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Q08109 (HRD1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ERAD-associated E3 ubiquitin-protein ligase HRD1

EC=6.3.2.-
Alternative name(s):
HMG-CoA reductase degradation protein 1
Gene names
Name:HRD1
Synonyms:DER3
Ordered Locus Names:YOL013C
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length551 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC1 and UBC7 E2 ligases, and transfers it to substrates promoting their degradation. Mediates the degradation of endoplasmic reticulum proteins (ERQC), also called ER-associated degradation (ERAD). Component of the HRD1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M). ERAD-L substrates are ubiquitinated through HRD1 in conjunction with the E2 ubiquitin-conjugating enzymes UBC1 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. ERAD-M substrates are processed by the same HRD1-HRD3 core complex, but only a subset of the other components is required for ERAD-M. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Ref.15

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Component of the HRD1 complex which contains HRD1, HRD3, USA1, DER1, YOS9, KAR2, CDC48, NPL4, UFD1 AND UBX2/SEL1. The complex is composed of the core membrane complex, consisting of the E3 ligase HRD1 and its cofactors HRD3, DER1 and USA1, the substrate recruiting factors KAR2 and YOS9, and the heterotrimeric UFD1-NPL4-CDC48/p97 (UNC) ATPase complex recruited by UBX2/SEL1. Interacts with HRD3. The complex interacts with the ERAD substrates HMG1 and HMG2. Interacts with HRD3. Interacts also with its associated E2 ubiquitin conjugating enzymes UBC1 and UBC7 with its membrane anchor CUE1. Ref.7 Ref.10 Ref.11 Ref.14 Ref.15

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Potential Ref.7 Ref.12.

Miscellaneous

Present with 2660 molecules/cell in log phase SD medium.

Sequence similarities

Belongs to the HRD1 family.

Contains 1 RING-type zinc finger.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 551551ERAD-associated E3 ubiquitin-protein ligase HRD1
PRO_0000240367

Regions

Topological domain1 – 88Cytoplasmic Ref.7 Ref.9
Transmembrane9 – 2921Helical; Name=1
Topological domain30 – 4516Lumenal Ref.7 Ref.9
Transmembrane46 – 6621Helical; Name=2
Topological domain67 – 8216Cytoplasmic Ref.7 Ref.9
Transmembrane83 – 10321Helical; Name=3
Topological domain1041Lumenal Ref.7 Ref.9
Transmembrane105 – 12521Helical; Name=4
Topological domain126 – 14419Cytoplasmic Ref.7 Ref.9
Transmembrane145 – 16521Helical; Name=5
Topological domain166 – 18419Lumenal Ref.7 Ref.9
Transmembrane185 – 20521Helical; Name=6
Topological domain206 – 551346Cytoplasmic Ref.7 Ref.9
Zinc finger349 – 40052RING-type; atypical
Compositional bias413 – 48371Thr-rich

Experimental info

Mutagenesis3991C → S: Stabilizes HRD1. Ref.7 Ref.9 Ref.11

Sequences

Sequence LengthMass (Da)Tools
Q08109 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: CAA6341E7A94DB0B

FASTA55163,535
        10         20         30         40         50         60 
MVPENRRKQL AIFVVVTYLL TFYCVYSATK TSVSFLQVTL KLNEGFNLMV LSIFILLNST 

        70         80         90        100        110        120 
LLWQLLTKLL FGELRLIEHE HIFERLPFTI INTLFMSSLF HERYFFTVAF FGLLLLYLKV 

       130        140        150        160        170        180 
FHWILKDRLE ALLQSINDST TMKTLIFSRF SFNLVLLAVV DYQIITRCIS SIYTNQKSDI 

       190        200        210        220        230        240 
ESTSLYLIQV MEFTMLLIDL LNLFLQTCLN FWEFYRSQQS LSNENNHIVH GDPTDENTVE 

       250        260        270        280        290        300 
SDQSQPVLND DDDDDDDDRQ FTGLEGKFMY EKAIDVFTRF LKTALHLSML IPFRMPMMLL 

       310        320        330        340        350        360 
KDVVWDILAL YQSGTSLWKI WRNNKQLDDT LVTVTVEQLQ NSANDDNICI ICMDELIHSP 

       370        380        390        400        410        420 
NQQTWKNKNK KPKRLPCGHI LHLSCLKNWM ERSQTCPICR LPVFDEKGNV VQTTFTSNSD 

       430        440        450        460        470        480 
ITTQTTVTDS TGIATDQQGF ANEVDLLPTR TTSPDIRIVP TQNIDTLAMR TRSTSTPSPT 

       490        500        510        520        530        540 
WYTFPLHKTG DNSVGSSRSA YEFLITNSDE KENGIPVKLT IENHEVNSLH GDGGEQIAKK 

       550 
IVIPDKFIQH I 

« Hide

References

« Hide 'large scale' references
[1]"The nucleotide sequence of Saccharomyces cerevisiae chromosome XV."
Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., Dang V.-D. expand/collapse author list , de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.
Nature 387:98-102(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[2]Saccharomyces Genome Database
Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[3]"Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein."
Hampton R.Y., Gardner R.G., Rine J.
Mol. Biol. Cell 7:2029-2044(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins."
Bordallo J., Plemper R.K., Finger A., Wolf D.H.
Mol. Biol. Cell 9:209-222(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"A RING-H2 finger motif is essential for the function of Der3/Hrd1 in endoplasmic reticulum associated protein degradation in the yeast Saccharomyces cerevisiae."
Bordallo J., Wolf D.H.
FEBS Lett. 448:244-248(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Genetic interactions of Hrd3p and Der3p/Hrd1p with Sec61p suggest a retro-translocation complex mediating protein transport for ER degradation."
Plemper R.K., Bordallo J., Deak P.M., Taxis C., Hitt R., Wolf D.H.
J. Cell Sci. 112:4123-4134(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Endoplasmic reticulum degradation requires lumen to cytosol signaling. Transmembrane control of Hrd1p by Hrd3p."
Gardner R.G., Swarbrick G.M., Bays N.W., Cronin S.R., Wilhovsky S., Seelig L.P., Kim C., Hampton R.Y.
J. Cell Biol. 151:69-82(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HRD3, TOPOLOGY, MUTAGENESIS OF CYS-399.
[8]"HRD gene dependence of endoplasmic reticulum-associated degradation."
Wilhovsky S., Gardner R.G., Hampton R.Y.
Mol. Biol. Cell 11:1697-1708(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Membrane topology and function of Der3/Hrd1p as a ubiquitin-protein ligase (E3) involved in endoplasmic reticulum degradation."
Deak P.M., Wolf D.H.
J. Biol. Chem. 276:10663-10669(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-399, TOPOLOGY.
[10]"In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation."
Gardner R.G., Shearer A.G., Hampton R.Y.
Mol. Cell. Biol. 21:4276-4291(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HMG1 AND HMG2.
[11]"Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation."
Bays N.W., Gardner R.G., Seelig L.P., Joazeiro C.A., Hampton R.Y.
Nat. Cell Biol. 3:24-29(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH UBC1 AND UBC7, MUTAGENESIS OF CYS-399.
[12]"Global analysis of protein localization in budding yeast."
Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K.
Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[13]"Global analysis of protein expression in yeast."
Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S.
Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[14]"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 HRD1 COMPLEX WITH UBX2; HRD3; USA1; DER1; YOS9; KAR2; CDC48; NPL4 AND UFD1.
[15]"The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment."
Gauss R., Sommer T., Jarosch E.
EMBO J. 25:1827-1835(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CDC48 AND DER1.
[16]"Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae."
Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., Elias J.E., Gygi S.P.
J. Proteome Res. 6:1190-1197(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Strain: ADR376.
[17]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z74755 Genomic DNA. Translation: CAA99012.1.
BK006948 Genomic DNA. Translation: DAA10770.1.
PIRS66695.
RefSeqNP_014630.1. NM_001183267.1.

3D structure databases

ProteinModelPortalQ08109.
SMRQ08109. Positions 344-401.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid34391. 122 interactions.
DIPDIP-8850N.
IntActQ08109. 11 interactions.
MINTMINT-1956720.
STRING4932.YOL013C.

Protein family/group databases

TCDB3.A.16.1.2. the endoplasmic reticular retrotranslocon (er-rt) family.

Proteomic databases

PaxDbQ08109.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYOL013C; YOL013C; YOL013C.
GeneID854149.
KEGGsce:YOL013C.

Organism-specific databases

CYGDYOL013c.
SGDS000005373. HRD1.

Phylogenomic databases

eggNOGCOG5243.
GeneTreeENSGT00530000062938.
HOGENOMHOG000112947.
KOK10601.
OMASATRISA.
OrthoDBEOG7MWH87.

Enzyme and pathway databases

BioCycYEAST:G3O-33429-MONOMER.
UniPathwayUPA00143.

Gene expression databases

GenevestigatorQ08109.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
PROSITEPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio975899.

Entry information

Entry nameHRD1_YEAST
AccessionPrimary (citable) accession number: Q08109
Secondary accession number(s): D6W254
Entry history
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome XV

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

Yeast

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

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways