Q9D1A2 (CNDP2_MOUSE) 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

Gene names

Name:	Cndp2
Synonyms:	Cn2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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. Has a strong preference for Cys-Gly By similarity.
Catalytic activity	Hydrolysis of dipeptides, preferentially hydrophobic dipeptides including prolyl amino acids. Ref.5
Cofactor	Binds 2 manganese ions per subunit. Ref.5 Ref.6
Enzyme regulation	Inhibited by bestatin. Ref.5
Subunit structure	Homodimer By similarity. Ref.6
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Highly expressed in the parafascicular nucleus of the thalamus, tuberomammillary nucleus of the hypothalamus and the mitral cell layer of the olfactory bulb. Ref.5
Sequence similarities	Belongs to the peptidase M20A family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Manganese Metal-binding
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from direct assay PubMed 1235912. Source: MGI
Cellular_component	cytosol Inferred from sequence alignment PubMed 12473676. Source: MGI
Molecular_function	carboxypeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW dipeptidase activity Inferred from direct assay PubMed 198184PubMed 204065PubMed 4187938PubMed 736882PubMed 7444718. Source: MGI 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...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 475

474

Cytosolic non-specific dipeptidase

PRO_0000185273

Regions

Region

166 – 167

2

Substrate binding

Sites

Active site

101

1

By similarity

Active site

166

1

Proton acceptor By similarity

Metal binding

99

1

Manganese 2

Metal binding

132

1

Manganese 1

Metal binding

132

1

Manganese 2

Metal binding

167

1

Manganese 1

Metal binding

195

1

Manganese 2

Metal binding

445

1

Manganese 1

Binding site

195

1

Substrate; via carbonyl oxygen

Binding site

228

1

Substrate; shared with homodimeric partner

Binding site

330

1

Substrate; shared with homodimeric partner

Binding site

343

1

Substrate

Binding site

417

1

Substrate; via amide nitrogen and carbonyl oxygen

Binding site

445

1

Substrate

Site

228

1

Important for catalytic activity

Experimental info

Mutagenesis

228

1

H → A: Loss of activity. Ref.6

Sequence conflict

45

1

M → I in BAE31451. Ref.2

Sequence conflict

105

1

A → T in BAE42789. Ref.2

Sequence conflict

357

1

V → A in BAB21596. Ref.1

Secondary structure

1

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475

Helix Strand Turn

Details...

Helix

2 – 13

12

Helix

15 – 27

13

Helix

35 – 37

3

Helix

38 – 54

17

Beta strand

58 – 62

5

Beta strand

66 – 68

3

Beta strand

74 – 76

3

Beta strand

80 – 85

6

Beta strand

93 – 99

7

Helix

107 – 109

3

Beta strand

119 – 121

3

Beta strand

124 – 127

4

Turn

128 – 133

6

Helix

134 – 149

16

Beta strand

155 – 164

10

Helix

166 – 168

3

Helix

173 – 179

7

Turn

180 – 187

8

Beta strand

190 – 193

4

Beta strand

199 – 203

5

Beta strand

205 – 210

6

Beta strand

212 – 221

10

Helix

229 – 232

4

Turn

233 – 235

3

Helix

239 – 247

9

Turn

260 – 265

6

Helix

271 – 276

6

Helix

284 – 290

7

Helix

301 – 309

9

Beta strand

313 – 322

10

Beta strand

325 – 327

3

Beta strand

334 – 344

11

Helix

350 – 366

17

Beta strand

372 – 382

11

Helix

392 – 405

14

Beta strand

410 – 416

7

Helix

420 – 428

9

Beta strand

430 – 434

5

Beta strand

450 – 452

3

Helix

453 – 472

20

Sequences

	Sequence		Length	Mass (Da)
	Q9D1A2 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 086950275A698500	FASTA	475	52,767
	10 20 30 40 50 60 MSALKAVFQY IDENQDRYVK KLAEWVAIQS VSAWPEKRGE IRRMMEVAAA DVQRLGGSVE 70 80 90 100 110 120 LVDIGKQKLP DGSEIPLPPI LLGKLGSDPQ KKTVCIYGHL DVQPAALEDG WDSEPFTLVE 130 140 150 160 170 180 REGKLYGRGS TDDKGPVAGW MNALEAYQKT GQEIPVNLRF CLEGMEESGS EGLDELIFAQ 190 200 210 220 230 240 KDKFFKDVDY VCISDNYWLG KNKPCITYGL RGICYFFIEV ECSDKDLHSG VYGGSVHEAM 250 260 270 280 290 300 TDLISLMGCL VDKKGKILIP GINDAVAPVT DEEHALYDHI DFDMEEFAKD VGAETLLHSC 310 320 330 340 350 360 KKDILMHRWR YPSLSLHGIE GAFSGSGAKT VIPRKVVGKF SIRLVPDMIP EVVSEQVSSY 370 380 390 400 410 420 LSKKFAELQS PNKFKVYMGH GGKPWVSDFN HPHYQAGRRA LKTVFGVEPD LTREGGSIPV 430 440 450 460 470 TLTFQEATGK NVMLLPVGSA DDGAHSQNEK LNRLNYIEGT KMLAAYLYEV SQLKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel mouse gene differentially expressed in kidney." Yoshikawa T., Nagasugi Y., Sugano S., Hashimoto K., Masuho Y., Seki N. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: BALB/c, C57BL/6J and NOD. Tissue: Bone marrow macrophage, Embryonic heart, Heart and Spleen.
[3]	"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]. Tissue: Mammary gland.
[4]	Lubec G., Klug S. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 6-17; 311-329 AND 414-430, MASS SPECTROMETRY. Tissue: Hippocampus.
[5]	"Identification and characterization of a mouse dipeptidase that hydrolyzes L-carnosine." Otani H., Okumura N., Hashida-Okumura A., Nagai K. J. Biochem. 137:167-175(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, COFACTOR, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
[6]	"Structural basis for substrate recognition and hydrolysis by mouse carnosinase CN2." Unno H., Yamashita T., Ujita S., Okumura N., Otani H., Okumura A., Nagai K., Kusunoki M. J. Biol. Chem. 283:27289-27299(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH MANGANESE AND BESTATIN, MUTAGENESIS OF HIS-228, COFACTOR, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB046738 mRNA. Translation: BAB21596.1.
AK003779 mRNA. Translation: BAB22991.1.
AK151013 mRNA. Translation: BAE30033.1.
AK152729 mRNA. Translation: BAE31451.1.
AK168029 mRNA. Translation: BAE40014.1.
AK168652 mRNA. Translation: BAE40509.1.
AK172034 mRNA. Translation: BAE42789.1.
BC005532 mRNA. Translation: AAH05532.1.

IPI

IPI00315879.

RefSeq

NP_075638.2. NM_023149.2.

UniGene

Mm.29646.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZOF	X-ray	2.30	A/B	1-475	[»]
2ZOG	X-ray	1.70	A/B	1-475	[»]

ProteinModelPortal

Q9D1A2.

SMR

Q9D1A2. Positions 1-474.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000025546.

Protein family/group databases

MEROPS

M20.005.

PTM databases

PhosphoSite

Q9D1A2.

2D gel databases

REPRODUCTION-2DPAGE

Q9D1A2.

Proteomic databases

PaxDb

Q9D1A2.

PRIDE

Q9D1A2.

Protocols and materials databases

DNASU

66054.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000025546; ENSMUSP00000025546; ENSMUSG00000024644.
ENSMUST00000168419; ENSMUSP00000128696; ENSMUSG00000024644.

GeneID

66054.

KEGG

mmu:66054.

UCSC

uc008fut.1. mouse.

Organism-specific databases

CTD

55748.

MGI

MGI:1913304. Cndp2.

Phylogenomic databases

eggNOG

COG0624.

GeneTree

ENSGT00390000009682.

HOGENOM

HOG000216709.

HOVERGEN

HBG051103.

InParanoid

Q3U7B9.

KO

K08660.

OMA

KPWTEDP.

OrthoDB

EOG4P2Q25.

Gene expression databases

ArrayExpress

Q9D1A2.

Bgee

Q9D1A2.

CleanEx

MM_CNDP2.

Genevestigator

Q9D1A2.

GermOnline

ENSMUSG00000024644. Mus musculus.

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

EvolutionaryTrace

Q9D1A2.

NextBio

320490.

SOURCE

Search...

Entry information

Entry name

CNDP2_MOUSE

Accession

Primary (citable) accession number: Q9D1A2
Secondary accession number(s): Q3TA80 , Q3TI32, Q3U7B9, Q99PV1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	June 1, 2001
Last modified:	April 3, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program