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RHDF1_DROME
ID   RHDF1_DROME             Reviewed;        1429 AA.
AC   Q76NQ1; E1NZB2;
DT   31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 119.
DE   RecName: Full=Inactive rhomboid protein 1;
DE            Short=iRhom;
DE   AltName: Full=Rhomboid family protein rhomboid-5;
GN   Name=rho-5; Synonyms=iRhom; ORFNames=CG33304;
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] OF 162-1429.
RA   Carlson J., Booth B., Frise E., Sandler J., Wan K., Yu C., Celniker S.E.;
RL   Submitted (SEP-2010) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP   AND TISSUE SPECIFICITY.
RX   PubMed=21439629; DOI=10.1016/j.cell.2011.02.047;
RA   Zettl M., Adrain C., Strisovsky K., Lastun V., Freeman M.;
RT   "Rhomboid family pseudoproteases use the ER quality control machinery to
RT   regulate intercellular signaling.";
RL   Cell 145:79-91(2011).
CC   -!- FUNCTION: Rhomboid protease-like protein which has no protease activity
CC       but regulates the secretion of several ligands of the epidermal growth
CC       factor receptor. Indirectly activates the epidermal growth factor
CC       receptor signaling pathway and may thereby regulate sleep, cell
CC       survival, proliferation and migration. {ECO:0000269|PubMed:21439629}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:21439629}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:21439629}.
CC   -!- TISSUE SPECIFICITY: Specifically expressed in the nervous system and in
CC       brain. {ECO:0000269|PubMed:21439629}.
CC   -!- DEVELOPMENTAL STAGE: Expressed exclusively in the central nervous
CC       system of embryos. In the third instar larva, expression is also
CC       restricted to neural tissue with specific expression behind the
CC       morphogenetic furrow in the developing eye and in the optic lobes
CC       within brain. {ECO:0000269|PubMed:21439629}.
CC   -!- DISRUPTION PHENOTYPE: Flies display a severe decrease in daytime
CC       activity pattern and an increase in sleeping periods.
CC       {ECO:0000269|PubMed:21439629}.
CC   -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000305}.
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DR   EMBL; AE014134; AAS64674.1; -; Genomic_DNA.
DR   EMBL; BT125661; ADN43898.1; -; mRNA.
DR   RefSeq; NP_995679.1; NM_205957.3.
DR   AlphaFoldDB; Q76NQ1; -.
DR   BioGRID; 77793; 6.
DR   STRING; 7227.FBpp0088796; -.
DR   PaxDb; Q76NQ1; -.
DR   EnsemblMetazoa; FBtr0089855; FBpp0088796; FBgn0041723.
DR   GeneID; 2768944; -.
DR   KEGG; dme:Dmel_CG33304; -.
DR   UCSC; CG33304-RA; d. melanogaster.
DR   CTD; 2768944; -.
DR   FlyBase; FBgn0041723; rho-5.
DR   VEuPathDB; VectorBase:FBgn0041723; -.
DR   eggNOG; KOG2290; Eukaryota.
DR   eggNOG; KOG2291; Eukaryota.
DR   GeneTree; ENSGT00940000168598; -.
DR   HOGENOM; CLU_004028_0_0_1; -.
DR   InParanoid; Q76NQ1; -.
DR   OMA; HERETAC; -.
DR   OrthoDB; 65171at2759; -.
DR   PhylomeDB; Q76NQ1; -.
DR   BioGRID-ORCS; 2768944; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 2768944; -.
DR   PRO; PR:Q76NQ1; -.
DR   Proteomes; UP000000803; Chromosome 2L.
DR   Bgee; FBgn0041723; Expressed in insect adult head and 9 other tissues.
DR   Genevisible; Q76NQ1; DM.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:FlyBase.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0010841; P:positive regulation of circadian sleep/wake cycle, wakefulness; IMP:UniProtKB.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0050708; P:regulation of protein secretion; IBA:GO_Central.
DR   Gene3D; 1.20.1540.10; -; 1.
DR   InterPro; IPR022764; Peptidase_S54_rhomboid_dom.
DR   InterPro; IPR035952; Rhomboid-like_sf.
DR   Pfam; PF01694; Rhomboid; 1.
DR   SUPFAM; SSF144091; SSF144091; 1.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Membrane; Protein transport; Reference proteome;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..1429
FT                   /note="Inactive rhomboid protein 1"
FT                   /id="PRO_0000408514"
FT   TOPO_DOM        1..843
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        844..864
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        865..1099
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1100..1120
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1121..1131
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1132..1152
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1153..1156
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1157..1177
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1178..1186
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1187..1207
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1208..1210
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1211..1231
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1232..1245
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1246..1266
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1267..1429
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   REGION          1..36
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          560..579
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          740..766
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        22..36
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        560..574
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   1429 AA;  157302 MW;  20C570E02BCFB68B CRC64;
     MSSNGSDLGH NNRRNEKGNP DSVHSSMRGS MSSTRRKSIN FQNQLQLALE SNECDVMYCS
     LSSGRFRAPN GENFPPHGGK LKLSPLEKYD DANRGVPPPS PAPNSDCFAT CVANQLPSQS
     CSVGSAKPET SVMQKHGMAG NGMVGSGMSG NGMAANGTNY HQRGVSPNSR YRLERYRESQ
     STPQSKLMDN MGGMPSAVPS VSATRLLLPS NVPLPLAQCE NYNAYLGSTV HTPVKRYVPT
     PPPAMELYSD LSISSSPAAN LPTPAAAVAS SASTSASAMQ SQYANMPYNY RSKCCHSEAS
     HGSLSRTSQT YASCSPACTS PSPAPSTSMS MVFSAASSCS PIMTATSSAR SGNHRGDDSD
     SVIVVPPGGG AMAQIEAENP SGTCLHCNTV RRTTGVHQTT QTTGPISPVP ISLPVPMAMP
     VMSGLNEQMP SQSLESSMVS VQAKRLEGGG NMAVPPGSNQ HQLYRSQMAS NPRLQHIHHQ
     TQQHQSLQVL PQPQNHHLSC KKRIGMYMRR TTSQFFGVEP STEAADCALW QGRHRRLAIR
     CFGMFDTELE YHMQQAIGGG NEDAGQSNGT NGNYAPDRPD ILPVQDAIGM DMTMSGDSRR
     QKCYTNRDFL AGEFVERKAS VGYMFVAMVS YLVHMFNKRR PIQMHRVRCP WQWSRSFAPI
     HVQSHSNQQT DADGCLTDGL EAIIDDEVFF DSPCEITTSA VNDESSDIGR QAAKPRPCAD
     QSGVGVSVYM AERQQNGWRT SALNSGGNAT SDINLTGDQS SHQPGAAHIP LCSSVSSQMQ
     PAMRSSHSTT STCNRGNRIT AQLLDGVLEN SRRPPLRCIK YFSVNDLDDR TDHRPFFTYW
     INTVQVVVLI LSIICYGIAP IGIGSEQKTG QVLVTSLSLQ TVQHVEQRNL WIGPRNIDLV
     HMGAKFAACM RRDIKITEVV TKTRRHERET ACCIRNDDSG CVQSSQAECS IRGLYPTKSI
     STWKKWSPSE SGPGGRISGS VCGLDPKFCD APASIAPYEW PDDITKWPIC RKTNSFTQRY
     RYKDHTSEHM VCEVIGHPCC TGLYGECRIT TREYCDFIKG YFHEEASLCS QISCLNNVCG
     MFPFISVETP DQLYRLLTSL CMHAGILHLA ITLIFQHLFL ADLERLIGTV RTAIVYIMSG
     FAGNLTSAIL VPHRPEVGPS ASLSGVVASL IALLVWMHWK YLHKPHIALF KLLLLCSVLV
     GIGTLPYQLN FLGLLAGVIC GCLLTMSLVP FTTFSKYGRK KKINLIWTCV LFHVVVYTAM
     IVTFYIHPSE FHSISFVDMF SNSNGYDNFT NADHHGVDVV SSNTRYSQTQ NSQYYYHHHS
     DDIIRKSVTF TEKALVSHIL YPTAPRKTSA QQWQEVEYSR SFNHLSNYSD RIKKSIGNIS
     KLKQVFTSPI RFSNKNNHSN LMTELTSVHS ENKQKYLGYI NNNTEFNVL
 
 
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