CNDP2_HUMAN
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 03-AUG-2022, entry version 173.
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}.
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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; 71.
DR IntAct; Q96KP4; 11.
DR STRING; 9606.ENSP00000325548; -.
DR MEROPS; M20.005; -.
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; Q96KP4; -.
DR PeptideAtlas; Q96KP4; -.
DR PRIDE; Q96KP4; -.
DR ProteomicsDB; 77098; -. [Q96KP4-1]
DR ProteomicsDB; 77099; -. [Q96KP4-2]
DR Antibodypedia; 23332; 420 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 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; 733473at2759; -.
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 1081 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 196 other tissues.
DR ExpressionAtlas; Q96KP4; baseline and differential.
DR Genevisible; Q96KP4; HS.
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:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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 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
