ERAD-associated E3 ubiquitin-protein ligase HRD1 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

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Q08109 (HRD1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 100. History...

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

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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 HRD1
EC=6.3.2.-

Alternative name(s):
HMG-CoA reductase degradation protein 1

Gene names

Name:	HRD1
Synonyms:	DER3
Ordered Locus Names:	YOL013C

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	551 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 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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Endoplasmic reticulum Membrane
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.11. Source: SGD fungal-type cell wall organization Inferred from genetic interaction PubMed 18971375. Source: SGD
Cellular_component	Hrd1p ubiquitin ligase ERAD-L complex Inferred from direct assay Ref.14. Source: SGD Hrd1p ubiquitin ligase ERAD-M complex Inferred from direct assay Ref.14. Source: SGD integral to membrane Inferred from sequence model PubMed 12192589. Source: SGD
Molecular_function	ubiquitin-protein ligase activity Inferred from direct assay Ref.9. Source: SGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct
itself		5	EBI-37613,EBI-37613
PRC1	P00729	2	EBI-37613,EBI-4153
YOS9	Q99220	6	EBI-37613,EBI-34938

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 551

551

ERAD-associated E3 ubiquitin-protein ligase HRD1

PRO_0000240367

Regions

Topological domain

1 – 8

Cytoplasmic Ref.7 Ref.9

Transmembrane

9 – 29

Helical; Name=1

Topological domain

30 – 45

Lumenal Ref.7 Ref.9

Transmembrane

46 – 66

Helical; Name=2

Topological domain

67 – 82

Cytoplasmic Ref.7 Ref.9

Transmembrane

83 – 103

Helical; Name=3

Topological domain

104

Lumenal Ref.7 Ref.9

Transmembrane

105 – 125

Helical; Name=4

Topological domain

126 – 144

Cytoplasmic Ref.7 Ref.9

Transmembrane

145 – 165

Helical; Name=5

Topological domain

166 – 184

Lumenal Ref.7 Ref.9

Transmembrane

185 – 205

Helical; Name=6

Topological domain

206 – 551

346

Cytoplasmic Ref.7 Ref.9

Zinc finger

349 – 400

RING-type; atypical

Compositional bias

413 – 483

Thr-rich

Amino acid modifications

Modified residue

475

Phosphoserine Ref.16

Modified residue

528

Phosphoserine Ref.16

Experimental info

Mutagenesis

399

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

Sequences

Sequence

Length

Mass (Da)

Tools

Q08109 [UniParc].

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

FASTA

551

63,535

        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' referencesShow '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. Kleine K. Nature 387:98-102(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[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]	"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-475 AND SER-528, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z74755 Genomic DNA. Translation: CAA99012.1. BK006948 Genomic DNA. Translation: DAA10770.1.
PIR	S66695.
RefSeq	NP_014630.1. NM_001183267.1.
3D structure databases
ProteinModelPortal	Q08109.
SMR	Q08109. Positions 324-400.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-8850N.
IntAct	Q08109. 10 interactions.
MINT	MINT-1956720.
STRING	4932.YOL013C.
Proteomic databases
PaxDb	Q08109.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YOL013C; YOL013C; YOL013C.
GeneID	854149.
KEGG	sce:YOL013C.
Organism-specific databases
CYGD	YOL013c.
SGD	S000005373. HRD1.
Phylogenomic databases
eggNOG	COG5243.
GeneTree	ENSGT00530000062938.
HOGENOM	HOG000112947.
KO	K10601.
OMA	SATRISA.
OrthoDB	EOG4W3WW9.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
Genevestigator	Q08109.
GermOnline	YOL013C. Saccharomyces cerevisiae.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF13639. zf-RING_2. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	975899.

Entry information

Entry name

HRD1_YEAST

Accession

Primary (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:	May 1, 2013
This is version 100 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 XV

Yeast (Saccharomyces cerevisiae) chromosome XV: 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