UniProtKB - O60725 (ICMT_HUMAN)
Protein
Protein-S-isoprenylcysteine O-methyltransferase
Gene
ICMT
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.1 Publication
Catalytic activityi
- [protein]-C-terminal S-[(2E,6E)-farnesyl]-L-cysteine + S-adenosyl-L-methionine = [protein]-C-terminal S-[(2E,6E)-farnesyl]-L-cysteine methyl ester + S-adenosyl-L-homocysteine1 PublicationEC:2.1.1.1001 Publication
Activity regulationi
Competitively inhibited by N-acetyl-S-trans,trans-farnesyl-l-cysteine (AFC).1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 190 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 205 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 247 | SubstrateBy similarity | 1 | |
Binding sitei | 251 | S-adenosyl-L-methionineBy similarity | 1 |
GO - Molecular functioni
- protein C-terminal carboxyl O-methyltransferase activity Source: ProtInc
- protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity Source: GO_Central
GO - Biological processi
- cellular protein modification process Source: ProtInc
- C-terminal protein methylation Source: GO_Central
- post-translational protein modification Source: Reactome
- protein targeting to membrane Source: ProtInc
Keywordsi
Molecular function | Methyltransferase, Transferase |
Ligand | S-adenosyl-L-methionine |
Enzyme and pathway databases
PathwayCommonsi | O60725 |
Reactomei | R-HSA-163841, Gamma carboxylation, hypusine formation and arylsulfatase activation R-HSA-9648002, RAS processing |
SABIO-RKi | O60725 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein-S-isoprenylcysteine O-methyltransferase (EC:2.1.1.1001 Publication)Alternative name(s): Isoprenylcysteine carboxylmethyltransferase Prenylated protein carboxyl methyltransferase Short name: PPMT Prenylcysteine carboxyl methyltransferase Short name: pcCMT |
Gene namesi | Name:ICMT Synonyms:PCCMT |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5350, ICMT |
MIMi | 605851, gene |
neXtProti | NX_O60725 |
VEuPathDBi | HostDB:ENSG00000116237.15 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 2 Publications; Multi-pass membrane protein 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: MGI
- endoplasmic reticulum membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: ProtInc
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 16 | CytoplasmicSequence analysisAdd BLAST | 16 | |
Transmembranei | 17 – 33 | HelicalSequence analysisAdd BLAST | 17 | |
Topological domaini | 34 – 41 | LumenalSequence analysis | 8 | |
Transmembranei | 42 – 59 | HelicalSequence analysisAdd BLAST | 18 | |
Topological domaini | 60 – 69 | CytoplasmicSequence analysis | 10 | |
Transmembranei | 70 – 87 | HelicalSequence analysisAdd BLAST | 18 | |
Topological domaini | 88 – 92 | LumenalSequence analysis | 5 | |
Transmembranei | 93 – 112 | HelicalSequence analysisAdd BLAST | 20 | |
Topological domaini | 113 – 131 | CytoplasmicSequence analysisAdd BLAST | 19 | |
Transmembranei | 132 – 149 | HelicalSequence analysisAdd BLAST | 18 | |
Topological domaini | 150 – 154 | LumenalSequence analysis | 5 | |
Transmembranei | 155 – 174 | HelicalSequence analysisAdd BLAST | 20 | |
Topological domaini | 175 – 212 | CytoplasmicSequence analysisAdd BLAST | 38 | |
Transmembranei | 213 – 228 | HelicalSequence analysisAdd BLAST | 16 | |
Topological domaini | 229 | LumenalSequence analysis | 1 | |
Transmembranei | 230 – 244 | HelicalSequence analysisAdd BLAST | 15 | |
Topological domaini | 245 – 284 | CytoplasmicSequence analysisAdd BLAST | 40 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 23463 |
OpenTargetsi | ENSG00000116237 |
PharmGKBi | PA29598 |
Miscellaneous databases
Pharosi | O60725, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4699 |
Genetic variation databases
BioMutai | ICMT |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000209894 | 1 – 284 | Protein-S-isoprenylcysteine O-methyltransferaseAdd BLAST | 284 |
Proteomic databases
EPDi | O60725 |
jPOSTi | O60725 |
MassIVEi | O60725 |
PaxDbi | O60725 |
PeptideAtlasi | O60725 |
PRIDEi | O60725 |
ProteomicsDBi | 49571 |
PTM databases
iPTMneti | O60725 |
PhosphoSitePlusi | O60725 |
Expressioni
Tissue specificityi
Ubiquitously expressed. Expressed at higher levels in the cerebellum and putamen than in other brain regions. Abundant expression seen in the Purkinje cells and pontine neurons.1 Publication
Gene expression databases
Bgeei | ENSG00000116237, Expressed in adrenal tissue and 249 other tissues |
ExpressionAtlasi | O60725, baseline and differential |
Genevisiblei | O60725, HS |
Organism-specific databases
HPAi | ENSG00000116237, Low tissue specificity |
Interactioni
Binary interactionsi
Hide detailsO60725
Protein-protein interaction databases
BioGRIDi | 117026, 38 interactors |
IntActi | O60725, 24 interactors |
MINTi | O60725 |
STRINGi | 9606.ENSP00000343552 |
Chemistry databases
BindingDBi | O60725 |
Miscellaneous databases
RNActi | O60725, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 197 – 200 | S-adenosyl-L-methionine bindingBy similarity | 4 | |
Regioni | 210 – 213 | S-adenosyl-L-methionine bindingBy similarity | 4 |
Sequence similaritiesi
Belongs to the class VI-like SAM-binding methyltransferase superfamily. Isoprenylcysteine carboxyl methyltransferase family.PROSITE-ProRule annotation
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2628, Eukaryota |
GeneTreei | ENSGT00390000017394 |
HOGENOMi | CLU_065200_0_1_1 |
InParanoidi | O60725 |
OMAi | LPFIRGY |
OrthoDBi | 1479599at2759 |
PhylomeDBi | O60725 |
TreeFami | TF313769 |
Family and domain databases
InterProi | View protein in InterPro IPR007269, ICMT_MeTrfase IPR025770, PPMT_MeTrfase |
Pfami | View protein in Pfam PF04140, ICMT, 1 hit |
PROSITEi | View protein in PROSITE PS51564, SAM_ICMT, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
O60725-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAGCAARAPP GSEARLSLAT FLLGASVLAL PLLTRAGLQG RTGLALYVAG
60 70 80 90 100
LNALLLLLYR PPRYQIAIRA CFLGFVFGCG TLLSFSQSSW SHFGWYMCSL
110 120 130 140 150
SLFHYSEYLV TAVNNPKSLS LDSFLLNHSL EYTVAALSSW LEFTLENIFW
160 170 180 190 200
PELKQITWLS VTGLLMVVFG ECLRKAAMFT AGSNFNHVVQ NEKSDTHTLV
210 220 230 240 250
TSGVYAWFRH PSYVGWFYWS IGTQVMLCNP ICGVSYALTV WRFFRDRTEE
260 270 280
EEISLIHFFG EEYLEYKKRV PTGLPFIKGV KVDL
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ7Z750 | Q7Z750_HUMAN | Protein-S-isoprenylcysteine O-methy... | ICMT | 116 | Annotation score: | ||
K7EQW0 | K7EQW0_HUMAN | Protein-S-isoprenylcysteine O-methy... | ICMT | 94 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF064084 mRNA Translation: AAC16554.1 CR541671 mRNA Translation: CAG46472.1 CR541711 mRNA Translation: CAG46512.1 AL031847 Genomic DNA No translation available. CH471130 Genomic DNA Translation: EAW71522.1 BC028168 mRNA Translation: AAH28168.1 |
CCDSi | CCDS61.1 |
RefSeqi | NP_036537.1, NM_012405.3 |
Genome annotation databases
Ensembli | ENST00000343813; ENSP00000343552; ENSG00000116237 |
GeneIDi | 23463 |
KEGGi | hsa:23463 |
UCSCi | uc001amk.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF064084 mRNA Translation: AAC16554.1 CR541671 mRNA Translation: CAG46472.1 CR541711 mRNA Translation: CAG46512.1 AL031847 Genomic DNA No translation available. CH471130 Genomic DNA Translation: EAW71522.1 BC028168 mRNA Translation: AAH28168.1 |
CCDSi | CCDS61.1 |
RefSeqi | NP_036537.1, NM_012405.3 |
3D structure databases
SMRi | O60725 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 117026, 38 interactors |
IntActi | O60725, 24 interactors |
MINTi | O60725 |
STRINGi | 9606.ENSP00000343552 |
Chemistry databases
BindingDBi | O60725 |
ChEMBLi | CHEMBL4699 |
PTM databases
iPTMneti | O60725 |
PhosphoSitePlusi | O60725 |
Genetic variation databases
BioMutai | ICMT |
Proteomic databases
EPDi | O60725 |
jPOSTi | O60725 |
MassIVEi | O60725 |
PaxDbi | O60725 |
PeptideAtlasi | O60725 |
PRIDEi | O60725 |
ProteomicsDBi | 49571 |
Protocols and materials databases
Antibodypediai | 27272, 182 antibodies |
DNASUi | 23463 |
Genome annotation databases
Ensembli | ENST00000343813; ENSP00000343552; ENSG00000116237 |
GeneIDi | 23463 |
KEGGi | hsa:23463 |
UCSCi | uc001amk.4, human |
Organism-specific databases
CTDi | 23463 |
DisGeNETi | 23463 |
GeneCardsi | ICMT |
HGNCi | HGNC:5350, ICMT |
HPAi | ENSG00000116237, Low tissue specificity |
MIMi | 605851, gene |
neXtProti | NX_O60725 |
OpenTargetsi | ENSG00000116237 |
PharmGKBi | PA29598 |
VEuPathDBi | HostDB:ENSG00000116237.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2628, Eukaryota |
GeneTreei | ENSGT00390000017394 |
HOGENOMi | CLU_065200_0_1_1 |
InParanoidi | O60725 |
OMAi | LPFIRGY |
OrthoDBi | 1479599at2759 |
PhylomeDBi | O60725 |
TreeFami | TF313769 |
Enzyme and pathway databases
PathwayCommonsi | O60725 |
Reactomei | R-HSA-163841, Gamma carboxylation, hypusine formation and arylsulfatase activation R-HSA-9648002, RAS processing |
SABIO-RKi | O60725 |
Miscellaneous databases
BioGRID-ORCSi | 23463, 59 hits in 883 CRISPR screens |
ChiTaRSi | ICMT, human |
GeneWikii | ICMT |
GenomeRNAii | 23463 |
Pharosi | O60725, Tchem |
PROi | PR:O60725 |
RNActi | O60725, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000116237, Expressed in adrenal tissue and 249 other tissues |
ExpressionAtlasi | O60725, baseline and differential |
Genevisiblei | O60725, HS |
Family and domain databases
InterProi | View protein in InterPro IPR007269, ICMT_MeTrfase IPR025770, PPMT_MeTrfase |
Pfami | View protein in Pfam PF04140, ICMT, 1 hit |
PROSITEi | View protein in PROSITE PS51564, SAM_ICMT, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ICMT_HUMAN | |
Accessioni | O60725Primary (citable) accession number: O60725 Secondary accession number(s): Q6FHT0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 20, 2001 |
Last sequence update: | August 1, 1998 | |
Last modified: | February 10, 2021 | |
This is version 167 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM