Q9P2P5 (HECW2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	HECW2
Synonyms:	KIAA1301, NEDL2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1572 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Repeat
Molecular function	Ligase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome nucleus Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ubiquitin-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1572

1572

E3 ubiquitin-protein ligase HECW2

PRO_0000277667

Regions

Domain

172 – 282

111

C2

Domain

807 – 840

34

WW 1

Domain

985 – 1018

34

WW 2

Domain

1237 – 1572

336

HECT

Region

737 – 1068

332

Interaction with TP73

Coiled coil

847 – 874

28

Potential

Sites

Active site

1540

1

Glycyl thioester intermediate By similarity

Natural variations

Alternative sequence

1 – 356

356

Missing in isoform 2.

VSP_023077

Experimental info

Sequence conflict

1074

1

Q → H in CAH18262. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1572

Helix Strand Turn

Details...

Beta strand

60 – 64

5

Beta strand

66 – 69

4

Beta strand

76 – 81

6

Beta strand

91 – 96

6

Beta strand

117 – 123

7

Beta strand

133 – 144

12

Turn

145 – 148

4

Beta strand

149 – 153

5

Beta strand

157 – 160

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 20, 2007. Version 2. Checksum: DCFF0146ADFAF8BE	FASTA	1,572	175,769
	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
	Isoform 2 [UniParc]. Checksum: 51B974BF1F83D6D1	FASTA	1,216	135,905
	10 20 30 40 50 60 MPGSHHDSQV CSNGPVSEDS AADGTPKHSF RTSSTLEIDT EELTSTSSRT SPPRGRQDSL 70 80 90 100 110 120 NDYLDAIEHN GHSRPGTATC SERSMGASPK LRSSFPTDTR LNAMLHIDSD EEDHEFQQDL 130 140 150 160 170 180 GYPSSLEEEG GLIMFSRASR ADDGSLTSQT KLEDNPVENE EASTHEAASF EDKPENLPEL 190 200 210 220 230 240 AESSLPAGPA PEEGEGGPEP QPSADQGSAE LCGSQEVDQP TSGADTGTSD ASGGSRRAVS 250 260 270 280 290 300 ETESLDQGSE PSQVSSETEP SDPARTESVS EASTRPEGES DLECADSSCN ESVTTQLSSV 310 320 330 340 350 360 DTRCSSLESA RFPETPAFSS QEEEDGACAA EPTSSGPAEG SQESVCTAGS LPVVQVPSGE 370 380 390 400 410 420 DEGPGAESAT VPDQEELGEV WQRRGSLEGA AAAAESPPQE EGSAGEAQGT CEGATAQEEG 430 440 450 460 470 480 ATGGSQANGH QPLRSLPSVR QDVSRYQRVD EALPPNWEAR IDSHGRIFYV DHVNRTTTWQ 490 500 510 520 530 540 RPTAPPAPQV LQRSNSIQQM EQLNRRYQSI RRTMTNERPE ENTNAIDGAG EEADFHQASA 550 560 570 580 590 600 DFRRENILPH STSRSRITLL LQSPPVKFLI SPEFFTVLHS NPSAYRMFTN NTCLKHMITK 610 620 630 640 650 660 VRRDTHHFER YQHNRDLVGF LNMFANKQLE LPRGWEMKHD HQGKAFFVDH NSRTTTFIDP 670 680 690 700 710 720 RLPLQSSRPT SALVHRQHLT RQRSHSAGEV GEDSRHAGPP VLPRPSSTFN TVSRPQYQDM 730 740 750 760 770 780 VPVAYNDKIV AFLRQPNIFE ILQERQPDLT RNHSLREKIQ FIRTEGTPGL VRLSSDADLV 790 800 810 820 830 840 MLLSLFEEEI MSYVPPHALL HPSYCQSPRG SPVSSPQNSP GTQRANARAP APYKRDFEAK 850 860 870 880 890 900 LRNFYRKLET KGYGQGPGKL KLIIRRDHLL EDAFNQIMGY SRKDLQRNKL YVTFVGEEGL 910 920 930 940 950 960 DYSGPSREFF FLVSRELFNP YYGLFEYSAN DTYTVQISPM SAFVDNHHEW FRFSGRILGL 970 980 990 1000 1010 1020 ALIHQYLLDA FFTRPFYKAL LRILCDLSDL EYLDEEFHQS LQWMKDNDIH DILDLTFTVN 1030 1040 1050 1060 1070 1080 EEVFGQITER ELKPGGANIP VTEKNKKEYI ERMVKWRIER GVVQQTESLV RGFYEVVDAR 1090 1100 1110 1120 1130 1140 LVSVFDAREL ELVIAGTAEI DLSDWRNNTE YRGGYHDNHI VIRWFWAAVE RFNNEQRLRL 1150 1160 1170 1180 1190 1200 LQFVTGTSSI PYEGFASLRG SNGPRRFCVE KWGKITALPR AHTCFNRLDL PPYPSFSMLY 1210 EKLLTAVEET STFGLE

References

	« Hide 'large scale' referencesShow '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. , 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.

PIR

T51886.

RefSeq

NP_065811.1. NM_020760.1.

UniGene

Hs.654742.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LFE	NMR	-	A	43-162	[»]

ProteinModelPortal

Q9P2P5.

SMR

Q9P2P5. Positions 57-162, 189-290, 806-898, 915-1022, 1168-1569.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

121581. 284 interactions.

IntAct

Q9P2P5. 1 interaction.

MINT

MINT-2820726.

STRING

9606.ENSP00000260983.

PTM databases

PhosphoSite

Q9P2P5.

Polymorphism databases

DMDM

126215718.

Proteomic databases

PaxDb

Q9P2P5.

PeptideAtlas

Q9P2P5.

PRIDE

Q9P2P5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000260983; ENSP00000260983; ENSG00000138411. [Q9P2P5-1]
ENST00000409111; ENSP00000386775; ENSG00000138411. [Q9P2P5-2]

GeneID

57520.

KEGG

hsa:57520.

UCSC

uc002utl.1. human. [Q9P2P5-1]

Organism-specific databases

CTD

57520.

GeneCards

GC02M197064.

HGNC

HGNC:29853. HECW2.

HPA

HPA034609.
HPA044858.

neXtProt

NX_Q9P2P5.

PharmGKB

PA134925001.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5021.

HOGENOM

HOG000069940.

HOVERGEN

HBG057414.

InParanoid

Q9P2P5.

KO

K12168.

OMA

PTDTRLS.

OrthoDB

EOG7BKCTS.

PhylomeDB

Q9P2P5.

TreeFam

TF313938.

Enzyme and pathway databases

SignaLink

Q9P2P5.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q9P2P5.

Bgee

Q9P2P5.

CleanEx

HS_HECW2.

Genevestigator

Q9P2P5.

Family and domain databases

Gene3D

2.60.40.150. 1 hit.

InterPro

IPR000008. C2_dom.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view]

Pfam

PF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]

SMART

SM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 2 hits.
[Graphical view]

SUPFAM

SSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 2 hits.
SSF56204. SSF56204. 1 hit.

PROSITE

PS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

HECW2. human.

GenomeRNAi

57520.

NextBio

63895.

PRO

Q9P2P5.

Entry information

Entry name

HECW2_HUMAN

Accession

Primary (citable) accession number: Q9P2P5
Secondary accession number(s): B8ZZB4 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.