SLM1_YEAST
ID SLM1_YEAST Reviewed; 686 AA.
AC P40485; D6VVI2;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate-binding protein SLM1;
DE AltName: Full=Synthetic lethal with MSS4 protein 1;
DE AltName: Full=TORC2 effector protein SLM1;
GN Name=SLM1; Synonyms=LIT2; OrderedLocusNames=YIL105C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169870;
RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D.,
RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E.,
RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C.,
RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V.,
RA Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.";
RL Nature 387:84-87(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY TORC2, MUTAGENESIS OF
RP LYS-483 AND LYS-487, AND INTERACTION WITH SLM2 AND AVO2.
RX PubMed=15372071; DOI=10.1038/sj.emboj.7600384;
RA Audhya A., Loewith R., Parsons A.B., Gao L., Tabuchi M., Zhou H., Boone C.,
RA Hall M.N., Emr S.D.;
RT "Genome-wide lethality screen identifies new PI4,5P2 effectors that
RT regulate the actin cytoskeleton.";
RL EMBO J. 23:3747-3757(2004).
RN [5]
RP PHOSPHOINOSITIDE-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=15023338; DOI=10.1016/s1097-2765(04)00083-8;
RA Yu J.W., Mendrola J.M., Audhya A., Singh S., Keleti D., DeWald D.B.,
RA Murray D., Emr S.D., Lemmon M.A.;
RT "Genome-wide analysis of membrane targeting by S.cerevisiae pleckstrin
RT homology domains.";
RL Mol. Cell 13:677-688(2004).
RN [6]
RP FUNCTION, PHOSPHOINOSITIDE-BINDING, INTERACTION WITH AVO2; BIT2; BIT61 AND
RP TOR2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 477-ARG-ARG-478; LYS-483 AND
RP LYS-487.
RX PubMed=15689497; DOI=10.1091/mbc.e04-07-0564;
RA Fadri M., Daquinag A., Wang S., Xue T., Kunz J.;
RT "The pleckstrin homology domain proteins Slm1 and Slm2 are required for
RT actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-
RT bisphosphate and TORC2.";
RL Mol. Biol. Cell 16:1883-1900(2005).
RN [7]
RP FUNCTION, AND INTERACTION WITH CNA1 AND TOR2.
RX PubMed=16959779; DOI=10.1074/jbc.m604244200;
RA Mulet J.M., Martin D.E., Loewith R., Hall M.N.;
RT "Mutual antagonism of TOR and calcineurin signaling.";
RL J. Biol. Chem. 281:33000-33007(2006).
RN [8]
RP FUNCTION, DEPHOSPHORYLATION BY CALCINEURIN, AND INTERACTION WITH CNA1 AND
RP CNA2.
RX PubMed=16738335; DOI=10.1128/mcb.01973-05;
RA Bultynck G., Heath V.L., Majeed A.P., Galan J.-M., Haguenauer-Tsapis R.,
RA Cyert M.S.;
RT "Slm1 and slm2 are novel substrates of the calcineurin phosphatase required
RT for heat stress-induced endocytosis of the yeast uracil permease.";
RL Mol. Cell. Biol. 26:4729-4745(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145; SER-150 AND SER-153, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
CC -!- FUNCTION: Together with SLM2, effector of the TORC2- and calcineurin-
CC signaling pathways. Phosphorylated and activated by TORC2 under
CC favorable growth conditions. Mediates actin polarization via inhibition
CC of calcineurin-dependent transcription. Upon nutrient limitation or
CC environmental stress, gets dephosphorylated by calcineurin.
CC Dephosphorylation inhibits its interaction with TORC2, thereby
CC antagonizing TORC2 signaling and mediating calcineurin-dependent actin
CC depolarization. Also functions in heat-induced, calcineurin-mediated
CC uracil permease (FUR4) endocytosis. {ECO:0000269|PubMed:15372071,
CC ECO:0000269|PubMed:15689497, ECO:0000269|PubMed:16738335,
CC ECO:0000269|PubMed:16959779}.
CC -!- SUBUNIT: Heterodimer of SLM1-SLM2. Binds phosphatidylinositol 4,5-
CC bisphosphate, which is required for function. Interacts with the TORC2
CC subunits AVO2, BIT61 and TOR2. Interacts with the calcineurin catalytic
CC subunits CNA1 and CNA2. {ECO:0000269|PubMed:15372071,
CC ECO:0000269|PubMed:15689497, ECO:0000269|PubMed:16738335,
CC ECO:0000269|PubMed:16959779}.
CC -!- INTERACTION:
CC P40485; P40485: SLM1; NbExp=4; IntAct=EBI-25172, EBI-25172;
CC P40485; P53955: SLM2; NbExp=3; IntAct=EBI-25172, EBI-28706;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15023338,
CC ECO:0000269|PubMed:15372071, ECO:0000269|PubMed:15689497}; Peripheral
CC membrane protein {ECO:0000269|PubMed:15023338,
CC ECO:0000269|PubMed:15372071, ECO:0000269|PubMed:15689497}; Cytoplasmic
CC side {ECO:0000269|PubMed:15023338, ECO:0000269|PubMed:15372071,
CC ECO:0000269|PubMed:15689497}. Note=Localizes to cortical punctate
CC structures. Correct localization requires phosphatidylinositol 4,5-
CC bisphosphate and functional TORC2.
CC -!- PTM: Phosphorylated by the target of rapamycin complex 2 (TORC2) and
CC dephosphorylated by serine/threonine-protein phosphatase 2B
CC (calcineurin). {ECO:0000269|PubMed:15372071}.
CC -!- MISCELLANEOUS: Present with 5190 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
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DR EMBL; Z38125; CAA86275.1; -; Genomic_DNA.
DR EMBL; BK006942; DAA08448.1; -; Genomic_DNA.
DR PIR; S48467; S48467.
DR RefSeq; NP_012161.1; NM_001179453.1.
DR PDB; 3NSU; X-ray; 2.00 A; A/B=469-583.
DR PDB; 4A5K; X-ray; 1.76 A; A/B/C/D=469-583.
DR PDB; 4A6F; X-ray; 1.68 A; A/B=469-583.
DR PDB; 4A6H; X-ray; 1.45 A; A/B/C/D=469-583.
DR PDB; 4A6K; X-ray; 1.80 A; A/B/C/D=469-583.
DR PDBsum; 3NSU; -.
DR PDBsum; 4A5K; -.
DR PDBsum; 4A6F; -.
DR PDBsum; 4A6H; -.
DR PDBsum; 4A6K; -.
DR AlphaFoldDB; P40485; -.
DR SMR; P40485; -.
DR BioGRID; 34886; 174.
DR DIP; DIP-1353N; -.
DR ELM; P40485; -.
DR IntAct; P40485; 27.
DR MINT; P40485; -.
DR STRING; 4932.YIL105C; -.
DR iPTMnet; P40485; -.
DR MaxQB; P40485; -.
DR PaxDb; P40485; -.
DR PRIDE; P40485; -.
DR EnsemblFungi; YIL105C_mRNA; YIL105C; YIL105C.
DR GeneID; 854701; -.
DR KEGG; sce:YIL105C; -.
DR SGD; S000001367; SLM1.
DR VEuPathDB; FungiDB:YIL105C; -.
DR eggNOG; ENOG502QRAF; Eukaryota.
DR GeneTree; ENSGT00940000176324; -.
DR HOGENOM; CLU_013663_1_0_1; -.
DR InParanoid; P40485; -.
DR OMA; PQFEWDN; -.
DR BioCyc; YEAST:G3O-31361-MON; -.
DR PRO; PR:P40485; -.
DR Proteomes; UP000002311; Chromosome IX.
DR RNAct; P40485; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR GO; GO:0031932; C:TORC2 complex; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:SGD.
DR GO; GO:0046625; F:sphingolipid binding; IDA:SGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; IGI:SGD.
DR GO; GO:0051017; P:actin filament bundle assembly; IGI:SGD.
DR GO; GO:0070941; P:eisosome assembly; IGI:SGD.
DR GO; GO:0016197; P:endosomal transport; IGI:SGD.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; IPI:SGD.
DR GO; GO:0072659; P:protein localization to plasma membrane; IGI:SGD.
DR GO; GO:0001558; P:regulation of cell growth; IGI:SGD.
DR GO; GO:0031929; P:TOR signaling; IPI:SGD.
DR GO; GO:0038203; P:TORC2 signaling; IEA:InterPro.
DR CDD; cd13311; PH_Slm1; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR033191; Slm1/Slm2.
DR InterPro; IPR043453; Slm1_PH.
DR PANTHER; PTHR31941:SF12; PTHR31941:SF12; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Coiled coil; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..686
FT /note="Phosphatidylinositol 4,5-bisphosphate-binding
FT protein SLM1"
FT /id="PRO_0000202965"
FT DOMAIN 468..581
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 33..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 157..176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 626..669
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 296..381
FT /evidence="ECO:0000255"
FT MOTIF 673..678
FT /note="PXIXIT-like, required for interaction with CNA1 and
FT CNA2, and calcineurin-dependent dephosphorylation"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MUTAGEN 477..478
FT /note="RR->AA: In SLM1-PHM2; reduces phosphoinositide
FT binding by 95%; when associated with A-487."
FT /evidence="ECO:0000269|PubMed:15689497"
FT MUTAGEN 483
FT /note="K->A: In SLM1-PHM1; reduces phosphoinositide binding
FT by 80% and causes mislocalization to the cytoplasm; when
FT associated with A-487."
FT /evidence="ECO:0000269|PubMed:15372071,
FT ECO:0000269|PubMed:15689497"
FT MUTAGEN 487
FT /note="K->A: In SLM1-PHM1; reduces phosphoinositide binding
FT by 80% and causes mislocalization to the cytoplasm; when
FT associated with A-483. In SLM1-PHM2; reduces
FT phosphoinositide binding by 95%; when associated with 477-
FT AA-478."
FT /evidence="ECO:0000269|PubMed:15372071,
FT ECO:0000269|PubMed:15689497"
FT STRAND 470..479
FT /evidence="ECO:0007829|PDB:4A6H"
FT TURN 480..483
FT /evidence="ECO:0007829|PDB:4A6H"
FT STRAND 484..492
FT /evidence="ECO:0007829|PDB:4A6H"
FT STRAND 494..502
FT /evidence="ECO:0007829|PDB:4A6H"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:4A6H"
FT STRAND 512..516
FT /evidence="ECO:0007829|PDB:4A6H"
FT HELIX 517..519
FT /evidence="ECO:0007829|PDB:4A6H"
FT STRAND 520..525
FT /evidence="ECO:0007829|PDB:4A6H"
FT STRAND 530..533
FT /evidence="ECO:0007829|PDB:3NSU"
FT STRAND 542..553
FT /evidence="ECO:0007829|PDB:4A6H"
FT STRAND 558..562
FT /evidence="ECO:0007829|PDB:4A6H"
FT HELIX 566..579
FT /evidence="ECO:0007829|PDB:4A6H"
SQ SEQUENCE 686 AA; 77995 MW; 849C82CC0960014B CRC64;
MSKNNTMTSA VSDMLSQQQL NLQHLHNLQQ HTRSMTSADH ANVLQQQQQQ QQQQQQQQQQ
QQQSASFQNG SLTSDINQQS YLNGQPVPST SNSTFQNNRT LTMNSGGLQG IISNGSPNID
SNTNVTIAVP DPNNNNGKQL QGKNSLTNTS ILSRARSSLQ RQRLAQQQQQ QQDPRSPLVI
LVPTAAQPTD ILAARFSAWR NVIKSVIVYL TEIASIQDEI VRQQLRLSHA VQFPFFSIEN
QYQPSSQEDK SVQKFFLPLG NGSIQDLPTI LNQYHESLAS SASKASRELT NDVIPRLEDL
RRDLIVKIKE IKSLQSDFKN SCSKELQQTK QAMKQFQESL KDARYSVPKQ DPFLTKLALD
RQIKKQLQEE NFLHEAFDNL ETSGAELEKI VVMEIQNSLT IYARLLGQEA QLVFDILISK
LDSGFFNVDP QFEWDNFISR DPNFLLPNLP MRTFKEIVYK YQFDPLTYEI KSGFLERRSK
FLKSYSKGYY VLTPNFLHEF KTADRKKDLV PVMSLALSEC TVTEHSRKNS TSSPNSTGSD
AKFVLHAKQN GIIRRGHNWV FKADSYESMM SWFDNLKILT STSNIQDKYK FITQKLNLNS
DGKPKLTNNH TSINKYQLSN ANSTMVENDE NDDINSNYVG STVTPKLDNQ TNTNTSMSSL
PDTNDSELQD QVPNIYIQTP INDFKS
