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    CPM carboxypeptidase M [ Homo sapiens (human) ]

    Gene ID: 1368, updated on 28-Oct-2024

    Summary

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    Official Symbol
    CPMprovided by HGNC
    Official Full Name
    carboxypeptidase Mprovided by HGNC
    Primary source
    HGNC:HGNC:2311
    See related
    Ensembl:ENSG00000135678 MIM:114860; AllianceGenome:HGNC:2311
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    The protein encoded by this gene is a membrane-bound arginine/lysine carboxypeptidase. Its expression is associated with monocyte to macrophage differentiation. This encoded protein contains hydrophobic regions at the amino and carboxy termini and has 6 potential asparagine-linked glycosylation sites. The active site residues of carboxypeptidases A and B are conserved in this protein. Three alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in fat (RPKM 56.0), lung (RPKM 21.3) and 19 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CPM in Genome Data Viewer
    Location:
    12q15
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (68842197..68963469, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (68821776..68943048, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (69235977..69357249, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene MAPK activated protein kinase 2 pseudogene Neighboring gene solute carrier family 35 member E3 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:69181025-69181579 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:69181580-69182133 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4648 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:69202246-69203445 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6647 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:69225023-69225696 Neighboring gene SZRD1 pseudogene 1 Neighboring gene MDM2 proto-oncogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4649 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4650 Neighboring gene RNA, U7 small nuclear 4 pseudogene Neighboring gene PRELI domain containing 2 pseudogene 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr12:69401223-69401916 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:69417938-69419137 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:69420279-69420508 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:69436381-69436882 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:69436883-69437382 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:69447351-69447948 Neighboring gene transcript overexpressed in dedifferentiated liposarcoma Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:69461643-69462842 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:69509413-69510201 Neighboring gene MPRA-validated peak1782 silencer Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:69633505-69634085 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:69634086-69634665 Neighboring gene Sharpr-MPRA regulatory region 12312 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:69639551-69640050 Neighboring gene MPRA-validated peak1783 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6648 Neighboring gene cleavage and polyadenylation specific factor 6 Neighboring gene microRNA 1279

    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. Carboxypeptidase M in brain and peripheral nerves. Nagae A, et al. J Neurochem, 1992 Dec. PMID 1431901
    2. Crystal structure of human carboxypeptidase M, a membrane-bound enzyme that regulates peptide hormone activity. Reverter D, et al. J Mol Biol, 2004 Apr 23. PMID 15066430
    3. Effect of mutation of two critical glutamic acid residues on the activity and stability of human carboxypeptidase M and characterization of its signal for glycosylphosphatidylinositol anchoring. Tan F, et al. Biochem J, 2003 Mar 1. PMID 12457462, Free PMC Article
    4. Carboxypeptidase M modulates BMSCs osteogenesis-adipogenesis via the MAPK/ERK pathway: An integrated single-cell and bulk transcriptomic study. Liao Z, et al. FASEB J, 2024 May 15. PMID 38713087
    5. Molecular structure and alternative splicing of the human carboxypeptidase M gene. Pessoa LG, et al. Biol Chem, 2002 Feb. PMID 11934264

    See all (58) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Carboxypeptidase M modulates BMSCs osteogenesis-adipogenesis via the MAPK/ERK pathway: An integrated single-cell and bulk transcriptomic study.
      Title: Carboxypeptidase M modulates BMSCs osteogenesis-adipogenesis via the MAPK/ERK pathway: An integrated single-cell and bulk transcriptomic study.
    2. Our work shows for the first time that the interaction between CPM and kinin B1 receptor alters not only B1R pharmacology, but also modulates enzyme expression and activity.
      Title: Interactions between carboxypeptidase M and kinin B1 receptor in endothelial cells.
    3. The rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility.
      Title: Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.
    4. Low CPM expression is associated with colorectal cancer.
      Title: MicroRNA-146a promote cell migration and invasion in human colorectal cancer via carboxypeptidase M/src-FAK pathway.
    5. CPM binding to extracellular loop 2 of the B1R results in positive allosteric modulation of B1R signaling, and disruption of this interaction could provide a novel therapeutic approach to reduce pathological B1R signaling.
      Title: Carboxypeptidase M is a positive allosteric modulator of the kinin B1 receptor.
    6. Carboxypeptidase M expression is lost in human renal cell carcinoma tumor cells, whereas it is abundant in tumor-associated foam cells and neovasculature.
      Title: Mapping of carboxypeptidase m in normal human kidney and renal cell carcinoma: expression in tumor-associated neovasculature and macrophages.
    7. novel marker and cellular player in lipid uptake and/or metabolism of activated macrophages by promoting foam cell formation
      Title: Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells.
    8. CPM and B1Rs on cell membranes form a critical complex that potentiates B1R signaling.
      Title: Cross-talk between carboxypeptidase M and the kinin B1 receptor mediates a new mode of G protein-coupled receptor signaling.
    9. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression.
    10. CPM amplification could be used as an alternative diagnostic tool for the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumors.
      Title: Carboxypeptidase M: a biomarker for the discrimination of well-differentiated liposarcoma from lipoma.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    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
    A genome-wide association study identifies susceptibility loci of silica related pneumoconiosis in Han Chinese.
    EBI GWAS Catalog
    Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression.
    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of carboxypeptidase M (CPM) in primary human brain microvascular endothelial cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables carboxypeptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables metallocarboxypeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in anatomical structure morphogenesis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in peptide metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cell surface HDA PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in side of membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    carboxypeptidase M
    Names
    renal carboxypeptidase
    urinary carboxypeptidase B
    NP_001005502.1
    NP_001400316.1
    NP_001400317.1
    NP_001400318.1
    NP_001400319.1
    NP_001400320.1
    NP_001400321.1
    NP_001400322.1
    NP_001400323.1
    NP_001400324.1
    NP_001400325.1
    NP_001400326.1
    NP_001400327.1
    NP_001400328.1
    NP_001400329.1
    NP_001400330.1
    NP_001400331.1
    NP_001400332.1
    NP_001400333.1
    NP_001865.1
    NP_938079.1

    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_001005502.3 → NP_001005502.1  carboxypeptidase M isoform b precursor

      See identical proteins and their annotated locations for NP_001005502.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variants 1, 2, and 5-8. Variants 1-3 and 5-8 all encode the same isoform (b).
      Source sequence(s)
      AC025423
      Consensus CDS
      CCDS8987.1
      UniProtKB/Swiss-Prot
      B2R800, P14384, Q9H2K9
      Conserved Domains (2) summary
      cd03866
      Location:18 → 310
      M14_CPM; Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup
      cd11308
      Location:314 → 394
      Peptidase_M14NE-CP-C_like; Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, regulation, or interaction domain

    2. NM_001413387.1 → NP_001400316.1  carboxypeptidase M isoform a precursor

      Status: REVIEWED

      Source sequence(s)
      AC025423

    3. NM_001413388.1 → NP_001400317.1  carboxypeptidase M isoform b precursor

      Status: REVIEWED

      Source sequence(s)
      AC025423, AC133749
      UniProtKB/Swiss-Prot
      B2R800, P14384, Q9H2K9

    4. NM_001413389.1 → NP_001400318.1  carboxypeptidase M isoform b precursor

      Status: REVIEWED

      Source sequence(s)
      AC025423
      UniProtKB/Swiss-Prot
      B2R800, P14384, Q9H2K9

    5. NM_001413390.1 → NP_001400319.1  carboxypeptidase M isoform b precursor

      Status: REVIEWED

      Source sequence(s)
      AC025423
      UniProtKB/Swiss-Prot
      B2R800, P14384, Q9H2K9
      Related
      ENSP00000339157.3, ENST00000338356.7

    6. NM_001413391.1 → NP_001400320.1  carboxypeptidase M isoform b precursor

      Status: REVIEWED

      Source sequence(s)
      AC025423
      UniProtKB/Swiss-Prot
      B2R800, P14384, Q9H2K9

    7. NM_001413392.1 → NP_001400321.1  carboxypeptidase M isoform c

      Status: REVIEWED

      Source sequence(s)
      AC025423

    8. NM_001413393.1 → NP_001400322.1  carboxypeptidase M isoform d precursor

      Status: REVIEWED

      Source sequence(s)
      AC025423, AC133749

    9. NM_001413394.1 → NP_001400323.1  carboxypeptidase M isoform d precursor

      Status: REVIEWED

      Source sequence(s)
      AC025423

    10. NM_001413395.1 → NP_001400324.1  carboxypeptidase M isoform e

      Status: REVIEWED

      Source sequence(s)
      AC025423

    11. NM_001413396.1 → NP_001400325.1  carboxypeptidase M isoform e

      Status: REVIEWED

      Source sequence(s)
      AC025423

    12. NM_001413397.1 → NP_001400326.1  carboxypeptidase M isoform f

      Status: REVIEWED

      Source sequence(s)
      AC025423, AC133749

    13. NM_001413398.1 → NP_001400327.1  carboxypeptidase M isoform f

      Status: REVIEWED

      Source sequence(s)
      AC025423, AC133749

    14. NM_001413399.1 → NP_001400328.1  carboxypeptidase M isoform f

      Status: REVIEWED

      Source sequence(s)
      AC025423

    15. NM_001413400.1 → NP_001400329.1  carboxypeptidase M isoform f

      Status: REVIEWED

      Source sequence(s)
      AC025423

    16. NM_001413401.1 → NP_001400330.1  carboxypeptidase M isoform f

      Status: REVIEWED

      Source sequence(s)
      AC025423

    17. NM_001413402.1 → NP_001400331.1  carboxypeptidase M isoform g precursor

      Status: REVIEWED

      Source sequence(s)
      AC025423

    18. NM_001413403.1 → NP_001400332.1  carboxypeptidase M isoform h

      Status: REVIEWED

      Source sequence(s)
      AC025423

    19. NM_001413404.1 → NP_001400333.1  carboxypeptidase M isoform h

      Status: REVIEWED

      Source sequence(s)
      AC025423

    20. NM_001874.5 → NP_001865.1  carboxypeptidase M isoform b precursor

      See identical proteins and their annotated locations for NP_001865.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR compared to variants 2, 3, and 5-8. Variants 1-3 and 5-8 all encode the same isoform (b).
      Source sequence(s)
      AC025423, AC133749
      Consensus CDS
      CCDS8987.1
      UniProtKB/Swiss-Prot
      B2R800, P14384, Q9H2K9
      Related
      ENSP00000447255.1, ENST00000546373.5
      Conserved Domains (2) summary
      cd03866
      Location:18 → 310
      M14_CPM; Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup
      cd11308
      Location:314 → 394
      Peptidase_M14NE-CP-C_like; Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, regulation, or interaction domain

    21. NM_198320.5 → NP_938079.1  carboxypeptidase M isoform b precursor

      See identical proteins and their annotated locations for NP_938079.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variants 1, 3, and 5-8. Variants 1-3 and 5-8 all encode the same isoform (b).
      Source sequence(s)
      AC025423
      Consensus CDS
      CCDS8987.1
      UniProtKB/Swiss-Prot
      B2R800, P14384, Q9H2K9
      Related
      ENSP00000448517.1, ENST00000551568.6
      Conserved Domains (2) summary
      cd03866
      Location:18 → 310
      M14_CPM; Peptidase M14 carboxypeptidase subfamily N/E-like; Carboxypeptidase M subgroup
      cd11308
      Location:314 → 394
      Peptidase_M14NE-CP-C_like; Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, regulation, or interaction domain

    RNA

    1. NR_182142.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC025423

    2. NR_182143.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC025423

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      68842197..68963469 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RNA

    1. XR_001748580.3 RNA Sequence

    2. XR_001748577.3 RNA Sequence

    3. XR_001748578.3 RNA Sequence

    4. XR_007063051.1 RNA Sequence

    5. XR_007063050.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      68821776..68943048 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RNA

    1. XR_008488534.1 RNA Sequence

    2. XR_008488532.1 RNA Sequence

    3. XR_008488533.1 RNA Sequence

    4. XR_008488536.1 RNA Sequence

    5. XR_008488535.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P14384.2 GenPept UniProtKB/Swiss-Prot:P14384

    Gene LinkOut

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