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Protein

E3 ubiquitin-protein ligase HECW2

Gene

HECW2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138411-MONOMER.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:29853. HECW2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi57520.
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

Keywords - PTMi

Phosphoprotein

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.
HPA044858.

Interactioni

Subunit structurei

Interacts with TP73.1 Publication

Protein-protein interaction databases

BioGridi121581. 294 interactors.
IntActiQ9P2P5. 1 interactor.
MINTiMINT-2820726.
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

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

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

Family and domain databases

CDDicd00078. HECTc. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT_dom.
IPR032348. HECW_N.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF16562. HECW_N. 1 hit.
PF00397. WW. 1 hit.
[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. 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:
     1-356: Missing.

Note: No experimental confirmation available.
Show »
Length:1,216
Mass (Da):135,905
Checksum:i51B974BF1F83D6D1
GO

Sequence cautioni

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

Experimental Info

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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0230771 – 356Missing in isoform 2. 1 PublicationAdd BLAST356

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]
CCDS77499.1. [Q9P2P5-2]
PIRiT51886.
RefSeqiNP_001291769.1. NM_001304840.1. [Q9P2P5-2]
NP_065811.1. NM_020760.2. [Q9P2P5-1]
XP_016860052.1. XM_017004563.1. [Q9P2P5-1]
UniGeneiHs.654742.

Genome annotation databases

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

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.
CCDSiCCDS33354.1. [Q9P2P5-1]
CCDS77499.1. [Q9P2P5-2]
PIRiT51886.
RefSeqiNP_001291769.1. NM_001304840.1. [Q9P2P5-2]
NP_065811.1. NM_020760.2. [Q9P2P5-1]
XP_016860052.1. XM_017004563.1. [Q9P2P5-1]
UniGeneiHs.654742.

3D structure databases

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

Protein-protein interaction databases

BioGridi121581. 294 interactors.
IntActiQ9P2P5. 1 interactor.
MINTiMINT-2820726.
STRINGi9606.ENSP00000260983.

PTM databases

iPTMnetiQ9P2P5.
PhosphoSitePlusiQ9P2P5.

Polymorphism and mutation databases

BioMutaiHECW2.
DMDMi126215718.

Proteomic databases

EPDiQ9P2P5.
MaxQBiQ9P2P5.
PaxDbiQ9P2P5.
PeptideAtlasiQ9P2P5.
PRIDEiQ9P2P5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi57520.
DisGeNETi57520.
GeneCardsiHECW2.
HGNCiHGNC:29853. HECW2.
HPAiHPA034609.
HPA044858.
neXtProtiNX_Q9P2P5.
OpenTargetsiENSG00000138411.
PharmGKBiPA134925001.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000138411-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ9P2P5.

Miscellaneous databases

ChiTaRSiHECW2. human.
GenomeRNAii57520.
PROiQ9P2P5.

Gene expression databases

BgeeiENSG00000138411.
CleanExiHS_HECW2.
ExpressionAtlasiQ9P2P5. baseline and differential.
GenevisibleiQ9P2P5. HS.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT_dom.
IPR032348. HECW_N.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF16562. HECW_N. 1 hit.
PF00397. WW. 1 hit.
[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]
ProtoNetiSearch...

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 30, 2016
This is version 126 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.