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Q96KP4 (CNDP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytosolic non-specific dipeptidase

EC=3.4.13.18
Alternative name(s):
CNDP dipeptidase 2
Glutamate carboxypeptidase-like protein 1
Peptidase A
Gene names
Name:CNDP2
Synonyms:CN2, CPGL, PEPA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length475 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes a variety of dipeptides including L-carnosine but has a strong preference for Cys-Gly. Isoform 2 may be play a role as tumor suppressor in hepatocellular carcinoma (HCC) cells. Ref.9 Ref.10

Catalytic activity

Hydrolysis of dipeptides, preferentially hydrophobic dipeptides including prolyl amino acids. Ref.1

Cofactor

Binds 2 manganese ions per subunit By similarity.

Enzyme regulation

Inhibited by p-hydroxymercurybenzoate. The inhibitory concentration 50% (IC50) is 13 µM. Inhibited by bestatin. The inhibitory concentration 50% (IC50) is 7 nM at pH 9.5. Ref.1

Subunit structure

Homodimer. Ref.1

Subcellular location

Cytoplasm Ref.1 Ref.9.

Tissue specificity

Isoform 1 is ubiquitously expressed with higher levels in kidney and liver (at protein level). Isoform 2 is expressed in fetal tissues, it is only expressed in adult liver and placental tissues. Ref.1 Ref.9

Sequence similarities

Belongs to the peptidase M20A family.

Biophysicochemical properties

Kinetic parameters:

KM=1.04 mM for Ser-Gln (at pH 7.5 and in the presence of 0.1 mM manganese ions) Ref.1 Ref.10

KM=0.6 mM for Cys-Gly (at pH 8.0 and in the presence of 50 µM manganese ions)

KM=15 mM for carnosine (at pH 9.5 and in the presence of 0.1 mM manganese ions)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NDRG1Q925971EBI-1190734,EBI-716486

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96KP4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96KP4-2)

Also known as: CPGL-B;

The sequence of this isoform differs from the canonical sequence as follows:
     69-152: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 475474Cytosolic non-specific dipeptidase
PRO_0000185272

Regions

Region166 – 1672Substrate binding By similarity

Sites

Active site1011 By similarity
Active site1661Proton acceptor By similarity
Metal binding991Manganese 2 By similarity
Metal binding1321Manganese 1 By similarity
Metal binding1321Manganese 2 By similarity
Metal binding1671Manganese 1 By similarity
Metal binding1951Manganese 2 By similarity
Metal binding4451Manganese 1 By similarity
Binding site1951Substrate; via carbonyl oxygen By similarity
Binding site2281Substrate; shared with homodimeric partner By similarity
Binding site3301Substrate; shared with homodimeric partner By similarity
Binding site3431Substrate By similarity
Binding site4171Substrate; via amide nitrogen and carbonyl oxygen By similarity
Binding site4451Substrate By similarity
Site2281Important for catalytic activity By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.8 Ref.11 Ref.13 Ref.14
Modified residue91N6-acetyllysine Ref.11

Natural variations

Alternative sequence69 – 15284Missing in isoform 2.
VSP_038203
Natural variant1261Y → H. Ref.2
Corresponds to variant rs2278161 [ dbSNP | Ensembl ].
VAR_057154

Experimental info

Sequence conflict1281R → G in BAA91840. Ref.3
Sequence conflict3481M → T in BAG53426. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: 43FA0668B0587A39

FASTA47552,878
        10         20         30         40         50         60 
MAALTTLFKY IDENQDRYIK KLAKWVAIQS VSAWPEKRGE IRRMMEVAAA DVKQLGGSVE 

        70         80         90        100        110        120 
LVDIGKQKLP DGSEIPLPPI LLGRLGSDPQ KKTVCIYGHL DVQPAALEDG WDSEPFTLVE 

       130        140        150        160        170        180 
RDGKLYGRGS TDDKGPVAGW INALEAYQKT GQEIPVNVRF CLEGMEESGS EGLDELIFAR 

       190        200        210        220        230        240 
KDTFFKDVDY VCISDNYWLG KKKPCITYGL RGICYFFIEV ECSNKDLHSG VYGGSVHEAM 

       250        260        270        280        290        300 
TDLILLMGSL VDKRGNILIP GINEAVAAVT EEEHKLYDDI DFDIEEFAKD VGAQILLHSH 

       310        320        330        340        350        360 
KKDILMHRWR YPSLSLHGIE GAFSGSGAKT VIPRKVVGKF SIRLVPNMTP EVVGEQVTSY 

       370        380        390        400        410        420 
LTKKFAELRS PNEFKVYMGH GGKPWVSDFS HPHYLAGRRA MKTVFGVEPD LTREGGSIPV 

       430        440        450        460        470 
TLTFQEATGK NVMLLPVGSA DDGAHSQNEK LNRYNYIEGT KMLAAYLYEV SQLKD 

« Hide

Isoform 2 (CPGL-B) [UniParc].

Checksum: 07E5F4464C8FC179
Show »

FASTA39143,833

References

« Hide 'large scale' references
[1]"Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase."
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.
J. Biol. Chem. 278:6521-6531(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 129-137; 276-289; 311-329; 370-375 AND 462-474, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Cloning and sequencing of human glutamate carboxypeptidase homologue in peptidase family M20."
Chen J.M., Barrett A.J.
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT HIS-126.
Tissue: Uterus.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Spleen and Teratocarcinoma.
[4]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon and Kidney.
[8]Bienvenut W.V., Heiserich L., Gottlieb E.
Submitted (MAR-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-9; 54-66; 255-275 AND 403-430, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Colon carcinoma.
[9]"Identification of carboxypeptidase of glutamate like-B as a candidate suppressor in cell growth and metastasis in human hepatocellular carcinoma."
Zhang P., Chan D.W., Zhu Y., Li J.J., Ng I.-O., Wan D., Gu J.
Clin. Cancer Res. 12:6617-6625(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION.
[10]"Dug1p Is a Cys-Gly peptidase of the gamma-glutamyl cycle of Saccharomyces cerevisiae and represents a novel family of Cys-Gly peptidases."
Kaur H., Kumar C., Junot C., Toledano M.B., Bachhawat A.K.
J. Biol. Chem. 284:14493-14502(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[11]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 AND LYS-9, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AX523938 Unassigned DNA. Translation: CAD56843.1.
AJ347717 mRNA. Translation: CAC69883.1.
AK001692 mRNA. Translation: BAA91840.1.
AK097155 mRNA. Translation: BAG53426.1.
AF258592 mRNA. Translation: AAG23795.1.
AC009704 Genomic DNA. No translation available.
CH471117 Genomic DNA. Translation: EAW66551.1.
BC001375 mRNA. Translation: AAH01375.1.
BC003176 mRNA. Translation: AAH03176.1.
RefSeqNP_001161971.1. NM_001168499.1.
NP_060705.2. NM_018235.2.
XP_005266785.1. XM_005266728.1.
UniGeneHs.149185.

3D structure databases

ProteinModelPortalQ96KP4.
SMRQ96KP4. Positions 1-474.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120866. 34 interactions.
IntActQ96KP4. 1 interaction.
STRING9606.ENSP00000325548.

Protein family/group databases

MEROPSM20.005.

PTM databases

PhosphoSiteQ96KP4.

Polymorphism databases

DMDM23396498.

2D gel databases

OGPQ96KP4.

Proteomic databases

PaxDbQ96KP4.
PRIDEQ96KP4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324262; ENSP00000325548; ENSG00000133313. [Q96KP4-1]
ENST00000324301; ENSP00000325756; ENSG00000133313. [Q96KP4-2]
ENST00000579847; ENSP00000462311; ENSG00000133313. [Q96KP4-1]
GeneID55748.
KEGGhsa:55748.
UCSCuc002llm.2. human. [Q96KP4-1]
uc002lln.2. human. [Q96KP4-2]

Organism-specific databases

CTD55748.
GeneCardsGC18P072163.
H-InvDBHIX0136845.
HGNCHGNC:24437. CNDP2.
HPACAB026196.
MIM169800. gene.
neXtProtNX_Q96KP4.
PharmGKBPA134975242.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0624.
HOGENOMHOG000216709.
HOVERGENHBG051103.
InParanoidQ96KP4.
KOK08660.
OMADYALVCD.
PhylomeDBQ96KP4.
TreeFamTF300633.

Enzyme and pathway databases

BRENDA3.4.13.18. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ96KP4.

Gene expression databases

ArrayExpressQ96KP4.
BgeeQ96KP4.
CleanExHS_CNDP2.
GenevestigatorQ96KP4.

Family and domain databases

Gene3D3.30.70.360. 1 hit.
InterProIPR001261. ArgE/DapE_CS.
IPR017153. GSH_degradosome_DUG1.
IPR002933. Peptidase_M20.
IPR011650. Peptidase_M20_dimer.
[Graphical view]
PfamPF07687. M20_dimer. 1 hit.
PF01546. Peptidase_M20. 1 hit.
[Graphical view]
PIRSFPIRSF037242. CNDP_dipeptidase. 1 hit.
PROSITEPS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCNDP2. human.
GenomeRNAi55748.
NextBio60729.
PROQ96KP4.
SOURCESearch...

Entry information

Entry nameCNDP2_HUMAN
AccessionPrimary (citable) accession number: Q96KP4
Secondary accession number(s): B3KUG4 expand/collapse secondary AC list , Q8WY59, Q9BQ94, Q9NVB4
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: September 19, 2002
Last modified: April 16, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM