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Q96KN2

- CNDP1_HUMAN

UniProt

Q96KN2 - CNDP1_HUMAN

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Protein
Beta-Ala-His dipeptidase
Gene
CNDP1, CN1, CPGL2, UNQ1915/PRO4380
Organism
Homo sapiens (Human)
Status
Reviewed - 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

Binds 2 zinc 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)
  3. KM=0.20 µM for homocarnosine (at 30 degrees Celsius and in the absence of cadmium ions)
  4. KM=1.0 µM for homocarnosine (at 30 degrees Celsius and in the presence of 200 µM cadmium ions)

pH dependencei

Optimum pH is 8.5.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi132 – 1321Zinc 2
Active sitei134 – 1341 By similarity
Metal bindingi165 – 1651Zinc 1
Metal bindingi165 – 1651Zinc 2
Active sitei199 – 1991Proton acceptor By 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.
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: 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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626 Reviewed prediction
Add
BLAST
Chaini27 – 507481Beta-Ala-His dipeptidase
PRO_0000026809Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei219 – 2191Phosphoserine By 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

ArrayExpressiQ96KN2.
BgeeiQ96KN2.
CleanExiHS_CNDP1.
GenevestigatoriQ96KN2.

Organism-specific databases

HPAiHPA008933.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi124230. 1 interaction.
STRINGi9606.ENSP00000351682.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3DLJX-ray2.26A/B27-507[»]
ProteinModelPortaliQ96KN2.
SMRiQ96KN2. Positions 30-506.

Miscellaneous databases

EvolutionaryTraceiQ96KN2.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M20A family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG0624.
HOGENOMiHOG000216709.
HOVERGENiHBG051103.
InParanoidiQ96KN2.
KOiK05604.
OMAiWINAVSA.
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

MDPKLGRMAA SLLAVLLLLL ERGMFSSPSP PPALLEKVFQ YIDLHQDEFV    50
QTLKEWVAIE SDSVQPVPRF RQELFRMMAV AADTLQRLGA RVASVDMGPQ 100
QLPDGQSLPI PPIILAELGS DPTKGTVCFY GHLDVQPADR GDGWLTDPYV 150
LTEVDGKLYG RGATDNKGPV LAWINAVSAF RALEQDLPVN IKFIIEGMEE 200
AGSVALEELV EKEKDRFFSG VDYIVISDNL WISQRKPAIT YGTRGNSYFM 250
VEVKCRDQDF HSGTFGGILH EPMADLVALL GSLVDSSGHI LVPGIYDEVV 300
PLTEEEINTY KAIHLDLEEY RNSSRVEKFL FDTKEEILMH LWRYPSLSIH 350
GIEGAFDEPG TKTVIPGRVI GKFSIRLVPH MNVSAVEKQV TRHLEDVFSK 400
RNSSNKMVVS MTLGLHPWIA NIDDTQYLAA KRAIRTVFGT EPDMIRDGST 450
IPIAKMFQEI VHKSVVLIPL GAVDDGEHSQ NEKINRWNYI EGTKLFAAFF 500
LEMAQLH 507
Length:507
Mass (Da):56,706
Last modified:January 11, 2011 - v4
Checksum:i756CCD872996F192
GO

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 conflict

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

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 databases

DMDMi317373563.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS12007.1.
RefSeqi NP_116038.4. NM_032649.5.
UniGenei Hs.400613.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3DLJ X-ray 2.26 A/B 27-507 [» ]
ProteinModelPortali Q96KN2.
SMRi Q96KN2. Positions 30-506.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 124230. 1 interaction.
STRINGi 9606.ENSP00000351682.

Protein family/group databases

MEROPSi M20.006.

PTM databases

PhosphoSitei Q96KN2.

Polymorphism databases

DMDMi 317373563.

Proteomic databases

PaxDbi Q96KN2.
PeptideAtlasi Q96KN2.
PRIDEi Q96KN2.

Protocols and materials databases

DNASUi 84735.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000358821 ; ENSP00000351682 ; ENSG00000150656 .
GeneIDi 84735.
KEGGi hsa:84735.
UCSCi uc002llq.3. human.

Organism-specific databases

CTDi 84735.
GeneCardsi GC18P072201.
HGNCi HGNC:20675. CNDP1.
HPAi HPA008933.
MIMi 609064. gene.
neXtProti NX_Q96KN2.
PharmGKBi PA134907547.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0624.
HOGENOMi HOG000216709.
HOVERGENi HBG051103.
InParanoidi Q96KN2.
KOi K05604.
OMAi WINAVSA.
OrthoDBi EOG7JHM55.
PhylomeDBi Q96KN2.
TreeFami TF300633.

Enzyme and pathway databases

BioCyci MetaCyc:HS07681-MONOMER.
SABIO-RK Q96KN2.

Miscellaneous databases

EvolutionaryTracei Q96KN2.
GeneWikii CNDP1.
GenomeRNAii 84735.
NextBioi 74860.
PROi Q96KN2.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q96KN2.
Bgeei Q96KN2.
CleanExi HS_CNDP1.
Genevestigatori Q96KN2.

Family and domain databases

Gene3Di 3.30.70.360. 1 hit.
InterProi IPR001261. ArgE/DapE_CS.
IPR017153. GSH_degradosome_DUG1.
IPR002933. Peptidase_M20.
IPR011650. Peptidase_M20_dimer.
[Graphical view ]
Pfami PF07687. M20_dimer. 1 hit.
PF01546. Peptidase_M20. 1 hit.
[Graphical view ]
PIRSFi PIRSF037242. CNDP_dipeptidase. 1 hit.
PROSITEi PS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: July 9, 2014
This is version 113 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

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