Q96KN2 (CNDP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-Ala-His dipeptidase
EC=3.4.13.20

Alternative name(s):
CNDP dipeptidase 1
Carnosine dipeptidase 1
Glutamate carboxypeptidase-like protein 2
Serum carnosinase

Gene names

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

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	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.6 Ref.8
Cofactor	Binds 2 zinc ions per subunit. Ref.10
Enzyme regulation	Inhibited by the metal chelator 1,10-o-phenantrolin. The inhibitory concentration 50% (IC50) is 5 µM.
Subunit structure	Homodimer. Ref.6
Subcellular location	Secreted.
Tissue specificity	Found in serum and adult nervous central system. Absent in serum from patients with homocarnosinosis. Ref.7 Ref.8
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. Diabetic patients with the CNDP1 Mannheim allele are less susceptible for nephropathy.
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) Ref.8 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 Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carboxypeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW 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...

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

Metal binding

165

1

Zinc 1

Metal binding

165

1

Zinc 2

Metal binding

200

1

Zinc 1

Metal binding

228

1

Zinc 2

Metal binding

478

1

Zinc 1

Amino acid modifications

Glycosylation

322

1

N-linked (GlcNAc...) Ref.9

Glycosylation

382

1

N-linked (GlcNAc...) Ref.9

Natural variations

Natural variant

6

1

G → R.
Corresponds to variant rs11151964 [ dbSNP | Ensembl ].

VAR_027147

Natural variant

20

1

L → LL. Ref.2 Ref.5

VAR_027148

Natural variant

113

1

I → V. Ref.2 Ref.3 Ref.5 Ref.10
Corresponds to variant rs4263028 [ dbSNP | Ensembl ].

VAR_027149

Experimental info

Mutagenesis

132

1

H → A: Loss of activity. Ref.8

Mutagenesis

165

1

D → A: Loss of activity. Ref.8

Mutagenesis

200

1

E → A: Loss of activity. Ref.8

Sequence conflict

155

1

D → G in CAD10388. Ref.1

Sequence conflict

155

1

D → G in AAI10296. Ref.5

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

99 – 101

3

Beta strand

107 – 109

3

Beta strand

113 – 118

6

Beta strand

126 – 132

7

Helix

140 – 142

3

Beta strand

152 – 154

3

Beta strand

157 – 160

4

Turn

161 – 166

6

Helix

167 – 182

16

Beta strand

188 – 197

10

Helix

199 – 201

3

Turn

202 – 205

4

Helix

206 – 213

8

Turn

214 – 217

4

Beta strand

223 – 226

4

Beta strand

238 – 243

6

Beta strand

245 – 255

11

Turn

262 – 264

3

Helix

272 – 280

9

Turn

293 – 298

6

Helix

304 – 311

8

Helix

317 – 324

8

Helix

334 – 342

9

Beta strand

346 – 355

10

Beta strand

358 – 360

3

Beta strand

367 – 377

11

Helix

383 – 399

17

Beta strand

404 – 415

12

Helix

425 – 438

14

Beta strand

443 – 449

7

Helix

452 – 460

9

Beta strand

483 – 485

3

Helix

486 – 504

19

Sequences

	Sequence		Length	Mass (Da)
	Q96KN2 [UniParc]. Last modified January 11, 2011. Version 4. Checksum: 756CCD872996F192	FASTA	507	56,706
	10 20 30 40 50 60 MDPKLGRMAA SLLAVLLLLL ERGMFSSPSP PPALLEKVFQ YIDLHQDEFV QTLKEWVAIE 70 80 90 100 110 120 SDSVQPVPRF RQELFRMMAV AADTLQRLGA RVASVDMGPQ QLPDGQSLPI PPIILAELGS 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], VARIANT VAL-113. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-20 INS AND VAL-113.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-113.
[4]	"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].
[5]	"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], VARIANTS LEU-20 INS AND VAL-113. Tissue: Brain and Skin.
[6]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, SUBUNIT, CATALYTIC ACTIVITY.
[7]	"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] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"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: BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-132; ASP-165 AND GLU-200.
[9]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-322 AND ASN-382, MASS SPECTROMETRY. Tissue: Plasma.
[10]	"Crystal structure of human carnosine dipeptidase 1." Structural genomics consortium (SGC) Submitted (JUL-2011) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 27-507 IN COMPLEX WITH ZINC IONS, COFACTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_032649.5.

UniGene

Hs.400613.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

Q96KN2.

SMR

Q96KN2. Positions 30-506.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000351682.

Protein family/group databases

MEROPS

M20.006.

PTM databases

PhosphoSite

Q96KN2.

Polymorphism databases

DMDM

110825714.

Proteomic databases

PaxDb

Q96KN2.

PeptideAtlas

Q96KN2.

PRIDE

Q96KN2.

Protocols and materials databases

DNASU

84735.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000358821; ENSP00000351682; ENSG00000150656.

GeneID

84735.

KEGG

hsa:84735.

UCSC

uc002llq.3. human.

Organism-specific databases

CTD

84735.

GeneCards

GC18P072201.

HGNC

HGNC:20675. CNDP1.

HPA

HPA008933.

MIM

609064. gene.

neXtProt

NX_Q96KN2.

PharmGKB

PA134907547.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0624.

HOGENOM

HOG000216709.

HOVERGEN

HBG051103.

InParanoid

Q96KN2.

KO

K05604.

OMA

HPWIANI.

OrthoDB

EOG4N04DR.

PhylomeDB

Q96KN2.

Enzyme and pathway databases

SABIO-RK

Q96KN2.

Gene expression databases

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

EvolutionaryTrace

Q96KN2.

GenomeRNAi

84735.

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:	January 11, 2011
Last modified:	April 3, 2013
This is version 102 of the entry and version 4 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.