ICMT_METAC
ID ICMT_METAC Reviewed; 194 AA.
AC Q8TMG0;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Protein-S-isoprenylcysteine O-methyltransferase {ECO:0000305};
DE EC=2.1.1.100 {ECO:0000305|PubMed:22195972};
DE AltName: Full=Isoprenylcysteine carboxyl methyltransferase {ECO:0000303|PubMed:22195972};
DE Short=ICMT {ECO:0000303|PubMed:22195972};
GN OrderedLocusNames=MA_2698 {ECO:0000312|EMBL:AAM06077.1};
OS Methanosarcina acetivorans (strain ATCC 35395 / DSM 2834 / JCM 12185 /
OS C2A).
OC Archaea; Euryarchaeota; Stenosarchaea group; Methanomicrobia;
OC Methanosarcinales; Methanosarcinaceae; Methanosarcina.
OX NCBI_TaxID=188937;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 35395 / DSM 2834 / JCM 12185 / C2A;
RX PubMed=11932238; DOI=10.1101/gr.223902;
RA Galagan J.E., Nusbaum C., Roy A., Endrizzi M.G., Macdonald P., FitzHugh W.,
RA Calvo S., Engels R., Smirnov S., Atnoor D., Brown A., Allen N., Naylor J.,
RA Stange-Thomann N., DeArellano K., Johnson R., Linton L., McEwan P.,
RA McKernan K., Talamas J., Tirrell A., Ye W., Zimmer A., Barber R.D.,
RA Cann I., Graham D.E., Grahame D.A., Guss A.M., Hedderich R.,
RA Ingram-Smith C., Kuettner H.C., Krzycki J.A., Leigh J.A., Li W., Liu J.,
RA Mukhopadhyay B., Reeve J.N., Smith K., Springer T.A., Umayam L.A.,
RA White O., White R.H., de Macario E.C., Ferry J.G., Jarrell K.F., Jing H.,
RA Macario A.J.L., Paulsen I.T., Pritchett M., Sowers K.R., Swanson R.V.,
RA Zinder S.H., Lander E., Metcalf W.W., Birren B.;
RT "The genome of Methanosarcina acetivorans reveals extensive metabolic and
RT physiological diversity.";
RL Genome Res. 12:532-542(2002).
RN [2] {ECO:0007744|PDB:4A2N}
RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, TOPOLOGY, AND MUTAGENESIS OF HIS-113; HIS-126; ARG-163 AND
RP GLU-167.
RX PubMed=22195972; DOI=10.1016/j.molcel.2011.10.020;
RA Yang J., Kulkarni K., Manolaridis I., Zhang Z., Dodd R.B., Mas-Droux C.,
RA Barford D.;
RT "Mechanism of isoprenylcysteine carboxyl methylation from the crystal
RT structure of the integral membrane methyltransferase ICMT.";
RL Mol. Cell 44:997-1004(2011).
CC -!- FUNCTION: Carboxyl methyltransferase with activity toward prenyl
CC lipids. In vitro, displays activity toward N-acetyl-S-farnesyl-L-
CC cysteine (AFC) and S-farnesylthioacetic acid (FTA), an analog of AFC.
CC {ECO:0000269|PubMed:22195972}.
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:0000305|PubMed:22195972};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22195972};
CC Multi-pass membrane protein {ECO:0000269|PubMed:22195972}.
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; AE010299; AAM06077.1; -; Genomic_DNA.
DR RefSeq; WP_011022658.1; NC_003552.1.
DR PDB; 4A2N; X-ray; 3.40 A; B=1-194.
DR PDBsum; 4A2N; -.
DR AlphaFoldDB; Q8TMG0; -.
DR SMR; Q8TMG0; -.
DR EnsemblBacteria; AAM06077; AAM06077; MA_2698.
DR GeneID; 1474591; -.
DR KEGG; mac:MA_2698; -.
DR HOGENOM; CLU_065200_1_1_2; -.
DR InParanoid; Q8TMG0; -.
DR OMA; FSLWLFR; -.
DR OrthoDB; 94584at2157; -.
DR PhylomeDB; Q8TMG0; -.
DR Proteomes; UP000002487; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004671; F:protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity; IEA:UniProtKB-EC.
DR InterPro; IPR007269; ICMT_MeTrfase.
DR Pfam; PF04140; ICMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Membrane; Methyltransferase;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..194
FT /note="Protein-S-isoprenylcysteine O-methyltransferase"
FT /id="PRO_0000449360"
FT TOPO_DOM 1
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TRANSMEM 2..28
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TOPO_DOM 29..37
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TRANSMEM 38..62
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TOPO_DOM 63..73
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TRANSMEM 74..98
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TOPO_DOM 99..125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TRANSMEM 126..144
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TOPO_DOM 145
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:22195972"
FT TOPO_DOM 167..194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:22195972"
FT BINDING 108
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:22195972"
FT BINDING 113..116
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:22195972"
FT BINDING 121
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:22195972"
FT BINDING 126..129
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:22195972"
FT BINDING 163
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 167
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:22195972"
FT MUTAGEN 113
FT /note="H->A: Abolishes FTA methylation."
FT /evidence="ECO:0000269|PubMed:22195972"
FT MUTAGEN 126
FT /note="H->A: Abolishes FTA methylation."
FT /evidence="ECO:0000269|PubMed:22195972"
FT MUTAGEN 163
FT /note="R->A: Abolishes FTA methylation."
FT /evidence="ECO:0000269|PubMed:22195972"
FT MUTAGEN 167
FT /note="E->A: Abolishes FTA methylation."
FT /evidence="ECO:0000269|PubMed:22195972"
FT HELIX 3..28
FT /evidence="ECO:0007829|PDB:4A2N"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:4A2N"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:4A2N"
FT HELIX 39..53
FT /evidence="ECO:0007829|PDB:4A2N"
FT HELIX 55..61
FT /evidence="ECO:0007829|PDB:4A2N"
FT HELIX 65..69
FT /evidence="ECO:0007829|PDB:4A2N"
FT HELIX 75..99
FT /evidence="ECO:0007829|PDB:4A2N"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:4A2N"
FT TURN 120..123
FT /evidence="ECO:0007829|PDB:4A2N"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:4A2N"
FT HELIX 127..143
FT /evidence="ECO:0007829|PDB:4A2N"
FT HELIX 146..175
FT /evidence="ECO:0007829|PDB:4A2N"
FT HELIX 177..185
FT /evidence="ECO:0007829|PDB:4A2N"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:4A2N"
SQ SEQUENCE 194 AA; 22811 MW; 11A8176F4E8B4EA9 CRC64;
MNENLWKICF IVMFIIWVFV RKVYGTRAMK NKSKKKVRPN FEKSLVFLNF IGMVFLPLTA
VFSSYLDSFN INLPDSIRLF ALIVTFLNIG LFTKIHKDLG NNWSAILEIK DGHKLVKEGI
YKNIRHPMYA HLWLWVITQG IILSNWVVLI FGIVAWAILY FIRVPKEEEL LIEEFGDEYI
EYMGKTGRLF PKVV
