CARME_RAT
ID CARME_RAT Reviewed; 400 AA.
AC Q5BJZ6;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Carnosine N-methyltransferase {ECO:0000303|PubMed:26001783, ECO:0000305, ECO:0000312|RGD:1311863};
DE EC=2.1.1.22 {ECO:0000269|PubMed:26001783};
DE AltName: Full=Anserine-producing methyltransferase {ECO:0000303|PubMed:26001783};
GN Name=Carnmt1 {ECO:0000312|RGD:1311863};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=26001783; DOI=10.1074/jbc.m115.640037;
RA Drozak J., Piecuch M., Poleszak O., Kozlowski P., Chrobok L., Baelde H.J.,
RA de Heer E.;
RT "UPF0586 protein C9orf41 homolog is anserine-producing methyltransferase.";
RL J. Biol. Chem. 290:17190-17205(2015).
CC -!- FUNCTION: N-methyltransferase that catalyzes the formation of anserine
CC (beta-alanyl-N(Pi)-methyl-L-histidine) from carnosine. Anserine, a
CC methylated derivative of carnosine (beta-alanyl-L-histidine), is an
CC abundant constituent of vertebrate skeletal muscles. Also methylates
CC other L-histidine-containing di- and tripeptides such as Gly-Gly-His,
CC Gly-His and homocarnosine (GABA-His). {ECO:0000269|PubMed:26001783}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carnosine + S-adenosyl-L-methionine = anserine + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:14205, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57485, ChEBI:CHEBI:57856, ChEBI:CHEBI:58445,
CC ChEBI:CHEBI:59789; EC=2.1.1.22;
CC Evidence={ECO:0000269|PubMed:26001783};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.33 mM for carnosine {ECO:0000269|PubMed:26001783};
CC KM=0.042 mM for S-adenosyl-L-methionine
CC {ECO:0000269|PubMed:26001783};
CC Vmax=2.93 nmol/min/mg enzyme with carnosine as substrate
CC {ECO:0000269|PubMed:26001783};
CC Note=kcat is 0.15 min(-1) for carnosine. kcat is 4.69 min(-1) for S-
CC adenosyl-L-methionine. {ECO:0000269|PubMed:26001783};
CC pH dependence:
CC Optimum pH is 7.0-7.5. {ECO:0000269|PubMed:26001783};
CC Temperature dependence:
CC Optimum temperature is 50 degrees Celsius.
CC {ECO:0000269|PubMed:26001783};
CC -!- SUBUNIT: Homodimer. Each monomer accommodates one molecule of carnosine
CC in its active pocket, precisely anchoring the histidine imidazole ring
CC such that only N1 is exposed and deprotonated for methylation.
CC {ECO:0000250|UniProtKB:Q8N4J0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:26001783}.
CC Nucleus {ECO:0000269|PubMed:26001783}.
CC -!- TISSUE SPECIFICITY: Expressed at higher level in skeletal muscle
CC compared to other tissues. {ECO:0000269|PubMed:26001783}.
CC -!- DOMAIN: The Gly-Xaa-Gly-Xaa-Gly (GXGXG) motif binds the adenosyl part
CC of S-adenosyl-L-methionine. {ECO:0000250|UniProtKB:Q8N4J0}.
CC -!- DOMAIN: The carnosine-binding region forms hydrophobic and hydrogen
CC bonds with carnosine, defining a flipping orientation of the imidazole
CC ring so that N1 is present next to S-adenosyl-L-methionine for
CC methylation. {ECO:0000250|UniProtKB:Q8N4J0}.
CC -!- SIMILARITY: Belongs to the carnosine N-methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; BC091268; AAH91268.1; -; mRNA.
DR RefSeq; NP_001020145.1; NM_001024974.1.
DR AlphaFoldDB; Q5BJZ6; -.
DR SMR; Q5BJZ6; -.
DR STRING; 10116.ENSRNOP00000017405; -.
DR iPTMnet; Q5BJZ6; -.
DR PhosphoSitePlus; Q5BJZ6; -.
DR PaxDb; Q5BJZ6; -.
DR GeneID; 293871; -.
DR KEGG; rno:293871; -.
DR UCSC; RGD:1311863; rat.
DR CTD; 138199; -.
DR RGD; 1311863; Carnmt1.
DR eggNOG; KOG2798; Eukaryota.
DR HOGENOM; CLU_030612_0_1_1; -.
DR InParanoid; Q5BJZ6; -.
DR OrthoDB; 1437030at2759; -.
DR PhylomeDB; Q5BJZ6; -.
DR TreeFam; TF313564; -.
DR BRENDA; 2.1.1.22; 5301.
DR Reactome; R-RNO-70921; Histidine catabolism.
DR SABIO-RK; Q5BJZ6; -.
DR PRO; PR:Q5BJZ6; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030735; F:carnosine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; ISO:RGD.
DR GO; GO:0035498; P:carnosine metabolic process; IDA:UniProtKB.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR012901; CARME.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR12303; PTHR12303; 1.
DR Pfam; PF07942; N2227; 1.
DR SMART; SM01296; N2227; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Methyltransferase; Nucleus; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..400
FT /note="Carnosine N-methyltransferase"
FT /id="PRO_0000089687"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 155
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 158
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 199
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 220
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 286
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 287
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 303
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 307
FT /ligand="carnosine"
FT /ligand_id="ChEBI:CHEBI:57485"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 315
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 338
FT /ligand="carnosine"
FT /ligand_id="ChEBI:CHEBI:57485"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 389
FT /ligand="carnosine"
FT /ligand_id="ChEBI:CHEBI:57485"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
SQ SEQUENCE 400 AA; 46385 MW; 293A02908569D836 CRC64;
MQRRRRAPPA SQPAQDSGHS EEVEVQFSAG RLGSAAPAGP PVRGTAEDEE RLEREHFWKV
INAFRYYGTS MHERVNRTER QFRSLPDNQQ KLLPQFPLHL DKIRKCVDHN QEILLTIVND
CIHMFENKEY GEDANGKIMP ASTFDMDKLK STLKQFVRDW SGTGKAERDA CYKPIIKEII
KNFPKERWDP SKVNILVPGA GLGRLAWEIA MLGYACQGNE WSFFMLFSSN FVLNRCSEVD
KYKLYPWIHQ FSNNRRSADQ IRPIFFPDVD PHSLPPGSNF SMTAGDFQEI YSECNTWDCI
ATCFFIDTAH NVIDYIDTIW RILKPGGIWI NLGPLLYHFE NLANELSIEL SYEDIKNVVL
QYGFQLEVEK ESVLSTYTVN DLSMMKYYYE CVLFVVRKPQ
