CNDP2_PONAB
ID CNDP2_PONAB Reviewed; 475 AA.
AC Q5R432; Q5R5I0;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 78.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex, and Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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=(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 -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
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DR EMBL; CR860879; CAH92986.1; -; mRNA.
DR EMBL; CR861428; CAH93484.1; -; mRNA.
DR RefSeq; NP_001127615.1; NM_001134143.1.
DR AlphaFoldDB; Q5R432; -.
DR SMR; Q5R432; -.
DR STRING; 9601.ENSPPYP00000010372; -.
DR MEROPS; M20.005; -.
DR GeneID; 100174694; -.
DR KEGG; pon:100174694; -.
DR CTD; 55748; -.
DR eggNOG; KOG2276; Eukaryota.
DR InParanoid; Q5R432; -.
DR OrthoDB; 733473at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0103046; F:alanylglutamate dipeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Acetylation; Carboxypeptidase; Cytoplasm; Hydrolase; Manganese;
KW Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT CHAIN 2..475
FT /note="Cytosolic non-specific dipeptidase"
FT /id="PRO_0000288495"
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 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT MOD_RES 9
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6Q0N1"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96KP4"
FT CONFLICT 126
FT /note="H -> Y (in Ref. 1; CAH92986)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="Y -> N (in Ref. 1; CAH92986)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="V -> A (in Ref. 1; CAH92986)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 475 AA; 52877 MW; A4FCD76223044194 CRC64;
MAALTTLFKY IDENQDRYIK KLAKWVAIQS VSAWPEKRGE IRRMMEVAAA DVKQLGGSVE
LVDIGKQKLP DGSEIPLPPI LLGRLGSDPQ KKTVCIYGHL DVQPAALEDG WDSEPFTLVE
RDGKLHGRGS TDDKGPVAGW INALEAYQKT DQEIPVNVRF CLEGMEESGS EGLDELIFAQ
KDTFFKDVDY VCISDNYWLG KKKPCITYGL RGICYFFIEV ECSNKDLHSG VYGGSVHEAM
TDLILLMGSL VDKRGNILIP GINEAVAAVT EEEHKLYDDI DFDIEEFAKD VGAQILLHSN
KKDILMHRWR YPSLSLHGIE GAFSGSGAKT VIPRKVVGKF SIRLVPNMTP EVVSEQVTSY
LTKKFAELRS PNEFKVYMGH GGKPWVSDFS HPHYVAGRRA MRTVFGVEPD LTREGGSIPV
TLTFQEATGK NVMLLPVGSA DDGAHSQNEK LNRHNYIEGT KMLAAYLYEV SQLKD
