CARME_CHICK
ID CARME_CHICK Reviewed; 449 AA.
AC F1N9S8;
DT 22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 2.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Carnosine N-methyltransferase {ECO:0000303|PubMed:26001783};
DE EC=2.1.1.22 {ECO:0000269|PubMed:26001783};
GN Name=CARNMT1 {ECO:0000250|UniProtKB:Q8N4J0};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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=6.590 mM for carnosine {ECO:0000269|PubMed:26001783};
CC KM=0.025 mM for S-adenosyl-L-methionine
CC {ECO:0000269|PubMed:26001783};
CC Vmax=2.50 nmol/min/mg enzyme with carnosine as substrate
CC {ECO:0000269|PubMed:26001783};
CC Note=kcat is 0.14 min(-1) for carnosine. kcat is 2.51 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 40 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
CC {ECO:0000250|UniProtKB:Q5BJZ6}. Nucleus {ECO:0000250|UniProtKB:Q5BJZ6}.
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 -!- MISCELLANEOUS: Two different proteins belonging to two different
CC protein families are able to mediate carnosine N-methyltransferase
CC activity in chicken. This protein, which is conserved from human to
CC yeast, and another protein (AC U3NEE3), which is not conserved in
CC mammals. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the carnosine N-methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AC187120; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_003643080.1; XM_003643032.3.
DR AlphaFoldDB; F1N9S8; -.
DR SMR; F1N9S8; -.
DR STRING; 9031.ENSGALP00000032180; -.
DR Ensembl; ENSGALT00000032817; ENSGALP00000032180; ENSGALG00000015155.
DR GeneID; 427256; -.
DR KEGG; gga:427256; -.
DR CTD; 138199; -.
DR VEuPathDB; HostDB:geneid_427256; -.
DR eggNOG; KOG2798; Eukaryota.
DR GeneTree; ENSGT00390000005323; -.
DR HOGENOM; CLU_030612_0_0_1; -.
DR OMA; PNGLWIN; -.
DR OrthoDB; 1437030at2759; -.
DR BRENDA; 2.1.1.22; 1306.
DR Reactome; R-GGA-70921; Histidine catabolism.
DR SABIO-RK; F1N9S8; -.
DR PRO; PR:F1N9S8; -.
DR Proteomes; UP000000539; Chromosome Z.
DR Bgee; ENSGALG00000015155; Expressed in muscle tissue and 13 other tissues.
DR ExpressionAtlas; F1N9S8; baseline and differential.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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; IBA:GO_Central.
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..449
FT /note="Carnosine N-methyltransferase"
FT /id="PRO_0000433610"
FT REGION 1..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..91
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 199
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 202
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 243
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 264
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 330
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 331
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 347
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 351
FT /ligand="carnosine"
FT /ligand_id="ChEBI:CHEBI:57485"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 359
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 382
FT /ligand="carnosine"
FT /ligand_id="ChEBI:CHEBI:57485"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
FT BINDING 433
FT /ligand="carnosine"
FT /ligand_id="ChEBI:CHEBI:57485"
FT /evidence="ECO:0000250|UniProtKB:Q8N4J0"
SQ SEQUENCE 449 AA; 52077 MW; 478B0B6D4B45EE49 CRC64;
MSAACAVSRE AQPALPPPPR GDRDPPAKAM RRGLRRGREE EQDQERLPWP AESGGGDPEG
EQEAWRSGER RRRQPQEPRA LAAAARVEEE AEEERMEREH FRRIINAFRY YGTNMHERVN
RTERQFKSLP ANQQSLLPQF LPHLDKIRKC IDHNQEILQT IVNDCVHMFE NKEYGEDGGG
KITPASTFDM DKLKSTLKQF VRDWSEEGKP ERDSCYQPII SEIVKNFPKE RWDFSKVNIL
VPGAGLGRLA WEIAMLGYAC QGNEWSLFML FSSNFVLNRC SEVNSCKLYP WIHQFSNNKR
SADQIRPIYF PDVDPHSLPS GSNFSMTAGD FQEIYSECNT WDCIATCFFI DTAHNVIDYI
DTIWKILKPG GIWINVGPLL YHFENLANEL SIELSYEDIK NVILQYGFHI EVEKESVLST
YTVNELSMMK YYYECVLFVV RKPEEKCFE
