Full text data of CNDP2
CNDP2
(CN2, CPGL, PEPA)
[Confidence: low (only semi-automatic identification from reviews)]
Cytosolic non-specific dipeptidase; 3.4.13.18 (CNDP dipeptidase 2; Glutamate carboxypeptidase-like protein 1; Peptidase A)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Cytosolic non-specific dipeptidase; 3.4.13.18 (CNDP dipeptidase 2; Glutamate carboxypeptidase-like protein 1; Peptidase A)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q96KP4
ID CNDP2_HUMAN Reviewed; 475 AA.
AC Q96KP4; B3KUG4; Q8WY59; Q9BQ94; Q9NVB4;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 19-SEP-2002, sequence version 2.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Cytosolic non-specific dipeptidase;
DE EC=3.4.13.18;
DE AltName: Full=CNDP dipeptidase 2;
DE AltName: Full=Glutamate carboxypeptidase-like protein 1;
DE AltName: Full=Peptidase A;
GN Name=CNDP2; Synonyms=CN2, CPGL, PEPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 129-137; 276-289;
RP 311-329; 370-375 AND 462-474, CATALYTIC ACTIVITY, ENZYME REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=12473676; DOI=10.1074/jbc.M209764200;
RA Teufel M., Saudek V., Ledig J.P., Bernhardt A., Boularand S.,
RA Carreau A., Cairns N.J., Carter C., Cowley D.J., Duverger D.,
RA Ganzhorn A.J., Guenet C., Heintzelmann B., Laucher V., Sauvage C.,
RA Smirnova T.;
RT "Sequence identification and characterization of human carnosinase and
RT a 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
RT in peptidase family M20.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
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.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA 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 [5]
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.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-9; 54-66; 255-275 AND 403-430, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E.;
RL Submitted (MAR-2008) to UniProtKB.
RN [9]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, 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 [10]
RP FUNCTION, 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
RT Saccharomyces cerevisiae and represents a novel family of Cys-Gly
RT peptidases.";
RL J. Biol. Chem. 284:14493-14502(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 AND LYS-9, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [12]
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.,
RA Buerckstuemmer T., 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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Hydrolyzes a variety of dipeptides including L-carnosine
CC but has a strong preference for Cys-Gly. Isoform 2 may be play a
CC role as tumor suppressor in hepatocellular carcinoma (HCC) cells.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of dipeptides, preferentially
CC hydrophobic dipeptides including prolyl amino acids.
CC -!- COFACTOR: Binds 2 manganese ions per subunit (By similarity).
CC -!- ENZYME REGULATION: Inhibited by p-hydroxymercurybenzoate. The
CC inhibitory concentration 50% (IC(50)) is 13 uM. Inhibited by
CC bestatin. The inhibitory concentration 50% (IC(50)) is 7 nM at pH
CC 9.5.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.04 mM for Ser-Gln (at pH 7.5 and in the presence of 0.1 mM
CC manganese ions);
CC KM=0.6 mM for Cys-Gly (at pH 8.0 and in the presence of 50 uM
CC manganese ions);
CC KM=15 mM for carnosine (at pH 9.5 and in the presence of 0.1 mM
CC manganese ions);
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC Q92597:NDRG1; NbExp=1; IntAct=EBI-1190734, EBI-716486;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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;
CC IsoId=Q96KP4-2; Sequence=VSP_038203;
CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed with
CC higher levels in kidney and liver (at protein level). Isoform 2 is
CC expressed in fetal tissues, it is only expressed in adult liver
CC and placental tissues.
CC -!- SIMILARITY: Belongs to the peptidase M20A family.
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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; AC009704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471117; EAW66551.1; -; Genomic_DNA.
DR EMBL; BC001375; AAH01375.1; -; mRNA.
DR EMBL; BC003176; AAH03176.1; -; mRNA.
DR RefSeq; NP_001161971.1; NM_001168499.1.
DR RefSeq; NP_060705.2; NM_018235.2.
DR RefSeq; XP_005266785.1; XM_005266728.1.
DR UniGene; Hs.149185; -.
DR ProteinModelPortal; Q96KP4; -.
DR SMR; Q96KP4; 1-474.
DR IntAct; Q96KP4; 1.
DR STRING; 9606.ENSP00000325548; -.
DR MEROPS; M20.005; -.
DR PhosphoSite; Q96KP4; -.
DR DMDM; 23396498; -.
DR OGP; Q96KP4; -.
DR PaxDb; Q96KP4; -.
DR PRIDE; Q96KP4; -.
DR Ensembl; ENST00000324262; ENSP00000325548; ENSG00000133313.
DR Ensembl; ENST00000324301; ENSP00000325756; ENSG00000133313.
DR Ensembl; ENST00000579847; ENSP00000462311; ENSG00000133313.
DR GeneID; 55748; -.
DR KEGG; hsa:55748; -.
DR UCSC; uc002llm.2; human.
DR CTD; 55748; -.
DR GeneCards; GC18P072163; -.
DR H-InvDB; HIX0136845; -.
DR HGNC; HGNC:24437; CNDP2.
DR HPA; CAB026196; -.
DR MIM; 169800; gene.
DR neXtProt; NX_Q96KP4; -.
DR PharmGKB; PA134975242; -.
DR eggNOG; COG0624; -.
DR HOGENOM; HOG000216709; -.
DR HOVERGEN; HBG051103; -.
DR InParanoid; Q96KP4; -.
DR KO; K08660; -.
DR OMA; DYALVCD; -.
DR PhylomeDB; Q96KP4; -.
DR BRENDA; 3.4.13.18; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q96KP4; -.
DR ChiTaRS; CNDP2; human.
DR GenomeRNAi; 55748; -.
DR NextBio; 60729; -.
DR PRO; PR:Q96KP4; -.
DR ArrayExpress; Q96KP4; -.
DR Bgee; Q96KP4; -.
DR CleanEx; HS_CNDP2; -.
DR Genevestigator; Q96KP4; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004180; F:carboxypeptidase activity; TAS:Reactome.
DR GO; GO:0016805; F:dipeptidase activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0034701; F:tripeptidase activity; IEA:InterPro.
DR GO; GO:0006750; P:glutathione biosynthetic process; TAS:Reactome.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0000096; P:sulfur amino acid metabolic process; TAS:Reactome.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.30.70.360; -; 1.
DR InterPro; IPR001261; ArgE/DapE_CS.
DR InterPro; IPR017153; GSH_degradosome_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; PS00758; ARGE_DAPE_CPG2_1; FALSE_NEG.
DR PROSITE; PS00759; ARGE_DAPE_CPG2_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Carboxypeptidase;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Manganese; Metal-binding; Metalloprotease; Polymorphism; Protease;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 475 Cytosolic non-specific dipeptidase.
FT /FTId=PRO_0000185272.
FT REGION 166 167 Substrate binding (By similarity).
FT ACT_SITE 101 101 By similarity.
FT ACT_SITE 166 166 Proton acceptor (By similarity).
FT METAL 99 99 Manganese 2 (By similarity).
FT METAL 132 132 Manganese 1 (By similarity).
FT METAL 132 132 Manganese 2 (By similarity).
FT METAL 167 167 Manganese 1 (By similarity).
FT METAL 195 195 Manganese 2 (By similarity).
FT METAL 445 445 Manganese 1 (By similarity).
FT BINDING 195 195 Substrate; via carbonyl oxygen (By
FT similarity).
FT BINDING 228 228 Substrate; shared with homodimeric
FT partner (By similarity).
FT BINDING 330 330 Substrate; shared with homodimeric
FT partner (By similarity).
FT BINDING 343 343 Substrate (By similarity).
FT BINDING 417 417 Substrate; via amide nitrogen and
FT carbonyl oxygen (By similarity).
FT BINDING 445 445 Substrate (By similarity).
FT SITE 228 228 Important for catalytic activity (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 9 9 N6-acetyllysine.
FT VAR_SEQ 69 152 Missing (in isoform 2).
FT /FTId=VSP_038203.
FT VARIANT 126 126 Y -> H (in dbSNP:rs2278161).
FT /FTId=VAR_057154.
FT CONFLICT 128 128 R -> G (in Ref. 3; BAA91840).
FT CONFLICT 348 348 M -> T (in Ref. 3; BAG53426).
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
//
ID CNDP2_HUMAN Reviewed; 475 AA.
AC Q96KP4; B3KUG4; Q8WY59; Q9BQ94; Q9NVB4;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 19-SEP-2002, sequence version 2.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Cytosolic non-specific dipeptidase;
DE EC=3.4.13.18;
DE AltName: Full=CNDP dipeptidase 2;
DE AltName: Full=Glutamate carboxypeptidase-like protein 1;
DE AltName: Full=Peptidase A;
GN Name=CNDP2; Synonyms=CN2, CPGL, PEPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 129-137; 276-289;
RP 311-329; 370-375 AND 462-474, CATALYTIC ACTIVITY, ENZYME REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=12473676; DOI=10.1074/jbc.M209764200;
RA Teufel M., Saudek V., Ledig J.P., Bernhardt A., Boularand S.,
RA Carreau A., Cairns N.J., Carter C., Cowley D.J., Duverger D.,
RA Ganzhorn A.J., Guenet C., Heintzelmann B., Laucher V., Sauvage C.,
RA Smirnova T.;
RT "Sequence identification and characterization of human carnosinase and
RT a 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
RT in peptidase family M20.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
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.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA 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 [5]
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.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-9; 54-66; 255-275 AND 403-430, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E.;
RL Submitted (MAR-2008) to UniProtKB.
RN [9]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, 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 [10]
RP FUNCTION, 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
RT Saccharomyces cerevisiae and represents a novel family of Cys-Gly
RT peptidases.";
RL J. Biol. Chem. 284:14493-14502(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 AND LYS-9, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [12]
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.,
RA Buerckstuemmer T., 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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Hydrolyzes a variety of dipeptides including L-carnosine
CC but has a strong preference for Cys-Gly. Isoform 2 may be play a
CC role as tumor suppressor in hepatocellular carcinoma (HCC) cells.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of dipeptides, preferentially
CC hydrophobic dipeptides including prolyl amino acids.
CC -!- COFACTOR: Binds 2 manganese ions per subunit (By similarity).
CC -!- ENZYME REGULATION: Inhibited by p-hydroxymercurybenzoate. The
CC inhibitory concentration 50% (IC(50)) is 13 uM. Inhibited by
CC bestatin. The inhibitory concentration 50% (IC(50)) is 7 nM at pH
CC 9.5.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.04 mM for Ser-Gln (at pH 7.5 and in the presence of 0.1 mM
CC manganese ions);
CC KM=0.6 mM for Cys-Gly (at pH 8.0 and in the presence of 50 uM
CC manganese ions);
CC KM=15 mM for carnosine (at pH 9.5 and in the presence of 0.1 mM
CC manganese ions);
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC Q92597:NDRG1; NbExp=1; IntAct=EBI-1190734, EBI-716486;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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;
CC IsoId=Q96KP4-2; Sequence=VSP_038203;
CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed with
CC higher levels in kidney and liver (at protein level). Isoform 2 is
CC expressed in fetal tissues, it is only expressed in adult liver
CC and placental tissues.
CC -!- SIMILARITY: Belongs to the peptidase M20A family.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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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; AC009704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471117; EAW66551.1; -; Genomic_DNA.
DR EMBL; BC001375; AAH01375.1; -; mRNA.
DR EMBL; BC003176; AAH03176.1; -; mRNA.
DR RefSeq; NP_001161971.1; NM_001168499.1.
DR RefSeq; NP_060705.2; NM_018235.2.
DR RefSeq; XP_005266785.1; XM_005266728.1.
DR UniGene; Hs.149185; -.
DR ProteinModelPortal; Q96KP4; -.
DR SMR; Q96KP4; 1-474.
DR IntAct; Q96KP4; 1.
DR STRING; 9606.ENSP00000325548; -.
DR MEROPS; M20.005; -.
DR PhosphoSite; Q96KP4; -.
DR DMDM; 23396498; -.
DR OGP; Q96KP4; -.
DR PaxDb; Q96KP4; -.
DR PRIDE; Q96KP4; -.
DR Ensembl; ENST00000324262; ENSP00000325548; ENSG00000133313.
DR Ensembl; ENST00000324301; ENSP00000325756; ENSG00000133313.
DR Ensembl; ENST00000579847; ENSP00000462311; ENSG00000133313.
DR GeneID; 55748; -.
DR KEGG; hsa:55748; -.
DR UCSC; uc002llm.2; human.
DR CTD; 55748; -.
DR GeneCards; GC18P072163; -.
DR H-InvDB; HIX0136845; -.
DR HGNC; HGNC:24437; CNDP2.
DR HPA; CAB026196; -.
DR MIM; 169800; gene.
DR neXtProt; NX_Q96KP4; -.
DR PharmGKB; PA134975242; -.
DR eggNOG; COG0624; -.
DR HOGENOM; HOG000216709; -.
DR HOVERGEN; HBG051103; -.
DR InParanoid; Q96KP4; -.
DR KO; K08660; -.
DR OMA; DYALVCD; -.
DR PhylomeDB; Q96KP4; -.
DR BRENDA; 3.4.13.18; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q96KP4; -.
DR ChiTaRS; CNDP2; human.
DR GenomeRNAi; 55748; -.
DR NextBio; 60729; -.
DR PRO; PR:Q96KP4; -.
DR ArrayExpress; Q96KP4; -.
DR Bgee; Q96KP4; -.
DR CleanEx; HS_CNDP2; -.
DR Genevestigator; Q96KP4; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004180; F:carboxypeptidase activity; TAS:Reactome.
DR GO; GO:0016805; F:dipeptidase activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0034701; F:tripeptidase activity; IEA:InterPro.
DR GO; GO:0006750; P:glutathione biosynthetic process; TAS:Reactome.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0000096; P:sulfur amino acid metabolic process; TAS:Reactome.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.30.70.360; -; 1.
DR InterPro; IPR001261; ArgE/DapE_CS.
DR InterPro; IPR017153; GSH_degradosome_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; PS00758; ARGE_DAPE_CPG2_1; FALSE_NEG.
DR PROSITE; PS00759; ARGE_DAPE_CPG2_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Carboxypeptidase;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Manganese; Metal-binding; Metalloprotease; Polymorphism; Protease;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 475 Cytosolic non-specific dipeptidase.
FT /FTId=PRO_0000185272.
FT REGION 166 167 Substrate binding (By similarity).
FT ACT_SITE 101 101 By similarity.
FT ACT_SITE 166 166 Proton acceptor (By similarity).
FT METAL 99 99 Manganese 2 (By similarity).
FT METAL 132 132 Manganese 1 (By similarity).
FT METAL 132 132 Manganese 2 (By similarity).
FT METAL 167 167 Manganese 1 (By similarity).
FT METAL 195 195 Manganese 2 (By similarity).
FT METAL 445 445 Manganese 1 (By similarity).
FT BINDING 195 195 Substrate; via carbonyl oxygen (By
FT similarity).
FT BINDING 228 228 Substrate; shared with homodimeric
FT partner (By similarity).
FT BINDING 330 330 Substrate; shared with homodimeric
FT partner (By similarity).
FT BINDING 343 343 Substrate (By similarity).
FT BINDING 417 417 Substrate; via amide nitrogen and
FT carbonyl oxygen (By similarity).
FT BINDING 445 445 Substrate (By similarity).
FT SITE 228 228 Important for catalytic activity (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 9 9 N6-acetyllysine.
FT VAR_SEQ 69 152 Missing (in isoform 2).
FT /FTId=VSP_038203.
FT VARIANT 126 126 Y -> H (in dbSNP:rs2278161).
FT /FTId=VAR_057154.
FT CONFLICT 128 128 R -> G (in Ref. 3; BAA91840).
FT CONFLICT 348 348 M -> T (in Ref. 3; BAG53426).
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
//
MIM
169800
*RECORD*
*FIELD* NO
169800
*FIELD* TI
*169800 PEPTIDASE A; PEPA
;;CARNOSINASE 2; CN2;;
CNDP2;;
NONSPECIFIC DIPEPTIDASE, CYTOSOLIC;;
read moreCARNOSINASE, TISSUE
*FIELD* TX
DESCRIPTION
CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18),
is a nonspecific dipeptidase rather than a selective carnosinase (Teufel
et al., 2003).
CLONING
Lewis et al. (1968) identified genetically variable peptidases
determined by alleles at 2 separate and not closely linked structural
loci, PEPA and PEPB (169900). The peptidases were present in red cells.
Teufel et al. (2003) assembled overlapping ESTs derived from human brain
cDNA libraries to obtain full-length CN2. The deduced 473-amino acid
protein has a calculated molecular mass of 52.9 kD. CN2 contains
essential histidine and carboxyl residues in the metal-binding site, as
well as 3 N-glycosylation sites. CN2 shares 49% amino acid identity with
CN1 (CNDP1; 609064), but it lacks the N-terminal signal sequence found
in CN1. mRNA dot blot analysis detected CN2 expression in all adult and
fetal tissues examined. Western blot analysis detected widespread
protein expression. Highest levels were in kidney and liver, with lower
levels in brain, spleen, ovary, testis, lung, and pancreas. No protein
expression was found in heart. Size-exclusion chromatography indicated
that purified recombinant CN2 created a homodimer of 90 kD. The monomer
migrated at 54 kD, as indicated by SDS-PAGE.
GENE FUNCTION
Lewis et al. (1968) showed that PEPA and PEPB were capable of
hydrolyzing di- and tripeptides.
Teufel et al. (2003) found carnosinase activity in the cytoplasmic
fraction of CN2-transfected Chinese hamster ovary cells. Strong
carnosine degradation was found at the nonphysiologic pH of 9.5.
Carnosine degradation was increased 5-fold in the presence of 0.1 mM
Mn(2+). CN2 did not hydrolyze carnosine at pH 7.5. In the presence of
Mn(2+), CN2 degraded pro-ala and ser-gln at pH 7.5. However, the
velocity of pro-ala degradation was higher at pH 9.5. CN2 also degraded
leu-his, ser-his, and tyr-his, but it did not hydrolyze homocarnosine.
MAPPING
Lewis and Harris (1969) stated that peptidases A, B, C (170000), and D
(613230) are products of separate gene loci and that E (170200) probably
is also. Cook et al. (1972) found no sign of close linkage of peptidases
A, B, C and D. There were 'hints' of linkage between PEPB and Gm (see
147100), between PEPC and Rh (111700), and between PEPD, Lutheran
(111200), and secretor (182100). The second is noteworthy because of the
assignment of both PEPC and Rh to chromosome 1.
By analysis of mouse-human somatic cell hybrids, Creagan et al. (1973)
concluded that the structural locus for peptidase A is on chromosome 18.
Arthur et al. (1975) presented evidence to narrow the localization to
chromosome 18q23.
MOLECULAR GENETICS
In the cell line with the ring(18) from a patient with ring(18)
mosaicism, Rocchi et al. (1984) found that the level of PEPA was 55% of
that in the 46,XX line from the same patient. Namba et al. (1988) showed
dosage effect in 2 patients with trisomy 18.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
*FIELD* SA
Danesino et al. (1978); Junien et al. (1980); Kuhnl et al. (1979);
Lewis (1973); Lewis and Harris (1967); McAlpine et al. (1975)
*FIELD* RF
1. Arthur, E.; Steel, C. M.; Evans, H. J.: Genetic studies on human
lymphoblastoid cell lines: isozyme and cytogenetic heterogeneity in
a cell line, with evidence for localization of the Pep A locus in
man. Ann. Hum. Genet. 39: 33-42, 1975.
2. Cook, P. J. L.; Povey, S.; Robson, E. B.: Linkage studies on peptidases
A, B, C and D in man. Ann. Hum. Genet. 36: 89-98, 1972.
3. Creagan, R.; Tischfield, J.; McMorris, F. A.; Chen, S.-H.; Hirschi,
M.; Chen, T.-R.; Ricciuti, F.; Ruddle, F. H.: Assignment of the genes
for human peptidase A to chromosome 18 and cytoplasmic glutamic oxaloacetate
transaminase to chromosome 10 using somatic cell hybrids. Cytogenet.
Cell Genet. 12: 187-198, 1973.
4. Danesino, C.; D'Azzo, A.; Maraschio, P.; Fraccaro, M.: The gene
for human peptidase A is on band 18q23 and shows triplex and uniplex
dosage effect. Hum. Genet. 43: 299-305, 1978.
5. Junien, C.; de Grouchy, J.; Turleau, C.; Serville, F.: Confirmation
of the regional assignment of peptidase A (PEPA) to 18q23 by gene
dosage studies. Ann. Genet. 23: 89-90, 1980.
6. Kuhnl, P.; Anneken, K.; Spielmann, W.: PEP A(9), a new, unstable
variant in the peptidase A system. Hum. Genet. 47: 187-191, 1979.
7. Lewis, W. H. P.: Common polymorphism of peptidase A. Electrophoretic
variants associated with quantitative variation of red cell levels. Ann.
Hum. Genet. 36: 267-271, 1973.
8. Lewis, W. H. P.; Corney, G.; Harris, H.: Pep A5-1 and pep A6-1:
two new variants of peptidase A with features of special interest. Ann.
Hum. Genet. 32: 35-42, 1968.
9. Lewis, W. H. P.; Harris, H.: Human red cell peptidases. Nature 215:
351-355, 1967.
10. Lewis, W. H. P.; Harris, H.: Molecular size estimates of human
peptidases determined by separate gene loci. Ann. Hum. Genet. 33:
89-92, 1969.
11. McAlpine, P. J.; Mohandas, T.; Komarnicki, L.; Niewczas-Late,
V.; Vust, A.; Hamerton, J. L.: Tentative assignment of the peptidase
A (pep-A) gene locus to the (q21-to-qter) region of chromosome 18
in man. Birth Defects Orig. Art. Ser. 11(3): 200-201, 1975. Note:
Alternate: Cytogenet. Cell Genet. 14: 370-371, 1975.
12. Namba, M.; Nakatsuka, S.; Etoh, H.; Kataoka, N.; Kimoto, T.:
Fibroblasts of two patients with trisomy 18 show 1.5-fold increase
in peptidase A activity over normal human diploid fibroblasts. Clin.
Genet. 34: 161-164, 1988.
13. Rocchi, M.; Cigui, I.; Archidiacono, N.; Pecile, V.; Porcelli,
G.; Filippi, G.: A young girl with ring(18) mosaicism: cytogenetic
studies and PEP A mapping. Clin. Genet. 26: 156-160, 1984.
14. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
15. Teufel, M.; Saudek, V.; Ledig, J.-P.; Bernhardt, A.; Boularand,
S.; Carreau, A.; Cairns, N. J.; Carter, C.; Cowley, D. J.; Duverger,
D.; Ganzhorn, A. J.; Guenet, C.; Heintzelmann, B.; Laucher, V.; Sauvage,
C.; Smirnova, T.: Sequence identification and characterization of
human carnosinase and a closely related non-specific dipeptidase. J.
Biol. Chem. 278: 6521-6531, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 12/7/2004
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 01/26/2010
carol: 12/11/2009
mgross: 12/9/2004
mgross: 12/7/2004
mimadm: 4/1/1994
warfield: 3/29/1994
supermim: 3/16/1992
carol: 2/26/1991
carol: 2/8/1991
supermim: 5/1/1990
*RECORD*
*FIELD* NO
169800
*FIELD* TI
*169800 PEPTIDASE A; PEPA
;;CARNOSINASE 2; CN2;;
CNDP2;;
NONSPECIFIC DIPEPTIDASE, CYTOSOLIC;;
read moreCARNOSINASE, TISSUE
*FIELD* TX
DESCRIPTION
CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18),
is a nonspecific dipeptidase rather than a selective carnosinase (Teufel
et al., 2003).
CLONING
Lewis et al. (1968) identified genetically variable peptidases
determined by alleles at 2 separate and not closely linked structural
loci, PEPA and PEPB (169900). The peptidases were present in red cells.
Teufel et al. (2003) assembled overlapping ESTs derived from human brain
cDNA libraries to obtain full-length CN2. The deduced 473-amino acid
protein has a calculated molecular mass of 52.9 kD. CN2 contains
essential histidine and carboxyl residues in the metal-binding site, as
well as 3 N-glycosylation sites. CN2 shares 49% amino acid identity with
CN1 (CNDP1; 609064), but it lacks the N-terminal signal sequence found
in CN1. mRNA dot blot analysis detected CN2 expression in all adult and
fetal tissues examined. Western blot analysis detected widespread
protein expression. Highest levels were in kidney and liver, with lower
levels in brain, spleen, ovary, testis, lung, and pancreas. No protein
expression was found in heart. Size-exclusion chromatography indicated
that purified recombinant CN2 created a homodimer of 90 kD. The monomer
migrated at 54 kD, as indicated by SDS-PAGE.
GENE FUNCTION
Lewis et al. (1968) showed that PEPA and PEPB were capable of
hydrolyzing di- and tripeptides.
Teufel et al. (2003) found carnosinase activity in the cytoplasmic
fraction of CN2-transfected Chinese hamster ovary cells. Strong
carnosine degradation was found at the nonphysiologic pH of 9.5.
Carnosine degradation was increased 5-fold in the presence of 0.1 mM
Mn(2+). CN2 did not hydrolyze carnosine at pH 7.5. In the presence of
Mn(2+), CN2 degraded pro-ala and ser-gln at pH 7.5. However, the
velocity of pro-ala degradation was higher at pH 9.5. CN2 also degraded
leu-his, ser-his, and tyr-his, but it did not hydrolyze homocarnosine.
MAPPING
Lewis and Harris (1969) stated that peptidases A, B, C (170000), and D
(613230) are products of separate gene loci and that E (170200) probably
is also. Cook et al. (1972) found no sign of close linkage of peptidases
A, B, C and D. There were 'hints' of linkage between PEPB and Gm (see
147100), between PEPC and Rh (111700), and between PEPD, Lutheran
(111200), and secretor (182100). The second is noteworthy because of the
assignment of both PEPC and Rh to chromosome 1.
By analysis of mouse-human somatic cell hybrids, Creagan et al. (1973)
concluded that the structural locus for peptidase A is on chromosome 18.
Arthur et al. (1975) presented evidence to narrow the localization to
chromosome 18q23.
MOLECULAR GENETICS
In the cell line with the ring(18) from a patient with ring(18)
mosaicism, Rocchi et al. (1984) found that the level of PEPA was 55% of
that in the 46,XX line from the same patient. Namba et al. (1988) showed
dosage effect in 2 patients with trisomy 18.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
*FIELD* SA
Danesino et al. (1978); Junien et al. (1980); Kuhnl et al. (1979);
Lewis (1973); Lewis and Harris (1967); McAlpine et al. (1975)
*FIELD* RF
1. Arthur, E.; Steel, C. M.; Evans, H. J.: Genetic studies on human
lymphoblastoid cell lines: isozyme and cytogenetic heterogeneity in
a cell line, with evidence for localization of the Pep A locus in
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*FIELD* CN
Patricia A. Hartz - updated: 12/7/2004
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 01/26/2010
carol: 12/11/2009
mgross: 12/9/2004
mgross: 12/7/2004
mimadm: 4/1/1994
warfield: 3/29/1994
supermim: 3/16/1992
carol: 2/26/1991
carol: 2/8/1991
supermim: 5/1/1990