ID CNDP2_HUMAN Reviewed; 475 AA. AC Q96KP4; B3KUG4; Q8WY59; Q9BQ94; Q9NVB4; V9HWE5; DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot. DT 19-SEP-2002, sequence version 2. DT 27-MAR-2024, entry version 182. DE RecName: Full=Cytosolic non-specific dipeptidase {ECO:0000303|PubMed:24395568}; DE EC=3.4.13.18 {ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:19346245}; DE AltName: Full=CNDP dipeptidase 2; DE AltName: Full=Glutamate carboxypeptidase-like protein 1; DE AltName: Full=Peptidase A; DE AltName: Full=Threonyl dipeptidase {ECO:0000250|UniProtKB:Q9D1A2}; GN Name=CNDP2 {ECO:0000303|PubMed:25964343, ECO:0000312|HGNC:HGNC:24437}; GN Synonyms=CN2, CPGL, HEL-S-13, PEPA; 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], PROTEIN SEQUENCE OF 129-137; 276-289; 311-329; RP 370-375 AND 462-474, CATALYTIC ACTIVITY, ACTIVITY REGULATION, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Brain; 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT HIS-126. RC TISSUE=Uterus; RA Chen J.M., Barrett A.J.; RT "Cloning and sequencing of human glutamate carboxypeptidase homologue in RT peptidase family M20."; RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Li J.Y., Wang H.Y., Liu F.J., Liu J.; RL Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Spleen, and Teratocarcinoma; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J., RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, and 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 [9] RP PROTEIN SEQUENCE OF 2-9; 54-66; 255-275 AND 403-430, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Heiserich L., Gottlieb E.; RL Submitted (MAR-2008) to UniProtKB. RN [10] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY (ISOFORM 2), AND FUNCTION. RX PubMed=17121880; DOI=10.1158/1078-0432.ccr-06-1307; RA Zhang P., Chan D.W., Zhu Y., Li J.J., Ng I.-O., Wan D., Gu J.; RT "Identification of carboxypeptidase of glutamate like-B as a candidate RT suppressor in cell growth and metastasis in human hepatocellular RT carcinoma."; RL Clin. Cancer Res. 12:6617-6625(2006). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=19346245; DOI=10.1074/jbc.m808952200; RA Kaur H., Kumar C., Junot C., Toledano M.B., Bachhawat A.K.; RT "Dug1p Is a Cys-Gly peptidase of the gamma-glutamyl cycle of Saccharomyces RT cerevisiae and represents a novel family of Cys-Gly peptidases."; RL J. Biol. Chem. 284:14493-14502(2009). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-9, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP FUNCTION, AND TISSUE SPECIFICITY (ISOFORM 1). RX PubMed=24395568; DOI=10.2119/molmed.2013.00102; RA Zhang Z., Miao L., Xin X., Zhang J., Yang S., Miao M., Kong X., Jiao B.; RT "Underexpressed CNDP2 participates in gastric cancer growth inhibition RT through activating the MAPK signaling pathway."; RL Mol. Med. 20:17-28(2014). RN [18] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=25964343; DOI=10.1073/pnas.1424638112; RA Jansen R.S., Addie R., Merkx R., Fish A., Mahakena S., Bleijerveld O.B., RA Altelaar M., Ijlst L., Wanders R.J., Borst P., van de Wetering K.; RT "N-lactoyl-amino acids are ubiquitous metabolites that originate from RT CNDP2-mediated reverse proteolysis of lactate and amino acids."; RL Proc. Natl. Acad. Sci. U.S.A. 112:6601-6606(2015). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH MANGANESE, AND RP COFACTOR. RA Pandya V., Kaushik A., Singh A.K., Singh R.P., Kumaran S.; RT "Crystal structure of Human Carnosinase-2 (CN2) in complex with inhibitor, RT Bestatin at 2.25 A."; RL Submitted (NOV-2014) to the PDB data bank. CC -!- FUNCTION: Catalyzes the peptide bond hydrolysis in dipeptides, CC displaying a non-redundant activity toward threonyl dipeptides (By CC similarity). Mediates threonyl dipeptide catabolism in a tissue- CC specific way (By similarity). Has high dipeptidase activity toward CC cysteinylglycine, an intermediate metabolite in glutathione metabolism CC (PubMed:19346245, PubMed:12473676). Metabolizes N-lactoyl-amino acids, CC both through hydrolysis to form lactic acid and amino acids, as well as CC through their formation by reverse proteolysis (PubMed:25964343). Plays CC a role in the regulation of cell cycle arrest and apoptosis CC (PubMed:17121880, PubMed:24395568). {ECO:0000250|UniProtKB:Q9D1A2, CC ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:17121880, CC ECO:0000269|PubMed:19346245, ECO:0000269|PubMed:24395568, CC ECO:0000269|PubMed:25964343}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of dipeptides, preferentially hydrophobic CC dipeptides including prolyl amino acids.; EC=3.4.13.18; CC Evidence={ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:19346245}; 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:0000269|PubMed:19346245}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28784; CC Evidence={ECO:0000305|PubMed:19346245}; 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:0000269|PubMed:19346245}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67381; CC Evidence={ECO:0000305|PubMed:19346245}; 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:0000269|PubMed:25964343}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66725; CC Evidence={ECO:0000305|PubMed:25964343}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:66726; CC Evidence={ECO:0000305|PubMed:25964343}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|Ref.19}; CC Note=Binds 2 manganese ions per subunit. {ECO:0000269|Ref.19}; CC -!- ACTIVITY REGULATION: Inhibited by p-hydroxymercurybenzoate. The CC inhibitory concentration 50% (IC(50)) is 13 uM. Inhibited by bestatin. CC The inhibitory concentration 50% (IC(50)) is 7 nM at pH 9.5. CC {ECO:0000269|PubMed:12473676}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.04 mM for L-serylglutamine (at pH 7.5 and in the presence of 0.1 CC mM manganese ions) {ECO:0000269|PubMed:12473676}; CC KM=0.6 mM for L-cysteinylglycine (at pH 8.0 and in the presence of 50 CC uM manganese ions) {ECO:0000269|PubMed:19346245}; CC KM=15 mM for carnosine (at pH 9.5 and in the presence of 0.1 mM CC manganese ions) {ECO:0000269|PubMed:12473676}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12473676}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12473676, CC ECO:0000269|PubMed:17121880}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96KP4-1; Sequence=Displayed; CC Name=2; Synonyms=CPGL-B {ECO:0000303|PubMed:17121880}; CC IsoId=Q96KP4-2; Sequence=VSP_038203; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Ubiquitously expressed with higher CC levels in kidney and liver (at protein level). Expressed in peripheral CC blood leukocytes (PubMed:12473676). Expressed in gastric mucosa and CC down-regulated in gastric cancer mucosal tissues (at protein level) CC (PubMed:24395568). {ECO:0000269|PubMed:12473676, CC ECO:0000269|PubMed:24395568}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Broadly expressed in fetal tissues. CC Expressed in adult liver and placenta. {ECO:0000269|PubMed:17121880}. CC -!- MISCELLANEOUS: The reverse proteolysis is not negligible in vivo as CC long as the substrates are present in considerable concentrations, such CC as upon physical exercice. N-lac-Phe plasma levels are increased in CC patients with PKU with increased plasma Phe levels. N-lactoyl-amino CC acids are present in many tissues. {ECO:0000269|PubMed:25964343}. CC -!- MISCELLANEOUS: [Isoform 2]: Lacks a part of the catalytic domain. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AX523938; CAD56843.1; -; Unassigned_DNA. DR EMBL; AJ347717; CAC69883.1; -; mRNA. DR EMBL; AK001692; BAA91840.1; -; mRNA. DR EMBL; AK097155; BAG53426.1; -; mRNA. DR EMBL; AF258592; AAG23795.1; -; mRNA. DR EMBL; EU794600; ACJ13654.1; -; mRNA. DR EMBL; AC009704; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471117; EAW66551.1; -; Genomic_DNA. DR EMBL; CH471117; EAW66552.1; -; Genomic_DNA. DR EMBL; CH471117; EAW66554.1; -; Genomic_DNA. DR EMBL; BC001375; AAH01375.1; -; mRNA. DR EMBL; BC003176; AAH03176.1; -; mRNA. DR CCDS; CCDS12006.1; -. [Q96KP4-1] DR CCDS; CCDS54190.1; -. [Q96KP4-2] DR RefSeq; NP_001161971.1; NM_001168499.1. [Q96KP4-2] DR RefSeq; NP_060705.2; NM_018235.2. [Q96KP4-1] DR RefSeq; XP_005266785.1; XM_005266728.2. DR RefSeq; XP_006722566.1; XM_006722503.2. DR RefSeq; XP_011524373.1; XM_011526071.2. DR RefSeq; XP_011524374.1; XM_011526072.2. DR PDB; 4RUH; X-ray; 2.25 A; A/B=1-475. DR PDBsum; 4RUH; -. DR AlphaFoldDB; Q96KP4; -. DR SMR; Q96KP4; -. DR BioGRID; 120866; 135. DR IntAct; Q96KP4; 13. DR STRING; 9606.ENSP00000325548; -. DR MEROPS; M20.005; -. DR GlyGen; Q96KP4; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96KP4; -. DR MetOSite; Q96KP4; -. DR PhosphoSitePlus; Q96KP4; -. DR SwissPalm; Q96KP4; -. DR BioMuta; CNDP2; -. DR DMDM; 23396498; -. DR OGP; Q96KP4; -. DR CPTAC; CPTAC-47; -. DR CPTAC; CPTAC-48; -. DR EPD; Q96KP4; -. DR jPOST; Q96KP4; -. DR MassIVE; Q96KP4; -. DR MaxQB; Q96KP4; -. DR PaxDb; 9606-ENSP00000325548; -. DR PeptideAtlas; Q96KP4; -. DR ProteomicsDB; 77098; -. [Q96KP4-1] DR ProteomicsDB; 77099; -. [Q96KP4-2] DR Pumba; Q96KP4; -. DR Antibodypedia; 23332; 457 antibodies from 31 providers. DR DNASU; 55748; -. DR Ensembl; ENST00000324262.9; ENSP00000325548.4; ENSG00000133313.15. [Q96KP4-1] DR Ensembl; ENST00000324301.12; ENSP00000325756.8; ENSG00000133313.15. [Q96KP4-2] DR Ensembl; ENST00000579847.5; ENSP00000462311.1; ENSG00000133313.15. [Q96KP4-1] DR GeneID; 55748; -. DR KEGG; hsa:55748; -. DR MANE-Select; ENST00000324262.9; ENSP00000325548.4; NM_018235.3; NP_060705.2. DR UCSC; uc002llm.3; human. DR UCSC; uc002lln.3; human. [Q96KP4-1] DR AGR; HGNC:24437; -. DR CTD; 55748; -. DR DisGeNET; 55748; -. DR GeneCards; CNDP2; -. DR HGNC; HGNC:24437; CNDP2. DR HPA; ENSG00000133313; Low tissue specificity. DR MIM; 169800; gene. DR neXtProt; NX_Q96KP4; -. DR OpenTargets; ENSG00000133313; -. DR PharmGKB; PA134975242; -. DR VEuPathDB; HostDB:ENSG00000133313; -. DR eggNOG; KOG2276; Eukaryota. DR GeneTree; ENSGT00940000156500; -. DR HOGENOM; CLU_029469_3_1_1; -. DR InParanoid; Q96KP4; -. DR OMA; HITIPGF; -. DR OrthoDB; 177966at2759; -. DR PhylomeDB; Q96KP4; -. DR TreeFam; TF300633; -. DR BRENDA; 3.4.13.18; 2681. DR PathwayCommons; Q96KP4; -. DR Reactome; R-HSA-174403; Glutathione synthesis and recycling. DR Reactome; R-HSA-9753281; Paracetamol ADME. DR SABIO-RK; Q96KP4; -. DR SignaLink; Q96KP4; -. DR BioGRID-ORCS; 55748; 10 hits in 1161 CRISPR screens. DR ChiTaRS; CNDP2; human. DR GenomeRNAi; 55748; -. DR Pharos; Q96KP4; Tbio. DR PRO; PR:Q96KP4; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; Q96KP4; Protein. DR Bgee; ENSG00000133313; Expressed in adult mammalian kidney and 198 other cell types or tissues. DR ExpressionAtlas; Q96KP4; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. 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; IBA:GO_Central. 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; IBA:GO_Central. DR CDD; cd05676; M20_dipept_like_CNDP; 1. DR Gene3D; 3.30.70.360; -; 1. DR Gene3D; 3.40.630.10; Zn peptidases; 1. DR InterPro; IPR001261; ArgE/DapE_CS. DR InterPro; IPR017153; CNDP/DUG1. DR InterPro; IPR002933; Peptidase_M20. DR InterPro; IPR011650; Peptidase_M20_dimer. DR PANTHER; PTHR43270; BETA-ALA-HIS DIPEPTIDASE; 1. DR PANTHER; PTHR43270:SF11; CYTOSOLIC NON-SPECIFIC DIPEPTIDASE; 1. DR Pfam; PF07687; M20_dimer; 1. DR Pfam; PF01546; Peptidase_M20; 1. DR PIRSF; PIRSF037242; CNDP_dipeptidase; 1. DR SUPFAM; SSF53187; Zn-dependent exopeptidases; 1. DR PROSITE; PS00759; ARGE_DAPE_CPG2_2; 1. DR Genevisible; Q96KP4; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Carboxypeptidase; KW Cytoplasm; Direct protein sequencing; Hydrolase; Manganese; Metal-binding; KW Metalloprotease; Phosphoprotein; Protease; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..475 FT /note="Cytosolic non-specific dipeptidase" FT /id="PRO_0000185272" 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:0000269|Ref.19" FT BINDING 132 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000269|Ref.19" FT BINDING 132 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000269|Ref.19" 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:0000269|Ref.19" FT BINDING 195 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000269|Ref.19" 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:0000269|Ref.19" 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:0000269|Ref.9, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 9 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 58 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6Q0N1" FT MOD_RES 299 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 69..152 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15498874" FT /id="VSP_038203" FT VARIANT 126 FT /note="Y -> H (in dbSNP:rs2278161)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_057154" FT CONFLICT 128 FT /note="R -> G (in Ref. 4; BAA91840)" FT /evidence="ECO:0000305" FT CONFLICT 348 FT /note="M -> T (in Ref. 4; BAG53426)" FT /evidence="ECO:0000305" FT HELIX 5..13 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 15..27 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 31..33 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 35..37 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 38..54 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 58..62 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 80..85 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 93..99 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 107..109 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 124..127 FT /evidence="ECO:0007829|PDB:4RUH" FT TURN 128..133 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 134..149 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 155..164 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 173..180 FT /evidence="ECO:0007829|PDB:4RUH" FT TURN 181..184 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 190..193 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 199..203 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 205..210 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 212..221 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 229..232 FT /evidence="ECO:0007829|PDB:4RUH" FT TURN 233..235 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 239..247 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 284..289 FT /evidence="ECO:0007829|PDB:4RUH" FT TURN 290..292 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 301..309 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 313..322 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 334..344 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 350..368 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 372..382 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 392..405 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 410..416 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 420..428 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 430..434 FT /evidence="ECO:0007829|PDB:4RUH" FT STRAND 450..452 FT /evidence="ECO:0007829|PDB:4RUH" FT HELIX 453..471 FT /evidence="ECO:0007829|PDB:4RUH" SQ SEQUENCE 475 AA; 52878 MW; 43FA0668B0587A39 CRC64; MAALTTLFKY IDENQDRYIK KLAKWVAIQS VSAWPEKRGE IRRMMEVAAA DVKQLGGSVE LVDIGKQKLP DGSEIPLPPI LLGRLGSDPQ KKTVCIYGHL DVQPAALEDG WDSEPFTLVE RDGKLYGRGS TDDKGPVAGW INALEAYQKT GQEIPVNVRF CLEGMEESGS EGLDELIFAR KDTFFKDVDY VCISDNYWLG KKKPCITYGL RGICYFFIEV ECSNKDLHSG VYGGSVHEAM TDLILLMGSL VDKRGNILIP GINEAVAAVT EEEHKLYDDI DFDIEEFAKD VGAQILLHSH KKDILMHRWR YPSLSLHGIE GAFSGSGAKT VIPRKVVGKF SIRLVPNMTP EVVGEQVTSY LTKKFAELRS PNEFKVYMGH GGKPWVSDFS HPHYLAGRRA MKTVFGVEPD LTREGGSIPV TLTFQEATGK NVMLLPVGSA DDGAHSQNEK LNRYNYIEGT KMLAAYLYEV SQLKD //