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Q96KN2 (CNDP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference 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.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

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
Metal binding1651Zinc 1
Metal binding1651Zinc 2
Metal binding2001Zinc 1
Metal binding2281Zinc 2
Metal binding4781Zinc 1

Amino acid modifications

Modified residue2191Phosphoserine By similarity
Glycosylation3221N-linked (GlcNAc...) Ref.9
Glycosylation3821N-linked (GlcNAc...) Ref.9

Natural variations

Natural variant61G → R.
Corresponds to variant rs11151964 [ dbSNP | Ensembl ].
VAR_027147
Natural variant201L → LL. Ref.2 Ref.5
VAR_027148
Natural variant1131I → V. Ref.2 Ref.3 Ref.5 Ref.10
Corresponds to variant rs4263028 [ dbSNP | Ensembl ].
VAR_027149

Experimental info

Mutagenesis1321H → A: Loss of activity. Ref.8
Mutagenesis1651D → A: Loss of activity. Ref.8
Mutagenesis2001E → A: Loss of activity. Ref.8
Sequence conflict1551D → G in CAD10388. Ref.1
Sequence conflict1551D → G in AAI10296. Ref.5
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 [UniParc].

Last modified January 11, 2011. Version 4.
Checksum: 756CCD872996F192

FASTA50756,706
        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 

« 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], 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. 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] [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. 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] [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. expand/collapse author list , 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.
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.
RefSeqNP_116038.4. NM_032649.5.
UniGeneHs.400613.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3DLJX-ray2.26A/B27-507[»]
ProteinModelPortalQ96KN2.
SMRQ96KN2. Positions 30-506.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124230. 1 interaction.
STRING9606.ENSP00000351682.

Protein family/group databases

MEROPSM20.006.

PTM databases

PhosphoSiteQ96KN2.

Polymorphism databases

DMDM110825714.

Proteomic databases

PaxDbQ96KN2.
PeptideAtlasQ96KN2.
PRIDEQ96KN2.

Protocols and materials databases

DNASU84735.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358821; ENSP00000351682; ENSG00000150656.
GeneID84735.
KEGGhsa:84735.
UCSCuc002llq.3. human.

Organism-specific databases

CTD84735.
GeneCardsGC18P072201.
HGNCHGNC:20675. CNDP1.
HPAHPA008933.
MIM609064. gene.
neXtProtNX_Q96KN2.
PharmGKBPA134907547.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0624.
HOGENOMHOG000216709.
HOVERGENHBG051103.
InParanoidQ96KN2.
KOK05604.
OMAKFVIEGM.
OrthoDBEOG7JHM55.
PhylomeDBQ96KN2.
TreeFamTF300633.

Enzyme and pathway databases

SABIO-RKQ96KN2.

Gene expression databases

ArrayExpressQ96KN2.
BgeeQ96KN2.
CleanExHS_CNDP1.
GenevestigatorQ96KN2.

Family and domain databases

Gene3D3.30.70.360. 1 hit.
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.
PROSITEPS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ96KN2.
GeneWikiCNDP1.
GenomeRNAi84735.
NextBio74860.
PROQ96KN2.
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: January 11, 2011
Last modified: March 19, 2014
This is version 110 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

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