ERAD-associated E3 ubiquitin-protein ligase DOA10 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

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P40318 (DOA10_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 116. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
ERAD-associated E3 ubiquitin-protein ligase DOA10
EC=6.3.2.-

Gene names

Name:	SSM4
Synonyms:	DOA10
Ordered Locus Names:	YIL030C
ORF Names:	YI3299.01C, YI9905.18C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces ›

Protein attributes

Sequence length	1319 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC6 and UBC7 E2 ligases, and transfers it to substrates promoting their degradation. Mediates the degradation of a broad range of substrates, inluding endoplasmic reticulum membrane proteins (ERQC), soluble nuclear proteins and soluble cytoplasmic proteins (CytoQC). Component of the DOA10 ubiquitin ligase complex, which is part of the ERAD-C pathway responsible for the rapid degradation of membrane proteins with misfolded cytoplasmic domains. ERAD-C substrates are ubiquitinated through DOA10 in conjunction with the E2 ubiquitin-conjugating enzymes UBC6 and UBC7-CUE1. Ubiquitinated substrates are then removed to the cytosol via the action of the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex and targeted to the proteasome. Also recognizes the N-terminally acetylated residue of proteins as degradation signal (degron). N-terminally acetylated target proteins include MATALPHA2, TBF1, SLK19, YMR090W, HIS3, HSP104, UBP6 and ARO8. Ref.4 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.14
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of the DOA10 complex which contains SSM4/DOA10, CDC48, NPL4, UFD1 AND UBX2/SEL1. The complex is composed of the membrane integral E3 ligase SSM4/DOA10 and the heterotrimeric UFD1-NPL4-CDC48/p97 (UNC) ATPase complex recruited by UBX2/SEL1. Interacts with UBX2/SEL1. Interacts also with its associated ubiquitin conjugating enzymesh UBC6 and UBC7 with its membrane anchor CUE1. Interacts with PEX29. Ref.5 Ref.6 Ref.7 Ref.13
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Nucleus inner membrane; Multi-pass membrane protein Ref.4 Ref.10.
Domain	The RING-CH-type zinc finger domain is required for E3 ligase activity.
Sequence similarities	Belongs to the DOA10/MARCH6 family. Contains 1 RING-CH-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Endoplasmic reticulum Membrane Nucleus
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated protein catabolic process Inferred from mutant phenotype Ref.4 PubMed 15252059. Source: SGD
Cellular_component	Doa10p ubiquitin ligase complex Inferred from direct assay Ref.7. Source: SGD integral to endoplasmic reticulum membrane Inferred from direct assay Ref.4. Source: SGD nuclear inner membrane Inferred from direct assay Ref.10. Source: SGD
Molecular_function	ubiquitin-protein ligase activity Inferred from direct assay Ref.4. Source: SGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct
CDC48	P25694	4	EBI-18208,EBI-4308
CUE1	P38428	2	EBI-18208,EBI-27580
STE6	P12866	2	EBI-18208,EBI-18383
UBX2	Q04228	5	EBI-18208,EBI-27730

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1319

1319

ERAD-associated E3 ubiquitin-protein ligase DOA10

PRO_0000072214

Regions

Topological domain

1 – 131

131

Cytoplasmic Potential

Transmembrane

132 – 152

Helical; Potential

Topological domain

153 – 203

Lumenal Potential

Transmembrane

204 – 224

Helical; Potential

Topological domain

225 – 468

244

Cytoplasmic Potential

Transmembrane

469 – 489

Helical; Potential

Topological domain

490 – 491

Lumenal Potential

Transmembrane

492 – 512

Helical; Potential

Topological domain

513 – 626

114

Cytoplasmic Potential

Transmembrane

627 – 647

Helical; Potential

Topological domain

648 – 660

Lumenal Potential

Transmembrane

661 – 681

Helical; Potential

Topological domain

682 – 739

Cytoplasmic Potential

Transmembrane

740 – 760

Helical; Potential

Topological domain

761 – 777

Lumenal Potential

Transmembrane

778 – 797

Helical; Potential

Topological domain

798 – 965

168

Cytoplasmic Potential

Transmembrane

966 – 986

Helical; Potential

Topological domain

987 – 1019

Lumenal Potential

Transmembrane

1020 – 1040

Helical; Potential

Topological domain

1041 – 1113

Cytoplasmic Potential

Transmembrane

1114 – 1134

Helical; Potential

Topological domain

1135 – 1168

Lumenal Potential

Transmembrane

1169 – 1189

Helical; Potential

Topological domain

1190 – 1213

Cytoplasmic Potential

Transmembrane

1214 – 1234

Helical; Potential

Topological domain

1235 – 1270

Lumenal Potential

Transmembrane

1271 – 1291

Helical; Potential

Topological domain

1292 – 1319

Cytoplasmic Potential

Zinc finger

31 – 100

RING-CH-type

Compositional bias

288 – 291

Poly-Ala

Compositional bias

293 – 296

Poly-Asn

Compositional bias

332 – 341

Asp/Gln/Ser-rich (acidic)

Compositional bias

369 – 374

Poly-Gln

Amino acid modifications

Modified residue

897

Phosphoserine Ref.12

Experimental info

Sequence conflict

241

L → F in CAA54133. Ref.1

Sequence conflict

743

A → T in CAA54133. Ref.1

Sequence conflict

1085

N → D in CAA54133. Ref.1

Sequence conflict

1186

Y → F in CAA54133. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

P40318 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 3EDFF7F9D90A0C8C
Show »

FASTA

1,319

151,455

        10         20         30         40         50         60 
MDVDSDVNVS RLRDELHKVA NEETDTATFN DDAPSGATCR ICRGEATEDN PLFHPCKCRG 

        70         80         90        100        110        120 
SIKYMHESCL LEWVASKNID ISKPGADVKC DICHYPIQFK TIYAENMPEK IPFSLLLSKS 

       130        140        150        160        170        180 
ILTFFEKARL ALTIGLAAVL YIIGVPLVWN MFGKLYTMML DGSSPYPGDF LKSLIYGYDQ 

       190        200        210        220        230        240 
SATPELTTRA IFYQLLQNHS FTSLQFIMIV ILHIALYFQY DMIVREDVFS KMVFHKIGPR 

       250        260        270        280        290        300 
LSPKDLKSRL KERFPMMDDR MVEYLAREMR AHDENRQEQG HDRLNMPAAA ADNNNNVINP 

       310        320        330        340        350        360 
RNDNVPPQDP NDHRNFENLR HVDELDHDEA TEEHENNDSD NSLPSGDDSS RILPGSSSDN 

       370        380        390        400        410        420 
EEDEEAEGQQ QQQQPEEEAD YRDHIEPNPI DMWANRRAQN EFDDLIAAQQ NAINRPNAPV 

       430        440        450        460        470        480 
FIPPPAQNRA GNVDQDEQDF GAAVGVPPAQ ANPDDQGQGP LVINLKLKLL NVIAYFIIAV 

       490        500        510        520        530        540 
VFTAIYLAIS YLFPTFIGFG LLKIYFGIFK VILRGLCHLY YLSGAHIAYN GLTKLVPKVD 

       550        560        570        580        590        600 
VAMSWISDHL IHDIIYLYNG YTENTMKHSI FIRALPALTT YLTSVSIVCA SSNLVSRGYG 

       610        620        630        640        650        660 
RENGMSNPTR RLIFQILFAL KCTFKVFTLF FIELAGFPIL AGVMLDFSLF CPILASNSRM 

       670        680        690        700        710        720 
LWVPSICAIW PPFSLFVYWT IGTLYMYWFA KYIGMIRKNI IRPGVLFFIR SPEDPNIKIL 

       730        740        750        760        770        780 
HDSLIHPMSI QLSRLCLSMF IYAIFIVLGF GFHTRIFFPF MLKSNLLSVP EAYKPTSIIS 

       790        800        810        820        830        840 
WKFNTILLTL YFTKRILESS SYVKPLLERY WKTIFKLCSR KLRLSSFILG KDTPTERGHI 

       850        860        870        880        890        900 
VYRNLFYKYI AAKNAEWSNQ ELFTKPKTLE QAEELFGQVR DVHAYFVPDG VLMRVPSSDI 

       910        920        930        940        950        960 
VSRNYVQTMF VPVTKDDKLL KPLDLERIKE RNKRAAGEFG YLDEQNTEYD QYYIVYVPPD 

       970        980        990       1000       1010       1020 
FRLRYMTLLG LVWLFASILM LGVTFISQAL INFVCSFGFL PVVKLLLGER NKVYVAWKEL 

      1030       1040       1050       1060       1070       1080 
SDISYSYLNI YYVCVGSVCL SKIAKDILHF TEGQNTLDEH AVDENEVEEV EHDIPERDIN 

      1090       1100       1110       1120       1130       1140 
NAPVNNINNV EEGQGIFMAI FNSIFDSMLV KYNLMVFIAI MIAVIRTMVS WVVLTDGILA 

      1150       1160       1170       1180       1190       1200 
CYNYLTIRVF GNSSYTIGNS KWFKYDESLL FVVWIISSMV NFGTGYKSLK LFFRNRNTSK 

      1210       1220       1230       1240       1250       1260 
LNFLKTMALE LFKQGFLHMV IYVLPIIILS LVFLRDVSTK QIIDISHGSR SFTLSLNESF 

      1270       1280       1290       1300       1310 
PTWTRMQDIY FGLLIALESF TFFFQATVLF IQWFKSTVQN VKDEVYTKGR ALENLPDES

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Inactivation of SSM4, a new Saccharomyces cerevisiae gene, suppresses mRNA instability due to RNA14 mutations." Mandart E., Dufour M.-E., Lacroute F. Mol. Gen. Genet. 245:323-333(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 28383 / FL100 / VTT C-80102.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome IX." Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D., Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E., Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C. Barrell B.G. Nature 387:84-87(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum that functions in both ER-associated and Matalpha2 repressor degradation." Swanson R., Locher M., Hochstrasser M. Genes Dev. 15:2660-2674(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[5]	"Ubx2 links the Cdc48 complex to ER-associated protein degradation." Neuber O., Jarosch E., Volkwein C., Walter J., Sommer T. Nat. Cell Biol. 7:993-998(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBX2; UBC6 AND UBC7, IDENTIFICATION IN COMPLEX WITH UBX2 AND CDC48.
[6]	"Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their substrates to ensure efficient ER-associated protein degradation." Schuberth C., Buchberger A. Nat. Cell Biol. 7:999-1006(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN COMPLEX WITH UBX2; CDC48 AND UFD1.
[7]	"Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins." Carvalho P., Goder V., Rapoport T.A. Cell 126:361-373(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE DOA10 COMPLEX WITH CDC48; NPL4; UFD1 AND UBX2.
[8]	"Membrane and soluble substrates of the Doa10 ubiquitin ligase are degraded by distinct pathways." Ravid T., Kreft S.G., Hochstrasser M. EMBO J. 25:533-543(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Membrane topology of the yeast endoplasmic reticulum-localized ubiquitin ligase Doa10 and comparison with its human ortholog TEB4 (MARCH-VI)." Kreft S.G., Wang L., Hochstrasser M. J. Biol. Chem. 281:4646-4653(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY.
[10]	"Spatially regulated ubiquitin ligation by an ER/nuclear membrane ligase." Deng M., Hochstrasser M. Nature 443:827-831(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION.
[11]	"Degradation of a cytosolic protein requires endoplasmic reticulum-associated degradation machinery." Metzger M.B., Maurer M.J., Dancy B.M., Michaelis S. J. Biol. Chem. 283:32302-32316(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CYTOSOLIC PROTEIN DEGRADATION.
[12]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-897, MASS SPECTROMETRY.
[13]	"Ubiquitin chain elongation enzyme Ufd2 regulates a subset of Doa10 substrates." Liu C., van Dyk D., Xu P., Choe V., Pan H., Peng J., Andrews B., Rao H. J. Biol. Chem. 285:10265-10272(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEX29.
[14]	"N-terminal acetylation of cellular proteins creates specific degradation signals." Hwang C.S., Shemorry A., Varshavsky A. Science 327:973-977(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN N-ACETYLATED PROTEIN DEGRADATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X76715 Genomic DNA. Translation: CAA54133.1. Z46881 Genomic DNA. Translation: CAA86961.1. Z46861 Genomic DNA. Translation: CAA86921.1. BK006942 Genomic DNA. Translation: DAA08517.1.
PIR	S49951.
RefSeq	NP_012234.3. NM_001179380.3.
3D structure databases
ProteinModelPortal	P40318.
SMR	P40318. Positions 39-101.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-7286N.
IntAct	P40318. 80 interactions.
MINT	MINT-1361830.
STRING	4932.YIL030C.
Proteomic databases
PaxDb	P40318.
PeptideAtlas	P40318.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YIL030C; YIL030C; YIL030C.
GeneID	854781.
KEGG	sce:YIL021W. sce:YIL030C.
Organism-specific databases
CYGD	YIL030c.
SGD	S000001292. SSM4.
Phylogenomic databases
eggNOG	COG5183.
GeneTree	ENSGT00500000044902.
KO	K03011. K10661.
OMA	IVILHIA.
OrthoDB	EOG4SJ8P3.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
Genevestigator	P40318.
GermOnline	YIL030C. Saccharomyces cerevisiae.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR011016. Znf_RING-CH. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF12906. RINGv. 1 hit. [Graphical view]
SMART	SM00744. RINGv. 1 hit. [Graphical view]
PROSITE	PS51292. ZF_RING_CH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	977562.

Entry information

Entry name

DOA10_YEAST

Accession

Primary (citable) accession number: P40318
Secondary accession number(s): D6VVQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program

Relevant documents

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

Yeast chromosome IX

Yeast (Saccharomyces cerevisiae) chromosome IX: entries and gene names

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents