CRNS1_HUMAN
ID CRNS1_HUMAN Reviewed; 827 AA.
AC A5YM72; A8K1M3; B4DFC6; E9PK38; F5H427; Q8N467; Q9P2F3;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 120.
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|HGNC:HGNC:29268}; Synonyms=ATPGD1, KIAA1394;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Schupp I.;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Cerebellum, and Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT LEU-498.
RC TISSUE=Kidney;
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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;
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=0.09 mM for beta-alanine {ECO:0000269|PubMed:20097752};
CC KM=1.84 mM for 4-aminobutanoate {ECO:0000269|PubMed:20097752};
CC KM=0.37 mM for L-histidine {ECO:0000269|PubMed:20097752};
CC KM=4.67 mM for L-lysine {ECO:0000269|PubMed:20097752};
CC KM=7.66 mM for L-ornithine {ECO:0000269|PubMed:20097752};
CC KM=24.7 mM for N-methylhistidine {ECO:0000269|PubMed:20097752};
CC Vmax=65.3 nmol/min/mg enzyme toward beta-alanine
CC {ECO:0000269|PubMed:20097752};
CC Vmax=54.7 nmol/min/mg enzyme toward gamma-aminobutyrate
CC {ECO:0000269|PubMed:20097752};
CC Vmax=0.76 nmol/min/mg enzyme toward L-histidine
CC {ECO:0000269|PubMed:20097752};
CC Vmax=0.61 nmol/min/mg enzyme toward L-lysine
CC {ECO:0000269|PubMed:20097752};
CC Vmax=0.28 nmol/min/mg enzyme toward L-ornithine
CC {ECO:0000269|PubMed:20097752};
CC Vmax=0.62 nmol/min/mg enzyme toward N-methylhistidine
CC {ECO:0000269|PubMed:20097752};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:D3KCC4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=A5YM72-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A5YM72-2; Sequence=VSP_032925;
CC Name=3;
CC IsoId=A5YM72-3; Sequence=VSP_032926;
CC Name=4;
CC IsoId=A5YM72-4; Sequence=VSP_053735, VSP_053736;
CC Name=5;
CC IsoId=A5YM72-5; Sequence=VSP_053735;
CC -!- SEQUENCE CAUTION:
CC Sequence=ABQ59056.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA92632.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; EF560746; ABQ59056.1; ALT_INIT; mRNA.
DR EMBL; AB037815; BAA92632.1; ALT_INIT; mRNA.
DR EMBL; AK289938; BAF82627.1; -; mRNA.
DR EMBL; AK294035; BAG57387.1; -; mRNA.
DR EMBL; AP003419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036557; AAH36557.1; -; mRNA.
DR CCDS; CCDS44658.1; -. [A5YM72-1]
DR CCDS; CCDS53667.1; -. [A5YM72-5]
DR RefSeq; NP_001159694.1; NM_001166222.1. [A5YM72-5]
DR RefSeq; NP_065862.1; NM_020811.1. [A5YM72-1]
DR RefSeq; XP_011543491.1; XM_011545189.2.
DR RefSeq; XP_016873543.1; XM_017018054.1. [A5YM72-3]
DR AlphaFoldDB; A5YM72; -.
DR SMR; A5YM72; -.
DR BioGRID; 121624; 3.
DR IntAct; A5YM72; 3.
DR STRING; 9606.ENSP00000389009; -.
DR iPTMnet; A5YM72; -.
DR PhosphoSitePlus; A5YM72; -.
DR SwissPalm; A5YM72; -.
DR BioMuta; CARNS1; -.
DR EPD; A5YM72; -.
DR MassIVE; A5YM72; -.
DR MaxQB; A5YM72; -.
DR PaxDb; A5YM72; -.
DR PeptideAtlas; A5YM72; -.
DR PRIDE; A5YM72; -.
DR ProteomicsDB; 21338; -.
DR ProteomicsDB; 26449; -.
DR ProteomicsDB; 764; -. [A5YM72-1]
DR ProteomicsDB; 765; -. [A5YM72-2]
DR ProteomicsDB; 766; -. [A5YM72-3]
DR Antibodypedia; 30386; 89 antibodies from 19 providers.
DR DNASU; 57571; -.
DR Ensembl; ENST00000307823.7; ENSP00000308268.3; ENSG00000172508.11. [A5YM72-1]
DR Ensembl; ENST00000445895.2; ENSP00000389009.2; ENSG00000172508.11. [A5YM72-5]
DR Ensembl; ENST00000531040.5; ENSP00000431670.1; ENSG00000172508.11. [A5YM72-4]
DR Ensembl; ENST00000687366.1; ENSP00000510668.1; ENSG00000172508.11. [A5YM72-5]
DR GeneID; 57571; -.
DR KEGG; hsa:57571; -.
DR MANE-Select; ENST00000687366.1; ENSP00000510668.1; NM_001166222.2; NP_001159694.1. [A5YM72-5]
DR UCSC; uc009yrp.3; human. [A5YM72-1]
DR CTD; 57571; -.
DR DisGeNET; 57571; -.
DR GeneCards; CARNS1; -.
DR HGNC; HGNC:29268; CARNS1.
DR HPA; ENSG00000172508; Group enriched (brain, skeletal muscle).
DR MIM; 613368; gene.
DR neXtProt; NX_A5YM72; -.
DR OpenTargets; ENSG00000172508; -.
DR PharmGKB; PA165543288; -.
DR VEuPathDB; HostDB:ENSG00000172508; -.
DR eggNOG; ENOG502QRI6; Eukaryota.
DR GeneTree; ENSGT00390000018717; -.
DR HOGENOM; CLU_315906_0_0_1; -.
DR InParanoid; A5YM72; -.
DR OrthoDB; 106215at2759; -.
DR PhylomeDB; A5YM72; -.
DR TreeFam; TF337030; -.
DR BioCyc; MetaCyc:MON66-34422; -.
DR BRENDA; 6.3.2.11; 2681.
DR PathwayCommons; A5YM72; -.
DR Reactome; R-HSA-70921; Histidine catabolism.
DR SignaLink; A5YM72; -.
DR BioGRID-ORCS; 57571; 24 hits in 1063 CRISPR screens.
DR GenomeRNAi; 57571; -.
DR Pharos; A5YM72; Tbio.
DR PRO; PR:A5YM72; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; A5YM72; protein.
DR Bgee; ENSG00000172508; Expressed in inferior vagus X ganglion and 137 other tissues.
DR Genevisible; A5YM72; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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 GO; GO:0006548; P:histidine catabolic process; TAS:Reactome.
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_0000329036"
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..442
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_032925"
FT VAR_SEQ 1
FT /note="M -> MCPLAHPAQDLPLLPSQLSLDPSGPEWDCPLGSKDLEEEGPWGGGSG
FT LPPTGCFPGSWRQDVGLDCKGSPEGAEARAWTVYYYSLLQSCLQQAGLPETQDRGQVPR
FT TGCPGAEVTLCVLGSPSTFLPVLLEGGVQSPGNM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10718198"
FT /id="VSP_032926"
FT VAR_SEQ 1
FT /note="M -> MLSLDPSGPEWDCPLGSKDLEEEGPWGGGSGLPPTGCFPGSWRQDVG
FT LDCKGSPEGAEARAWTVYYYSLLQSCLQQAGLPETQDRGQVPRTGCPGAEVTLCVLGSP
FT STFLPVLLEGGVQSPGNM (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053735"
FT VAR_SEQ 272..297
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053736"
FT VARIANT 14
FT /note="P -> T (in dbSNP:rs868167)"
FT /id="VAR_042625"
FT VARIANT 498
FT /note="M -> L (in dbSNP:rs17853668)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060320"
FT CONFLICT 23
FT /note="A -> T (in Ref. 1; ABQ59056)"
FT /evidence="ECO:0000305"
FT CONFLICT 576
FT /note="S -> P (in Ref. 3; BAF82627)"
FT /evidence="ECO:0000305"
FT CONFLICT 800
FT /note="R -> H (in Ref. 3; BAF82627)"
FT /evidence="ECO:0000305"
FT CONFLICT A5YM72-4:2
FT /note="L -> F (in Ref. 3; BAG57387)"
FT /evidence="ECO:0000305"
FT CONFLICT A5YM72-4:395
FT /note="A -> V (in Ref. 3; BAG57387)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 827 AA; 88484 MW; 18AEFC6A5299B8EF CRC64;
MLLCLSPAWL MKVPAPGQPG EAALLVSKAV SFHPGGLTFL DDFVPPRRAT YFLAGLGLGP
GRGREAAELA RDLTCPTGAS AELARLLEDR LLTRQLLAQQ GGVAVPATLA FTYKPPGLLR
GGDASLGLRL VELSGKEGQE TLVKEEVEAF LRSEALGDIL QVAVKLSGWR WRGRQAWRLH
PRAELGAVVD TVLALLEKLE EEESVLVEAV YPPAQLPCSD GPSPGPGLAV RICAVVCRTQ
GDRPLLSKVV CGVGRGDRPL RHHNSLPRTL EVALAQCGLG EEAQVAAVRQ RVKAAAEAAL
AAVLALEAGL SAEQRGGRRA HTDFLGVDFA LTAAGGVLTP VALELNGGLC LEACGALEGL
WAAPRLGPAA DEAVAAPLVE TMLRRSARCL MEGKQLLVVG AGGVSKKFVW EAARDYGLQL
HLVESDPNHF ASQLVQTFIH FDMTEHRRDE ENARLLAELV RARGLKLDGC FSYWDDCLVL
TALLCQELGL PCSSPAAMRL AKQKSLTQLH LLHHHGPPWP APSLHAVPCC PLESEADVER
AVHQVPLPGV MKLEFGAGAV GVRLVEDAPQ CHEHFSRITR DLQGEADHPG IGLGWGNAML
LMEFVEGTEH DVDLVLFGGR LLAAFVSDNG PTRLPGFTET AACMPTGLAP EQEAQMVQAA
FRCCLGCGLL DGVFNVELKL TGAGPRLIEI NPRMGGFYLR DWILELYGVD LLLAAVMVAC
GLRPALPTRP RARGHLVGVM CLVSQHLQAL SSTASRETLQ ALHDRGLLRL NLLEEALVPG
EYEEPYCSVA CAGPSPTEAR LRLLGLCQGL GIDGPSYPVA HFLSHFK
