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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

    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

    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.
    GenevisibleiQ96KN2. HS.

    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[»]
    ProteinModelPortaliQ96KN2.
    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.
    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.

    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[»]
    ProteinModelPortaliQ96KN2.
    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.
    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.
    GenevisibleiQ96KN2. HS.

    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: July 22, 2015
    This is version 123 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.