Reviewed, UniProtKB/Swiss-Prot Q96KN2 (CNDP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Beta-Ala-His dipeptidase
    EC=3.4.13.20
Alternative name(s):
    Carnosine dipeptidase 1
    CNDP dipeptidase 1
    Serum carnosinase
    Glutamate carboxypeptidase-like protein 2

Gene names

Name:	CNDP1
Synonyms:	CN1, CPGL2
ORF Names:	UNQ1915/PRO4380

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	507 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)

Catalytic activity	Preferential hydrolysis of the beta-Ala-|-His dipeptide (carnosine), and also anserine, Xaa-|-His dipeptides and other dipeptides including homocarnosine. Ref.5 Ref.7
Cofactor	Binds 2 zinc ions per subunit By similarity.
Enzyme regulation	Inhibited by the metal chelator 1,10-o-phenantrolin. The inhibitory concentration 50% (IC50) is 5 µM.
Subunit structure	Homodimer. Ref.5
Subcellular location	Secreted.
Tissue specificity	Expressed in adult nervous central system. Ref.7
Polymorphism	The number of trinucleotide (CTG) repeat varies among different alleles leading to insertion of Leu residues in the signal peptide. The allele with 5 leucines (as shown in the reference entry) is known as the Mannheim allele.
Involvement in disease	Diabetic patients with the CNDP1 Mannheim allele are less susceptible for nephropathy. Ref.6 Deficiency of CNDP1 may be the cause of homocarnosinosis. Ref.6
Sequence similarities	Belongs to the peptidase M20A family.
Biophysicochemical properties	Kinetic parameters: 1 hour incubation in 50 mM Tris-HCl, pH 7.5. KM=1.27 µM for carnosine (at 30 degrees Celsius and in the absence of cadmium ions) KM=11.00 µM for carnosine (at 30 degrees Celsius and in the presence of 200 µM cadmium ions) KM=0.20 µM for homocarnosine (at 30 degrees Celsius and in the absence of cadmium ions) KM=1.0 µM for homocarnosine (at 30 degrees Celsius and in the presence of 200 µM cadmium ions) pH dependence: Optimum pH is 8.5.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	carboxypeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW protein dimerization activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Potential

Chain

27 – 507

481

Beta-Ala-His dipeptidase

PRO_0000026809

Sites

Active site

134

1

By similarity

Active site

199

1

Proton acceptor By similarity

Metal binding

132

1

Zinc 2 By similarity

Metal binding

165

1

Zinc 1 By similarity

Metal binding

165

1

Zinc 2 By similarity

Metal binding

200

1

Zinc 1 By similarity

Metal binding

228

1

Zinc 2 By similarity

Metal binding

478

1

Zinc 1 By similarity

Amino acid modifications

Glycosylation

322

1

N-linked (GlcNAc...) Ref.8

Glycosylation

382

1

N-linked (GlcNAc...) Ref.8

Natural variations

Natural variant

6

1

G → R: dbSNP rs11151964.

VAR_027147

Natural variant

20

1

L → LL Ref.2 Ref.4

VAR_027148

Natural variant

113

1

V → I: dbSNP rs4263028.

VAR_027149

Experimental info

Mutagenesis

132

1

H → A: Loss of activity. Ref.7

Mutagenesis

165

1

D → A: Loss of activity. Ref.7

Mutagenesis

200

1

E → A: Loss of activity. Ref.7

Sequence conflict

155

1

D → G in CAD10388. Ref.1

Sequence conflict

155

1

D → G in AAI10296. Ref.4

Sequence conflict

237

1

P → L in CAD10388. Ref.1

Sequence conflict

272

1

P → L in CAD10388. Ref.1

Secondary structure

1

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507

Helix Strand Turn

Details...

Helix

35 – 44

10

Helix

46 – 57

12

Beta strand

62 – 65

4

Helix

68 – 87

20

Beta strand

91 – 95

5

Beta strand

113 – 118

6

Beta strand

127 – 130

4

Helix

170 – 182

13

Beta strand

191 – 195

5

Helix

206 – 213

8

Turn

214 – 217

4

Beta strand

223 – 226

4

Beta strand

238 – 240

3

Beta strand

247 – 255

9

Helix

272 – 279

8

Helix

304 – 311

8

Helix

317 – 324

8

Helix

334 – 342

9

Beta strand

346 – 350

5

Beta strand

372 – 376

5

Helix

383 – 399

17

Beta strand

404 – 413

10

Helix

425 – 437

13

Beta strand

443 – 445

3

Helix

452 – 460

9

Helix

486 – 490

5

Helix

494 – 504

11

Sequences

	Sequence		Length	Mass (Da)
	Q96KN2-1 [UniParc]. Last modified July 25, 2006. Version 3. Checksum: F3B51A9123C927C0	FASTA	507	56,692
	10 20 30 40 50 60 MDPKLGRMAA SLLAVLLLLL ERGMFSSPSP PPALLEKVFQ YIDLHQDEFV QTLKEWVAIE 70 80 90 100 110 120 SDSVQPVPRF RQELFRMMAV AADTLQRLGA RVASVDMGPQ QLPDGQSLPI PPVILAELGS 130 140 150 160 170 180 DPTKGTVCFY GHLDVQPADR GDGWLTDPYV LTEVDGKLYG RGATDNKGPV LAWINAVSAF 190 200 210 220 230 240 RALEQDLPVN IKFIIEGMEE AGSVALEELV EKEKDRFFSG VDYIVISDNL WISQRKPAIT 250 260 270 280 290 300 YGTRGNSYFM VEVKCRDQDF HSGTFGGILH EPMADLVALL GSLVDSSGHI LVPGIYDEVV 310 320 330 340 350 360 PLTEEEINTY KAIHLDLEEY RNSSRVEKFL FDTKEEILMH LWRYPSLSIH GIEGAFDEPG 370 380 390 400 410 420 TKTVIPGRVI GKFSIRLVPH MNVSAVEKQV TRHLEDVFSK RNSSNKMVVS MTLGLHPWIA 430 440 450 460 470 480 NIDDTQYLAA KRAIRTVFGT EPDMIRDGST IPIAKMFQEI VHKSVVLIPL GAVDDGEHSQ 490 500 NEKINRWNYI EGTKLFAAFF LEMAQLH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of a second human homologue of glutamate carboxypeptidase in peptidase family M20." Chen J.M., Barrett A.J. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1." Janssen B., Hohenadel D., Brinkkoetter P., Peters V., Rind N., Fischer C., Rychlik I., Cerna M., Romzova M., de Heer E., Baelde H., Bakker S.J., Zirie M., Rondeau E., Mathieson P., Saleem M.A., Meyer J., Koppel H. , Sauerhoefer S., Bartram C.R., Nawroth P., Hammes H.P., Yard B.A., Zschocke J., van der Woude F.J. Diabetes 54:2320-2327(2005) [PubMed: 16046297] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-20 INS.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-20 INS. Tissue: Brain and Skin.
[5]	"Human serum carnosinase: characterization, distinction from cellular carnosinase, and activation by cadmium." Lenney J.F., George R.P., Weiss A.M., Kucera C.M., Chan P.W., Rinzler G.S. Clin. Chim. Acta 123:221-231(1982) [PubMed: 7116644] [Abstract] Cited for: CHARACTERIZATION, SUBUNIT, CATALYTIC ACTIVITY.
[6]	"Homocarnosinosis: lack of serum carnosinase is the defect probably responsible for elevated brain and CSF homocarnosine." Lenney J.F., Peppers S.C., Kucera C.M., Sjaastad O. Clin. Chim. Acta 132:157-165(1983) [PubMed: 6616870] [Abstract] Cited for: DISEASE.
[7]	"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: 12473676] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-132; ASP-165 AND GLU-200.
[8]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-322 AND ASN-382, MASS SPECTROMETRY. Tissue: Plasma.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AJ417564 mRNA. Translation: CAD10388.1.
AY358756 mRNA. Translation: AAQ89116.1.
BC004271 mRNA. No translation available.
BC110295 mRNA. Translation: AAI10296.1.
BC113512 mRNA. Translation: AAI13513.1.
BC117122 mRNA. Translation: AAI17123.1.

IPI

IPI00064667.

RefSeq

NP_116038.4.

UniGene

Hs.400613

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DLJ	X-ray	2.26	A/B	27-507	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q96KN2.

Protein family/group databases

MEROPS

M20.006.

Proteomic databases

PeptideAtlas

Q96KN2.

PRIDE

Q96KN2.

Genome annotation databases

Ensembl

ENST00000358821; ENSP00000351682; ENSG00000150656; Homo sapiens. [Genome view]
ENST00000430634; ENSP00000416242; ENSG00000150656; Homo sapiens. [Genome view]

GeneID

84735.

KEGG

hsa:84735.

UCSC

uc002llq.1. human.

Organism-specific databases

CTD

84735.

GeneCards

GC18P070352.

HGNC

HGNC:20675. CNDP1.

HPA

HPA008933.

MIM

609064. gene.

PharmGKB

PA134907547.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96KN2.

HOVERGEN

Q96KN2.

Enzyme and pathway databases

BRENDA

3.4.13.20. 247.

Gene expression databases

ArrayExpress

Q96KN2.

Bgee

Q96KN2.

CleanEx

HS_CNDP1.

Genevestigator

Q96KN2.

GermOnline

ENSG00000150656. 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 Resources

NextBio

74860.

SOURCE

Search...

Entry information

Entry name

CNDP1_HUMAN

Accession

Primary (citable) accession number: Q96KN2
Secondary accession number(s): Q14D40 , Q17S05, Q2TBG0, Q6UWK2, Q9BT98

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	July 25, 2006
Last modified:	October 13, 2009
This is version 72 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.