CNDP1_MOUSE
ID CNDP1_MOUSE Reviewed; 492 AA.
AC Q8BUG2; Q80XP5;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Beta-Ala-His dipeptidase;
DE EC=3.4.13.20 {ECO:0000269|PubMed:24891507, ECO:0000269|PubMed:31587987};
DE AltName: Full=CNDP dipeptidase 1;
DE AltName: Full=Carnosine dipeptidase 1;
GN Name=Cndp1; Synonyms=Cn1;
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].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=12473676; DOI=10.1074/jbc.m209764200;
RA Teufel M., Saudek V., Ledig J.P., Bernhardt A., Boularand S., Carreau A.,
RA Cairns N.J., Carter C., Cowley D.J., Duverger D., Ganzhorn A.J., Guenet C.,
RA Heintzelmann B., Laucher V., Sauvage C., Smirnova T.;
RT "Sequence identification and characterization of human carnosinase and a
RT closely related non-specific dipeptidase.";
RL J. Biol. Chem. 278:6521-6531(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24891507; DOI=10.1074/jbc.m114.576579;
RA Veiga-da-Cunha M., Chevalier N., Stroobant V., Vertommen D.,
RA Van Schaftingen E.;
RT "Metabolite proofreading in carnosine and homocarnosine synthesis:
RT molecular identification of PM20D2 as beta-alanyl-lysine dipeptidase.";
RL J. Biol. Chem. 289:19726-19736(2014).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31587987; DOI=10.1016/j.chembiol.2019.09.009;
RA Kim J.T., Li V.L., Terrell S.M., Fischer C.R., Long J.Z.;
RT "Family-wide Annotation of Enzymatic Pathways by Parallel In Vivo
RT Metabolomics.";
RL Cell Chem. Biol. 26:1623-1629(2019).
CC -!- FUNCTION: Catalyzes the peptide bond hydrolysis in Xaa-His dipeptides,
CC displaying the highest activity toward carnosine (beta-alanyl-L-
CC histidine) and anserine (beta-alanyl-3-methyl-histidine).
CC {ECO:0000269|PubMed:24891507, ECO:0000269|PubMed:31587987}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential hydrolysis of the beta-Ala-|-His dipeptide
CC (carnosine), and also anserine, Xaa-|-His dipeptides and other
CC dipeptides including homocarnosine.; EC=3.4.13.20;
CC Evidence={ECO:0000269|PubMed:24891507, ECO:0000269|PubMed:31587987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carnosine + H2O = beta-alanine + L-histidine;
CC Xref=Rhea:RHEA:59360, ChEBI:CHEBI:15377, ChEBI:CHEBI:57485,
CC ChEBI:CHEBI:57595, ChEBI:CHEBI:57966; EC=3.4.13.20;
CC Evidence={ECO:0000269|PubMed:24891507, ECO:0000269|PubMed:31587987};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59361;
CC Evidence={ECO:0000269|PubMed:31587987};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=anserine + H2O = beta-alanine + N(pros)-methyl-L-histidine;
CC Xref=Rhea:RHEA:59576, ChEBI:CHEBI:15377, ChEBI:CHEBI:57966,
CC ChEBI:CHEBI:58445, ChEBI:CHEBI:143076; EC=3.4.13.20;
CC Evidence={ECO:0000250|UniProtKB:Q96KN2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59577;
CC Evidence={ECO:0000250|UniProtKB:Q96KN2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-alanyl-L-histidine = L-alanine + L-histidine;
CC Xref=Rhea:RHEA:37283, ChEBI:CHEBI:15377, ChEBI:CHEBI:57595,
CC ChEBI:CHEBI:57972, ChEBI:CHEBI:74388;
CC Evidence={ECO:0000250|UniProtKB:Q96KN2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37284;
CC Evidence={ECO:0000250|UniProtKB:Q96KN2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycyl-L-histidine + H2O = glycine + L-histidine;
CC Xref=Rhea:RHEA:67376, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:57595, ChEBI:CHEBI:169956;
CC Evidence={ECO:0000250|UniProtKB:Q96KN2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67377;
CC Evidence={ECO:0000250|UniProtKB:Q96KN2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-homocarnosine = 4-aminobutanoate + L-histidine;
CC Xref=Rhea:RHEA:59572, ChEBI:CHEBI:15377, ChEBI:CHEBI:57595,
CC ChEBI:CHEBI:59888, ChEBI:CHEBI:143075; EC=3.4.13.20;
CC Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59573;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q96KN2};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q96KN2};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.28 mM for carnosine {ECO:0000269|PubMed:24891507};
CC KM=1.78 mM for homocarnosine {ECO:0000269|PubMed:24891507};
CC Vmax=4.8 umol/min/mg enzyme toward carnosine
CC {ECO:0000269|PubMed:24891507};
CC Vmax=0.086 umol/min/mg enzyme toward homocarnosine
CC {ECO:0000269|PubMed:24891507};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q96KN2}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q96KN2}.
CC -!- TISSUE SPECIFICITY: Detected exclusively in kidney.
CC {ECO:0000269|PubMed:12473676}.
CC -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
CC -!- CAUTION: In contrast to human counterpart, it lacks a signal sequence.
CC {ECO:0000305}.
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DR EMBL; AK085308; BAC39417.1; -; mRNA.
DR EMBL; BC043305; AAH43305.1; -; mRNA.
DR CCDS; CCDS29382.1; -.
DR RefSeq; NP_803233.2; NM_177450.4.
DR AlphaFoldDB; Q8BUG2; -.
DR SMR; Q8BUG2; -.
DR STRING; 10090.ENSMUSP00000069699; -.
DR MEROPS; M20.006; -.
DR PhosphoSitePlus; Q8BUG2; -.
DR MaxQB; Q8BUG2; -.
DR PaxDb; Q8BUG2; -.
DR PeptideAtlas; Q8BUG2; -.
DR PRIDE; Q8BUG2; -.
DR ProteomicsDB; 283647; -.
DR DNASU; 338403; -.
DR GeneID; 338403; -.
DR KEGG; mmu:338403; -.
DR UCSC; uc008fur.2; mouse.
DR CTD; 84735; -.
DR MGI; MGI:2451097; Cndp1.
DR eggNOG; KOG2276; Eukaryota.
DR InParanoid; Q8BUG2; -.
DR OrthoDB; 733473at2759; -.
DR PhylomeDB; Q8BUG2; -.
DR TreeFam; TF300633; -.
DR BRENDA; 3.4.13.20; 3474.
DR BioGRID-ORCS; 338403; 1 hit in 74 CRISPR screens.
DR PRO; PR:Q8BUG2; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8BUG2; protein.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0016805; F:dipeptidase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IEA:InterPro.
DR GO; GO:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IDA:MGI.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IDA:MGI.
DR InterPro; IPR001261; ArgE/DapE_CS.
DR InterPro; IPR017153; CNDP/DUG1.
DR InterPro; IPR002933; Peptidase_M20.
DR InterPro; IPR011650; Peptidase_M20_dimer.
DR Pfam; PF07687; M20_dimer; 1.
DR Pfam; PF01546; Peptidase_M20; 1.
DR PIRSF; PIRSF037242; CNDP_dipeptidase; 1.
DR PROSITE; PS00759; ARGE_DAPE_CPG2_2; 1.
PE 1: Evidence at protein level;
KW Carboxypeptidase; Hydrolase; Metal-binding; Metalloprotease;
KW Phosphoprotein; Protease; Reference proteome; Secreted; Zinc.
FT CHAIN 1..492
FT /note="Beta-Ala-His dipeptidase"
FT /id="PRO_0000250530"
FT ACT_SITE 109
FT /evidence="ECO:0000250"
FT ACT_SITE 174
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96KN2"
FT BINDING 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96KN2"
FT BINDING 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96KN2"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96KN2"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96KN2"
FT BINDING 453
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96KN2"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66HG3"
FT CONFLICT 168
FT /note="F -> L (in Ref. 2; AAH43305)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 492 AA; 55090 MW; 5A3E3F984CBF4567 CRC64;
MFSSAHSGLL EKLFHYIDLH QDEFVQTLKE WVAIESDSVQ PVPRLRQKLF QMMALAADKL
RNLGAGVESI DLGSQQMPDG QSLPIPPILL AELGSDPEKP TVCFYGHLDV QPAQKDDGWL
TDPYTLTEVD GKLYGRGATD NKGPVLAWIN AVSTFRALQQ DLPVNIKFIL EGMEEAGSIA
LEELVMREKD HFFSSVDYIV ISDNLWLSQR KPALTYGTRG NCYFTVEVKC RDQDFHSGTF
GGILNEPMAD LVALLGSLVD SSGHILIPGI YDQMAPITEG EKTMYKNIDM DLEEYQNINQ
VEKFLFDTKE ELLMHLWRYP SLSIHGIEGA FDEPGTKTVI PGRVLGKFSI RLVPTMSPSV
VEKQVTQHLE AVFSKRNSFN KMAVSMVLGL HPWTANVNDT QYLAAQRTIK TVFGVNPDMI
RDGSTIPIAK IFQAITQKSV MMLPLGAVDD GEHSQNEKIN RWNYIQGSKL FAAFFLELSK
QHSGHQMPSS VY
