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Q08109

- HRD1_YEAST

UniProt

Q08109 - HRD1_YEAST

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Protein

ERAD-associated E3 ubiquitin-protein ligase HRD1

Gene

HRD1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.13 Publications

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri349 – 40052RING-type; atypicalPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. identical protein binding Source: IntAct
  2. ligase activity Source: UniProtKB-KW
  3. ubiquitin-protein transferase activity Source: SGD
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. endoplasmic reticulum unfolded protein response Source: SGD
  2. ER-associated ubiquitin-dependent protein catabolic process Source: SGD
  3. fungal-type cell wall organization Source: SGD
  4. retrograde protein transport, ER to cytosol Source: SGD
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciYEAST:G3O-33429-MONOMER.
UniPathwayiUPA00143.

Protein family/group databases

TCDBi3.A.16.1.2. the endoplasmic reticular retrotranslocon (er-rt) family.

Names & Taxonomyi

Protein namesi
Recommended name:
ERAD-associated E3 ubiquitin-protein ligase HRD1 (EC:6.3.2.-)
Alternative name(s):
HMG-CoA reductase degradation protein 1
Gene namesi
Name:HRD1
Synonyms:DER3
Ordered Locus Names:YOL013C
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
ProteomesiUP000002311: Chromosome XV

Organism-specific databases

CYGDiYOL013c.
SGDiS000005373. HRD1.

Subcellular locationi

Endoplasmic reticulum membrane 2 Publications; Multi-pass membrane protein 2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 88Cytoplasmic
Transmembranei9 – 2921Helical; Name=1Add
BLAST
Topological domaini30 – 4516LumenalAdd
BLAST
Transmembranei46 – 6621Helical; Name=2Add
BLAST
Topological domaini67 – 8216CytoplasmicAdd
BLAST
Transmembranei83 – 10321Helical; Name=3Add
BLAST
Topological domaini104 – 1041Lumenal
Transmembranei105 – 12521Helical; Name=4Add
BLAST
Topological domaini126 – 14419CytoplasmicAdd
BLAST
Transmembranei145 – 16521Helical; Name=5Add
BLAST
Topological domaini166 – 18419LumenalAdd
BLAST
Transmembranei185 – 20521Helical; Name=6Add
BLAST
Topological domaini206 – 551346CytoplasmicAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: SGD
  2. Hrd1p ubiquitin ligase ERAD-L complex Source: SGD
  3. Hrd1p ubiquitin ligase ERAD-M complex Source: SGD
  4. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Disruption phenotypei

Impaired degradation of proteins with misfolded intramembrane or lumenal domains.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi399 – 3991C → S: Stabilizes HRD1. Reduced interaction with substrate. Formation of oligmer with or without USA1. 5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 551551ERAD-associated E3 ubiquitin-protein ligase HRD1PRO_0000240367Add
BLAST

Proteomic databases

MaxQBiQ08109.
PaxDbiQ08109.

Expressioni

Gene expression databases

GenevestigatoriQ08109.

Interactioni

Subunit structurei

Forms homooligomers in a USA1-dependent manner: HRD1 oligomerization appears to be important for ERAD-L function but less important for ERAD-M function, although the underlying molecular mechanisms are unclear. Component of the HRD1 complex which contains HRD1, HRD3, USA1, DER1, YOS9, 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 factor YOS9, and the heterotrimeric UFD1-NPL4-CDC48/p97 (UNC) ATPase complex recruited by UBX2/SEL1. Interacts with HRD3 and DER1. The complex interacts with the ERAD substrates HMG1 and HMG2. Interacts with the associated E2 ubiquitin conjugating enzymes UBC1 and UBC7 with its membrane anchor CUE1.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-37613,EBI-37613
CDC48P256945EBI-37613,EBI-4308
DER1P383075EBI-37613,EBI-5761
HRD3Q057879EBI-37613,EBI-31647
PRC1P007294EBI-37613,EBI-4153
YOS9Q992206EBI-37613,EBI-34938

Protein-protein interaction databases

BioGridi34391. 126 interactions.
DIPiDIP-8850N.
IntActiQ08109. 11 interactions.
MINTiMINT-1956720.
STRINGi4932.YOL013C.

Structurei

3D structure databases

ProteinModelPortaliQ08109.
SMRiQ08109. Positions 344-401.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni517 – 55135Interaction with USA1Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi413 – 48371Thr-richAdd
BLAST

Sequence similaritiesi

Belongs to the HRD1 family.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri349 – 40052RING-type; atypicalPROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiCOG5243.
GeneTreeiENSGT00530000062938.
HOGENOMiHOG000112947.
InParanoidiQ08109.
KOiK10601.
OMAiISMLQGT.
OrthoDBiEOG7MWH87.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q08109-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVPENRRKQL AIFVVVTYLL TFYCVYSATK TSVSFLQVTL KLNEGFNLMV
60 70 80 90 100
LSIFILLNST LLWQLLTKLL FGELRLIEHE HIFERLPFTI INTLFMSSLF
110 120 130 140 150
HERYFFTVAF FGLLLLYLKV FHWILKDRLE ALLQSINDST TMKTLIFSRF
160 170 180 190 200
SFNLVLLAVV DYQIITRCIS SIYTNQKSDI ESTSLYLIQV MEFTMLLIDL
210 220 230 240 250
LNLFLQTCLN FWEFYRSQQS LSNENNHIVH GDPTDENTVE SDQSQPVLND
260 270 280 290 300
DDDDDDDDRQ FTGLEGKFMY EKAIDVFTRF LKTALHLSML IPFRMPMMLL
310 320 330 340 350
KDVVWDILAL YQSGTSLWKI WRNNKQLDDT LVTVTVEQLQ NSANDDNICI
360 370 380 390 400
ICMDELIHSP NQQTWKNKNK KPKRLPCGHI LHLSCLKNWM ERSQTCPICR
410 420 430 440 450
LPVFDEKGNV VQTTFTSNSD ITTQTTVTDS TGIATDQQGF ANEVDLLPTR
460 470 480 490 500
TTSPDIRIVP TQNIDTLAMR TRSTSTPSPT WYTFPLHKTG DNSVGSSRSA
510 520 530 540 550
YEFLITNSDE KENGIPVKLT IENHEVNSLH GDGGEQIAKK IVIPDKFIQH

I
Length:551
Mass (Da):63,535
Last modified:November 1, 1996 - v1
Checksum:iCAA6341E7A94DB0B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z74755 Genomic DNA. Translation: CAA99012.1.
BK006948 Genomic DNA. Translation: DAA10770.1.
PIRiS66695.
RefSeqiNP_014630.1. NM_001183267.1.

Genome annotation databases

EnsemblFungiiYOL013C; YOL013C; YOL013C.
GeneIDi854149.
KEGGisce:YOL013C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z74755 Genomic DNA. Translation: CAA99012.1 .
BK006948 Genomic DNA. Translation: DAA10770.1 .
PIRi S66695.
RefSeqi NP_014630.1. NM_001183267.1.

3D structure databases

ProteinModelPortali Q08109.
SMRi Q08109. Positions 344-401.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 34391. 126 interactions.
DIPi DIP-8850N.
IntActi Q08109. 11 interactions.
MINTi MINT-1956720.
STRINGi 4932.YOL013C.

Protein family/group databases

TCDBi 3.A.16.1.2. the endoplasmic reticular retrotranslocon (er-rt) family.

Proteomic databases

MaxQBi Q08109.
PaxDbi Q08109.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblFungii YOL013C ; YOL013C ; YOL013C .
GeneIDi 854149.
KEGGi sce:YOL013C.

Organism-specific databases

CYGDi YOL013c.
SGDi S000005373. HRD1.

Phylogenomic databases

eggNOGi COG5243.
GeneTreei ENSGT00530000062938.
HOGENOMi HOG000112947.
InParanoidi Q08109.
KOi K10601.
OMAi ISMLQGT.
OrthoDBi EOG7MWH87.

Enzyme and pathway databases

UniPathwayi UPA00143 .
BioCyci YEAST:G3O-33429-MONOMER.

Miscellaneous databases

NextBioi 975899.

Gene expression databases

Genevestigatori Q08109.

Family and domain databases

Gene3Di 3.30.40.10. 1 hit.
InterProi IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view ]
Pfami PF13639. zf-RING_2. 1 hit.
[Graphical view ]
SMARTi SM00184. RING. 1 hit.
[Graphical view ]
PROSITEi PS50089. ZF_RING_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
  13. 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, INTERACTION WITH HRD3; YOS9; DER1; USA1; UBX2; CDC48 AND NPL4, DISRUPTION PHENOTYPE.
  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].
  18. Cited for: FUNCTION, SUBUNIT, INTERACTION WITH DER1 AND USA1, DISRUPTION PHENOTYPE, MUTAGENESIS OF CYS-399.
  19. "Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-ligase Hrd1p."
    Carvalho P., Stanley A.M., Rapoport T.A.
    Cell 143:579-591(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, INTERACTION WITH USA1, MUTAGENESIS OF CYS-399.

Entry informationi

Entry nameiHRD1_YEAST
AccessioniPrimary (citable) accession number: Q08109
Secondary accession number(s): D6W254
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: November 1, 1996
Last modified: November 26, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 2660 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome XV
    Yeast (Saccharomyces cerevisiae) chromosome XV: entries and gene names

External Data

Dasty 3