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Protein

Beta-Ala-His dipeptidase

Gene

CNDP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

Preferential hydrolysis of the beta-Ala-|-His dipeptide (carnosine), and also anserine, Xaa-|-His dipeptides and other dipeptides including homocarnosine.2 Publications

Cofactori

Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit.1 Publication

Enzyme regulationi

Inhibited by the metal chelator 1,10-o-phenantrolin. The inhibitory concentration 50% (IC50) is 5 µM.

Kineticsi

1 hour incubation in 50 mM Tris-HCl, pH 7.5.

  1. KM=1.27 µM for carnosine (at 30 degrees Celsius and in the absence of cadmium ions)1 Publication
  2. KM=11.00 µM for carnosine (at 30 degrees Celsius and in the presence of 200 µM cadmium ions)1 Publication
  3. KM=0.20 µM for homocarnosine (at 30 degrees Celsius and in the absence of cadmium ions)1 Publication
  4. KM=1.0 µM for homocarnosine (at 30 degrees Celsius and in the presence of 200 µM cadmium ions)1 Publication

pH dependencei

Optimum pH is 8.5.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi132 – 1321Zinc 2
Active sitei134 – 1341By similarity
Metal bindingi165 – 1651Zinc 1
Metal bindingi165 – 1651Zinc 2
Active sitei199 – 1991Proton acceptorBy similarity
Metal bindingi200 – 2001Zinc 1
Metal bindingi228 – 2281Zinc 2
Metal bindingi478 – 4781Zinc 1

GO - Molecular functioni

  1. carboxypeptidase activity Source: UniProtKB-KW
  2. dipeptidase activity Source: InterPro
  3. metal ion binding Source: UniProtKB-KW
  4. metallopeptidase activity Source: UniProtKB-KW
  5. tripeptidase activity Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS07681-MONOMER.
BRENDAi3.4.13.20. 2681.
SABIO-RKQ96KN2.

Protein family/group databases

MEROPSiM20.006.

Names & Taxonomyi

Protein namesi
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 namesi
Name:CNDP1
Synonyms:CN1, CPGL2
ORF Names:UNQ1915/PRO4380
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:20675. CNDP1.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi132 – 1321H → A: Loss of activity. 1 Publication
Mutagenesisi165 – 1651D → A: Loss of activity. 1 Publication
Mutagenesisi200 – 2001E → A: Loss of activity. 1 Publication

Organism-specific databases

PharmGKBiPA134907547.

Polymorphism and mutation databases

BioMutaiCNDP1.
DMDMi317373563.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626Sequence AnalysisAdd
BLAST
Chaini27 – 507481Beta-Ala-His dipeptidasePRO_0000026809Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei219 – 2191PhosphoserineBy similarity
Glycosylationi322 – 3221N-linked (GlcNAc...)1 Publication
Glycosylationi382 – 3821N-linked (GlcNAc...)1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ96KN2.
PeptideAtlasiQ96KN2.
PRIDEiQ96KN2.

PTM databases

PhosphoSiteiQ96KN2.

Expressioni

Tissue specificityi

Found in serum and adult nervous central system. Absent in serum from patients with homocarnosinosis.2 Publications

Gene expression databases

BgeeiQ96KN2.
CleanExiHS_CNDP1.
ExpressionAtlasiQ96KN2. baseline and differential.
GenevestigatoriQ96KN2.

Organism-specific databases

HPAiHPA008933.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi124230. 11 interactions.
STRINGi9606.ENSP00000351682.

Structurei

Secondary structure

1
507
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi35 – 4410Combined sources
Helixi46 – 5712Combined sources
Beta strandi62 – 654Combined sources
Helixi68 – 8720Combined sources
Beta strandi91 – 955Combined sources
Beta strandi99 – 1013Combined sources
Beta strandi107 – 1093Combined sources
Beta strandi113 – 1186Combined sources
Beta strandi126 – 1327Combined sources
Helixi140 – 1423Combined sources
Beta strandi152 – 1543Combined sources
Beta strandi157 – 1604Combined sources
Turni161 – 1666Combined sources
Helixi167 – 18216Combined sources
Beta strandi188 – 19710Combined sources
Helixi199 – 2013Combined sources
Turni202 – 2054Combined sources
Helixi206 – 2138Combined sources
Turni214 – 2174Combined sources
Beta strandi223 – 2264Combined sources
Beta strandi238 – 2436Combined sources
Beta strandi245 – 25511Combined sources
Turni262 – 2643Combined sources
Helixi272 – 2809Combined sources
Turni293 – 2986Combined sources
Helixi304 – 3118Combined sources
Helixi317 – 3248Combined sources
Helixi334 – 3429Combined sources
Beta strandi346 – 35510Combined sources
Beta strandi358 – 3603Combined sources
Beta strandi367 – 37711Combined sources
Helixi383 – 39917Combined sources
Beta strandi404 – 41512Combined sources
Helixi425 – 43814Combined sources
Beta strandi443 – 4497Combined sources
Helixi452 – 4609Combined sources
Beta strandi483 – 4853Combined sources
Helixi486 – 50419Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3DLJX-ray2.26A/B27-507[»]
SMRiQ96KN2. Positions 30-506.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96KN2.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M20A family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG0624.
HOGENOMiHOG000216709.
HOVERGENiHBG051103.
InParanoidiQ96KN2.
KOiK05604.
OMAiPWIANIK.
OrthoDBiEOG7JHM55.
PhylomeDBiQ96KN2.
TreeFamiTF300633.

Family and domain databases

Gene3Di3.30.70.360. 1 hit.
InterProiIPR001261. ArgE/DapE_CS.
IPR017153. GSH_degradosome_DUG1.
IPR002933. Peptidase_M20.
IPR011650. Peptidase_M20_dimer.
[Graphical view]
PfamiPF07687. M20_dimer. 1 hit.
PF01546. Peptidase_M20. 1 hit.
[Graphical view]
PIRSFiPIRSF037242. CNDP_dipeptidase. 1 hit.
PROSITEiPS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q96KN2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPKLGRMAA SLLAVLLLLL ERGMFSSPSP PPALLEKVFQ YIDLHQDEFV
60 70 80 90 100
QTLKEWVAIE SDSVQPVPRF RQELFRMMAV AADTLQRLGA RVASVDMGPQ
110 120 130 140 150
QLPDGQSLPI PPIILAELGS DPTKGTVCFY GHLDVQPADR GDGWLTDPYV
160 170 180 190 200
LTEVDGKLYG RGATDNKGPV LAWINAVSAF RALEQDLPVN IKFIIEGMEE
210 220 230 240 250
AGSVALEELV EKEKDRFFSG VDYIVISDNL WISQRKPAIT YGTRGNSYFM
260 270 280 290 300
VEVKCRDQDF HSGTFGGILH EPMADLVALL GSLVDSSGHI LVPGIYDEVV
310 320 330 340 350
PLTEEEINTY KAIHLDLEEY RNSSRVEKFL FDTKEEILMH LWRYPSLSIH
360 370 380 390 400
GIEGAFDEPG TKTVIPGRVI GKFSIRLVPH MNVSAVEKQV TRHLEDVFSK
410 420 430 440 450
RNSSNKMVVS MTLGLHPWIA NIDDTQYLAA KRAIRTVFGT EPDMIRDGST
460 470 480 490 500
IPIAKMFQEI VHKSVVLIPL GAVDDGEHSQ NEKINRWNYI EGTKLFAAFF

LEMAQLH
Length:507
Mass (Da):56,706
Last modified:January 11, 2011 - v4
Checksum:i756CCD872996F192
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti155 – 1551D → G in CAD10388 (Ref. 1) Curated
Sequence conflicti155 – 1551D → G in AAI10296 (PubMed:15489334).Curated
Sequence conflicti237 – 2371P → L in CAD10388 (Ref. 1) Curated
Sequence conflicti272 – 2721P → L in CAD10388 (Ref. 1) Curated

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61G → R.
Corresponds to variant rs11151964 [ dbSNP | Ensembl ].
VAR_027147
Natural varianti20 – 201L → LL.2 Publications
VAR_027148
Natural varianti113 – 1131I → V.4 Publications
Corresponds to variant rs4263028 [ dbSNP | Ensembl ].
VAR_027149

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12007.1.
RefSeqiNP_116038.4. NM_032649.5.
UniGeneiHs.400613.

Genome annotation databases

EnsembliENST00000358821; ENSP00000351682; ENSG00000150656.
GeneIDi84735.
KEGGihsa:84735.
UCSCiuc002llq.3. human.

Polymorphism and mutation databases

BioMutaiCNDP1.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12007.1.
RefSeqiNP_116038.4. NM_032649.5.
UniGeneiHs.400613.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3DLJX-ray2.26A/B27-507[»]
SMRiQ96KN2. Positions 30-506.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124230. 11 interactions.
STRINGi9606.ENSP00000351682.

Protein family/group databases

MEROPSiM20.006.

PTM databases

PhosphoSiteiQ96KN2.

Polymorphism and mutation databases

BioMutaiCNDP1.
DMDMi317373563.

Proteomic databases

PaxDbiQ96KN2.
PeptideAtlasiQ96KN2.
PRIDEiQ96KN2.

Protocols and materials databases

DNASUi84735.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358821; ENSP00000351682; ENSG00000150656.
GeneIDi84735.
KEGGihsa:84735.
UCSCiuc002llq.3. human.

Organism-specific databases

CTDi84735.
GeneCardsiGC18P072201.
HGNCiHGNC:20675. CNDP1.
HPAiHPA008933.
MIMi609064. gene.
neXtProtiNX_Q96KN2.
PharmGKBiPA134907547.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0624.
HOGENOMiHOG000216709.
HOVERGENiHBG051103.
InParanoidiQ96KN2.
KOiK05604.
OMAiPWIANIK.
OrthoDBiEOG7JHM55.
PhylomeDBiQ96KN2.
TreeFamiTF300633.

Enzyme and pathway databases

BioCyciMetaCyc:HS07681-MONOMER.
BRENDAi3.4.13.20. 2681.
SABIO-RKQ96KN2.

Miscellaneous databases

EvolutionaryTraceiQ96KN2.
GeneWikiiCNDP1.
GenomeRNAii84735.
NextBioi74860.
PROiQ96KN2.
SOURCEiSearch...

Gene expression databases

BgeeiQ96KN2.
CleanExiHS_CNDP1.
ExpressionAtlasiQ96KN2. baseline and differential.
GenevestigatoriQ96KN2.

Family and domain databases

Gene3Di3.30.70.360. 1 hit.
InterProiIPR001261. ArgE/DapE_CS.
IPR017153. GSH_degradosome_DUG1.
IPR002933. Peptidase_M20.
IPR011650. Peptidase_M20_dimer.
[Graphical view]
PfamiPF07687. M20_dimer. 1 hit.
PF01546. Peptidase_M20. 1 hit.
[Graphical view]
PIRSFiPIRSF037242. CNDP_dipeptidase. 1 hit.
PROSITEiPS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-20 INS AND VAL-113.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-113.
  4. 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.

Entry informationi

Entry nameiCNDP1_HUMAN
AccessioniPrimary (citable) accession number: Q96KN2
Secondary accession number(s): Q14D40
, Q17S05, Q2TBG0, Q6UWK2, Q9BT98
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: January 11, 2011
Last modified: April 29, 2015
This is version 120 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.