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Protein

Beta-Ala-His dipeptidase

Gene

CNDP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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)DescriptionActionsGraphical viewLength
    Metal bindingi132Zinc 21
    Active sitei134By similarity1
    Metal bindingi165Zinc 11
    Metal bindingi165Zinc 21
    Active sitei199Proton acceptorBy similarity1
    Metal bindingi200Zinc 11
    Metal bindingi228Zinc 21
    Metal bindingi478Zinc 11

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionCarboxypeptidase, Hydrolase, Metalloprotease, Protease
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc:HS07681-MONOMER
    BRENDAi3.4.13.20 2681
    SABIO-RKiQ96KN2

    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
    Proteomesi
    • UP000005640 Componenti: Chromosome 18

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000150656.14
    HGNCiHGNC:20675 CNDP1
    MIMi609064 gene
    neXtProtiNX_Q96KN2

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi132H → A: Loss of activity. 1 Publication1
    Mutagenesisi165D → A: Loss of activity. 1 Publication1
    Mutagenesisi200E → A: Loss of activity. 1 Publication1

    Organism-specific databases

    DisGeNETi84735
    PharmGKBiPA134907547

    Polymorphism and mutation databases

    BioMutaiCNDP1
    DMDMi317373563

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 26Sequence analysisAdd BLAST26
    ChainiPRO_000002680927 – 507Beta-Ala-His dipeptidaseAdd BLAST481

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei219PhosphoserineBy similarity1
    Glycosylationi322N-linked (GlcNAc...) asparagine1 Publication1
    Glycosylationi382N-linked (GlcNAc...) asparagine1 Publication1

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiQ96KN2
    PeptideAtlasiQ96KN2
    PRIDEiQ96KN2
    ProteomicsDBi77085

    PTM databases

    GlyConnecti1035
    iPTMnetiQ96KN2
    PhosphoSitePlusiQ96KN2

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiENSG00000150656 Expressed in 109 organ(s), highest expression level in C1 segment of cervical spinal cord
    CleanExiHS_CNDP1
    ExpressionAtlasiQ96KN2 baseline and differential
    GenevisibleiQ96KN2 HS

    Organism-specific databases

    HPAiHPA008933

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Protein-protein interaction databases

    BioGridi124230, 16 interactors
    STRINGi9606.ENSP00000351682

    Structurei

    Secondary structure

    1507
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ96KN2
    SMRiQ96KN2
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ96KN2

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M20A family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG2276 Eukaryota
    COG0624 LUCA
    HOGENOMiHOG000216709
    HOVERGENiHBG051103
    InParanoidiQ96KN2
    KOiK05604
    OrthoDBiEOG091G05RU
    PhylomeDBiQ96KN2
    TreeFamiTF300633

    Family and domain databases

    CDDicd05676 M20_dipept_like_CNDP, 1 hit
    InterProiView protein in InterPro
    IPR001261 ArgE/DapE_CS
    IPR017153 CNDP/DUG1
    IPR002933 Peptidase_M20
    IPR011650 Peptidase_M20_dimer
    PfamiView protein in Pfam
    PF07687 M20_dimer, 1 hit
    PF01546 Peptidase_M20, 1 hit
    PIRSFiPIRSF037242 CNDP_dipeptidase, 1 hit
    PROSITEiView protein in PROSITE
    PS00759 ARGE_DAPE_CPG2_2, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

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

    This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    J3KRP0J3KRP0_HUMAN
    Beta-Ala-His dipeptidase
    CNDP1
    464Annotation score:
    J3QQM7J3QQM7_HUMAN
    Beta-Ala-His dipeptidase
    CNDP1
    38Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti155D → G in CAD10388 (Ref. 1) Curated1
    Sequence conflicti155D → G in AAI10296 (PubMed:15489334).Curated1
    Sequence conflicti237P → L in CAD10388 (Ref. 1) Curated1
    Sequence conflicti272P → L in CAD10388 (Ref. 1) Curated1

    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.1 Publication

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0271476G → R. Corresponds to variant dbSNP:rs11151964Ensembl.1
    Natural variantiVAR_02714820L → LL2 Publications1
    Natural variantiVAR_027149113I → V4 PublicationsCorresponds to variant dbSNP:rs4263028Ensembl.1

    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.5 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    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
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3DLJX-ray2.26A/B27-507[»]
    ProteinModelPortaliQ96KN2
    SMRiQ96KN2
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi124230, 16 interactors
    STRINGi9606.ENSP00000351682

    Protein family/group databases

    MEROPSiM20.006

    PTM databases

    GlyConnecti1035
    iPTMnetiQ96KN2
    PhosphoSitePlusiQ96KN2

    Polymorphism and mutation databases

    BioMutaiCNDP1
    DMDMi317373563

    Proteomic databases

    PaxDbiQ96KN2
    PeptideAtlasiQ96KN2
    PRIDEiQ96KN2
    ProteomicsDBi77085

    Protocols and materials databases

    DNASUi84735
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000358821; ENSP00000351682; ENSG00000150656
    GeneIDi84735
    KEGGihsa:84735
    UCSCiuc002llq.5 human

    Organism-specific databases

    CTDi84735
    DisGeNETi84735
    EuPathDBiHostDB:ENSG00000150656.14
    GeneCardsiCNDP1
    HGNCiHGNC:20675 CNDP1
    HPAiHPA008933
    MIMi609064 gene
    neXtProtiNX_Q96KN2
    PharmGKBiPA134907547
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2276 Eukaryota
    COG0624 LUCA
    HOGENOMiHOG000216709
    HOVERGENiHBG051103
    InParanoidiQ96KN2
    KOiK05604
    OrthoDBiEOG091G05RU
    PhylomeDBiQ96KN2
    TreeFamiTF300633

    Enzyme and pathway databases

    BioCyciMetaCyc:HS07681-MONOMER
    BRENDAi3.4.13.20 2681
    SABIO-RKiQ96KN2

    Miscellaneous databases

    ChiTaRSiCNDP1 human
    EvolutionaryTraceiQ96KN2
    GeneWikiiCNDP1
    GenomeRNAii84735
    PROiPR:Q96KN2
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000150656 Expressed in 109 organ(s), highest expression level in C1 segment of cervical spinal cord
    CleanExiHS_CNDP1
    ExpressionAtlasiQ96KN2 baseline and differential
    GenevisibleiQ96KN2 HS

    Family and domain databases

    CDDicd05676 M20_dipept_like_CNDP, 1 hit
    InterProiView protein in InterPro
    IPR001261 ArgE/DapE_CS
    IPR017153 CNDP/DUG1
    IPR002933 Peptidase_M20
    IPR011650 Peptidase_M20_dimer
    PfamiView protein in Pfam
    PF07687 M20_dimer, 1 hit
    PF01546 Peptidase_M20, 1 hit
    PIRSFiPIRSF037242 CNDP_dipeptidase, 1 hit
    PROSITEiView protein in PROSITE
    PS00759 ARGE_DAPE_CPG2_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCNDP1_HUMAN
    AccessioniPrimary (citable) accession number: Q96KN2
    Secondary accession number(s): Q14D40
    , Q17S05, Q2TBG0, Q6UWK2, Q9BT98
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
    Last sequence update: January 11, 2011
    Last modified: October 10, 2018
    This is version 142 of the entry and version 4 of the sequence. See 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. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
    7. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
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