STE14_YEAST
ID STE14_YEAST Reviewed; 239 AA.
AC P32584; D6VT42;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Protein-S-isoprenylcysteine O-methyltransferase;
DE Short=ICMT;
DE EC=2.1.1.100;
DE AltName: Full=Isoprenylcysteine carboxylmethyltransferase;
DE AltName: Full=Prenylated protein carboxyl methyltransferase;
DE Short=PPMT;
DE AltName: Full=Prenylcysteine carboxyl methyltransferase;
DE Short=pcCMT;
GN Name=STE14; OrderedLocusNames=YDR410C; ORFNames=D9461.1;
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.
RX PubMed=2050108; DOI=10.1002/j.1460-2075.1991.tb07694.x;
RA Hrycyna C.A., Sapperstein S.K., Clarke S., Michaelis S.;
RT "The Saccharomyces cerevisiae STE14 gene encodes a methyltransferase that
RT mediates C-terminal methylation of a-factor and RAS proteins.";
RL EMBO J. 10:1699-1709(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=8212897; DOI=10.1002/yea.320090810;
RA Ashby M.N., Errada P.R., Boyartchuk V.L., Rine J.;
RT "Isolation and DNA sequence of the STE14 gene encoding farnesyl cysteine:
RT carboxyl methyltransferase.";
RL Yeast 9:907-913(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE, AND FUNCTION.
RX PubMed=8289819; DOI=10.1128/mcb.14.2.1438-1449.1994;
RA Sapperstein S., Berkower C., Michaelis S.;
RT "Nucleotide sequence of the yeast STE14 gene, which encodes
RT farnesylcysteine carboxyl methyltransferase, and demonstration of its
RT essential role in a-factor export.";
RL Mol. Cell. Biol. 14:1438-1449(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [5]
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=9693378; DOI=10.1091/mbc.9.8.2231;
RA Romano J.D., Schmidt W.K., Michaelis S.;
RT "The Saccharomyces cerevisiae prenylcysteine carboxyl methyltransferase
RT Ste14p is in the endoplasmic reticulum membrane.";
RL Mol. Biol. Cell 9:2231-2247(1998).
RN [7]
RP FUNCTION, TOPOLOGY, AND MUTAGENESIS OF GLY-31; LEU-81; GLY-132; PRO-173;
RP GLU-213; GLU-214 AND LEU-217.
RX PubMed=11451995; DOI=10.1091/mbc.12.7.1957;
RA Romano J.D., Michaelis S.;
RT "Topological and mutational analysis of Saccharomyces cerevisiae Ste14p,
RT founding member of the isoprenylcysteine carboxyl methyltransferase
RT family.";
RL Mol. Biol. Cell 12:1957-1971(2001).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [9]
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 [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15611058; DOI=10.1074/jbc.m410292200;
RA Anderson J.L., Frase H., Michaelis S., Hrycyna C.A.;
RT "Purification, functional reconstitution, and characterization of the
RT Saccharomyces cerevisiae isoprenylcysteine carboxylmethyltransferase
RT Ste14p.";
RL J. Biol. Chem. 280:7336-7345(2005).
RN [11]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
CC -!- FUNCTION: Mediates C-terminal methylation of the isoprenylated C-
CC terminal cysteine in A-factor mating pheromone and Ras proteins
CC (PubMed:8289819, PubMed:11451995, PubMed:15611058). Does not have a
CC preference for the farnesyl or geranylgeranyl moieties in the model
CC substrates N-acetyl-S-farnesyl-L-cysteine (AFC) and N-acetyl-S-
CC geranylgeranyl-L-cysteine (AGGC) in vitro (PubMed:15611058).
CC {ECO:0000269|PubMed:11451995, ECO:0000269|PubMed:15611058,
CC ECO:0000269|PubMed:8289819}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-C-terminal S-[(2E,6E)-farnesyl]-L-cysteine + S-
CC adenosyl-L-methionine = [protein]-C-terminal S-[(2E,6E)-farnesyl]-L-
CC cysteine methyl ester + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:21672, Rhea:RHEA-COMP:12125, Rhea:RHEA-COMP:12126,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:90510,
CC ChEBI:CHEBI:90511; EC=2.1.1.100;
CC Evidence={ECO:0000269|PubMed:15611058};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3 uM for N-acetyl-S-farnesyl-L-cysteine (AFC)
CC {ECO:0000269|PubMed:15611058};
CC KM=3.2 uM for N-acetyl-S-geranylgeranyl-L-cysteine (AGGC)
CC {ECO:0000269|PubMed:15611058};
CC Vmax=50782 pmol/min/mg enzyme for N-acetyl-S-farnesyl-L-cysteine
CC (AFC) {ECO:0000269|PubMed:15611058};
CC Vmax=56667 pmol/min/mg enzyme for N-acetyl-S-geranylgeranyl-L-
CC cysteine (AGGC) {ECO:0000269|PubMed:15611058};
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:15611058};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:9693378}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- MISCELLANEOUS: Present with 2690 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the class VI-like SAM-binding methyltransferase
CC superfamily. Isoprenylcysteine carboxyl methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; L07952; AAA16520.1; -; Unassigned_DNA.
DR EMBL; L15442; AAA16840.1; -; Unassigned_DNA.
DR EMBL; U33007; AAB64880.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA12252.1; -; Genomic_DNA.
DR PIR; S37604; S37604.
DR RefSeq; NP_010698.1; NM_001180718.1.
DR AlphaFoldDB; P32584; -.
DR SMR; P32584; -.
DR BioGRID; 32470; 19.
DR DIP; DIP-2678N; -.
DR IntAct; P32584; 3.
DR MINT; P32584; -.
DR STRING; 4932.YDR410C; -.
DR BindingDB; P32584; -.
DR ChEMBL; CHEMBL4385; -.
DR MaxQB; P32584; -.
DR PaxDb; P32584; -.
DR PRIDE; P32584; -.
DR EnsemblFungi; YDR410C_mRNA; YDR410C; YDR410C.
DR GeneID; 852019; -.
DR KEGG; sce:YDR410C; -.
DR SGD; S000002818; STE14.
DR VEuPathDB; FungiDB:YDR410C; -.
DR eggNOG; KOG2628; Eukaryota.
DR GeneTree; ENSGT00390000017394; -.
DR HOGENOM; CLU_065200_0_2_1; -.
DR InParanoid; P32584; -.
DR OMA; SAFHWGE; -.
DR BioCyc; YEAST:G3O-29953-MON; -.
DR Reactome; R-SCE-163841; Gamma carboxylation, hypusine formation and arylsulfatase activation.
DR PRO; PR:P32584; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P32584; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005637; C:nuclear inner membrane; IMP:SGD.
DR GO; GO:0004671; F:protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity; IDA:SGD.
DR GO; GO:0006481; P:C-terminal protein methylation; IMP:SGD.
DR GO; GO:0007323; P:peptide pheromone maturation; IMP:SGD.
DR GO; GO:0019236; P:response to pheromone; IEA:UniProtKB-KW.
DR InterPro; IPR007269; ICMT_MeTrfase.
DR InterPro; IPR025770; PPMT_MeTrfase.
DR Pfam; PF04140; ICMT; 1.
DR PROSITE; PS51564; SAM_ICMT; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Methyltransferase; Pheromone response;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..239
FT /note="Protein-S-isoprenylcysteine O-methyltransferase"
FT /id="PRO_0000209899"
FT TOPO_DOM 1..23
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:11451995,
FT ECO:0000305|PubMed:16847258"
FT TRANSMEM 24..44
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 45..47
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:11451995,
FT ECO:0000305|PubMed:16847258"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 69..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:11451995,
FT ECO:0000305|PubMed:16847258"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 110
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:11451995,
FT ECO:0000305|PubMed:16847258"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..175
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:11451995,
FT ECO:0000305|PubMed:16847258"
FT INTRAMEM 176..206
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:11451995"
FT TOPO_DOM 207..239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:11451995,
FT ECO:0000269|PubMed:16847258"
FT BINDING 159..162
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TMG0"
FT BINDING 167
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TMG0"
FT BINDING 172..175
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TMG0"
FT BINDING 209
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 213
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TMG0"
FT MUTAGEN 31
FT /note="G->E: Abolishes function."
FT /evidence="ECO:0000269|PubMed:11451995"
FT MUTAGEN 81
FT /note="L->F: Abolishes function."
FT /evidence="ECO:0000269|PubMed:11451995"
FT MUTAGEN 132
FT /note="G->R: Abolishes function."
FT /evidence="ECO:0000269|PubMed:11451995"
FT MUTAGEN 173
FT /note="P->L: Abolishes function."
FT /evidence="ECO:0000269|PubMed:11451995"
FT MUTAGEN 213
FT /note="E->D: Abolishes function."
FT /evidence="ECO:0000269|PubMed:11451995"
FT MUTAGEN 214
FT /note="E->D,Q: Abolishes function."
FT /evidence="ECO:0000269|PubMed:11451995"
FT MUTAGEN 217
FT /note="L->S: Abolishes function."
FT /evidence="ECO:0000269|PubMed:11451995"
SQ SEQUENCE 239 AA; 27888 MW; 189829AFD0BD6BD5 CRC64;
MHQDFQEDEH EYPDIRRNPL HEVTMTSYIL GILLGIFVGL FPQIRFKNFN LFIIALSLFH
FLEYYITAKY NPLKVHSESF LLNNGKSYMA AHSFAILECL VESFLFPDLK IFSYSLATKL
CTVLGCLLVI LGQYTRTIAM HTAGHSFSHI VKTKKESDHV LVKTGVYSWS RHPSYLGFFW
WAIGTQLLLL NPLSLVIFIF VLWKFFSDRI RVEEKYLIEF FSAEYIEYKN KVGVGIPFI
