ICMT_TRICA
ID ICMT_TRICA Reviewed; 281 AA.
AC D6WJ77;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=Protein-S-isoprenylcysteine O-methyltransferase {ECO:0000303|PubMed:29342140};
DE EC=2.1.1.100 {ECO:0000269|PubMed:29342140};
GN Name=ICMT {ECO:0000303|PubMed:29342140};
GN ORFNames=TcasGA2_TC013078 {ECO:0000312|EMBL:EFA03159.1};
OS Tribolium castaneum (Red flour beetle).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Coleoptera; Polyphaga; Cucujiformia;
OC Tenebrionidae; Tenebrionidae incertae sedis; Tribolium.
OX NCBI_TaxID=7070 {ECO:0000312|Proteomes:UP000007266};
RN [1] {ECO:0000312|Proteomes:UP000007266}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Georgia GA2 {ECO:0000312|Proteomes:UP000007266};
RX PubMed=18362917; DOI=10.1038/nature06784;
RG Tribolium Genome Sequencing Consortium;
RA Richards S., Gibbs R.A., Weinstock G.M., Brown S.J., Denell R.,
RA Beeman R.W., Gibbs R., Beeman R.W., Brown S.J., Bucher G., Friedrich M.,
RA Grimmelikhuijzen C.J., Klingler M., Lorenzen M., Richards S., Roth S.,
RA Schroder R., Tautz D., Zdobnov E.M., Muzny D., Gibbs R.A., Weinstock G.M.,
RA Attaway T., Bell S., Buhay C.J., Chandrabose M.N., Chavez D.,
RA Clerk-Blankenburg K.P., Cree A., Dao M., Davis C., Chacko J., Dinh H.,
RA Dugan-Rocha S., Fowler G., Garner T.T., Garnes J., Gnirke A., Hawes A.,
RA Hernandez J., Hines S., Holder M., Hume J., Jhangiani S.N., Joshi V.,
RA Khan Z.M., Jackson L., Kovar C., Kowis A., Lee S., Lewis L.R., Margolis J.,
RA Morgan M., Nazareth L.V., Nguyen N., Okwuonu G., Parker D., Richards S.,
RA Ruiz S.J., Santibanez J., Savard J., Scherer S.E., Schneider B.,
RA Sodergren E., Tautz D., Vattahil S., Villasana D., White C.S., Wright R.,
RA Park Y., Beeman R.W., Lord J., Oppert B., Lorenzen M., Brown S., Wang L.,
RA Savard J., Tautz D., Richards S., Weinstock G., Gibbs R.A., Liu Y.,
RA Worley K., Weinstock G., Elsik C.G., Reese J.T., Elhaik E., Landan G.,
RA Graur D., Arensburger P., Atkinson P., Beeman R.W., Beidler J., Brown S.J.,
RA Demuth J.P., Drury D.W., Du Y.Z., Fujiwara H., Lorenzen M., Maselli V.,
RA Osanai M., Park Y., Robertson H.M., Tu Z., Wang J.J., Wang S., Richards S.,
RA Song H., Zhang L., Sodergren E., Werner D., Stanke M., Morgenstern B.,
RA Solovyev V., Kosarev P., Brown G., Chen H.C., Ermolaeva O., Hlavina W.,
RA Kapustin Y., Kiryutin B., Kitts P., Maglott D., Pruitt K., Sapojnikov V.,
RA Souvorov A., Mackey A.J., Waterhouse R.M., Wyder S., Zdobnov E.M.,
RA Zdobnov E.M., Wyder S., Kriventseva E.V., Kadowaki T., Bork P., Aranda M.,
RA Bao R., Beermann A., Berns N., Bolognesi R., Bonneton F., Bopp D.,
RA Brown S.J., Bucher G., Butts T., Chaumot A., Denell R.E., Ferrier D.E.,
RA Friedrich M., Gordon C.M., Jindra M., Klingler M., Lan Q., Lattorff H.M.,
RA Laudet V., von Levetsow C., Liu Z., Lutz R., Lynch J.A., da Fonseca R.N.,
RA Posnien N., Reuter R., Roth S., Savard J., Schinko J.B., Schmitt C.,
RA Schoppmeier M., Schroder R., Shippy T.D., Simonnet F., Marques-Souza H.,
RA Tautz D., Tomoyasu Y., Trauner J., Van der Zee M., Vervoort M.,
RA Wittkopp N., Wimmer E.A., Yang X., Jones A.K., Sattelle D.B., Ebert P.R.,
RA Nelson D., Scott J.G., Beeman R.W., Muthukrishnan S., Kramer K.J.,
RA Arakane Y., Beeman R.W., Zhu Q., Hogenkamp D., Dixit R., Oppert B.,
RA Jiang H., Zou Z., Marshall J., Elpidina E., Vinokurov K., Oppert C.,
RA Zou Z., Evans J., Lu Z., Zhao P., Sumathipala N., Altincicek B.,
RA Vilcinskas A., Williams M., Hultmark D., Hetru C., Jiang H.,
RA Grimmelikhuijzen C.J., Hauser F., Cazzamali G., Williamson M., Park Y.,
RA Li B., Tanaka Y., Predel R., Neupert S., Schachtner J., Verleyen P.,
RA Raible F., Bork P., Friedrich M., Walden K.K., Robertson H.M., Angeli S.,
RA Foret S., Bucher G., Schuetz S., Maleszka R., Wimmer E.A., Beeman R.W.,
RA Lorenzen M., Tomoyasu Y., Miller S.C., Grossmann D., Bucher G.;
RT "The genome of the model beetle and pest Tribolium castaneum.";
RL Nature 452:949-955(2008).
RN [2] {ECO:0007744|PDB:5V7P, ECO:0007744|PDB:5VG9}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN APO FORM AND IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE AND INHIBITOR, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TOPOLOGY.
RX PubMed=29342140; DOI=10.1038/nature25439;
RA Diver M.M., Pedi L., Koide A., Koide S., Long S.B.;
RT "Atomic structure of the eukaryotic intramembrane RAS methyltransferase
RT ICMT.";
RL Nature 553:526-529(2018).
CC -!- FUNCTION: Catalyzes the post-translational methylation of isoprenylated
CC C-terminal cysteine residues. {ECO:0000269|PubMed:29342140}.
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:29342140};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=25 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:29342140};
CC Vmax=101 pmol/min/ug enzyme towards S-adenosyl-L-methionine
CC {ECO:0000269|PubMed:29342140};
CC Vmax=42 pmol/min/ug enzyme towards biotin-S-farnesyl-L-cysteine (BFC)
CC {ECO:0000269|PubMed:29342140};
CC Note=kcat is 3.3 min(-1) for S-adenosyl-L-methionine. kcat is 1.4
CC min(-1) for biotin-S-farnesyl-L-cysteine (BFC).
CC {ECO:0000269|PubMed:29342140};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O60725}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:29342140}.
CC -!- SIMILARITY: Belongs to the class VI-like SAM-binding methyltransferase
CC superfamily. Isoprenylcysteine carboxyl methyltransferase family.
CC {ECO:0000255|RuleBase:RU362022}.
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DR EMBL; KQ971343; EFA03159.1; -; Genomic_DNA.
DR RefSeq; XP_008194418.1; XM_008196196.2.
DR PDB; 5V7P; X-ray; 2.30 A; A=1-281.
DR PDB; 5VG9; X-ray; 4.00 A; A=1-281.
DR PDBsum; 5V7P; -.
DR PDBsum; 5VG9; -.
DR AlphaFoldDB; D6WJ77; -.
DR SMR; D6WJ77; -.
DR STRING; 7070.TC013078-PA; -.
DR EnsemblMetazoa; TC013078_001; TC013078_001; TC013078.
DR GeneID; 663323; -.
DR KEGG; tca:663323; -.
DR eggNOG; KOG2628; Eukaryota.
DR HOGENOM; CLU_065200_0_1_1; -.
DR InParanoid; D6WJ77; -.
DR OMA; GMVPQVW; -.
DR OrthoDB; 1479599at2759; -.
DR PhylomeDB; D6WJ77; -.
DR Proteomes; UP000007266; Linkage group 5.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004671; F:protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0006481; P:C-terminal protein methylation; IBA:GO_Central.
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 3D-structure; Endoplasmic reticulum; Membrane; Methyltransferase;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..281
FT /note="Protein-S-isoprenylcysteine O-methyltransferase"
FT /id="PRO_0000451076"
FT TOPO_DOM 1..2
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TRANSMEM 3..29
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TOPO_DOM 30..35
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TRANSMEM 36..53
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TOPO_DOM 54..58
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TRANSMEM 59..85
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TOPO_DOM 86..88
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TRANSMEM 89..113
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TOPO_DOM 114..118
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TRANSMEM 119..149
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TOPO_DOM 150..155
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TRANSMEM 156..181
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TOPO_DOM 182..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TRANSMEM 209..226
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TOPO_DOM 227..229
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TRANSMEM 230..243
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:29342140"
FT TOPO_DOM 244..281
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:29342140"
FT BINDING 189
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:29342140,
FT ECO:0007744|PDB:5V7P, ECO:0007744|PDB:5VG9"
FT BINDING 196..199
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:29342140,
FT ECO:0007744|PDB:5V7P, ECO:0007744|PDB:5VG9"
FT BINDING 204
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:29342140,
FT ECO:0007744|PDB:5V7P, ECO:0007744|PDB:5VG9"
FT BINDING 209..212
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:29342140,
FT ECO:0007744|PDB:5V7P, ECO:0007744|PDB:5VG9"
FT BINDING 246
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:29342140"
FT BINDING 250
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:29342140,
FT ECO:0007744|PDB:5V7P, ECO:0007744|PDB:5VG9"
FT HELIX 4..29
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 35..56
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 59..84
FT /evidence="ECO:0007829|PDB:5V7P"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 90..113
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 129..148
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 156..180
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 203..206
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 210..225
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 231..258
FT /evidence="ECO:0007829|PDB:5V7P"
FT HELIX 260..268
FT /evidence="ECO:0007829|PDB:5V7P"
SQ SEQUENCE 281 AA; 32103 MW; 0EBBE2577621EEF7 CRC64;
MLSPAGKISL QSFTGSSLVF FVICMFNHYY GITNLVVNTL IVFFYAVNVY FFLKFFYNEF
AFAIAIRAAF LGLVLVLGLY IKLVAPPNIQ IFGGYMSVMA LFHYSEFLAI AIVQPKQVST
DSFVINHSPQ YTIAAVSSWV EFFIETYFFP GLKEIHWLSN IGLCVCILGE VLRKTAILTA
GSNFNHLVQC EKSSDHVLVT HGVYAWFRHP SYVGWFYWSI GTQIILINPL CIPAYTLASW
MFFKERIYIE ESMLLSFFGQ QYCDYQQQVG TGIPFIEGYK I
