ICMT_MOUSE
ID ICMT_MOUSE Reviewed; 283 AA.
AC Q9EQK7;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Protein-S-isoprenylcysteine O-methyltransferase;
DE EC=2.1.1.100 {ECO:0000250|UniProtKB:O60725};
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=Icmt;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-283.
RX PubMed=10649571; DOI=10.1038/72101;
RA Lin X., Antalffy B., Kang D., Orr H.T., Zoghbi H.Y.;
RT "Polyglutamine expansion down-regulates specific neuronal genes before
RT pathologic changes in SCA1.";
RL Nat. Neurosci. 3:157-163(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-153.
RC STRAIN=C57BL/6J; TISSUE=Placenta;
RA Marra M., Hillier L., Allen M., Bowles M., Dietrich N., Dubuque T.,
RA Geisel S., Kucaba T., Lacy M., Le M., Martin J., Morris M.,
RA Schellenberg K., Steptoe M., Tan F., Underwood K., Moore B., Theising B.,
RA Wylie T., Lennon G., Soares B., Wilson R., Waterston R.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the post-translational methylation of isoprenylated
CC C-terminal cysteine residues. {ECO:0000250|UniProtKB:O60725}.
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:0000250|UniProtKB:O60725};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O60725}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O60725}.
CC -!- TISSUE SPECIFICITY: Highly enriched in adult cerebellum, with a low
CC level expression in other brain regions.
CC -!- DEVELOPMENTAL STAGE: During cerebellar development expression was low
CC before postnatal day P6 and dramatically increased after P12.
CC -!- SIMILARITY: Belongs to the class VI-like SAM-binding methyltransferase
CC superfamily. Isoprenylcysteine carboxyl methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU00897}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF209926; AAG48552.1; -; mRNA.
DR EMBL; AA022288; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_598549.1; NM_133788.2.
DR AlphaFoldDB; Q9EQK7; -.
DR SMR; Q9EQK7; -.
DR BioGRID; 208249; 3.
DR STRING; 10090.ENSMUSP00000043390; -.
DR iPTMnet; Q9EQK7; -.
DR PhosphoSitePlus; Q9EQK7; -.
DR MaxQB; Q9EQK7; -.
DR PaxDb; Q9EQK7; -.
DR PRIDE; Q9EQK7; -.
DR ProteomicsDB; 267089; -.
DR DNASU; 57295; -.
DR GeneID; 57295; -.
DR KEGG; mmu:57295; -.
DR CTD; 23463; -.
DR MGI; MGI:1888594; Icmt.
DR eggNOG; KOG2628; Eukaryota.
DR InParanoid; Q9EQK7; -.
DR OrthoDB; 1479599at2759; -.
DR PhylomeDB; Q9EQK7; -.
DR BRENDA; 2.1.1.100; 3474.
DR Reactome; R-MMU-163841; Gamma carboxylation, hypusine formation and arylsulfatase activation.
DR Reactome; R-MMU-9648002; RAS processing.
DR SABIO-RK; Q9EQK7; -.
DR BioGRID-ORCS; 57295; 14 hits in 74 CRISPR screens.
DR PRO; PR:Q9EQK7; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9EQK7; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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:0016020; C:membrane; ISO:MGI.
DR GO; GO:0008140; F:cAMP response element binding protein binding; IMP:MGI.
DR GO; GO:0004671; F:protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity; IMP:MGI.
DR GO; GO:0030282; P:bone mineralization; IGI:MGI.
DR GO; GO:0006481; P:C-terminal protein methylation; IMP:MGI.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:MGI.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0001889; P:liver development; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0050905; P:neuromuscular process; IGI:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0006479; P:protein methylation; IMP:MGI.
DR GO; GO:2000772; P:regulation of cellular senescence; IGI:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR GO; GO:0046578; P:regulation of Ras protein signal transduction; IGI:MGI.
DR GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; ISO:MGI.
DR GO; GO:0046499; P:S-adenosylmethioninamine metabolic process; ISO:MGI.
DR GO; GO:0031929; P:TOR signaling; IMP:MGI.
DR InterPro; IPR007269; ICMT_MeTrfase.
DR InterPro; IPR025770; PPMT_MeTrfase.
DR Pfam; PF04140; ICMT; 1.
DR PROSITE; PS51564; SAM_ICMT; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Membrane; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..283
FT /note="Protein-S-isoprenylcysteine O-methyltransferase"
FT /id="PRO_0000209895"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..40
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..86
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 87..91
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 92..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..130
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 149..153
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..211
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..227
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 228
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 244..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 189
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 196..199
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 204
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 209..212
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 246
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT BINDING 250
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:D6WJ77"
FT CONFLICT 24
FT /note="A -> D (in Ref. 2; AA022288)"
FT /evidence="ECO:0000305"
FT CONFLICT 42
FT /note="G -> A (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 283 AA; 31790 MW; A6C17436EDC27F40 CRC64;
MAAARRGSAG SEARLSLATF LLGASVLALP LLTRAGLQGR TGLALYVAGL NALLLLLYRP
PRYQIAIRAC FLGFVFGCGV LLSFSQSSWN HFGWYVCSLS LFHYSEYLVT AVNNPKSLSL
DSFLLNHSLE YTVAALSSWI EFTLENIFWP ELKQITWLSA TGLLMVVFGE CLRKAAMFTA
GSNFNHVVQS EKSDTHTLVT SGVYAWCRHP SYVGWFYWSI GTQVMLCNPI CGVVYALTVW
RFFRDRTEEE EISLIHFFGE EYLDYKKRVP TGLPFIKGVK VEL
