UniProtKB - Q76N89 (HECW1_HUMAN)
Protein
E3 ubiquitin-protein ligase HECW1
Gene
HECW1
Organism
Homo sapiens (Human)
Status
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. EC:2.3.2.26
: protein ubiquitination Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 1574 | Glycyl thioester intermediatePROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- ubiquitin protein ligase activity Source: GO_Central
GO - Biological processi
- negative regulation of canonical Wnt signaling pathway Source: Reactome
- negative regulation of sodium ion transmembrane transporter activity Source: GO_Central
- positive regulation of protein catabolic process Source: GO_Central
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
- protein polyubiquitination Source: GO_Central
- protein ubiquitination Source: GO_Central
- regulation of dendrite morphogenesis Source: GO_Central
- ubiquitin-dependent protein catabolic process Source: GO_Central
Keywordsi
Molecular function | Transferase |
Biological process | Ubl conjugation pathway |
Enzyme and pathway databases
BRENDAi | 2.3.2.B9, 2681 6.3.2.19, 2681 |
PathwayCommonsi | Q76N89 |
Reactomei | R-HSA-4641258, Degradation of DVL |
SignaLinki | Q76N89 |
UniPathwayi | UPA00143 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000002746.14 |
HGNCi | HGNC:22195, HECW1 |
MIMi | 610384, gene |
neXtProti | NX_Q76N89 |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 23072 |
OpenTargetsi | ENSG00000002746 |
PharmGKBi | PA134964191 |
Miscellaneous databases
Pharosi | Q76N89, Tdark |
Polymorphism and mutation databases
BioMutai | HECW1 |
DMDMi | 223590222 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000277665 | 1 – 1606 | E3 ubiquitin-protein ligase HECW1Add BLAST | 1606 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 874 | PhosphoserineBy similarity | 1 | |
Modified residuei | 937 | PhosphoserineBy similarity | 1 | |
Modified residuei | 939 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q76N89 |
MassIVEi | Q76N89 |
MaxQBi | Q76N89 |
PaxDbi | Q76N89 |
PeptideAtlasi | Q76N89 |
PRIDEi | Q76N89 |
ProteomicsDBi | 4192 68692 [Q76N89-1] |
PTM databases
iPTMneti | Q76N89 |
PhosphoSitePlusi | Q76N89 |
Expressioni
Tissue specificityi
Predominantly expressed in neurons of adult and fetal brain. Weakly expressed in the kidney.1 Publication
Gene expression databases
Bgeei | ENSG00000002746, Expressed in middle temporal gyrus and 145 other tissues |
ExpressionAtlasi | Q76N89, baseline and differential |
Genevisiblei | Q76N89, HS |
Organism-specific databases
HPAi | ENSG00000002746, Tissue enhanced (brain, kidney) |
Interactioni
Subunit structurei
Interacts with DVL1 and SSR3.
Also interacts with mutant SOD1.
1 PublicationBinary interactionsi
Q76N89
With | #Exp. | IntAct |
---|---|---|
VAX1 - isoform 2 [Q5SQQ9-2] | 3 | EBI-949582,EBI-12227803 |
Protein-protein interaction databases
BioGRIDi | 116705, 26 interactors |
IntActi | Q76N89, 9 interactors |
MINTi | Q76N89 |
STRINGi | 9606.ENSP00000379228 |
Miscellaneous databases
RNActi | Q76N89, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q76N89 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q76N89 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 182 – 318 | C2PROSITE-ProRule annotationAdd BLAST | 137 | |
Domaini | 829 – 862 | WW 1PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 1018 – 1051 | WW 2PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 1271 – 1606 | HECTPROSITE-ProRule annotationAdd BLAST | 336 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 870 – 901 | Sequence analysisAdd BLAST | 32 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 456 – 519 | Glu-richAdd BLAST | 64 | |
Compositional biasi | 670 – 707 | Cys-richAdd BLAST | 38 |
Keywords - Domaini
Coiled coil, RepeatPhylogenomic databases
eggNOGi | KOG0940, Eukaryota |
GeneTreei | ENSGT00940000158294 |
HOGENOMi | CLU_002173_14_0_1 |
InParanoidi | Q76N89 |
OMAi | PGENECE |
OrthoDBi | 117748at2759 |
PhylomeDBi | Q76N89 |
TreeFami | TF313938 |
Family and domain databases
CDDi | cd08691, C2_NEDL1-like, 1 hit cd00078, HECTc, 1 hit cd00201, WW, 2 hits |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR037795, C2_HECW IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR040524, HECW1_helix IPR032348, HECW_N IPR001202, WW_dom IPR036020, WW_dom_sf |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF18436, HECW1_helix, 1 hit PF16562, HECW_N, 1 hit PF00397, WW, 1 hit |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 2 hits |
SUPFAMi | SSF51045, SSF51045, 2 hits SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 2 hits PS50020, WW_DOMAIN_2, 2 hits |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q76N89-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH7C3Q2 | H7C3Q2_HUMAN | E3 ubiquitin-protein ligase HECW1 | HECW1 | 138 | Annotation score: |
Sequence cautioni
The sequence BAA20780 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 404 | G → R in BAA20780 (PubMed:9205841).Curated | 1 | |
Sequence conflicti | 404 | G → R in AAI51228 (PubMed:12853948).Curated | 1 | |
Sequence conflicti | 404 | G → R in BAB13352 (PubMed:15489334).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054642 | 800 – 834 | GECPI…PLPPN → D in isoform 2. 1 PublicationAdd BLAST | 35 |
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 |
CCDSi | CCDS5469.2 [Q76N89-1] CCDS69286.1 [Q76N89-2] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000395891; ENSP00000379228; ENSG00000002746 [Q76N89-1] ENST00000453890; ENSP00000407774; ENSG00000002746 [Q76N89-2] |
GeneIDi | 23072 |
KEGGi | hsa:23072 |
UCSCi | uc003tid.2, human [Q76N89-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS5469.2 [Q76N89-1] CCDS69286.1 [Q76N89-2] |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3L4H | X-ray | 1.80 | A | 948-1056 | [»] | |
SMRi | Q76N89 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 116705, 26 interactors |
IntActi | Q76N89, 9 interactors |
MINTi | Q76N89 |
STRINGi | 9606.ENSP00000379228 |
PTM databases
iPTMneti | Q76N89 |
PhosphoSitePlusi | Q76N89 |
Polymorphism and mutation databases
BioMutai | HECW1 |
DMDMi | 223590222 |
Proteomic databases
jPOSTi | Q76N89 |
MassIVEi | Q76N89 |
MaxQBi | Q76N89 |
PaxDbi | Q76N89 |
PeptideAtlasi | Q76N89 |
PRIDEi | Q76N89 |
ProteomicsDBi | 4192 68692 [Q76N89-1] |
Protocols and materials databases
Antibodypediai | 1996, 44 antibodies |
Genome annotation databases
Ensembli | ENST00000395891; ENSP00000379228; ENSG00000002746 [Q76N89-1] ENST00000453890; ENSP00000407774; ENSG00000002746 [Q76N89-2] |
GeneIDi | 23072 |
KEGGi | hsa:23072 |
UCSCi | uc003tid.2, human [Q76N89-1] |
Organism-specific databases
CTDi | 23072 |
DisGeNETi | 23072 |
EuPathDBi | HostDB:ENSG00000002746.14 |
GeneCardsi | HECW1 |
HGNCi | HGNC:22195, HECW1 |
HPAi | ENSG00000002746, Tissue enhanced (brain, kidney) |
MIMi | 610384, gene |
neXtProti | NX_Q76N89 |
OpenTargetsi | ENSG00000002746 |
PharmGKBi | PA134964191 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0940, Eukaryota |
GeneTreei | ENSGT00940000158294 |
HOGENOMi | CLU_002173_14_0_1 |
InParanoidi | Q76N89 |
OMAi | PGENECE |
OrthoDBi | 117748at2759 |
PhylomeDBi | Q76N89 |
TreeFami | TF313938 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
BRENDAi | 2.3.2.B9, 2681 6.3.2.19, 2681 |
PathwayCommonsi | Q76N89 |
Reactomei | R-HSA-4641258, Degradation of DVL |
SignaLinki | Q76N89 |
Miscellaneous databases
BioGRID-ORCSi | 23072, 2 hits in 847 CRISPR screens |
ChiTaRSi | HECW1, human |
EvolutionaryTracei | Q76N89 |
GenomeRNAii | 23072 |
Pharosi | Q76N89, Tdark |
PROi | PR:Q76N89 |
RNActi | Q76N89, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000002746, Expressed in middle temporal gyrus and 145 other tissues |
ExpressionAtlasi | Q76N89, baseline and differential |
Genevisiblei | Q76N89, HS |
Family and domain databases
CDDi | cd08691, C2_NEDL1-like, 1 hit cd00078, HECTc, 1 hit cd00201, WW, 2 hits |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR037795, C2_HECW IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR040524, HECW1_helix IPR032348, HECW_N IPR001202, WW_dom IPR036020, WW_dom_sf |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF18436, HECW1_helix, 1 hit PF16562, HECW_N, 1 hit PF00397, WW, 1 hit |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 2 hits |
SUPFAMi | SSF51045, SSF51045, 2 hits SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 2 hits PS50020, WW_DOMAIN_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HECW1_HUMAN | |
Accessioni | Q76N89Primary (citable) accession number: Q76N89 Secondary accession number(s): A7E2X0 Q9HCC7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 20, 2007 |
Last sequence update: | February 10, 2009 | |
Last modified: | December 2, 2020 | |
This is version 146 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references