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Reviewed, UniProtKB/Swiss-Prot Q96KN2 (CNDP1_HUMAN)

Last modified October 13, 2009. Version 72. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length507 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandMetal-binding
Zinc
   Molecular functionCarboxypeptidase
Hydrolase
Metalloprotease
Protease
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processproteolysis

Inferred from electronic annotation. Source: InterPro

   Cellular componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functioncarboxypeptidase 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 507481Beta-Ala-His dipeptidase
PRO_0000026809

Sites

Active site1341 By similarity
Active site1991Proton acceptor By similarity
Metal binding1321Zinc 2 By similarity
Metal binding1651Zinc 1 By similarity
Metal binding1651Zinc 2 By similarity
Metal binding2001Zinc 1 By similarity
Metal binding2281Zinc 2 By similarity
Metal binding4781Zinc 1 By similarity

Amino acid modifications

Glycosylation3221N-linked (GlcNAc...) Ref.8
Glycosylation3821N-linked (GlcNAc...) Ref.8

Natural variations

Natural variant61G → R: dbSNP rs11151964.
VAR_027147
Natural variant201L → LL Ref.2 Ref.4
VAR_027148
Natural variant1131V → I: dbSNP rs4263028.
VAR_027149

Experimental info

Mutagenesis1321H → A: Loss of activity. Ref.7
Mutagenesis1651D → A: Loss of activity. Ref.7
Mutagenesis2001E → A: Loss of activity. Ref.7
Sequence conflict1551D → G in CAD10388. Ref.1
Sequence conflict1551D → G in AAI10296. Ref.4
Sequence conflict2371P → L in CAD10388. Ref.1
Sequence conflict2721P → L in CAD10388. Ref.1

Secondary structure

...................................................... 507
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96KN2-1 [UniParc].

Last modified July 25, 2006. Version 3.
Checksum: F3B51A9123C927C0

FASTA50756,692
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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

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.
IPIIPI00064667.
RefSeqNP_116038.4.
UniGeneHs.400613

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
3DLJX-ray2.26A/B27-507[»]
ModBaseSearch...

Protein-protein interaction databases

STRINGQ96KN2.

Protein family/group databases

MEROPSM20.006.

Proteomic databases

PeptideAtlasQ96KN2.
PRIDEQ96KN2.

Genome annotation databases

EnsemblENST00000358821; ENSP00000351682; ENSG00000150656; Homo sapiens. [Genome view]
ENST00000430634; ENSP00000416242; ENSG00000150656; Homo sapiens. [Genome view]
GeneID84735.
KEGGhsa:84735.
UCSCuc002llq.1. human.

Organism-specific databases

CTD84735.
GeneCardsGC18P070352.
HGNCHGNC:20675. CNDP1.
HPAHPA008933.
MIM609064. gene.
PharmGKBPA134907547.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ96KN2.
HOVERGENQ96KN2.

Enzyme and pathway databases

BRENDA3.4.13.20. 247.

Gene expression databases

ArrayExpressQ96KN2.
BgeeQ96KN2.
CleanExHS_CNDP1.
GenevestigatorQ96KN2.
GermOnlineENSG00000150656. Homo sapiens.

Family and domain databases

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.
PROSITEPS00758. ARGE_DAPE_CPG2_1. False negative.
PS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio74860.
SOURCESearch...

Entry information

Entry nameCNDP1_HUMAN
AccessionPrimary (citable) accession number: Q96KN2
Secondary accession number(s): Q14D40 expand/collapse secondary AC list , 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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 18

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents