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Protein

E3 ubiquitin-protein ligase HECW1

Gene

HECW1

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 and subsequent degradation of DVL1. Also targets the mutant SOD1 protein involved in familial amyotrophic lateral sclerosis (FALS). Forms cytotoxic aggregates with DVL1, SSR3 and mutant SOD1 that lead to motor neuron death in FALS.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 sitei1574Glycyl 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

BRENDAi2.3.2.B9. 2681.
6.3.2.19. 2681.
ReactomeiR-HSA-4641258. Degradation of DVL.
SignaLinkiQ76N89.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase HECW1 (EC:2.3.2.26)
Alternative name(s):
HECT, C2 and WW domain-containing protein 1
HECT-type E3 ubiquitin transferase HECW1
NEDD4-like E3 ubiquitin-protein ligase 1
Short name:
hNEDL1
Gene namesi
Name:HECW1
Synonyms:KIAA0322, NEDL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:22195. HECW1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi23072.
OpenTargetsiENSG00000002746.
PharmGKBiPA134964191.

Polymorphism and mutation databases

BioMutaiHECW1.
DMDMi223590222.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002776651 – 1606E3 ubiquitin-protein ligase HECW1Add BLAST1606

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei874PhosphoserineBy similarity1
Modified residuei937PhosphoserineBy similarity1
Modified residuei939PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ76N89.
PaxDbiQ76N89.
PeptideAtlasiQ76N89.
PRIDEiQ76N89.

PTM databases

iPTMnetiQ76N89.
PhosphoSitePlusiQ76N89.

Expressioni

Tissue specificityi

Predominantly expressed in neurons of adult and fetal brain. Weakly expressed in the kidney.1 Publication

Gene expression databases

BgeeiENSG00000002746.
CleanExiHS_HECW1.
ExpressionAtlasiQ76N89. baseline and differential.
GenevisibleiQ76N89. HS.

Organism-specific databases

HPAiHPA007593.
HPA007609.

Interactioni

Subunit structurei

Interacts with DVL1 and SSR3. Also interacts with mutant SOD1.1 Publication

Protein-protein interaction databases

BioGridi116705. 23 interactors.
IntActiQ76N89. 6 interactors.
MINTiMINT-4657746.
STRINGi9606.ENSP00000379228.

Structurei

Secondary structure

11606
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi953 – 958Combined sources6
Helixi963 – 968Combined sources6
Helixi971 – 979Combined sources9
Helixi982 – 992Combined sources11
Helixi995 – 1000Combined sources6
Helixi1004 – 1011Combined sources8
Beta strandi1024 – 1028Combined sources5
Beta strandi1034 – 1038Combined sources5
Turni1039 – 1042Combined sources4
Beta strandi1043 – 1047Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L4HX-ray1.80A948-1056[»]
ProteinModelPortaliQ76N89.
SMRiQ76N89.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ76N89.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini192 – 302C2PROSITE-ProRule annotationAdd BLAST111
Domaini829 – 862WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini1018 – 1051WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini1271 – 1606HECTPROSITE-ProRule annotationAdd BLAST336

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili870 – 901Sequence analysisAdd BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi456 – 519Glu-richAdd BLAST64
Compositional biasi670 – 707Cys-richAdd BLAST38

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.
InParanoidiQ76N89.
KOiK12167.
OMAiTHYIRIH.
OrthoDBiEOG091G0A54.
PhylomeDBiQ76N89.
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: Q76N89-1) [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
MLLHLCSVKN LYQNRFLGLA AMASPSRNSQ SRRRCKEPLR YSYNPDQFHN
60 70 80 90 100
MDLRGGPHDG VTIPRSTSDT DLVTSDSRST LMVSSSYYSI GHSQDLVIHW
110 120 130 140 150
DIKEEVDAGD WIGMYLIDEV LSENFLDYKN RGVNGSHRGQ IIWKIDASSY
160 170 180 190 200
FVEPETKICF KYYHGVSGAL RATTPSVTVK NSAAPIFKSI GADETVQGQG
210 220 230 240 250
SRRLISFSLS DFQAMGLKKG MFFNPDPYLK ISIQPGKHSI FPALPHHGQE
260 270 280 290 300
RRSKIIGNTV NPIWQAEQFS FVSLPTDVLE IEVKDKFAKS RPIIKRFLGK
310 320 330 340 350
LSMPVQRLLE RHAIGDRVVS YTLGRRLPTD HVSGQLQFRF EITSSIHPDD
360 370 380 390 400
EEISLSTEPE SAQIQDSPMN NLMESGSGEP RSEAPESSES WKPEQLGEGS
410 420 430 440 450
VPDGPGNQSI ELSRPAEEAA VITEAGDQGM VSVGPEGAGE LLAQVQKDIQ
460 470 480 490 500
PAPSAEELAE QLDLGEEASA LLLEDGEAPA STKEEPLEEE ATTQSRAGRE
510 520 530 540 550
EEEKEQEEEG DVSTLEQGEG RLQLRASVKR KSRPCSLPVS ELETVIASAC
560 570 580 590 600
GDPETPRTHY IRIHTLLHSM PSAQGGSAAE EEDGAEEEST LKDSSEKDGL
610 620 630 640 650
SEVDTVAADP SALEEDREEP EGATPGTAHP GHSGGHFPSL ANGAAQDGDT
660 670 680 690 700
HPSTGSESDS SPRQGGDHSC EGCDASCCSP SCYSSSCYST SCYSSSCYSA
710 720 730 740 750
SCYSPSCYNG NRFASHTRFS SVDSAKISES TVFSSQDDEE EENSAFESVP
760 770 780 790 800
DSMQSPELDP ESTNGAGPWQ DELAAPSGHV ERSPEGLESP VAGPSNRREG
810 820 830 840 850
ECPILHNSQP VSQLPSLRPE HHHYPTIDEP LPPNWEARID SHGRVFYVDH
860 870 880 890 900
VNRTTTWQRP TAAATPDGMR RSGSIQQMEQ LNRRYQNIQR TIATERSEED
910 920 930 940 950
SGSQSCEQAP AGGGGGGGSD SEAESSQSSL DLRREGSLSP VNSQKITLLL
960 970 980 990 1000
QSPAVKFITN PEFFTVLHAN YSAYRVFTSS TCLKHMILKV RRDARNFERY
1010 1020 1030 1040 1050
QHNRDLVNFI NMFADTRLEL PRGWEIKTDQ QGKSFFVDHN SRATTFIDPR
1060 1070 1080 1090 1100
IPLQNGRLPN HLTHRQHLQR LRSYSAGEAS EVSRNRGASL LARPGHSLVA
1110 1120 1130 1140 1150
AIRSQHQHES LPLAYNDKIV AFLRQPNIFE MLQERQPSLA RNHTLREKIH
1160 1170 1180 1190 1200
YIRTEGNHGL EKLSCDADLV ILLSLFEEEI MSYVPLQAAF HPGYSFSPRC
1210 1220 1230 1240 1250
SPCSSPQNSP GLQRASARAP SPYRRDFEAK LRNFYRKLEA KGFGQGPGKI
1260 1270 1280 1290 1300
KLIIRRDHLL EGTFNQVMAY SRKELQRNKL YVTFVGEEGL DYSGPSREFF
1310 1320 1330 1340 1350
FLLSQELFNP YYGLFEYSAN DTYTVQISPM SAFVENHLEW FRFSGRILGL
1360 1370 1380 1390 1400
ALIHQYLLDA FFTRPFYKAL LRLPCDLSDL EYLDEEFHQS LQWMKDNNIT
1410 1420 1430 1440 1450
DILDLTFTVN EEVFGQVTER ELKSGGANTQ VTEKNKKEYI ERMVKWRVER
1460 1470 1480 1490 1500
GVVQQTEALV RGFYEVVDSR LVSVFDAREL ELVIAGTAEI DLNDWRNNTE
1510 1520 1530 1540 1550
YRGGYHDGHL VIRWFWAAVE RFNNEQRLRL LQFVTGTSSV PYEGFAALRG
1560 1570 1580 1590 1600
SNGLRRFCIE KWGKITSLPR AHTCFNRLDL PPYPSYSMLY EKLLTAVEET

STFGLE
Length:1,606
Mass (Da):179,554
Last modified:February 10, 2009 - v3
Checksum:i22AE698F16276E98
GO
Isoform 2 (identifier: Q76N89-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     800-834: GECPILHNSQPVSQLPSLRPEHHHYPTIDEPLPPN → D

Note: No experimental confirmation available.
Show »
Length:1,572
Mass (Da):175,736
Checksum:i3C297CA810BFA4F2
GO

Sequence cautioni

The sequence BAA20780 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti404G → R in BAA20780 (PubMed:9205841).Curated1
Sequence conflicti404G → R in AAI51228 (PubMed:12853948).Curated1
Sequence conflicti404G → R in BAB13352 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054642800 – 834GECPI…PLPPN → D in isoform 2. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB002320 mRNA. Translation: BAA20780.2. Different initiation.
AK294918 mRNA. Translation: BAG58003.1.
AC004455 Genomic DNA. No translation available.
AC004692 Genomic DNA. No translation available.
AC005537 Genomic DNA. No translation available.
AC006365 Genomic DNA. No translation available.
AC011738 Genomic DNA. No translation available.
BC151227 mRNA. Translation: AAI51228.1.
AB048365 mRNA. Translation: BAB13352.1.
CCDSiCCDS5469.2. [Q76N89-1]
CCDS69286.1. [Q76N89-2]
RefSeqiNP_001273988.1. NM_001287059.1. [Q76N89-2]
NP_055867.3. NM_015052.4. [Q76N89-1]
XP_016867375.1. XM_017011886.1. [Q76N89-1]
XP_016867378.1. XM_017011889.1. [Q76N89-2]
UniGeneiHs.164453.

Genome annotation databases

EnsembliENST00000395891; ENSP00000379228; ENSG00000002746. [Q76N89-1]
ENST00000453890; ENSP00000407774; ENSG00000002746. [Q76N89-2]
GeneIDi23072.
KEGGihsa:23072.
UCSCiuc003tid.2. human. [Q76N89-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB002320 mRNA. Translation: BAA20780.2. Different initiation.
AK294918 mRNA. Translation: BAG58003.1.
AC004455 Genomic DNA. No translation available.
AC004692 Genomic DNA. No translation available.
AC005537 Genomic DNA. No translation available.
AC006365 Genomic DNA. No translation available.
AC011738 Genomic DNA. No translation available.
BC151227 mRNA. Translation: AAI51228.1.
AB048365 mRNA. Translation: BAB13352.1.
CCDSiCCDS5469.2. [Q76N89-1]
CCDS69286.1. [Q76N89-2]
RefSeqiNP_001273988.1. NM_001287059.1. [Q76N89-2]
NP_055867.3. NM_015052.4. [Q76N89-1]
XP_016867375.1. XM_017011886.1. [Q76N89-1]
XP_016867378.1. XM_017011889.1. [Q76N89-2]
UniGeneiHs.164453.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L4HX-ray1.80A948-1056[»]
ProteinModelPortaliQ76N89.
SMRiQ76N89.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116705. 23 interactors.
IntActiQ76N89. 6 interactors.
MINTiMINT-4657746.
STRINGi9606.ENSP00000379228.

PTM databases

iPTMnetiQ76N89.
PhosphoSitePlusiQ76N89.

Polymorphism and mutation databases

BioMutaiHECW1.
DMDMi223590222.

Proteomic databases

MaxQBiQ76N89.
PaxDbiQ76N89.
PeptideAtlasiQ76N89.
PRIDEiQ76N89.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395891; ENSP00000379228; ENSG00000002746. [Q76N89-1]
ENST00000453890; ENSP00000407774; ENSG00000002746. [Q76N89-2]
GeneIDi23072.
KEGGihsa:23072.
UCSCiuc003tid.2. human. [Q76N89-1]

Organism-specific databases

CTDi23072.
DisGeNETi23072.
GeneCardsiHECW1.
H-InvDBHIX0022191.
HIX0033890.
HGNCiHGNC:22195. HECW1.
HPAiHPA007593.
HPA007609.
MIMi610384. gene.
neXtProtiNX_Q76N89.
OpenTargetsiENSG00000002746.
PharmGKBiPA134964191.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOGENOMiHOG000069940.
HOVERGENiHBG057414.
InParanoidiQ76N89.
KOiK12167.
OMAiTHYIRIH.
OrthoDBiEOG091G0A54.
PhylomeDBiQ76N89.
TreeFamiTF313938.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi2.3.2.B9. 2681.
6.3.2.19. 2681.
ReactomeiR-HSA-4641258. Degradation of DVL.
SignaLinkiQ76N89.

Miscellaneous databases

ChiTaRSiHECW1. human.
EvolutionaryTraceiQ76N89.
GenomeRNAii23072.
PROiQ76N89.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000002746.
CleanExiHS_HECW1.
ExpressionAtlasiQ76N89. baseline and differential.
GenevisibleiQ76N89. 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 nameiHECW1_HUMAN
AccessioniPrimary (citable) accession number: Q76N89
Secondary accession number(s): A7E2X0
, A8MYS3, B4DH42, O15036, Q9HCC7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 10, 2009
Last modified: November 30, 2016
This is version 119 of the entry and version 3 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 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.