SCAP_SCHPO
ID SCAP_SCHPO Reviewed; 1086 AA.
AC O43043;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Sterol regulatory element-binding protein cleavage-activating protein;
DE Short=SCAP;
DE Short=SREBP cleavage-activating protein;
GN Name=scp1 {ECO:0000312|EMBL:CAA17795.1}; ORFNames=SPBC3B9.15c;
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, AND INTERACTION WITH SRE1.
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] {ECO:0000305}
RP FUNCTION, INTERACTION WITH 4-METHYL STEROLS, MUTAGENESIS OF TYR-247;
RP LEU-264 AND ASP-392, AND DISRUPTION PHENOTYPE.
RX PubMed=17595166; DOI=10.1074/jbc.m701326200;
RA Hughes A.L., Lee C.-Y.S., Bien C.M., Espenshade P.J.;
RT "4-methyl sterols regulate fission yeast SREBP-Scap under low oxygen and
RT cell stress.";
RL J. Biol. Chem. 282:24388-24396(2007).
RN [4] {ECO:0007744|PDB:4YHC}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 567-961 AND 986-1054, INTERACTION
RP WITH SRE1, AND MUTAGENESIS OF ARG-617; CYS-618; 635-LYS--LYS-643; LYS-659;
RP CYS-680; LYS-685 AND ASP-1023.
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 [5] {ECO:0007744|PDB:5GRS}
RP STRUCTURE BY ELECTRON MICROSCOPY (5.40 ANGSTROMS) OF 567-1085 IN COMPLEX
RP WITH SRE1, AND SUBUNIT.
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: Escort protein required for sre1 processing at low sterol as
CC well as oxygen levels. May regulate export of the scp1/sre1 complex
CC from the ER at low sterol or oxygen levels (PubMed:15797383,
CC PubMed:17595166). 4-methyl sterols bound to scp1 may mask an ER export
CC signal in scp1 leading to retention of the complex in the ER
CC (PubMed:15797383, PubMed:17595166). Release of 4-methyl sterols may
CC trigger a conformational change in the SSD domain of scp1 unmasking the
CC ER export signal leading to recruitment into COPII-coated vesicles,
CC transport to the Golgi complex, proteolytic cleavage of sre1 in the
CC Golgi, release of the transcription factor fragment of sre1 from the
CC membrane, its import into the nucleus and up-regulation of genes
CC required for ergosterol biosynthesis as well as anaerobic growth (By
CC similarity). Binds 4-methyl sterols (PubMed:17595166).
CC {ECO:0000250|UniProtKB:P97260, ECO:0000269|PubMed:15797383,
CC ECO:0000269|PubMed:17595166}.
CC -!- SUBUNIT: Forms a tight complex with scp1, composed of 4 copies of scp1
CC and 4 copies of sre1. {ECO:0000269|PubMed:15797383,
CC ECO:0000269|PubMed:25771684, ECO:0000269|PubMed:27811944}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P97260}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P97260}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P97260}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P97260}.
CC -!- DISRUPTION PHENOTYPE: Cells show absence of mature sre1 as well as
CC inability to grow in the absence of oxygen.
CC {ECO:0000269|PubMed:17595166}.
CC -!- SIMILARITY: Belongs to the WD repeat SCAP family. {ECO:0000305}.
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DR EMBL; CU329671; CAA17795.1; -; Genomic_DNA.
DR PIR; T40354; T40354.
DR RefSeq; NP_596673.1; NM_001022595.2.
DR PDB; 4YHC; X-ray; 2.05 A; A/B=567-961, A/B=986-1054.
DR PDB; 5GRS; EM; 5.40 A; A/B/C/D=567-961, I/J/K/L=986-1085.
DR PDBsum; 4YHC; -.
DR PDBsum; 5GRS; -.
DR AlphaFoldDB; O43043; -.
DR SMR; O43043; -.
DR BioGRID; 277580; 6.
DR STRING; 4896.SPBC3B9.15c.1; -.
DR MaxQB; O43043; -.
DR PaxDb; O43043; -.
DR PRIDE; O43043; -.
DR EnsemblFungi; SPBC3B9.15c.1; SPBC3B9.15c.1:pep; SPBC3B9.15c.
DR GeneID; 2541065; -.
DR KEGG; spo:SPBC3B9.15c; -.
DR PomBase; SPBC3B9.15c; scp1.
DR VEuPathDB; FungiDB:SPBC3B9.15c; -.
DR eggNOG; KOG1933; Eukaryota.
DR HOGENOM; CLU_287002_0_0_1; -.
DR InParanoid; O43043; -.
DR OMA; LIAQWHF; -.
DR PhylomeDB; O43043; -.
DR PRO; PR:O43043; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:PomBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0071458; C:integral component of cytoplasmic side of endoplasmic reticulum membrane; TAS:PomBase.
DR GO; GO:0030173; C:integral component of Golgi membrane; TAS:PomBase.
DR GO; GO:0032936; C:SREBP-SCAP complex; IPI:PomBase.
DR GO; GO:0032934; F:sterol binding; IEA:InterPro.
DR GO; GO:0071456; P:cellular response to hypoxia; TAS:PomBase.
DR GO; GO:0070452; P:positive regulation of ergosterol biosynthetic process; IC:PomBase.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0032933; P:SREBP signaling pathway; IMP:PomBase.
DR GO; GO:0008202; P:steroid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR030225; SCAP.
DR InterPro; IPR000731; SSD.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR46378; PTHR46378; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50156; SSD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Lipid metabolism; Lipid-binding; Membrane; Reference proteome; Repeat;
KW Steroid metabolism; Transmembrane; Transmembrane helix; WD repeat.
FT CHAIN 1..1086
FT /note="Sterol regulatory element-binding protein cleavage-
FT activating protein"
FT /id="PRO_0000315874"
FT TOPO_DOM 1..35
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 36..56
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..229
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 230..250
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 266..286
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 287..290
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 291..311
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 312..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 338..358
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..367
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 368..388
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 389..422
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 423..443
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 444..544
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT TRANSMEM 545..565
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..1086
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT DOMAIN 233..391
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REPEAT 593..632
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 637..675
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 680..727
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 736..776
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 963..1009
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REGION 640..1086
FT /note="Interaction with sre1"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT MOTIF 396..401
FT /note="ER export signal"
FT /evidence="ECO:0000250|UniProtKB:P97260"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 454
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 247
FT /note="Y->C: Loss of sterol dependence of sre1 proteolysis.
FT Constitutive maturation of sre1."
FT /evidence="ECO:0000269|PubMed:17595166"
FT MUTAGEN 264
FT /note="L->F: Loss of sterol dependence of sre1 proteolysis.
FT Constitutive maturation of sre1."
FT /evidence="ECO:0000269|PubMed:17595166"
FT MUTAGEN 392
FT /note="D->N: Loss of sterol dependence of sre1 proteolysis.
FT Constitutive maturation of sre1."
FT /evidence="ECO:0000269|PubMed:17595166"
FT MUTAGEN 617
FT /note="R->E: In Scp1-M1; strongly reduced interaction with
FT sre1."
FT /evidence="ECO:0000269|PubMed:25771684"
FT MUTAGEN 618
FT /note="C->S: In Scp1-M4; reduced interaction with sre1;
FT when associated with S-680."
FT /evidence="ECO:0000269|PubMed:25771684"
FT MUTAGEN 635..643
FT /note="KEQMPRTLK->EEQMPETLE: In Scp1-M2; strongly reduced
FT interaction with sre1."
FT /evidence="ECO:0000269|PubMed:25771684"
FT MUTAGEN 659
FT /note="K->E: In Scp1-M3; strongly reduced interaction with
FT sre1; when associated with E-685."
FT /evidence="ECO:0000269|PubMed:25771684"
FT MUTAGEN 680
FT /note="C->S: In Scp1-M4; reduced interaction with sre1;
FT when associated with S-618."
FT /evidence="ECO:0000269|PubMed:25771684"
FT MUTAGEN 685
FT /note="K->E: In Scp1-M3; strongly reduced interaction with
FT sre1; when associated with E-659."
FT /evidence="ECO:0000269|PubMed:25771684"
FT MUTAGEN 1023
FT /note="D->K: In Scp1-M5; reduced interaction with sre1."
FT /evidence="ECO:0000269|PubMed:25771684"
FT STRAND 569..573
FT /evidence="ECO:0007829|PDB:4YHC"
FT HELIX 580..584
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 585..589
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 598..603
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 609..614
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 619..623
FT /evidence="ECO:0007829|PDB:4YHC"
FT TURN 624..627
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 628..633
FT /evidence="ECO:0007829|PDB:4YHC"
FT HELIX 635..637
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 644..647
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 651..657
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 659..666
FT /evidence="ECO:0007829|PDB:4YHC"
FT TURN 667..670
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 671..677
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 686..692
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 697..699
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 701..709
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 712..721
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 726..735
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 740..747
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 752..758
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 763..769
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 772..777
FT /evidence="ECO:0007829|PDB:4YHC"
FT HELIX 782..784
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 791..795
FT /evidence="ECO:0007829|PDB:4YHC"
FT HELIX 796..798
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 800..804
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 806..813
FT /evidence="ECO:0007829|PDB:4YHC"
FT TURN 814..817
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 818..824
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 834..839
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 841..843
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 846..858
FT /evidence="ECO:0007829|PDB:4YHC"
FT TURN 859..861
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 864..869
FT /evidence="ECO:0007829|PDB:4YHC"
FT TURN 873..875
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 876..886
FT /evidence="ECO:0007829|PDB:4YHC"
FT TURN 895..898
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 899..902
FT /evidence="ECO:0007829|PDB:4YHC"
FT HELIX 904..906
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 909..914
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 919..922
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 926..939
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 992..1002
FT /evidence="ECO:0007829|PDB:4YHC"
FT TURN 1003..1006
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 1007..1018
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 1027..1031
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 1034..1039
FT /evidence="ECO:0007829|PDB:4YHC"
FT STRAND 1042..1049
FT /evidence="ECO:0007829|PDB:4YHC"
SQ SEQUENCE 1086 AA; 125129 MW; 62D1F23D568C8F7A CRC64;
MRIFTLGKGR ISRGYARQVN PSLFAKYSYC IANNPWYFIL VFTLLSITGI YSSLVAYQQS
LYDQSLARWS AWYAESINAE ANVITKQLYL LGTNTSVFSE DYLSNAYRWE TSFHQYLAEY
GYPCIRDEKS CVTISPIPKY YGKVDPVAQY SYTKGLPENE REVNKLRNDT IAEGFDSLSA
FVITYFLKPE QVDTFHVVLK KFISETPNLY ASLLDTSPTT VVARIPDLTV IYRWYLWVGF
GVGLFAYLYL SLVRLHDIRA KFGLTATIFI QSGTAYFSTC SLLYFFERTG PICPWPMAYY
IIIFMDIENS FRLLRAVIAS PQTKRVPSRI MEGFSSTIIA SFSSLLKKLL TLFVLSFFVY
PLVQEFCLFL ACSFVVSFLL HGSFFLAVLS VDIRRLELQD FLDSNSSNRN SKWWVPYLEY
VRFMWSPWII DNLGTVSFHM YVIYLQLQSS TDINGSWRLA SPNIRFLITL YHRLGRILRE
RKLFPLITTG WFGDPTFLEA LKEKTMAENL VIALYRPVIL DTVNRRDYTN VYNSFHDRRV
WRWSTFFSIL FAIDFAVGLL VKALLRGWSD HDELSTDTTL HEEKFRIEPV PVHHQLDILK
IAVSENYKTF ASVGLDRCLV VWDLRQWCTK LVLSKEQMPR TLKAIALDPQ GNYVSLFSKD
TLFILNVESP CLMLQHSYHC KPNSKLNVFW MPGTHKDDEW KNFELVVVES SGEIQVFSLT
IEIEGADIAL VEKFQLSSPI IKSISIVSPT ANRIACLTES GEVTVYSKKG PVWSPKILSQ
NKNYLTETKK DIYGIAMADI LFLARDSGVD MIDLKNDELL HSFTLPPIKV NTFSVGVSNS
RFVNGQFRVS SISFCFTHAV TEKVLYYYYG NECNESYIIL NKWDQQPNLV DVHDPDNSLA
CLTFDELQEN IHEVEDASEC VMSSDGLYIF GMRRKSSSGI CPTADEKNED NGFTLRNRKL
RTGHYNWTSY VPLLDSYMQD MEHKKNTHSG GETQVWEVWM YSQSEKKHRC KSLKMYNSLI
IADPGPSLAV SDRCVAIVLG NYVALVGYGS EIFRDFYQIR NSDEMDRILR RKRKNLQRKR
SGTIGC
