HRD1_DROME
ID HRD1_DROME Reviewed; 626 AA.
AC Q95SP2; Q9V9T8;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=E3 ubiquitin-protein ligase HRD1;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase HRD1 {ECO:0000305};
DE AltName: Full=Septin-interacting protein 3;
DE AltName: Full=Synoviolin;
DE Flags: Precursor;
GN Name=sip3; Synonyms=Syno; ORFNames=CG1937;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP POSSIBLE INTERACTION WITH SEP2.
RX PubMed=11884525; DOI=10.1242/jcs.115.6.1259;
RA Shih H.-P., Hales K.G., Pringle J.R., Peifer M.;
RT "Identification of septin-interacting proteins and characterization of the
RT Smt3/SUMO-conjugation system in Drosophila.";
RL J. Cell Sci. 115:1259-1271(2002).
RN [5]
RP FUNCTION, AND INTERACTION WITH P53.
RX PubMed=17170702; DOI=10.1038/sj.emboj.7601490;
RA Yamasaki S., Yagishita N., Sasaki T., Nakazawa M., Kato Y., Yamadera T.,
RA Bae E., Toriyama S., Ikeda R., Zhang L., Fujitani K., Yoo E.,
RA Tsuchimochi K., Ohta T., Araya N., Fujita H., Aratani S., Eguchi K.,
RA Komiya S., Maruyama I., Higashi N., Sato M., Senoo H., Ochi T.,
RA Yokoyama S., Amano T., Kim J., Gay S., Fukamizu A., Nishioka K., Tanaka K.,
RA Nakajima T.;
RT "Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident
RT ubiquitin ligase 'Synoviolin'.";
RL EMBO J. 26:113-122(2007).
CC -!- FUNCTION: Acts as an E3 ubiquitin-protein ligase which accepts
CC ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2
CC ligase and transfers it to substrates, promoting their degradation.
CC Component of the endoplasmic reticulum quality control (ERQC) system
CC also called ER-associated degradation (ERAD) involved in ubiquitin-
CC dependent degradation of misfolded endoplasmic reticulum proteins. Also
CC promotes the degradation of normal but naturally short-lived proteins.
CC Protects cells from ER stress-induced apoptosis. Sequesters p53 in the
CC cytoplasm and promotes its degradation, thereby negatively regulating
CC its biological function in transcription, cell cycle regulation and
CC apoptosis. {ECO:0000269|PubMed:17170702}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with p53. May interact
CC with Sep2. {ECO:0000250, ECO:0000269|PubMed:17170702}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- DOMAIN: The RING-type zinc finger is required for E3 ligase activity.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the HRD1 family. {ECO:0000305}.
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DR EMBL; AE014297; AAF57196.2; -; Genomic_DNA.
DR EMBL; AY060677; AAL28225.1; -; mRNA.
DR RefSeq; NP_001263152.1; NM_001276223.2.
DR RefSeq; NP_651894.3; NM_143637.5.
DR AlphaFoldDB; Q95SP2; -.
DR SMR; Q95SP2; -.
DR BioGRID; 68588; 10.
DR IntAct; Q95SP2; 2.
DR STRING; 7227.FBpp0303146; -.
DR PaxDb; Q95SP2; -.
DR PRIDE; Q95SP2; -.
DR DNASU; 43747; -.
DR EnsemblMetazoa; FBtr0085842; FBpp0085201; FBgn0039875.
DR EnsemblMetazoa; FBtr0330113; FBpp0303146; FBgn0039875.
DR GeneID; 43747; -.
DR KEGG; dme:Dmel_CG1937; -.
DR CTD; 43747; -.
DR FlyBase; FBgn0039875; sip3.
DR VEuPathDB; VectorBase:FBgn0039875; -.
DR eggNOG; KOG0802; Eukaryota.
DR GeneTree; ENSGT00940000172216; -.
DR HOGENOM; CLU_009169_3_1_1; -.
DR InParanoid; Q95SP2; -.
DR OMA; NILMQQY; -.
DR OrthoDB; 897451at2759; -.
DR PhylomeDB; Q95SP2; -.
DR Reactome; R-DME-5358346; Hedgehog ligand biogenesis.
DR SignaLink; Q95SP2; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 43747; 0 hits in 1 CRISPR screen.
DR ChiTaRS; sip3; fly.
DR GenomeRNAi; 43747; -.
DR PRO; PR:Q95SP2; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039875; Expressed in testis and 34 other tissues.
DR ExpressionAtlas; Q95SP2; baseline and differential.
DR Genevisible; Q95SP2; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0000836; C:Hrd1p ubiquitin ligase complex; IEA:InterPro.
DR GO; GO:0016021; C:integral component of membrane; ISM:FlyBase.
DR GO; GO:0002039; F:p53 binding; IPI:FlyBase.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IGI:FlyBase.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; IMP:FlyBase.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IGI:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IDA:FlyBase.
DR GO; GO:0036490; P:regulation of translation in response to endoplasmic reticulum stress; IMP:FlyBase.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:FlyBase.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR032832; E3_lig_synoviolin/Hrd1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR22763:SF169; PTHR22763:SF169; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Metal-binding; Reference proteome; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..626
FT /note="E3 ubiquitin-protein ligase HRD1"
FT /id="PRO_0000280554"
FT TOPO_DOM 16..38
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..59
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..128
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 129..149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..167
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..222
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 244..626
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 289..328
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 234..268
FT /note="Interaction with p53/TP53"
FT /evidence="ECO:0000250"
FT REGION 569..600
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 626 AA; 69272 MW; F881B88D51D724EC CRC64;
MQLLLSSVCM ALTSAVIGFA YYQKQQFYPA VVYITKSNAS MGVIYIQFFV IVFMFGKLLS
KIFLGTLRAA EFEHLLERFW YALTETCLAF TVFRDDFNPR FVALFTVLLF LKSFHWLAEE
RVDFMERSPV LGWLFHIRVG SLLTVLGILD YVLLIHAYNS TLVRGPTVQL VFGFEYAILL
TVIASTAIKY VLHAAEMRTD TPWENKAVFL LYTELVIGLI KVVLYILFVV IMAKIYALPM
FVFRPMFFTI RNFRKALNDV IMSRRAIRNM NTLYPDATPE ELRQSDNICI ICREDMVNHS
KKLPCGHIFH TTCLRSWFQR QQTCPTCRLN ILRTPTVNST AMPRQGDEAV AAAAGNPIPA
AAGVQPAGGV PPPAPTAVVD GNQARADVNV AGGQALPPNF ADLFGDASGL PNGLPNLAGL
QIPPPPVMPM ISPFMIPPHF GYLTPLPPPP IPQDLTNFTD EELRAMEGLQ RDHIVQRLKL
LQNINLMLDS AGIMMSQYQS LSARLQLTAV TPATAVNGSA DSSVYDMPST SATAMAQLET
HQVTPTAAAS SASPTMPAEK VTIEDLGADA DEDDIPSTAT EAVSIPNSDA DFEENSSELG
ELRKRRLKFL EERNKSAATN ERTTAE
