ID SIMA_DROME Reviewed; 1507 AA.
AC Q24167; Q9VAA5;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 24-JAN-2024, entry version 191.
DE RecName: Full=Protein similar;
GN Name=sima; ORFNames=CG45051;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8682312; DOI=10.1016/0378-1119(96)00060-1;
RA Nambu J.R., Chen W., Hu S., Crews S.T.;
RT "The Drosophila melanogaster similar bHLH-PAS gene encodes a protein
RT related to human hypoxia-inducible factor 1 alpha and Drosophila single-
RT minded.";
RL Gene 172:249-254(1996).
RN [2]
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 [3]
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]
RP FUNCTION, AND INDUCTION.
RX PubMed=9731218; DOI=10.1006/bbrc.1998.9234;
RA Bacon N.C., Wappner P., O'Rourke J.F., Bartlett S.M., Shilo B., Pugh C.W.,
RA Ratcliffe P.J.;
RT "Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional
RT evidence for homology with mammalian HIF-1 alpha.";
RL Biochem. Biophys. Res. Commun. 249:811-816(1998).
RN [5]
RP INTERACTION WITH VHL.
RX PubMed=11006129; DOI=10.1006/bbrc.2000.3451;
RA Aso T., Yamazaki K., Aigaki T., Kitajima S.;
RT "Drosophila von Hippel-Lindau tumor suppressor complex possesses E3
RT ubiquitin ligase activity.";
RL Biochem. Biophys. Res. Commun. 276:355-361(2000).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND ODD DOMAIN.
RX PubMed=12215541; DOI=10.1128/mcb.22.19.6842-6853.2002;
RA Lavista-Llanos S., Centanin L., Irisarri M., Russo D.M., Gleadle J.M.,
RA Bocca S.N., Muzzopappa M., Ratcliffe P.J., Wappner P.;
RT "Control of the hypoxic response in Drosophila melanogaster by the basic
RT helix-loop-helix PAS protein similar.";
RL Mol. Cell. Biol. 22:6842-6853(2002).
CC -!- FUNCTION: Functions as a transcriptional regulator of the adaptive
CC response to hypoxia. Binds to core DNA sequence 5'-[AG]CGTG-3' within
CC the hypoxia response element (HRE) of target gene promoters.
CC {ECO:0000269|PubMed:12215541, ECO:0000269|PubMed:9731218}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Interacts with Vhl. {ECO:0000269|PubMed:11006129}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12215541}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:12215541}.
CC Note=Cytoplasmic in normoxia, nuclear translocation in response to
CC hypoxia.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in the embryo.
CC {ECO:0000269|PubMed:8682312}.
CC -!- INDUCTION: By hypoxia. {ECO:0000269|PubMed:12215541,
CC ECO:0000269|PubMed:9731218}.
CC -!- DOMAIN: The oxygen-dependent degradation (ODD) domain is required for
CC cytoplasmic localization in normoxia.
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DR EMBL; U43090; AAC47303.1; -; mRNA.
DR EMBL; AE014297; AAF57008.2; -; Genomic_DNA.
DR PIR; JC4851; JC4851.
DR RefSeq; NP_524584.2; NM_079845.4.
DR AlphaFoldDB; Q24167; -.
DR SMR; Q24167; -.
DR BioGRID; 68436; 207.
DR ComplexPortal; CPX-2691; Hypoxia-inducible transcription factor complex.
DR DIP; DIP-21002N; -.
DR ELM; Q24167; -.
DR IntAct; Q24167; 5.
DR STRING; 7227.FBpp0310749; -.
DR PaxDb; 7227-FBpp0084931; -.
DR EnsemblMetazoa; FBtr0344374; FBpp0310747; FBgn0266411.
DR GeneID; 43580; -.
DR KEGG; dme:Dmel_CG45051; -.
DR AGR; FB:FBgn0266411; -.
DR CTD; 43580; -.
DR FlyBase; FBgn0266411; sima.
DR VEuPathDB; VectorBase:FBgn0266411; -.
DR eggNOG; KOG3558; Eukaryota.
DR HOGENOM; CLU_004124_0_0_1; -.
DR InParanoid; Q24167; -.
DR PhylomeDB; Q24167; -.
DR Reactome; R-DME-1234158; Regulation of gene expression by Hypoxia-inducible Factor.
DR Reactome; R-DME-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-DME-8951664; Neddylation.
DR SignaLink; Q24167; -.
DR BioGRID-ORCS; 43580; 0 hits in 3 CRISPR screens.
DR ChiTaRS; sima; fly.
DR GenomeRNAi; 43580; -.
DR PRO; PR:Q24167; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0266411; Expressed in brain and 29 other cell types or tissues.
DR ExpressionAtlas; Q24167; baseline and differential.
DR Genevisible; Q24167; DM.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IMP:FlyBase.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:FlyBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:FlyBase.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:FlyBase.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:FlyBase.
DR GO; GO:0048477; P:oogenesis; IMP:FlyBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:FlyBase.
DR GO; GO:0030334; P:regulation of cell migration; IMP:FlyBase.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:FlyBase.
DR GO; GO:0045088; P:regulation of innate immune response; IMP:FlyBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060438; P:trachea development; IMP:FlyBase.
DR CDD; cd11433; bHLH-PAS_HIF; 1.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 3.30.450.20; PAS domain; 2.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR013655; PAS_fold_3.
DR PANTHER; PTHR23043; HYPOXIA-INDUCIBLE FACTOR 1 ALPHA; 1.
DR PANTHER; PTHR23043:SF17; PROTEIN SIMILAR; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08447; PAS_3; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW Activator; Coiled coil; Cytoplasm; DNA-binding; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT CHAIN 1..1507
FT /note="Protein similar"
FT /id="PRO_0000127444"
FT DOMAIN 72..125
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 167..240
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 307..377
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 381..422
FT /note="PAC"
FT REGION 1..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 433..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 541..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 692..863
FT /note="ODD"
FT REGION 706..832
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 900..951
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1204..1228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1251..1287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1356..1460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 880..908
FT /evidence="ECO:0000255"
FT COILED 982..1054
FT /evidence="ECO:0000255"
FT COILED 1110..1162
FT /evidence="ECO:0000255"
FT COMPBIAS 12..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..85
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..459
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 544..558
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1204..1223
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1384..1400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1408..1426
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 38
FT /note="S -> A (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="S -> L (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 492
FT /note="A -> V (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 588
FT /note="T -> I (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 709
FT /note="T -> K (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 776
FT /note="Q -> QQQQ (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 895
FT /note="Q -> QQ (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 902
FT /note="G -> S (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 982
FT /note="A -> T (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 1125..1126
FT /note="Missing (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 1154..1157
FT /note="Missing (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 1444
FT /note="F -> L (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 1447
FT /note="G -> C (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 1451
FT /note="S -> N (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
FT CONFLICT 1494
FT /note="D -> G (in Ref. 1; AAC47303)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1507 AA; 165824 MW; 4102939C8FBFB0C6 CRC64;
MVSLIDTIEA AAEKQKQSQA VVTNTSASSS SCSSSFSSSP PSSSVGSPSP GAPKTNLTAS
GKPKEKRRNN EKRKEKSRDA ARCRRSKETE IFMELSAALP LKTDDVNQLD KASVMRITIA
FLKIREMLQF VPSLRDCNDD IKQDIETAED QQEVKPKLEV GTEDWLNGAE ARELLKQTMD
GFLLVLSHEG DITYVSENVV EYLGITKIDT LGQQIWEYSH QCDHAEIKEA LSLKRELAQK
VKDEPQQNSG VSTHHRDLFV RLKCTLTSRG RSINIKSASY KVIHITGHLV VNAKGERLLM
AIGRPIPHPS NIEIPLGTST FLTKHSLDMR FTYVDDKMHD LLGYSPKDLL DTSLFSCQHG
ADSERLMATF KSVLSKGQGE TSRYRFLGKY GGYCWILSQA TIVYDKLKPQ SVVCVNYVIS
NLENKHEIYS LAQQTAASEQ KEQHHQAAET EKEPEKAADP EIIAQETKET VNTPIHTSEL
QAKPLQLESE KAEKTIEETK TIATIPPVTA TSTADQIKQL PESNPYKQIL QAELLIKREN
HSPGPRTITA QLLSGSSSGL RPEEKRPKSV TASVLRPSPA PPLTPPPTAV LCKKTPLGVE
PNLPPTTTAT AAIISSSNQQ LQIAQQTQLQ NPQQPAQDMS KGFCSLFADD GRGLTMLKEE
PDDLSHHLAS TNCIQLDEMT PFSDMLVGLM GTCLLPEDIN SLDSTTCSTT ASGQHYQSPS
SSSTSAPSNT SSSNNSYANS PLSPLTPNST ATASNPSHQQ QQQHHNQQQQ QQQQQQHHPQ
HHDNSNSSSN IDPLFNYREE SNDTSCSQHL HSPSITSKSP EDSSLPSLCS PNSLTQEDDF
SFEAFAMRAP YIPIDDDMPL LTETDLMWCP PEDLQTMVPK EIDAIQQQLQ QLQQQHHQQY
AGNTGYQQQQ QQPQLQQQHF SNSLCSSPAS TVSSLSPSPV QQHHQQQQAA VFTSDSSELA
ALLCGSGNGT LSILAGSGVT VAEECNERLQ QHQQQQQQTS GNEFRTFQQL QQELQLQEEQ
QQRQQQQQQQ QQQQQQQQLL SLNIECKKEK YDVQMGGSLC HPMEDAFEND YSKDSANLDC
WDLIQMQVVD TEPVSPNAAS PTPCKVSAIQ LLQQQQQLQQ QQQQQQNIIL NAVPLITIQN
NKELMQQQQQ QQQQQQQEQL QQPAIKLLNG ASIAPVNTKA TIRLVESKPP TTTQSRMAKV
NLVPQQQQHG NKRHLNSATG AGNPVESKRL KSGTLCLDVQ SPQLLQQLIG KDPAQQQTQA
AKRAGSERWQ LSAESKQQKQ QQQQSNSVLK NLLVSGRDDD DSEAMIIDED NSLVQPIPLG
KYGLPLHCHT STSSVLRDYH NNPLISGTNF QLSPVFGGSD SSGGDGETGS VVSLDDSVPP
GLTACDTDAS SDSGIDENSL MDGASGSPRK RLSSTSNSTN QAESAPPALD VETPVTQKSV
EEEFEGGGSG SNAPSRKTSI SFLDSSNPLL HTPAMMDLVN DDYIMGEGGF EFSDNQLEQV
LGWPEIA
//
