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UniProtKB - Q76N89 (HECW1_HUMAN)

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Protein

E3 ubiquitin-protein ligase HECW1

Gene

HECW1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 + N6-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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionTransferase
Biological processUbl 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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000002746.14
HGNCiHGNC:22195 HECW1
MIMi610384 gene
neXtProtiNX_Q76N89

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi68692

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

HPAiHPA007203
HPA007593
HPA007609

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi116705, 23 interactors
IntActiQ76N89, 7 interactors
MINTiQ76N89
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

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

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

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

Family and domain databases

CDDicd08691 C2_NEDL1-like, 1 hit
cd00078 HECTc, 1 hit
cd00201 WW, 2 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR037795 C2_HECW
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR032348 HECW_N
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF00632 HECT, 1 hit
PF16562 HECW_N, 1 hit
PF00397 WW, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 2 hits
SUPFAMiSSF51045 SSF51045, 2 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 2 hits
PS50020 WW_DOMAIN_2, 2 hits

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

Similar proteinsi

Entry informationi

Entry nameiHECW1_HUMAN
AccessioniPrimary (citable) accession number: Q76N89
Secondary accession number(s): A7E2X0
, A8MYS3, B4DH42, O15036, Q9HCC7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 10, 2009
Last modified: July 18, 2018
This is version 130 of the entry and version 3 of the sequence. See 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

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