Q96KP4 (CNDP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	475 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Manganese Metal-binding
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	glutathione biosynthetic process Traceable author statement. Source: Reactome proteolysis Inferred from electronic annotation. Source: UniProtKB-KW sulfur amino acid metabolic process Traceable author statement. Source: Reactome xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	carboxypeptidase activity Traceable author statement. Source: Reactome dipeptidase activity Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW tripeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NDRG1	Q92597	1	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8
	Chain	2 – 475	474	Cytosolic non-specific dipeptidase		PRO_0000185272
Regions
	Region	166 – 167	2	Substrate binding By similarity
Sites
	Active site	101	1	By similarity
	Active site	166	1	Proton acceptor By similarity
	Metal binding	99	1	Manganese 2 By similarity
	Metal binding	132	1	Manganese 1 By similarity
	Metal binding	132	1	Manganese 2 By similarity
	Metal binding	167	1	Manganese 1 By similarity
	Metal binding	195	1	Manganese 2 By similarity
	Metal binding	445	1	Manganese 1 By similarity
	Binding site	195	1	Substrate; via carbonyl oxygen By similarity
	Binding site	228	1	Substrate; shared with homodimeric partner By similarity
	Binding site	330	1	Substrate; shared with homodimeric partner By similarity
	Binding site	343	1	Substrate By similarity
	Binding site	417	1	Substrate; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	445	1	Substrate By similarity
	Site	228	1	Important for catalytic activity By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.8 Ref.11
	Modified residue	9	1	N6-acetyllysine Ref.11
Natural variations
	Alternative sequence	69 – 152	84	Missing in isoform 2.		VSP_038203
	Natural variant	126	1	Y → H. Ref.2 Corresponds to variant rs2278161 [ dbSNP | Ensembl ].		VAR_057154
Experimental info
	Sequence conflict	128	1	R → G in BAA91840. Ref.3
	Sequence conflict	348	1	M → T in BAG53426. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 43FA0668B0587A39	FASTA	475	52,878
	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
	Isoform 2 (CPGL-B) [UniParc]. Checksum: 07E5F4464C8FC179	FASTA	391	43,833
	10 20 30 40 50 60 MAALTTLFKY IDENQDRYIK KLAKWVAIQS VSAWPEKRGE IRRMMEVAAA DVKQLGGSVE 70 80 90 100 110 120 LVDIGKQKEI PVNVRFCLEG MEESGSEGLD ELIFARKDTF FKDVDYVCIS DNYWLGKKKP 130 140 150 160 170 180 CITYGLRGIC YFFIEVECSN KDLHSGVYGG SVHEAMTDLI LLMGSLVDKR GNILIPGINE 190 200 210 220 230 240 AVAAVTEEEH KLYDDIDFDI EEFAKDVGAQ ILLHSHKKDI LMHRWRYPSL SLHGIEGAFS 250 260 270 280 290 300 GSGAKTVIPR KVVGKFSIRL VPNMTPEVVG EQVTSYLTKK FAELRSPNEF KVYMGHGGKP 310 320 330 340 350 360 WVSDFSHPHY LAGRRAMKTV FGVEPDLTRE GGSIPVTLTF QEATGKNVML LPVGSADDGA 370 380 390 HSQNEKLNRY NYIEGTKMLA AYLYEVSQLK D

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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, 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, MASS SPECTROMETRY.
[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].
+	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.
IPI	IPI00165579. IPI00177728.
RefSeq	NP_001161971.1. NM_001168499.1. NP_060705.2. NM_018235.2.
UniGene	Hs.149185.
3D structure databases
ProteinModelPortal	Q96KP4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96KP4. 1 interaction.
STRING	9606.ENSP00000325548.
Protein family/group databases
MEROPS	M20.005.
PTM databases
PhosphoSite	Q96KP4.
Polymorphism databases
DMDM	23396498.
2D gel databases
OGP	Q96KP4.
Proteomic databases
PaxDb	Q96KP4.
PRIDE	Q96KP4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324262; ENSP00000325548; ENSG00000133313. ENST00000324301; ENSP00000325756; ENSG00000133313. ENST00000579847; ENSP00000462311; ENSG00000133313.
GeneID	55748.
KEGG	hsa:55748.
UCSC	uc002llm.2. human. uc002lln.2. human.
Organism-specific databases
CTD	55748.
GeneCards	GC18P072163.
H-InvDB	HIX0136845.
HGNC	HGNC:24437. CNDP2.
HPA	CAB026196.
MIM	169800. gene.
neXtProt	NX_Q96KP4.
PharmGKB	PA134975242.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0624.
HOGENOM	HOG000216709.
HOVERGEN	HBG051103.
InParanoid	Q96KP4.
KO	K08660.
OMA	DYALVCD.
OrthoDB	EOG4P2Q25.
PhylomeDB	Q96KP4.
Enzyme and pathway databases
BRENDA	3.4.13.18. 2681.
Reactome	REACT_111217. Metabolism.
SABIO-RK	Q96KP4.
Gene expression databases
ArrayExpress	Q96KP4.
Bgee	Q96KP4.
CleanEx	HS_CNDP2.
Genevestigator	Q96KP4.
GermOnline	ENSG00000133313. Homo sapiens.
Family and domain databases
InterPro	IPR001261. ArgE/DapE_CS. IPR017153. GSH_degradosome_DUG1. IPR002933. Peptidase_M20. IPR011650. Peptidase_M20_dimer. [Graphical view]
Pfam	PF07687. M20_dimer. 1 hit. PF01546. Peptidase_M20. 1 hit. [Graphical view]
PIRSF	PIRSF037242. CNDP_dipeptidase. 1 hit.
PROSITE	PS00758. ARGE_DAPE_CPG2_1. False negative. PS00759. ARGE_DAPE_CPG2_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CNDP2. human.
GenomeRNAi	55748.
NextBio	60729.
SOURCE	Search...

Entry information

Entry name

CNDP2_HUMAN

Accession

Primary (citable) accession number: Q96KP4
Secondary accession number(s): B3KUG4 , Q8WY59, Q9BQ94, Q9NVB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	September 19, 2002
Last modified:	May 1, 2013
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.