CNDP2_RAT
ID CNDP2_RAT Reviewed; 475 AA.
AC Q6Q0N1;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Cytosolic non-specific dipeptidase;
DE EC=3.4.13.18 {ECO:0000250|UniProtKB:Q96KP4, ECO:0000250|UniProtKB:Q9D1A2};
DE AltName: Full=CNDP dipeptidase 2;
DE AltName: Full=Threonyl dipeptidase {ECO:0000250|UniProtKB:Q9D1A2};
GN Name=Cndp2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Iris, Ocular ciliary body, and Trabecular meshwork;
RX PubMed=15326124; DOI=10.1167/iovs.04-0302;
RA Ahmed F., Torrado M., Zinovieva R.D., Senatorov V.V., Wistow G.,
RA Tomarev S.I.;
RT "Gene expression profile of the rat eye iridocorneal angle: NEIBank
RT expressed sequence tag analysis.";
RL Invest. Ophthalmol. Vis. Sci. 45:3081-3090(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP PROTEIN SEQUENCE OF 55-66; 311-329; 403-413; 431-450 AND 462-474, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Diao W.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=18790006; DOI=10.1016/j.neulet.2008.09.008;
RA Otani H., Okumura A., Nagai K., Okumura N.;
RT "Colocalization of a carnosine-splitting enzyme, tissue carnosinase
RT (CN2)/cytosolic non-specific dipeptidase 2 (CNDP2), with histidine
RT decarboxylase in the tuberomammillary nucleus of the hypothalamus.";
RL Neurosci. Lett. 445:166-169(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RA Maurya D.K., Bhargava P.;
RL Submitted (DEC-2008) to UniProtKB.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the peptide bond hydrolysis in dipeptides,
CC displaying a non-redundant activity toward threonyl dipeptides.
CC Mediates threonyl dipeptide catabolism in a tissue-specific way (By
CC similarity). Has high dipeptidase activity toward cysteinylglycine, an
CC intermediate metabolite in glutathione metabolism. Metabolizes N-
CC lactoyl-amino acids, both through hydrolysis to form lactic acid and
CC amino acids, as well as through their formation by reverse proteolysis.
CC Plays a role in the regulation of cell cycle arrest and apoptosis (By
CC similarity). {ECO:0000250|UniProtKB:Q96KP4,
CC ECO:0000250|UniProtKB:Q9D1A2}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of dipeptides, preferentially hydrophobic
CC dipeptides including prolyl amino acids.; EC=3.4.13.18;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-threonyl-L-threonine = 2 L-threonine;
CC Xref=Rhea:RHEA:67360, ChEBI:CHEBI:15377, ChEBI:CHEBI:57926,
CC ChEBI:CHEBI:169953; Evidence={ECO:0000250|UniProtKB:Q9D1A2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67361;
CC Evidence={ECO:0000250|UniProtKB:Q9D1A2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-threonyl-L-serine = L-serine + L-threonine;
CC Xref=Rhea:RHEA:67364, ChEBI:CHEBI:15377, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:57926, ChEBI:CHEBI:169954;
CC Evidence={ECO:0000250|UniProtKB:Q9D1A2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67365;
CC Evidence={ECO:0000250|UniProtKB:Q9D1A2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-seryl-L-threonine = L-serine + L-threonine;
CC Xref=Rhea:RHEA:67372, ChEBI:CHEBI:15377, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:57926, ChEBI:CHEBI:169955;
CC Evidence={ECO:0000250|UniProtKB:Q9D1A2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67373;
CC Evidence={ECO:0000250|UniProtKB:Q9D1A2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-cysteinylglycine = glycine + L-cysteine;
CC Xref=Rhea:RHEA:28783, ChEBI:CHEBI:15377, ChEBI:CHEBI:35235,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:61694;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28784;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-alanyl-L-cysteine = L-alanine + L-cysteine;
CC Xref=Rhea:RHEA:67380, ChEBI:CHEBI:15377, ChEBI:CHEBI:35235,
CC ChEBI:CHEBI:57972, ChEBI:CHEBI:169958;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67381;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate + L-phenylalanine = H2O + N-[(S)-lactoyl]-L-
CC phenylalanine; Xref=Rhea:RHEA:66724, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16651, ChEBI:CHEBI:58095, ChEBI:CHEBI:167456;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66725;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:66726;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q96KP4};
CC Note=Binds 2 manganese ions per subunit.
CC {ECO:0000250|UniProtKB:Q96KP4};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q96KP4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96KP4}.
CC -!- TISSUE SPECIFICITY: Detected in neuronal cells in the dorsal part of
CC the tuberomammilary nucleus of the posterior hypothalamus (at protein
CC level). Expressed in the iris, ciliary body, trabecular meshwork,
CC Schlemm's canal, sclera, retina, brain, kidney and lung.
CC {ECO:0000269|PubMed:15326124, ECO:0000269|PubMed:18790006}.
CC -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
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DR EMBL; AY569013; AAS75316.1; -; mRNA.
DR EMBL; BC095904; AAH95904.1; -; mRNA.
DR RefSeq; NP_001010920.1; NM_001010920.1.
DR RefSeq; XP_006255061.1; XM_006254999.3.
DR AlphaFoldDB; Q6Q0N1; -.
DR SMR; Q6Q0N1; -.
DR BioGRID; 253502; 1.
DR IntAct; Q6Q0N1; 1.
DR MINT; Q6Q0N1; -.
DR STRING; 10116.ENSRNOP00000021400; -.
DR MEROPS; M20.005; -.
DR iPTMnet; Q6Q0N1; -.
DR PhosphoSitePlus; Q6Q0N1; -.
DR SwissPalm; Q6Q0N1; -.
DR jPOST; Q6Q0N1; -.
DR PaxDb; Q6Q0N1; -.
DR PRIDE; Q6Q0N1; -.
DR Ensembl; ENSRNOT00000021400; ENSRNOP00000021400; ENSRNOG00000015591.
DR GeneID; 291394; -.
DR KEGG; rno:291394; -.
DR CTD; 55748; -.
DR RGD; 1305827; Cndp2.
DR eggNOG; KOG2276; Eukaryota.
DR GeneTree; ENSGT00940000156500; -.
DR HOGENOM; CLU_029469_3_1_1; -.
DR InParanoid; Q6Q0N1; -.
DR OMA; HITIPGF; -.
DR OrthoDB; 733473at2759; -.
DR PhylomeDB; Q6Q0N1; -.
DR TreeFam; TF300633; -.
DR Reactome; R-RNO-174403; Glutathione synthesis and recycling.
DR Reactome; R-RNO-9753281; Paracetamol ADME.
DR PRO; PR:Q6Q0N1; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000015591; Expressed in adult mammalian kidney and 19 other tissues.
DR Genevisible; Q6Q0N1; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0103046; F:alanylglutamate dipeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0016805; F:dipeptidase activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
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; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Manganese; Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome.
FT CHAIN 1..475
FT /note="Cytosolic non-specific dipeptidase"
FT /id="PRO_0000288496"
FT ACT_SITE 101
FT /evidence="ECO:0000250"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 99
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT BINDING 132
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT BINDING 132
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT BINDING 166..167
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT BINDING 195
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT BINDING 195
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 228
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /evidence="ECO:0000250"
FT BINDING 343
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 417
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 445
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT BINDING 445
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT SITE 228
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
SQ SEQUENCE 475 AA; 52693 MW; 5B591868ABC02C55 CRC64;
MSALKAVFQY IDENQDRFVK KLAEWVAIQS VSAWPEKRGE IRRMTEAAAA DVQRLGGSVE
LVDIGKQKLP DGSEIPLPPI LLGKLGSDPQ KKTVCIYGHL DVQPAALEDG WDSEPFTLVE
REGKLYGRGS TDDKGPVAGW MNALEAYQKT GQEIPVNLRF CLEGMEESGS EGLDELIFAQ
KDKFFKDVDY VCISDNYWLG KNKPCITYGL RGICYFFIEV ECSDKDLHSG VYGGSVHEAM
TDLISLMGCL IDKKGKILIP GINDAVAPVT DEEHELYDHI DFDMEEFAKD VGAGTLLHSC
KKDILMHRWR YPSLSLHGIE GAFSGSGAKT VIPRKVVGKF SIRLVPDMIP EVVSEQVSSY
LSKKFAELQS PNKFKVYMGH GGKPWVSDFN HPHYQAGRRA LKTVFGVEPD LTREGGSIPV
TLTFQEATGK NVMLLPVGSA DDGAHSQNEK LNRLNYIEGT KMLAAYLYEV SQLKN
