CRNS1_MOUSE
ID CRNS1_MOUSE Reviewed; 827 AA.
AC Q6ZPS2; Q8CIK7; Q8VE56;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Carnosine synthase 1 {ECO:0000305|PubMed:20097752};
DE EC=6.3.2.11 {ECO:0000269|PubMed:20097752};
DE AltName: Full=ATP-grasp domain-containing protein 1;
GN Name=Carns1 {ECO:0000312|MGI:MGI:2147595}; Synonyms=Atpgd1, Kiaa1394;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=20097752; DOI=10.1074/jbc.m109.095505;
RA Drozak J., Veiga-da-Cunha M., Vertommen D., Stroobant V.,
RA Van Schaftingen E.;
RT "Molecular identification of carnosine synthase as ATP-grasp domain-
RT containing protein 1 (ATPGD1).";
RL J. Biol. Chem. 285:9346-9356(2010).
CC -!- FUNCTION: Catalyzes the synthesis of carnosine and homocarnosine.
CC Carnosine is synthesized more efficiently than homocarnosine.
CC {ECO:0000269|PubMed:20097752}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-alanine + L-histidine = ADP + carnosine + H(+) +
CC phosphate; Xref=Rhea:RHEA:19297, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57485,
CC ChEBI:CHEBI:57595, ChEBI:CHEBI:57966, ChEBI:CHEBI:456216;
CC EC=6.3.2.11; Evidence={ECO:0000269|PubMed:20097752};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19298;
CC Evidence={ECO:0000305|PubMed:20097752};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-aminobutanoate + ATP + L-histidine = ADP + H(+) + L-
CC homocarnosine + phosphate; Xref=Rhea:RHEA:59568, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57595,
CC ChEBI:CHEBI:59888, ChEBI:CHEBI:143075, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:20097752};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59569;
CC Evidence={ECO:0000305|PubMed:20097752};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.46 mM for beta-alanine {ECO:0000269|PubMed:20097752};
CC KM=6.44 mM for 4-aminobutanoate {ECO:0000269|PubMed:20097752};
CC KM=0.11 mM for L-histidine {ECO:0000269|PubMed:20097752};
CC KM=1.59 mM for L-lysine {ECO:0000269|PubMed:20097752};
CC KM=0.52 mM for L-ornithine {ECO:0000269|PubMed:20097752};
CC KM=4.51 mM for N-methylhistidine {ECO:0000269|PubMed:20097752};
CC Vmax=300 nmol/min/mg enzyme toward beta-alanine
CC {ECO:0000269|PubMed:20097752};
CC Vmax=238 nmol/min/mg enzyme toward gamma-aminobutyrate
CC {ECO:0000269|PubMed:20097752};
CC Vmax=0.60 nmol/min/mg enzyme toward L-histidine
CC {ECO:0000269|PubMed:20097752};
CC Vmax=0.78 nmol/min/mg enzyme toward L-lysine
CC {ECO:0000269|PubMed:20097752};
CC Vmax=1.92 nmol/min/mg enzyme toward L-ornithine
CC {ECO:0000269|PubMed:20097752};
CC Vmax=0.66 nmol/min/mg enzyme toward N-methylhistidine
CC {ECO:0000269|PubMed:20097752};
CC -!- SUBUNIT: Homotetramer. {ECO:0000305|PubMed:20097752}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6ZPS2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZPS2-2; Sequence=VSP_032928, VSP_032929;
CC Name=3;
CC IsoId=Q6ZPS2-3; Sequence=VSP_032927;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC98157.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK129347; BAC98157.1; ALT_INIT; Transcribed_RNA.
DR EMBL; AC109138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019736; AAH19736.1; -; mRNA.
DR EMBL; BC023699; AAH23699.1; -; mRNA.
DR RefSeq; XP_006531682.1; XM_006531619.2.
DR RefSeq; XP_017173530.1; XM_017318041.1.
DR AlphaFoldDB; Q6ZPS2; -.
DR SMR; Q6ZPS2; -.
DR BioGRID; 223221; 2.
DR STRING; 10090.ENSMUSP00000131624; -.
DR iPTMnet; Q6ZPS2; -.
DR PhosphoSitePlus; Q6ZPS2; -.
DR PaxDb; Q6ZPS2; -.
DR PRIDE; Q6ZPS2; -.
DR ProteomicsDB; 285361; -. [Q6ZPS2-1]
DR ProteomicsDB; 285362; -. [Q6ZPS2-2]
DR ProteomicsDB; 285363; -. [Q6ZPS2-3]
DR UCSC; uc012bge.1; mouse. [Q6ZPS2-3]
DR UCSC; uc029tqn.1; mouse. [Q6ZPS2-1]
DR MGI; MGI:2147595; Carns1.
DR eggNOG; ENOG502QRI6; Eukaryota.
DR InParanoid; Q6ZPS2; -.
DR OrthoDB; 106215at2759; -.
DR PhylomeDB; Q6ZPS2; -.
DR BRENDA; 6.3.2.11; 3474.
DR Reactome; R-MMU-70921; Histidine catabolism.
DR BioGRID-ORCS; 107239; 3 hits in 72 CRISPR screens.
DR PRO; PR:Q6ZPS2; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q6ZPS2; protein.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:MGI.
DR GO; GO:0047730; F:carnosine synthase activity; IDA:UniProtKB.
DR GO; GO:0102102; F:homocarnosine synthase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035499; P:carnosine biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR041472; BL00235/CARNS1_N.
DR InterPro; IPR031046; CARNS1.
DR PANTHER; PTHR48066; PTHR48066; 1.
DR Pfam; PF18130; ATPgrasp_N; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Ligase; Magnesium; Manganese;
KW Metal-binding; Nucleotide-binding; Reference proteome.
FT CHAIN 1..827
FT /note="Carnosine synthase 1"
FT /id="PRO_0000329037"
FT DOMAIN 516..720
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 542..611
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 677
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 677
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 689
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 689
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 689
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 689
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 691
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 691
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT VAR_SEQ 1..497
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032927"
FT VAR_SEQ 1
FT /note="M -> MLCLDPLGTEWDSKDLDGKEEPWKSGAGLPPTGCFPGPWRQDISLDC
FT KGSPEETEARAWTVYYYGLLQSCLQQAGLPETQDRSQAPRTGCPGAEVTLCILGSPSTF
FT LSLLLEGGVQSPGNM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_032928"
FT VAR_SEQ 163..267
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_032929"
FT CONFLICT 656
FT /note="V -> M (in Ref. 3; AAH19736/AAH23699)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 827 AA; 89281 MW; 5AB9CAEB92994FE9 CRC64;
MLLCLSPAWL MKVATPGQEG EAVLLVSKAV SFYPGGLTFL DDFVPPRHAT YFLAGLGPES
GRGKEAAELA RNLTCPTGTS SELSQLLENR LLMRWLLSQQ SGVAVPATLA FTYRPPGLLR
GGDASPGLRL VELSGKEGQE TLVKEEVEAF VHSEALGDAS QVAVRLSGCR WRGQQALPLH
LRVEPSTVVN TVLGLLEKLE EEESVLVEAM CPPVRLPLPG GPAPGPELAV RICAVVCRIQ
GDRPLLSKVV CGVGRGDRPV RHHYTLPRTL RVALAQCGLE EEAQVALLEQ GIKEAAEGAL
AAVLALEAGL SVEQRGGRQV HTDFLGVDLV LTVIGRTLTP VVLKLNSGLC LEACGALEGL
WAVPRLRRSA EEAAAAPLVE TMLRRSGRHL MDGKQLLVIG AGGVSKKFVW EAARDYGLTL
HLVESDPNHF ASQLVQTFIH FDVTEHRRDE ENALLLAELV RARNLKLDGC FSFWDDCLVL
TALLCRELGL PCSPPAAMCL AKQKSRTQLH LLRCQGPPWP STSLHAVACC PLENEADVER
AIYQVPLPGV MKLEFGSGAV GVQLVKDGPQ CREHFSRILH DLQGEADHPG IGLGWGNAML
LMEFVEGTEH DVDLVVFGGR LLAAFVSDNG PTRLPGFTET AACMPTGLAP EQEAQVVQAA
FRCCLGCGLL DGVFNVELKM TGAGPRLIEI NPRMGGFYLR DWILELYGVD LLLASTMVAC
GLQPALPAHP RARGYLVGIM CLVSQHLQLL SSPSSRETLQ TLHDQGQLRL NLLEEALIPG
QYEEPYCNVA CAGPSPAEAC HRLLGICQGL GIDRPNYPVA HFLSHFK
