A5YM72 (CRNS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carnosine synthase 1
EC=6.3.2.11

Alternative name(s):
ATP-grasp domain-containing protein 1

Gene names

Name:	CARNS1
Synonyms:	ATPGD1, KIAA1394

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	827 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the synthesis of carnosine and homocarnosine. Carnosine is synthesized more efficiently than homocarnosine. Ref.6
Catalytic activity	ATP + L-histidine + beta-alanine = ADP + phosphate + carnosine.
Cofactor	Binds 2 manganese ions per subunit By similarity.
Subunit structure	Homotetramer By similarity.
Sequence similarities	Contains 1 ATP-grasp domain.
Biophysicochemical properties	Kinetic parameters: KM=0.09 mM for beta-alanine Ref.6 KM=1.84 mM for gamma-aminobutyrate KM=0.37 mM for L-histidine KM=4.67 mM for L-lysine KM=7.66 mM for L-ornithine KM=24.7 mM for N-methylhistidine Vmax=65.3 nmol/min/mg enzyme toward beta-alanine Vmax=54.7 nmol/min/mg enzyme toward gamma-aminobutyrate Vmax=0.76 nmol/min/mg enzyme toward L-histidine Vmax=0.61 nmol/min/mg enzyme toward L-lysine Vmax=0.28 nmol/min/mg enzyme toward L-ornithine Vmax=0.62 nmol/min/mg enzyme toward N-methylhistidine
Sequence caution	The sequence ABQ59056.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAA92632.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Manganese Metal-binding Nucleotide-binding
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carnosine biosynthetic process Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity Inferred from direct assay Ref.6. Source: MGI carnosine synthase activity Inferred from direct assay Ref.6. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: A5YM72-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: A5YM72-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-442: Missing.

Isoform 3 (identifier: A5YM72-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MCPLAHPAQD...EGGVQSPGNM

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 827	827	Carnosine synthase 1		PRO_0000329036
Regions
	Domain	516 – 720	205	ATP-grasp
	Nucleotide binding	542 – 611	70	ATP By similarity
Sites
	Metal binding	677	1	Manganese 1 By similarity
	Metal binding	689	1	Manganese 1 By similarity
	Metal binding	689	1	Manganese 2 By similarity
	Metal binding	691	1	Manganese 2 By similarity
Natural variations
	Alternative sequence	1 – 442	442	Missing in isoform 2.		VSP_032925
	Alternative sequence	1	1	M → MCPLAHPAQDLPLLPSQLSL DPSGPEWDCPLGSKDLEEEG PWGGGSGLPPTGCFPGSWRQ DVGLDCKGSPEGAEARAWTV YYYSLLQSCLQQAGLPETQD RGQVPRTGCPGAEVTLCVLG SPSTFLPVLLEGGVQSPGNM in isoform 3.		VSP_032926
	Natural variant	14	1	P → T. Corresponds to variant rs868167 [ dbSNP | Ensembl ].		VAR_042625
	Natural variant	498	1	M → L. Ref.5 Corresponds to variant rs17853668 [ dbSNP | Ensembl ].		VAR_060320
Experimental info
	Sequence conflict	23	1	A → T in ABQ59056. Ref.1
	Sequence conflict	576	1	S → P in BAF82627. Ref.3
	Sequence conflict	800	1	R → H in BAF82627. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 3. Checksum: 18AEFC6A5299B8EF	FASTA	827	88,484
	10 20 30 40 50 60 MLLCLSPAWL MKVPAPGQPG EAALLVSKAV SFHPGGLTFL DDFVPPRRAT YFLAGLGLGP 70 80 90 100 110 120 GRGREAAELA RDLTCPTGAS AELARLLEDR LLTRQLLAQQ GGVAVPATLA FTYKPPGLLR 130 140 150 160 170 180 GGDASLGLRL VELSGKEGQE TLVKEEVEAF LRSEALGDIL QVAVKLSGWR WRGRQAWRLH 190 200 210 220 230 240 PRAELGAVVD TVLALLEKLE EEESVLVEAV YPPAQLPCSD GPSPGPGLAV RICAVVCRTQ 250 260 270 280 290 300 GDRPLLSKVV CGVGRGDRPL RHHNSLPRTL EVALAQCGLG EEAQVAAVRQ RVKAAAEAAL 310 320 330 340 350 360 AAVLALEAGL SAEQRGGRRA HTDFLGVDFA LTAAGGVLTP VALELNGGLC LEACGALEGL 370 380 390 400 410 420 WAAPRLGPAA DEAVAAPLVE TMLRRSARCL MEGKQLLVVG AGGVSKKFVW EAARDYGLQL 430 440 450 460 470 480 HLVESDPNHF ASQLVQTFIH FDMTEHRRDE ENARLLAELV RARGLKLDGC FSYWDDCLVL 490 500 510 520 530 540 TALLCQELGL PCSSPAAMRL AKQKSLTQLH LLHHHGPPWP APSLHAVPCC PLESEADVER 550 560 570 580 590 600 AVHQVPLPGV MKLEFGAGAV GVRLVEDAPQ CHEHFSRITR DLQGEADHPG IGLGWGNAML 610 620 630 640 650 660 LMEFVEGTEH DVDLVLFGGR LLAAFVSDNG PTRLPGFTET AACMPTGLAP EQEAQMVQAA 670 680 690 700 710 720 FRCCLGCGLL DGVFNVELKL TGAGPRLIEI NPRMGGFYLR DWILELYGVD LLLAAVMVAC 730 740 750 760 770 780 GLRPALPTRP RARGHLVGVM CLVSQHLQAL SSTASRETLQ ALHDRGLLRL NLLEEALVPG 790 800 810 820 EYEEPYCSVA CAGPSPTEAR LRLLGLCQGL GIDGPSYPVA HFLSHFK
	Isoform 2 [UniParc]. Checksum: 3FC2B6761C4B9192	FASTA	385	41,773
	10 20 30 40 50 60 MTEHRRDEEN ARLLAELVRA RGLKLDGCFS YWDDCLVLTA LLCQELGLPC SSPAAMRLAK 70 80 90 100 110 120 QKSLTQLHLL HHHGPPWPAP SLHAVPCCPL ESEADVERAV HQVPLPGVMK LEFGAGAVGV 130 140 150 160 170 180 RLVEDAPQCH EHFSRITRDL QGEADHPGIG LGWGNAMLLM EFVEGTEHDV DLVLFGGRLL 190 200 210 220 230 240 AAFVSDNGPT RLPGFTETAA CMPTGLAPEQ EAQMVQAAFR CCLGCGLLDG VFNVELKLTG 250 260 270 280 290 300 AGPRLIEINP RMGGFYLRDW ILELYGVDLL LAAVMVACGL RPALPTRPRA RGHLVGVMCL 310 320 330 340 350 360 VSQHLQALSS TASRETLQAL HDRGLLRLNL LEEALVPGEY EEPYCSVACA GPSPTEARLR 370 380 LLGLCQGLGI DGPSYPVAHF LSHFK
	Isoform 3 [UniParc]. Checksum: 24A529E929356016	FASTA	966	103,002
	10 20 30 40 50 60 MCPLAHPAQD LPLLPSQLSL DPSGPEWDCP LGSKDLEEEG PWGGGSGLPP TGCFPGSWRQ 70 80 90 100 110 120 DVGLDCKGSP EGAEARAWTV YYYSLLQSCL QQAGLPETQD RGQVPRTGCP GAEVTLCVLG 130 140 150 160 170 180 SPSTFLPVLL EGGVQSPGNM LLCLSPAWLM KVPAPGQPGE AALLVSKAVS FHPGGLTFLD 190 200 210 220 230 240 DFVPPRRATY FLAGLGLGPG RGREAAELAR DLTCPTGASA ELARLLEDRL LTRQLLAQQG 250 260 270 280 290 300 GVAVPATLAF TYKPPGLLRG GDASLGLRLV ELSGKEGQET LVKEEVEAFL RSEALGDILQ 310 320 330 340 350 360 VAVKLSGWRW RGRQAWRLHP RAELGAVVDT VLALLEKLEE EESVLVEAVY PPAQLPCSDG 370 380 390 400 410 420 PSPGPGLAVR ICAVVCRTQG DRPLLSKVVC GVGRGDRPLR HHNSLPRTLE VALAQCGLGE 430 440 450 460 470 480 EAQVAAVRQR VKAAAEAALA AVLALEAGLS AEQRGGRRAH TDFLGVDFAL TAAGGVLTPV 490 500 510 520 530 540 ALELNGGLCL EACGALEGLW AAPRLGPAAD EAVAAPLVET MLRRSARCLM EGKQLLVVGA 550 560 570 580 590 600 GGVSKKFVWE AARDYGLQLH LVESDPNHFA SQLVQTFIHF DMTEHRRDEE NARLLAELVR 610 620 630 640 650 660 ARGLKLDGCF SYWDDCLVLT ALLCQELGLP CSSPAAMRLA KQKSLTQLHL LHHHGPPWPA 670 680 690 700 710 720 PSLHAVPCCP LESEADVERA VHQVPLPGVM KLEFGAGAVG VRLVEDAPQC HEHFSRITRD 730 740 750 760 770 780 LQGEADHPGI GLGWGNAMLL MEFVEGTEHD VDLVLFGGRL LAAFVSDNGP TRLPGFTETA 790 800 810 820 830 840 ACMPTGLAPE QEAQMVQAAF RCCLGCGLLD GVFNVELKLT GAGPRLIEIN PRMGGFYLRD 850 860 870 880 890 900 WILELYGVDL LLAAVMVACG LRPALPTRPR ARGHLVGVMC LVSQHLQALS STASRETLQA 910 920 930 940 950 960 LHDRGLLRLN LLEEALVPGE YEEPYCSVAC AGPSPTEARL RLLGLCQGLG IDGPSYPVAH FLSHFK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Schupp I. Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Hippocampus.
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT LEU-498. Tissue: Kidney.
[6]	"Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1)." Drozak J., Veiga-da-Cunha M., Vertommen D., Stroobant V., Van Schaftingen E. J. Biol. Chem. 285:9346-9356(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.

Cross-references

Sequence databases
EMBL GenBank DDBJ	EF560746 mRNA. Translation: ABQ59056.1. Different initiation. AB037815 mRNA. Translation: BAA92632.1. Different initiation. AK289938 mRNA. Translation: BAF82627.1. AP003419 Genomic DNA. No translation available. BC036557 mRNA. Translation: AAH36557.1.
IPI	IPI00847271. IPI00889615. IPI00942719.
RefSeq	NP_001159694.1. NM_001166222.1. NP_065862.1. NM_020811.1.
UniGene	Hs.502982.
3D structure databases
ProteinModelPortal	A5YM72.
SMR	A5YM72. Positions 537-720.
ModBase	Search...
Protein-protein interaction databases
IntAct	A5YM72. 1 interaction.
PTM databases
PhosphoSite	A5YM72.
Proteomic databases
PaxDb	A5YM72.
PRIDE	A5YM72.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307823; ENSP00000308268; ENSG00000172508. ENST00000423745; ENSP00000401519; ENSG00000172508.
GeneID	57571.
KEGG	hsa:57571.
UCSC	uc001olc.4. human. uc009yrp.3. human. uc021qmh.1. human.
Organism-specific databases
CTD	57571.
GeneCards	GC11P067183.
H-InvDB	HIX0201593.
HGNC	HGNC:29268. CARNS1.
HPA	HPA038570.
MIM	613368. gene.
neXtProt	NX_A5YM72.
PharmGKB	PA165543288.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0439.
HOGENOM	HOG000168640.
HOVERGEN	HBG102303.
InParanoid	A5YM72.
KO	K14755.
Gene expression databases
ArrayExpress	A5YM72.
Bgee	A5YM72.
CleanEx	HS_ATPGD1.
Genevestigator	A5YM72.
Family and domain databases
Gene3D	3.30.470.20. 2 hits.
InterPro	IPR011761. ATP-grasp. IPR013816. ATP_grasp_subdomain_2. [Graphical view]
PROSITE	PS50975. ATP_GRASP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	57571.
NextBio	64094.
SOURCE	Search...

Entry information

Entry name

CRNS1_HUMAN

Accession

Primary (citable) accession number: A5YM72
Secondary accession number(s): A8K1M3, Q8N467, Q9P2F3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 8, 2008
Last sequence update:	November 24, 2009
Last modified:	May 1, 2013
This is version 58 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.