TRC8_DROME
ID TRC8_DROME Reviewed; 809 AA.
AC Q7KRW1; Q7KRW0; Q8IHG9; Q8MQX1; Q8T0E3; Q8WRY2; Q9VAK6;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Protein TRC8 homolog;
GN Name=Trc8 {ECO:0000312|FlyBase:FBgn0039668}; ORFNames=CG2304;
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] {ECO:0000305, ECO:0000312|EMBL:AAL57300.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), FUNCTION, INTERACTION WITH CSN5 AND
RP VHL, AND SUBCELLULAR LOCATION.
RX PubMed=12032852; DOI=10.1038/sj.onc.1205437;
RA Gemmill R.M., Bemis L.T., Lee J.P., Sozen M.A., Baron A., Zeng C.,
RA Erickson P.F., Hooper J.E., Drabkin H.A.;
RT "The TRC8 hereditary kidney cancer gene suppresses growth and functions
RT with VHL in a common pathway.";
RL Oncogene 21:3507-3516(2002).
RN [2] {ECO:0000312|EMBL:AAS65223.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAS65223.1};
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 [3] {ECO:0000312|EMBL:AAS65223.1}
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 [4] {ECO:0000305, ECO:0000312|EMBL:AAM52762.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM52762.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM52762.1}, and
RC Testis {ECO:0000312|EMBL:AAN71016.1};
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 [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=15735686; DOI=10.1038/sj.onc.1208509;
RA Gemmill R.M., Lee J.P., Chamovitz D.A., Segal D., Hooper J.E.,
RA Drabkin H.A.;
RT "Growth suppression induced by the TRC8 hereditary kidney cancer gene is
RT dependent upon JAB1/CSN5.";
RL Oncogene 24:3503-3511(2005).
RN [6]
RP INTERACTION WITH CSN5; EIF3F AND EIF3H.
RX PubMed=20068067; DOI=10.1158/1541-7786.mcr-08-0491;
RA Lee J.P., Brauweiler A., Rudolph M., Hooper J.E., Drabkin H.A.,
RA Gemmill R.M.;
RT "The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and
RT protein biosynthetic pathways.";
RL Mol. Cancer Res. 8:93-106(2010).
CC -!- FUNCTION: Plays a role in growth inhibition that is dependent upon COP9
CC signalosome subunits CSN5 and CSN6. May modulate signalosome levels or
CC compartmentalization. Probably functions in the same or a related
CC pathway to VHL during early midline development.
CC {ECO:0000269|PubMed:12032852, ECO:0000269|PubMed:15735686,
CC ECO:0000303|PubMed:15735686}.
CC -!- SUBUNIT: Interacts with VHL. Interacts with the MPN domain of CSN5.
CC Interacts with EIF3F and EIF3H. {ECO:0000269|PubMed:12032852,
CC ECO:0000269|PubMed:20068067}.
CC -!- INTERACTION:
CC Q7KRW1; Q9XZ58: CSN5; NbExp=3; IntAct=EBI-1011633, EBI-97187;
CC Q7KRW1; Q9V3C1: Vhl; NbExp=3; IntAct=EBI-1011633, EBI-169514;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12032852}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:12032852}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=D {ECO:0000312|FlyBase:FBgn0039668};
CC IsoId=Q7KRW1-1; Sequence=Displayed;
CC Name=A {ECO:0000312|FlyBase:FBgn0039668}; Synonyms=B
CC {ECO:0000312|FlyBase:FBgn0039668};
CC IsoId=Q7KRW1-2; Sequence=VSP_051924;
CC -!- DEVELOPMENTAL STAGE: Expressed in oocytes throughout development.
CC {ECO:0000269|PubMed:12032852}.
CC -!- DOMAIN: The RING-type zinc finger domain may be essential for ubiquitin
CC ligase activity. {ECO:0000250|UniProtKB:O75485}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL39520.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAN71016.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AF387786; AAL57300.1; -; mRNA.
DR EMBL; AE014297; AAF56900.1; -; Genomic_DNA.
DR EMBL; AE014297; AAS65223.1; -; Genomic_DNA.
DR EMBL; AY069375; AAL39520.1; ALT_INIT; mRNA.
DR EMBL; AY122250; AAM52762.1; -; mRNA.
DR EMBL; BT001260; AAN71016.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001263070.1; NM_001276141.1. [Q7KRW1-2]
DR RefSeq; NP_733292.1; NM_170413.3. [Q7KRW1-2]
DR RefSeq; NP_733293.1; NM_170414.2. [Q7KRW1-2]
DR RefSeq; NP_996303.1; NM_206580.2. [Q7KRW1-1]
DR AlphaFoldDB; Q7KRW1; -.
DR BioGRID; 68341; 6.
DR IntAct; Q7KRW1; 2.
DR STRING; 7227.FBpp0089379; -.
DR PaxDb; Q7KRW1; -.
DR PRIDE; Q7KRW1; -.
DR EnsemblMetazoa; FBtr0085429; FBpp0084797; FBgn0039668. [Q7KRW1-2]
DR EnsemblMetazoa; FBtr0085430; FBpp0084798; FBgn0039668. [Q7KRW1-2]
DR EnsemblMetazoa; FBtr0085432; FBpp0089379; FBgn0039668. [Q7KRW1-1]
DR EnsemblMetazoa; FBtr0333188; FBpp0305390; FBgn0039668. [Q7KRW1-2]
DR GeneID; 43476; -.
DR KEGG; dme:Dmel_CG2304; -.
DR UCSC; CG2304-RA; d. melanogaster. [Q7KRW1-1]
DR CTD; 43476; -.
DR FlyBase; FBgn0039668; Trc8.
DR VEuPathDB; VectorBase:FBgn0039668; -.
DR eggNOG; KOG0802; Eukaryota.
DR GeneTree; ENSGT00940000158932; -.
DR InParanoid; Q7KRW1; -.
DR OMA; TVKFVIC; -.
DR PhylomeDB; Q7KRW1; -.
DR SignaLink; Q7KRW1; -.
DR BioGRID-ORCS; 43476; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 43476; -.
DR PRO; PR:Q7KRW1; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039668; Expressed in wing disc and 22 other tissues.
DR ExpressionAtlas; Q7KRW1; baseline and differential.
DR Genevisible; Q7KRW1; DM.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0036503; P:ERAD pathway; IBA:GO_Central.
DR GO; GO:0045926; P:negative regulation of growth; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:FlyBase.
DR GO; GO:0007418; P:ventral midline development; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR025754; TRC8_N_dom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13705; TRC8_N; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Membrane; Metal-binding;
KW Reference proteome; Transmembrane; Transmembrane helix; Zinc; Zinc-finger.
FT CHAIN 1..809
FT /note="Protein TRC8 homolog"
FT /id="PRO_0000056100"
FT TRANSMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 200..220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 392..412
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 425..445
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 461..481
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 488..508
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 539..559
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 621..659
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 696..724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 752..788
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 561..565
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000305"
FT /id="VSP_051924"
FT CONFLICT 273
FT /note="M -> L (in Ref. 1; AAL57300 and 4; AAM52762)"
FT /evidence="ECO:0000305"
FT CONFLICT 779
FT /note="S -> P (in Ref. 1; AAL57300 and 4; AAM52762/
FT AAN71016)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 809 AA; 89235 MW; B61E172E80D05317 CRC64;
MSVRTKVLGL VDVMMRVPPV MVIDEILKMD MGMQSWLYPD KDKASGALAT PTEAPAVPSG
QDPFTSIKEL FSHMTTSAQS VLEQSIEKAS EAAKTHGMLS SGFNSLMNEL SKDQTLADVL
STTTVKFVLC VFAFLSAACI FMLWTRHLVM VYMFLTSLGL TFLSYWSNVS ALALTERSPS
MVEDLMSLNT TRLLDSGGVV MSLAPHLMAQ WFMGMLFAYI HLGPRFEHVQ RSMPIIFASP
ILLAMLPLPA KVVQHLPVVA VFTPIILTKI TLMQSAMEAS RTVYNGYQYA MNFVSNFGLS
ALIENEWQRL NVPNVLRVFW TIRLIQGGYA LATTESDEPL DLMTATQKLL VDGCETMTAV
LGMTGVISMF CHYIGRGFQW YLLTYDDEEK SLGTVSAVLF YILALQTGLT SLSPDKRFIR
LCRNLCLLMT ALLHFLHNIV SPILMSLSAA RNPSRKRHVR ALSVCAFLVV LSVSLLYHLW
SQQSISTWLL AVTAFSVEVV VKVLVSLATY TLFLLDARRQ FFWEKLDDYL YYVRAFGNSV
EFCFGILLFI NGAWILIFES AQNATGGGIR AIMMCIHAYF NIWCEARAGW SVFMKRRSAV
HKISALPEAT PAQLQAFDDV CAICYQEMYS AKITRCRHFF HGVCLRKWLY VQDRCPLCHE
IMMYTDKADE NAPEAEPAPA AQAEQPMRIY PRDDANNAAA QRRSPERAPV EASEQAPATS
SSSAAATIGA EAVSAIVESA AAVGEARSLV SVASSSSATH RISASGSSDS SYMTASAQSP
PPTATSAAAV ATAAASNTTH MFRMSQDQQ
