SREBP_SCHPO
ID SREBP_SCHPO Reviewed; 900 AA.
AC Q9UUD1;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Sterol regulatory element-binding protein 1;
DE Contains:
DE RecName: Full=Processed sterol regulatory element-binding protein 1;
GN Name=sre1 {ECO:0000312|EMBL:CAB52036.1}; ORFNames=SPBC19C2.09;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2] {ECO:0000305}
RP FUNCTION, INDUCTION, PHOSPHORYLATION, INTERACTION WITH SCP1, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15797383; DOI=10.1016/j.cell.2005.01.012;
RA Hughes A.L., Todd B.L., Espenshade P.J.;
RT "SREBP pathway responds to sterols and functions as an oxygen sensor in
RT fission yeast.";
RL Cell 120:831-842(2005).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND DNA-BINDING.
RX PubMed=16537923; DOI=10.1128/mcb.26.7.2817-2831.2006;
RA Todd B.L., Stewart E.V., Burg J.S., Hughes A.L., Espenshade P.J.;
RT "Sterol regulatory element binding protein is a principal regulator of
RT anaerobic gene expression in fission yeast.";
RL Mol. Cell. Biol. 26:2817-2831(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-898 AND SER-899, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18257517; DOI=10.1021/pr7006335;
RA Wilson-Grady J.T., Villen J., Gygi S.P.;
RT "Phosphoproteome analysis of fission yeast.";
RL J. Proteome Res. 7:1088-1097(2008).
RN [5]
RP FUNCTION.
RX PubMed=18276645; DOI=10.1093/nar/gkn027;
RA Sehgal A., Hughes B.T., Espenshade P.J.;
RT "Oxygen-dependent, alternative promoter controls translation of tco1+ in
RT fission yeast.";
RL Nucleic Acids Res. 36:2024-2031(2008).
RN [6]
RP INDUCTION, AND INTERACTION WITH SCP1.
RX PubMed=19520858; DOI=10.1074/jbc.m109.002436;
RA Hughes B.T., Nwosu C.C., Espenshade P.J.;
RT "Degradation of sterol regulatory element-binding protein precursor
RT requires the endoplasmic reticulum-associated degradation components Ubc7
RT and Hrd1 in fission yeast.";
RL J. Biol. Chem. 284:20512-20521(2009).
RN [7]
RP INTERACTION WITH SCP1.
RX PubMed=25771684; DOI=10.1038/cr.2015.32;
RA Gong X., Li J., Shao W., Wu J., Qian H., Ren R., Espenshade P., Yan N.;
RT "Structure of the WD40 domain of SCAP from fission yeast reveals the
RT molecular basis for SREBP recognition.";
RL Cell Res. 25:401-411(2015).
RN [8] {ECO:0007744|PDB:5GPD, ECO:0007744|PDB:5GRS}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 628-876 IN COMPLEX WITH SCP1,
RP INTERACTION WITH SCP1, SUBUNIT, AND MUTAGENESIS OF 783-LEU--ILE-785 AND
RP 855-GLU--GLY-866.
RX PubMed=27811944; DOI=10.1038/cr.2016.123;
RA Gong X., Qian H., Shao W., Li J., Wu J., Liu J.J., Li W., Wang H.W.,
RA Espenshade P., Yan N.;
RT "Complex structure of the fission yeast SREBP-SCAP binding domains reveals
RT an oligomeric organization.";
RL Cell Res. 26:1197-1211(2016).
CC -!- FUNCTION: [Sterol regulatory element-binding protein 1]: Precursor of
CC the transcription factor form (Processed sterol regulatory element-
CC binding protein 1), which is embedded in the endoplasmic reticulum
CC membrane (PubMed:15797383). Low oxygen or sterol conditions promote
CC processing of this form, releasing the transcription factor form that
CC translocates into the nucleus and activates transcription of genes
CC required for adaptation to anaerobic growth (PubMed:15797383).
CC {ECO:0000269|PubMed:15797383}.
CC -!- FUNCTION: [Processed sterol regulatory element-binding protein 1]:
CC Transcriptional activator required for transcription of genes required
CC for adaptation to anaerobic growth like those implicated in the
CC nonrespiratory oxygen-consumptive biosynthetic pathways of sterol,
CC heme, sphingolipid, and ubiquinone biosynthesis. May monitor oxygen
CC levels through sterol synthesis steps which require oxygen.
CC {ECO:0000269|PubMed:15797383, ECO:0000269|PubMed:16537923,
CC ECO:0000269|PubMed:18276645}.
CC -!- SUBUNIT: Forms a tight complex with scp1, composed of 4 copies of scp1
CC and 4 copies of sre1, which protects sre1 precursor from degradation by
CC the proteasome. {ECO:0000269|PubMed:15797383,
CC ECO:0000269|PubMed:25771684, ECO:0000269|PubMed:27811944}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P36956}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P36956}.
CC -!- SUBCELLULAR LOCATION: [Processed sterol regulatory element-binding
CC protein 1]: Nucleus {ECO:0000269|PubMed:16537923}. Note=Accumulates at
CC promoters of the target genes (PubMed:16537923).
CC {ECO:0000269|PubMed:16537923}.
CC -!- INDUCTION: Proteolytic processing to mature form is induced by low
CC oxygen or sterols. The processed form binds to its own promoter to
CC promote positive feedback regulation and ensure maximal activation.
CC {ECO:0000269|PubMed:15797383, ECO:0000269|PubMed:19520858}.
CC -!- PTM: In low oxygen or sterol conditions sre1 undergoes proteolytic
CC cleavage to release the soluble transcription factor from the membrane.
CC {ECO:0000269|PubMed:15797383}.
CC -!- PTM: Processed form is phosphorylated. {ECO:0000269|PubMed:15797383,
CC ECO:0000269|PubMed:18257517}.
CC -!- DISRUPTION PHENOTYPE: Cells fail to grow in the absence of oxygen or
CC sterols. {ECO:0000269|PubMed:15797383}.
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DR EMBL; CU329671; CAB52036.1; -; Genomic_DNA.
DR PIR; T39800; T39800.
DR RefSeq; NP_595694.1; NM_001021591.2.
DR PDB; 5GPD; X-ray; 3.50 A; A/B=628-876.
DR PDB; 5GRS; EM; 5.40 A; E/F/G/H=628-896.
DR PDBsum; 5GPD; -.
DR PDBsum; 5GRS; -.
DR AlphaFoldDB; Q9UUD1; -.
DR SMR; Q9UUD1; -.
DR BioGRID; 277253; 47.
DR STRING; 4896.SPBC19C2.09.1; -.
DR iPTMnet; Q9UUD1; -.
DR MaxQB; Q9UUD1; -.
DR PaxDb; Q9UUD1; -.
DR PRIDE; Q9UUD1; -.
DR EnsemblFungi; SPBC19C2.09.1; SPBC19C2.09.1:pep; SPBC19C2.09.
DR GeneID; 2540730; -.
DR KEGG; spo:SPBC19C2.09; -.
DR PomBase; SPBC19C2.09; sre1.
DR VEuPathDB; FungiDB:SPBC19C2.09; -.
DR eggNOG; KOG2588; Eukaryota.
DR HOGENOM; CLU_303504_0_0_1; -.
DR InParanoid; Q9UUD1; -.
DR OMA; NDRICEL; -.
DR PhylomeDB; Q9UUD1; -.
DR PRO; PR:Q9UUD1; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0000785; C:chromatin; IDA:PomBase.
DR GO; GO:0071458; C:integral component of cytoplasmic side of endoplasmic reticulum membrane; TAS:PomBase.
DR GO; GO:0005634; C:nucleus; TAS:PomBase.
DR GO; GO:0032936; C:SREBP-SCAP complex; IPI:PomBase.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:PomBase.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:PomBase.
DR GO; GO:0006629; P:lipid metabolic process; NAS:PomBase.
DR GO; GO:1900038; P:negative regulation of cellular response to hypoxia; IC:GOC-OWL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:PomBase.
DR GO; GO:0032933; P:SREBP signaling pathway; IDA:PomBase.
DR GO; GO:0008202; P:steroid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR019006; Sre1_C.
DR Pfam; PF09427; DUF2014; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Endoplasmic reticulum;
KW Lipid metabolism; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Steroid metabolism; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..900
FT /note="Sterol regulatory element-binding protein 1"
FT /id="PRO_0000317067"
FT CHAIN 1..407
FT /note="Processed sterol regulatory element-binding protein
FT 1"
FT /evidence="ECO:0000269|PubMed:15797383"
FT /id="PRO_0000317068"
FT TOPO_DOM 1..442
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..463
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 464..509
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 510..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 531..900
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 260..332
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..440
FT /note="Nuclear form of sre1; complements deletions of sre1
FT or scp1"
FT /evidence="ECO:0000269|PubMed:15797383"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 206..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 898
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MOD_RES 899
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MUTAGEN 783..785
FT /note="LKI->PPP: In PPP; abolished homotetramerization,
FT leading to the formation of a monomer."
FT /evidence="ECO:0000269|PubMed:27811944"
FT MUTAGEN 855..866
FT /note="EKMAMYVRTAIG->KKMAMYVETAID: In ERG; ; abolished
FT homotetramerization and formation of a complex with scp1."
FT /evidence="ECO:0000269|PubMed:27811944"
SQ SEQUENCE 900 AA; 98486 MW; CDE5A686642B098C CRC64;
MQSSIPSVSV SVASPAMETP TKASPDSKSP NSVGAIPSSS PLASSTKAST STPFVENCSN
LLCDLASIVE DSPPTLTNTS LSPHSFSLSD MESSMSNWLN PFAFDNTMNS APPLFTSTNM
GSPNSLENST NPLLSNCGSP NSFQNETFTG PSLNEFDADD KIQRQMKILH SVDTIDPSTV
QNYPSADMSN PEVKLKTEEI ITPMDTTCKP EPSAKKIKLS PSSEDSCSIP ETLPFSAPKS
RGSLSPSETP DFVAGPGGKP KKTAHNMIEK RYRTNLNDRI CELRDAVPSL RAAAALRCGN
SLDDEDLGGL TPARKLNKGT ILAKATEYIR HLEAKNKELQ KTNKQLSDRL AFYEDPSMAP
PSNDTRAVNS VNVVSSSDYS VHQSSRPNLT QRAFTSPTLN TMGRTALNGM VGLGLFNYFG
NDSSQSVYGL FALPPFLMSP FTGTVLFNML KIGVVLLGLF YLLHDNSLFK GFKGEKKSKV
STRSSMSPSS ILFRKTVFEK YCLLDHSTST ISLFFGLLIF TLKSAYGYLT HRLSALYTSS
ENWVYSEQQL AEVRNMEKLL DAQLMGGDAK VDRLRLLMVF ASSFSLPPSS HTCALQAMYC
QLIFSNTSVP SAIVSKCVAF FWNAAKKQHS KSSVHAELRE LPECTANLIE NSHADDVFSP
NMVERLWVLA KCTRDSAQMS DSIISSLSDV LVLSPLEVLA SWYAADLLDA LLMESLSRKV
EISEIEEIIS LCPKNSSIIR HALLAKLVLF PENTADSLNE VLAAYKNTLD LCSQDKRKQS
SVLKINLSKL FTLHSCLSLA LQRLGYGDVS KRMYQEIFVP DSDADITPLS FIISWTALNT
FAPICTSPKE NDVVEKMAMY VRTAIGTLKI QDLKLSRKLI NSCIDIGSRL QEDLGYVSSA
