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Q08109

- HRD1_YEAST

UniProt

Q08109 - HRD1_YEAST

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
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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. protein binding Source: IntAct
    4. ubiquitin-protein transferase activity Source: SGD
    5. 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

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciYEAST:G3O-33429-MONOMER.
    ReactomeiREACT_188969. XBP1(S) activates chaperone genes.
    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

    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

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

    Structurei

    3D structure databases

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

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 88Cytoplasmic
    Topological domaini30 – 4516LumenalAdd
    BLAST
    Topological domaini67 – 8216CytoplasmicAdd
    BLAST
    Topological domaini104 – 1041Lumenal
    Topological domaini126 – 14419CytoplasmicAdd
    BLAST
    Topological domaini166 – 18419LumenalAdd
    BLAST
    Topological domaini206 – 551346CytoplasmicAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei9 – 2921Helical; Name=1Add
    BLAST
    Transmembranei46 – 6621Helical; Name=2Add
    BLAST
    Transmembranei83 – 10321Helical; Name=3Add
    BLAST
    Transmembranei105 – 12521Helical; Name=4Add
    BLAST
    Transmembranei145 – 16521Helical; Name=5Add
    BLAST
    Transmembranei185 – 20521Helical; Name=6Add
    BLAST

    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.
    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

    MVPENRRKQL AIFVVVTYLL TFYCVYSATK TSVSFLQVTL KLNEGFNLMV    50
    LSIFILLNST LLWQLLTKLL FGELRLIEHE HIFERLPFTI INTLFMSSLF 100
    HERYFFTVAF FGLLLLYLKV FHWILKDRLE ALLQSINDST TMKTLIFSRF 150
    SFNLVLLAVV DYQIITRCIS SIYTNQKSDI ESTSLYLIQV MEFTMLLIDL 200
    LNLFLQTCLN FWEFYRSQQS LSNENNHIVH GDPTDENTVE SDQSQPVLND 250
    DDDDDDDDRQ FTGLEGKFMY EKAIDVFTRF LKTALHLSML IPFRMPMMLL 300
    KDVVWDILAL YQSGTSLWKI WRNNKQLDDT LVTVTVEQLQ NSANDDNICI 350
    ICMDELIHSP NQQTWKNKNK KPKRLPCGHI LHLSCLKNWM ERSQTCPICR 400
    LPVFDEKGNV VQTTFTSNSD ITTQTTVTDS TGIATDQQGF ANEVDLLPTR 450
    TTSPDIRIVP TQNIDTLAMR TRSTSTPSPT WYTFPLHKTG DNSVGSSRSA 500
    YEFLITNSDE KENGIPVKLT IENHEVNSLH GDGGEQIAKK IVIPDKFIQH 550
    I 551
    Length:551
    Mass (Da):63,535
    Last modified:November 1, 1996 - v1
    Checksum:iCAA6341E7A94DB0B
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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. 124 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.
    KOi K10601.
    OMAi ISMLQGT.
    OrthoDBi EOG7MWH87.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    BioCyci YEAST:G3O-33429-MONOMER.
    Reactomei REACT_188969. XBP1(S) activates chaperone genes.

    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

    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: October 1, 2014
    This is version 114 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