FNTA_YEAST
ID FNTA_YEAST Reviewed; 316 AA.
AC P29703; D6VXR6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha;
DE Short=PFTase/PGGTase I alpha;
DE EC=2.5.1.58 {ECO:0000269|PubMed:8424764, ECO:0000269|PubMed:8527442, ECO:0000269|PubMed:9174352};
DE EC=2.5.1.59 {ECO:0000269|PubMed:1400380, ECO:0000269|PubMed:7639519, ECO:0000269|PubMed:9109664};
DE AltName: Full=CAAX farnesyltransferase subunit alpha;
DE AltName: Full=FTase-alpha;
DE AltName: Full=Ras proteins prenyltransferase subunit alpha;
DE AltName: Full=Type I protein geranyl-geranyltransferase subunit alpha;
DE Short=GGTase-I-alpha;
GN Name=RAM2; OrderedLocusNames=YKL019W;
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 [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF ASN-143.
RX PubMed=1763050; DOI=10.1073/pnas.88.24.11373;
RA He B., Chen P., Chen S.-Y., Vancura K.L., Michaelis S., Powers S.;
RT "RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide
RT components of the farnesyltransferase that prenylates a-factor and Ras
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:11373-11377(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-110.
RX PubMed=8203154; DOI=10.1002/yea.320100108;
RA Burkett T.J., Garfinkel D.J.;
RT "Molecular characterization of the SPT23 gene: a dosage-dependent
RT suppressor of Ty-induced promoter mutations from Saccharomyces
RT cerevisiae.";
RL Yeast 10:81-92(1994).
RN [5]
RP FUNCTION.
RX PubMed=2124698; DOI=10.1073/pnas.87.24.9665;
RA Goodman L.E., Judd S.R., Farnsworth C.C., Powers S., Gelb M.H.,
RA Glomset J.A., Tamanoi F.;
RT "Mutants of Saccharomyces cerevisiae defective in the farnesylation of Ras
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9665-9669(1990).
RN [6]
RP FUNCTION.
RX PubMed=1860864; DOI=10.1016/s0021-9258(18)98729-6;
RA Moores S.L., Schaber M.D., Mosser S.D., Rands E., O'Hara M.B., Garsky V.M.,
RA Marshall M.S., Pompliano D.L., Gibbs J.B.;
RT "Sequence dependence of protein isoprenylation.";
RL J. Biol. Chem. 266:14603-14610(1991).
RN [7]
RP SUBUNIT.
RX PubMed=1918005; DOI=10.1016/s0021-9258(18)55146-2;
RA Kohl N.E., Diehl R.E., Schaber M.D., Rands E., Soderman D.D., He B.,
RA Moores S.L., Pompliano D.L., Ferro-Novick S., Powers S., Thomas K.A.,
RA Gibbs J.B.;
RT "Structural homology among mammalian and Saccharomyces cerevisiae
RT isoprenyl-protein transferases.";
RL J. Biol. Chem. 266:18884-18888(1991).
RN [8]
RP FUNCTION, SUBUNIT, AND COFACTOR.
RX PubMed=1400380; DOI=10.1016/s0021-9258(19)36727-4;
RA Mayer M.L., Caplin B.E., Marshall M.S.;
RT "CDC43 and RAM2 encode the polypeptide subunits of a yeast type I protein
RT geranylgeranyltransferase.";
RL J. Biol. Chem. 267:20589-20593(1992).
RN [9]
RP ERRATUM.
RA Mayer M.L., Caplin B.E., Marshall M.S.;
RL J. Biol. Chem. 268:4568-4568(1993).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8424764; DOI=10.1042/bj2890025;
RA Gomez R., Goodman L.E., Tripathy S.K., O'Rourke E., Manne V., Tamanoi F.;
RT "Purified yeast protein farnesyltransferase is structurally and
RT functionally similar to its mammalian counterpart.";
RL Biochem. J. 289:25-31(1993).
RN [11]
RP MUTAGENESIS OF ASN-143.
RX PubMed=8494894; DOI=10.1021/bi00070a028;
RA Omer C.A., Kral A.M., Diehl R.E., Prendergast G.C., Powers S., Allen C.M.,
RA Gibbs J.B., Kohl N.E.;
RT "Characterization of recombinant human farnesyl-protein transferase:
RT cloning, expression, farnesyl diphosphate binding, and functional homology
RT with yeast prenyl-protein transferases.";
RL Biochemistry 32:5167-5176(1993).
RN [12]
RP SUBUNIT, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=7639519; DOI=10.1006/abbi.1995.1384;
RA Stirtan W.G., Poulter C.D.;
RT "Yeast protein geranylgeranyltransferase type-I: overproduction,
RT purification, and characterization.";
RL Arch. Biochem. Biophys. 321:182-190(1995).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8527442; DOI=10.1021/bi00051a017;
RA Dolence J.M., Cassidy P.B., Mathis J.R., Poulter C.D.;
RT "Yeast protein farnesyltransferase: steady-state kinetic studies of
RT substrate binding.";
RL Biochemistry 34:16687-16694(1995).
RN [14]
RP CATALYTIC ACTIVITY.
RX PubMed=9109664; DOI=10.1021/bi962579c;
RA Stirtan W.G., Poulter C.D.;
RT "Yeast protein geranylgeranyltransferase type-I: steady-state kinetics and
RT substrate binding.";
RL Biochemistry 36:4552-4557(1997).
RN [15]
RP CATALYTIC ACTIVITY.
RX PubMed=9174352; DOI=10.1021/bi9629182;
RA Mathis J.R., Poulter C.D.;
RT "Yeast protein farnesyltransferase: a pre-steady-state kinetic analysis.";
RL Biochemistry 36:6367-6376(1997).
RN [16]
RP MUTAGENESIS OF ASP-140 AND HIS-145.
RX PubMed=10491163; DOI=10.1046/j.1432-1327.1999.00686.x;
RA Kim H., Yang C.H.;
RT "Active site determination of yeast geranylgeranyl protein transferase type
RT I expressed in Escherichia coli.";
RL Eur. J. Biochem. 265:105-111(1999).
RN [17]
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).
CC -!- FUNCTION: Essential subunit of both the farnesyltransferase and the
CC geranylgeranyltransferase complex. Contributes to the transfer of a
CC farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl
CC diphosphate to a cysteine at the fourth position from the C-terminus of
CC several proteins having the C-terminal sequence Cys-aliphatic-
CC aliphatic-X. If X is Ser, Ala, Met, Cys, or Gln, then the protein is
CC farnesylated, if X is Leu or Phe, then the protein is
CC geranylgeranylated. The alpha subunit wraps partly around the beta
CC subunit forming part of the active site. The beta subunit is
CC responsible for isoprenoid and peptide-binding.
CC {ECO:0000269|PubMed:1763050, ECO:0000269|PubMed:1860864,
CC ECO:0000269|PubMed:2124698, ECO:0000269|PubMed:8424764,
CC ECO:0000269|PubMed:8527442}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + L-cysteinyl-[protein] =
CC diphosphate + S-(2E,6E)-farnesyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:13345, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:11535,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:33019, ChEBI:CHEBI:86019,
CC ChEBI:CHEBI:175763; EC=2.5.1.58;
CC Evidence={ECO:0000269|PubMed:8424764, ECO:0000269|PubMed:8527442,
CC ECO:0000269|PubMed:9174352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13346;
CC Evidence={ECO:0000269|PubMed:8424764, ECO:0000269|PubMed:8527442,
CC ECO:0000269|PubMed:9174352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=geranylgeranyl diphosphate + L-cysteinyl-[protein] =
CC diphosphate + S-geranylgeranyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:21240, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:11537,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:33019, ChEBI:CHEBI:57533,
CC ChEBI:CHEBI:86021; EC=2.5.1.59; Evidence={ECO:0000269|PubMed:1400380,
CC ECO:0000269|PubMed:7639519, ECO:0000269|PubMed:9109664};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21241;
CC Evidence={ECO:0000269|PubMed:1400380, ECO:0000269|PubMed:7639519,
CC ECO:0000269|PubMed:9109664};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:1400380, ECO:0000269|PubMed:7639519};
CC -!- SUBUNIT: Farnesyltransferase and geranyl-geranyltransferase share a
CC common alpha subunit (RAM2) (Probable). Protein farnesyltransferase is
CC a heterodimer of alpha subunit RAM2 and beta subunit RAM1
CC (PubMed:1763050). Protein geranyl-geranyltransferase type-1 is a
CC heterodimer of alpha subunit RAM2 and beta subunit CDC43
CC (PubMed:1400380, PubMed:9174352). {ECO:0000269|PubMed:1400380,
CC ECO:0000269|PubMed:1763050, ECO:0000269|PubMed:9174352,
CC ECO:0000305|PubMed:1918005}.
CC -!- INTERACTION:
CC P29703; P18898: CDC43; NbExp=3; IntAct=EBI-14814, EBI-3961;
CC P29703; P22007: RAM1; NbExp=3; IntAct=EBI-14814, EBI-14806;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- MISCELLANEOUS: Present with 396 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the protein prenyltransferase subunit alpha
CC family. {ECO:0000305}.
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DR EMBL; M88584; AAA34957.1; -; Genomic_DNA.
DR EMBL; Z28019; CAA81854.1; -; Genomic_DNA.
DR EMBL; L24760; AAA20574.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA09136.1; -; Genomic_DNA.
DR PIR; A41626; A41626.
DR RefSeq; NP_012906.3; NM_001179585.3.
DR AlphaFoldDB; P29703; -.
DR SMR; P29703; -.
DR BioGRID; 34112; 137.
DR ComplexPortal; CPX-1634; Protein farnesyltransferase complex.
DR ComplexPortal; CPX-1635; Protein geranylgeranyltransferase type I complex.
DR DIP; DIP-1233N; -.
DR IntAct; P29703; 6.
DR MINT; P29703; -.
DR STRING; 4932.YKL019W; -.
DR BindingDB; P29703; -.
DR ChEMBL; CHEMBL2406; -.
DR MaxQB; P29703; -.
DR PaxDb; P29703; -.
DR PRIDE; P29703; -.
DR EnsemblFungi; YKL019W_mRNA; YKL019W; YKL019W.
DR GeneID; 853849; -.
DR KEGG; sce:YKL019W; -.
DR SGD; S000001502; RAM2.
DR VEuPathDB; FungiDB:YKL019W; -.
DR eggNOG; KOG0530; Eukaryota.
DR GeneTree; ENSGT00550000074935; -.
DR HOGENOM; CLU_026582_1_0_1; -.
DR InParanoid; P29703; -.
DR OMA; RRKYWQY; -.
DR BioCyc; YEAST:MON3O-38; -.
DR BRENDA; 2.5.1.58; 984.
DR Reactome; R-SCE-9648002; RAS processing.
DR PRO; PR:P29703; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P29703; protein.
DR GO; GO:0005953; C:CAAX-protein geranylgeranyltransferase complex; IDA:SGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005965; C:protein farnesyltransferase complex; IDA:SGD.
DR GO; GO:0004662; F:CAAX-protein geranylgeranyltransferase activity; IDA:SGD.
DR GO; GO:0004660; F:protein farnesyltransferase activity; IDA:SGD.
DR GO; GO:0004661; F:protein geranylgeranyltransferase activity; IDA:SGD.
DR GO; GO:0007323; P:peptide pheromone maturation; IDA:SGD.
DR GO; GO:0018343; P:protein farnesylation; IDA:UniProtKB.
DR GO; GO:0018344; P:protein geranylgeranylation; IDA:SGD.
DR InterPro; IPR002088; Prenyl_trans_a.
DR Pfam; PF01239; PPTA; 4.
DR PROSITE; PS51147; PFTA; 5.
PE 1: Evidence at protein level;
KW Cytoplasm; Magnesium; Prenyltransferase; Reference proteome; Repeat;
KW Transferase.
FT CHAIN 1..316
FT /note="Protein
FT farnesyltransferase/geranylgeranyltransferase type-1
FT subunit alpha"
FT /id="PRO_0000119754"
FT REPEAT 47..81
FT /note="PFTA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00488"
FT REPEAT 89..123
FT /note="PFTA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00488"
FT REPEAT 125..159
FT /note="PFTA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00488"
FT REPEAT 160..193
FT /note="PFTA 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00488"
FT REPEAT 199..233
FT /note="PFTA 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00488"
FT MUTAGEN 140
FT /note="D->N: Decreases catalytic activity 5-fold, but
FT retains substrate binding properties."
FT /evidence="ECO:0000269|PubMed:10491163"
FT MUTAGEN 143
FT /note="N->K: In ram2-1; completely abolishes
FT farnesyltransferase activity, but still has about 30%
FT geranyl-geranyl transferase activity."
FT /evidence="ECO:0000269|PubMed:1763050,
FT ECO:0000269|PubMed:8494894"
FT MUTAGEN 145
FT /note="H->D: Increases KM for peptide substrate 4-fold, but
FT retains catalytic activity."
FT /evidence="ECO:0000269|PubMed:10491163"
SQ SEQUENCE 316 AA; 37508 MW; D828519BB9914608 CRC64;
MEEYDYSDVK PLPIETDLQD ELCRIMYTED YKRLMGLARA LISLNELSPR ALQLTAEIID
VAPAFYTIWN YRFNIVRHMM SESEDTVLYL NKELDWLDEV TLNNPKNYQI WSYRQSLLKL
HPSPSFKREL PILKLMIDDD SKNYHVWSYR KWCCLFFSDF QHELAYASDL IETDIYNNSA
WTHRMFYWVN AKDVISKVEL ADELQFIMDK IQLVPQNISP WTYLRGFQEL FHDRLQWDSK
VVDFATTFIG DVLSLPIGSP EDLPEIESSY ALEFLAYHWG ADPCTRDNAV KAYSLLAIKY
DPIRKNLWHH KINNLN
