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    CNDP2 carnosine dipeptidase 2 [ Homo sapiens (human) ]

    Gene ID: 55748, updated on 28-Oct-2024

    Summary

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    Official Symbol
    CNDP2provided by HGNC
    Official Full Name
    carnosine dipeptidase 2provided by HGNC
    Primary source
    HGNC:HGNC:24437
    See related
    Ensembl:ENSG00000133313 MIM:169800; AllianceGenome:HGNC:24437
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CN2; CPGL; PEPA; HsT2298; HEL-S-13
    Summary
    CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18), is a nonspecific dipeptidase rather than a selective carnosinase (Teufel et al., 2003 [PubMed 12473676]).[supplied by OMIM, Mar 2008]
    Expression
    Ubiquitous expression in kidney (RPKM 58.4), small intestine (RPKM 41.5) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CNDP2 in Genome Data Viewer
    Location:
    18q22.3
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (74496363..74523454)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (74723735..74750816)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (72163598..72190689)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:72079090-72079848 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:72079849-72080607 Neighboring gene long intergenic non-protein coding RNA 1922 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:72112405-72112906 Neighboring gene divergent protein kinase domain 1C Neighboring gene CRISPRi-validated cis-regulatory element chr18.1476 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9542 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13496 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:72163711-72164223 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13497 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13498 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13499 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:72177239-72177740 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:72177741-72178240 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:72208118-72208618 Neighboring gene carnosine dipeptidase 1 Neighboring gene uncharacterized LOC124904324 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13500 Neighboring gene ZNF407 antisense RNA 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Molecular mechanism of flop selectivity and subsite recognition for an AMPA receptor allosteric modulator: structures of GluA2 and GluA3 in complexes with PEPA. Ahmed AH, et al. Biochemistry, 2010 Apr 6. PMID 20199107, Free PMC Article
    2. Loss of 18q22.3 involving the carboxypeptidase of glutamate-like gene is associated with poor prognosis in resected pancreatic cancer. Lee JH, et al. Clin Cancer Res, 2012 Jan 15. PMID 22128300, Free PMC Article
    3. Proteomic profiling of the substantia nigra demonstrates CNDP2 overexpression in Parkinson's disease. Licker V, et al. J Proteomics, 2012 Aug 3. PMID 22410244
    4. The zinc form of carnosine dipeptidase 2 (CN2) has dipeptidase activity but its substrate specificity is different from that of the manganese form. Okumura N, et al. Biochem Biophys Res Commun, 2017 Dec 16. PMID 29056506
    5. Underexpressed CNDP2 participates in gastric cancer growth inhibition through activating the MAPK signaling pathway. Zhang Z, et al. Mol Med, 2014 Mar 13. PMID 24395568, Free PMC Article

    See all (68) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Exploring the structural and dynamic differences between human carnosinase I (CN1) and II (CN2).
      Title: Exploring the structural and dynamic differences between human carnosinase I (CN1) and II (CN2).
    2. Cytosolic nonspecific dipeptidase 2 promotes the occurrence and development of ovarian cancer through the PI3K/AKT signaling pathway.
      Title: CNDP2 Acts as an Activator for Human Ovarian Cancer Growth and Metastasis via the PI3K/AKT Pathway.
    3. 2 SNPs (rs7244647 in CNDP1 and rs4891558 in CNDP2) were associated with obesity risk. In addition, these associations were observed only in the group with high carbohydrate and low carotene intake but not in the group with low carbohydrate and high carotene intake.
      Title: The Combined Effects of Genetic Variation in the CNDP1 and CNDP2 Genes and Dietary Carbohydrate and Carotene Intake on Obesity Risk.
    4. The CNDP2 rs6566810 (A/A genotype) is overrepresented in endurance athletes, but only in international-level endurance athletes. Three SNPs (CNDP2 rs3764509, CNDP2-CNDP1 rs2346061, and CNDP1 rs2887) were overrepresented in power athletes compared with nonathletes.
      Title: Single Nucleotide Polymorphisms in Carnosinase Genes (CNDP1 and CNDP2) are Associated With Power Athletic Status.
    5. These results suggest that the zinc form of CN2 is an active enzyme, but with a different substrate specificity from that of the manganese form.
      Title: The zinc form of carnosine dipeptidase 2 (CN2) has dipeptidase activity but its substrate specificity is different from that of the manganese form.
    6. To identify substrates of orphan transporter ATP-binding cassette subfamily C member 5 (ABCC5), identified a class of metabolites, N-lactoyl-amino acids, and found that a protease, cytosolic nonspecific dipeptidase 2 (CNDP2), catalyzes their formation.
      Title: N-lactoyl-amino acids are ubiquitous metabolites that originate from CNDP2-mediated reverse proteolysis of lactate and amino acids.
    7. Expression of CN2 in clinical colon tumors and colon cancer cell lines was significantly higher than that in normal colon mucosa cell lines. Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.
      Title: Up-regulation of CNDP2 facilitates the proliferation of colon cancer.
    8. Results suggest that CNDP2 acts as a functional tumor suppressor in gastric cancer via activation of the mitogen-activated protein kinase (MAPK) pathway.
      Title: Underexpressed CNDP2 participates in gastric cancer growth inhibition through activating the MAPK signaling pathway.
    9. a key role of CNDP2 in PD neurodegeneration, by mechanisms that could involve oxidative stress, protein aggregation or inflammation.
      Title: Proteomic profiling of the substantia nigra demonstrates CNDP2 overexpression in Parkinson's disease.
    10. deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer.
      Title: Loss of 18q22.3 involving the carboxypeptidase of glutamate-like gene is associated with poor prognosis in resected pancreatic cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ10830, FLJ35544

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables carboxypeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables dipeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables dipeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metallodipeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    cytosolic non-specific dipeptidase
    Names
    CNDP dipeptidase 2 (metallopeptidase M20 family)
    carnosinase-2
    carnosine dipeptidase II
    cytosolic nonspecific dipeptidase
    epididymis secretory protein Li 13
    glutamate carboxypeptidase-like protein 1
    peptidase A
    threonyl dipeptidase
    NP_001161971.1
    NP_001357177.1
    NP_001357178.1
    NP_001357179.1
    NP_001357183.1
    NP_060705.2
    XP_047293579.1
    XP_047293580.1
    XP_054174780.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001168499.2 → NP_001161971.1  cytosolic non-specific dipeptidase isoform 2

      See identical proteins and their annotated locations for NP_001161971.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) contains a distinct 5' UTR and lacks an in-frame portion of the central coding region, compared to variant 1. The resulting isoform (2) is shorter, compared to isoform 1.
      Source sequence(s)
      AC009704, AF258592, BM675304
      Consensus CDS
      CCDS54190.1
      UniProtKB/TrEMBL
      B4DV28
      Related
      ENSP00000325756.8, ENST00000324301.12
      Conserved Domains (2) summary
      PRK08201
      Location:10 → 389
      PRK08201; hypothetical protein; Provisional
      cd05676
      Location:7 → 389
      M20_dipept_like_CNDP; M20 cytosolic nonspecific dipeptidases including anserinase and serum carnosinase

    2. NM_001370248.1 → NP_001357177.1  cytosolic non-specific dipeptidase isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009704, BC001375, BQ223281
      Consensus CDS
      CCDS12006.1
      UniProtKB/Swiss-Prot
      B3KUG4, Q8WY59, Q96KP4, Q9BQ94, Q9NVB4, V9HWE5
      UniProtKB/TrEMBL
      B4DV28
      Related
      ENSP00000462311.1, ENST00000579847.5
      Conserved Domains (1) summary
      cd05676
      Location:7 → 473
      M20_dipept_like_CNDP; M20 cytosolic nonspecific dipeptidases including anserinase and serum carnosinase

    3. NM_001370249.1 → NP_001357178.1  cytosolic non-specific dipeptidase isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009704, BC001375, BQ223281
      Consensus CDS
      CCDS12006.1
      UniProtKB/Swiss-Prot
      B3KUG4, Q8WY59, Q96KP4, Q9BQ94, Q9NVB4, V9HWE5
      UniProtKB/TrEMBL
      B4DV28
      Conserved Domains (1) summary
      cd05676
      Location:7 → 473
      M20_dipept_like_CNDP; M20 cytosolic nonspecific dipeptidases including anserinase and serum carnosinase

    4. NM_001370250.1 → NP_001357179.1  cytosolic non-specific dipeptidase isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009704, BC001375, BQ223281
      Consensus CDS
      CCDS12006.1
      UniProtKB/Swiss-Prot
      B3KUG4, Q8WY59, Q96KP4, Q9BQ94, Q9NVB4, V9HWE5
      UniProtKB/TrEMBL
      B4DV28
      Conserved Domains (1) summary
      cd05676
      Location:7 → 473
      M20_dipept_like_CNDP; M20 cytosolic nonspecific dipeptidases including anserinase and serum carnosinase

    5. NM_001370254.1 → NP_001357183.1  cytosolic non-specific dipeptidase isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC009704, BC001375, DC313148
      Conserved Domains (1) summary
      cl14876
      Location:1 → 234
      Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

    6. NM_018235.3 → NP_060705.2  cytosolic non-specific dipeptidase isoform 1

      See identical proteins and their annotated locations for NP_060705.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1, 3, 4, and 5 encode the same isoform.
      Source sequence(s)
      AC009704, BC001375, BM675304, DC313148
      Consensus CDS
      CCDS12006.1
      UniProtKB/Swiss-Prot
      B3KUG4, Q8WY59, Q96KP4, Q9BQ94, Q9NVB4, V9HWE5
      UniProtKB/TrEMBL
      B4DV28
      Related
      ENSP00000325548.4, ENST00000324262.9
      Conserved Domains (1) summary
      cd05676
      Location:7 → 473
      M20_dipept_like_CNDP; M20 cytosolic nonspecific dipeptidases including anserinase and serum carnosinase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      74496363..74523454
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047437624.1 → XP_047293580.1  cytosolic non-specific dipeptidase isoform X1

      UniProtKB/Swiss-Prot
      B3KUG4, Q8WY59, Q96KP4, Q9BQ94, Q9NVB4, V9HWE5

    2. XM_047437623.1 → XP_047293579.1  cytosolic non-specific dipeptidase isoform X1

      UniProtKB/Swiss-Prot
      B3KUG4, Q8WY59, Q96KP4, Q9BQ94, Q9NVB4, V9HWE5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      74723735..74750816
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054318805.1 → XP_054174780.1  cytosolic non-specific dipeptidase isoform X1

      UniProtKB/Swiss-Prot
      B3KUG4, Q8WY59, Q96KP4, Q9BQ94, Q9NVB4, V9HWE5
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96KP4.2 GenPept UniProtKB/Swiss-Prot:Q96KP4

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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