoriQ9P2P5.

Organism-specific databases

HPAiHPA034609.
HPA044858.

Interactioni

Subunit structurei

Interacts with TP73.1 Publication

Protein-protein interaction databases

BioGridi121581. 290 interactions.
IntActiQ9P2P5. 1 interaction.
MINTiMINT-2820726.
STRINGi9606.ENSP00000260983.

Structurei

Secondary structure

1
1572
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi60 – 645Combined sources
Beta strandi66 – 694Combined sources
Beta strandi76 – 816Combined sources
Beta strandi91 – 966Combined sources
Beta strandi117 – 1237Combined sources
Beta strandi133 – 14412Combined sources
Turni145 – 1484Combined sources
Beta strandi149 – 1535Combined sources
Beta strandi157 – 1604Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LFENMR-A43-162[»]
ProteinModelPortaliQ9P2P5.
SMRiQ9P2P5. Positions 57-162, 806-898, 915-1022, 1168-1569.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini172 – 282111C2PROSITE-ProRule annotationAdd
BLAST
Domaini807 – 84034WW 1PROSITE-ProRule annotationAdd
BLAST
Domaini985 – 101834WW 2PROSITE-ProRule annotationAdd
BLAST
Domaini1237 – 1572336HECTPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni737 – 1068332Interaction with TP73Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili847 – 87428Sequence AnalysisAdd
BLAST

Sequence similaritiesi

Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
Contains 2 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiCOG5021.
GeneTreeiENSGT00760000118966.
HOGENOMiHOG000069940.
HOVERGENiHBG057414.
InParanoidiQ9P2P5.
KOiK12168.
OMAiTVCSNGP.
OrthoDBiEOG7BKCTS.
PhylomeDBiQ9P2P5.
TreeFamiTF313938.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 2 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

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:
     1-356: Missing.

Note: No experimental confirmation available.

Show »
Length:1,216
Mass (Da):135,905
Checksum:i51B974BF1F83D6D1
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1074 – 10741Q → H in CAH18262. (PubMed:17974005)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 356356Missing in isoform 2. 1 PublicationVSP_023077Add
BLAST

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.
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_020760.1. [Q9P2P5-1]
UniGeneiHs.654742.

Genome annotation databases

EnsembliENST00000260983; ENSP00000260983; ENSG00000138411. [Q9P2P5-1]
ENST00000409111; ENSP00000386775; ENSG00000138411. [Q9P2P5-2]
GeneIDi57520.
KEGGihsa:57520.
UCSCiuc002utl.1. human. [Q9P2P5-1]

Polymorphism databases

DMDMi126215718.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

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 .
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 .
CCDSi CCDS33354.1. [Q9P2P5-1 ]
PIRi T51886.
RefSeqi NP_065811.1. NM_020760.1. [Q9P2P5-1 ]
UniGenei Hs.654742.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2LFE NMR - A 43-162 [» ]
ProteinModelPortali Q9P2P5.
SMRi Q9P2P5. Positions 57-162, 806-898, 915-1022, 1168-1569.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 121581. 290 interactions.
IntActi Q9P2P5. 1 interaction.
MINTi MINT-2820726.
STRINGi 9606.ENSP00000260983.

PTM databases

PhosphoSitei Q9P2P5.

Polymorphism databases

DMDMi 126215718.

Proteomic databases

MaxQBi Q9P2P5.
PaxDbi Q9P2P5.
PeptideAtlasi Q9P2P5.
PRIDEi Q9P2P5.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000260983 ; ENSP00000260983 ; ENSG00000138411 . [Q9P2P5-1 ]
ENST00000409111 ; ENSP00000386775 ; ENSG00000138411 . [Q9P2P5-2 ]
GeneIDi 57520.
KEGGi hsa:57520.
UCSCi uc002utl.1. human. [Q9P2P5-1 ]

Organism-specific databases

CTDi 57520.
GeneCardsi GC02M197064.
HGNCi HGNC:29853. HECW2.
HPAi HPA034609.
HPA044858.
neXtProti NX_Q9P2P5.
PharmGKBi PA134925001.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5021.
GeneTreei ENSGT00760000118966.
HOGENOMi HOG000069940.
HOVERGENi HBG057414.
InParanoidi Q9P2P5.
KOi K12168.
OMAi TVCSNGP.
OrthoDBi EOG7BKCTS.
PhylomeDBi Q9P2P5.
TreeFami TF313938.

Enzyme and pathway databases

UniPathwayi UPA00143 .
SignaLinki Q9P2P5.

Miscellaneous databases

ChiTaRSi HECW2. human.
GenomeRNAii 57520.
NextBioi 63895.
PROi Q9P2P5.

Gene expression databases

Bgeei Q9P2P5.
CleanExi HS_HECW2.
ExpressionAtlasi Q9P2P5. baseline and differential.
Genevestigatori Q9P2P5.

Family and domain databases

Gene3Di 2.60.40.150. 1 hit.
InterProi IPR000008. C2_dom.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view ]
Pfami PF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 2 hits.
[Graphical view ]
SMARTi SM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 2 hits.
[Graphical view ]
SUPFAMi SSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 2 hits.
SSF56204. SSF56204. 1 hit.
PROSITEi PS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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. 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].

Entry informationi

Entry nameiHECW2_HUMAN
AccessioniPrimary (citable) accession number: Q9P2P5
Secondary accession number(s): B8ZZB4
, Q17RT5, Q68DF8, Q9NPS9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: November 26, 2014
This is version 106 of the entry and version 2 of the sequence. [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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3