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Protein

Carboxypeptidase M

Gene

CPM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins. It is believed to play important roles in the control of peptide hormone and growth factor activity at the cell surface, and in the membrane-localized degradation of extracellular proteins.1 Publication

Catalytic activityi

Cleavage of C-terminal arginine or lysine residues from polypeptides.1 Publication

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Activity regulationi

Inhibited by O-phenanthroline and MGTA and activated by cobalt.

Kineticsi

  1. KM=59 µM for synthetic dansyl-Ala-Arg1 Publication
  2. KM=57 µM for placental peptide hormones1 Publication

    pH dependencei

    Optimum pH is 7.0.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi83Zinc; catalyticCombined sources1 Publication1
    Metal bindingi86Zinc; catalyticCombined sources1 Publication1
    Metal bindingi190Zinc; catalyticCombined sources1 Publication1
    Sitei277Probable structural role1 Publication1
    Active sitei281Proton donor/acceptor1 Publication1

    GO - Molecular functioni

    • carboxypeptidase activity Source: ProtInc
    • metallocarboxypeptidase activity Source: GO_Central
    • zinc ion binding Source: InterPro

    GO - Biological processi

    Keywordsi

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

    Enzyme and pathway databases

    BRENDAi3.4.17.12 2681
    ReactomeiR-HSA-163125 Post-translational modification: synthesis of GPI-anchored proteins
    SABIO-RKiP14384

    Protein family/group databases

    MEROPSiM14.006

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carboxypeptidase M (EC:3.4.17.121 Publication)
    Short name:
    CPM
    Gene namesi
    Name:CPM
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 12

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000135678.11
    HGNCiHGNC:2311 CPM
    MIMi114860 gene
    neXtProtiNX_P14384

    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

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi277E → A: 5-fold decrease in substrate affinity. 22-fold decrease in specific affinity. 104-fold decrease in catalytic efficiency. Greatly reduced heat stability. 1 Publication1
    Mutagenesisi277E → Q: 2-fold decrease in substrate affinity. Small increase in specific affinity. Reduced heat stability by 50%. 1 Publication1
    Mutagenesisi281E → Q: Abolishes enzyme activity. 1 Publication1
    Mutagenesisi423S → A or T: Expressed on cell membrane. Released from membrane by PI-PLC. 1 Publication1
    Mutagenesisi423S → P: Little expression on cell membrane. Perinuclear localization. Not released from membrane by PI-PLC. 1 Publication1

    Organism-specific databases

    DisGeNETi1368
    OpenTargetsiENSG00000135678
    PharmGKBiPA26828

    Chemistry databases

    ChEMBLiCHEMBL3038
    GuidetoPHARMACOLOGYi1596

    Polymorphism and mutation databases

    BioMutaiCPM
    DMDMi14916957

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 172 PublicationsAdd BLAST17
    ChainiPRO_000000439118 – 423Carboxypeptidase MAdd BLAST406
    PropeptideiPRO_0000251910424 – 443Removed in mature formCuratedAdd BLAST20

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi38N-linked (GlcNAc...) asparagine1 Publication1
    Glycosylationi115N-linked (GlcNAc...) asparagineCombined sources2 Publications1
    Disulfide bondi138 ↔ 285Combined sources1 Publication
    Glycosylationi164N-linked (GlcNAc...) asparagine1 Publication1
    Disulfide bondi242 ↔ 284Combined sources1 Publication
    Disulfide bondi341 ↔ 410Combined sources1 Publication
    Glycosylationi363N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi384N-linked (GlcNAc...) asparagineSequence analysis1
    Lipidationi423GPI-anchor amidated serine1 Publication1

    Keywords - PTMi

    Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

    Proteomic databases

    EPDiP14384
    MaxQBiP14384
    PaxDbiP14384
    PeptideAtlasiP14384
    PRIDEiP14384
    ProteomicsDBi53049

    PTM databases

    iPTMnetiP14384
    PhosphoSitePlusiP14384

    Expressioni

    Gene expression databases

    BgeeiENSG00000135678 Expressed in 202 organ(s), highest expression level in upper lobe of lung
    CleanExiHS_CPM
    ExpressionAtlasiP14384 baseline and differential
    GenevisibleiP14384 HS

    Organism-specific databases

    HPAiHPA002657
    HPA077243

    Interactioni

    Protein-protein interaction databases

    BioGridi107760, 35 interactors
    IntActiP14384, 31 interactors
    STRINGi9606.ENSP00000339157

    Chemistry databases

    BindingDBiP14384

    Structurei

    Secondary structure

    1443
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP14384
    SMRiP14384
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP14384

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M14 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG2649 Eukaryota
    ENOG410XX0H LUCA
    GeneTreeiENSGT00760000119124
    HOGENOMiHOG000232185
    HOVERGENiHBG003410
    InParanoidiP14384
    KOiK01296
    OMAiYSNGREN
    OrthoDBiEOG091G06A9
    PhylomeDBiP14384
    TreeFamiTF315592

    Family and domain databases

    CDDicd03866 M14_CPM, 1 hit
    InterProiView protein in InterPro
    IPR008969 CarboxyPept-like_regulatory
    IPR033842 CPM_N
    IPR000834 Peptidase_M14
    PfamiView protein in Pfam
    PF00246 Peptidase_M14, 1 hit
    PRINTSiPR00765 CRBOXYPTASEA
    SMARTiView protein in SMART
    SM00631 Zn_pept, 1 hit
    SUPFAMiSSF49464 SSF49464, 1 hit
    PROSITEiView protein in PROSITE
    PS00132 CARBOXYPEPT_ZN_1, 1 hit
    PS00133 CARBOXYPEPT_ZN_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 6 potential isoforms that are computationally mapped.Show allAlign All

    P14384-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MDFPCLWLGL LLPLVAALDF NYHRQEGMEA FLKTVAQNYS SVTHLHSIGK
    60 70 80 90 100
    SVKGRNLWVL VVGRFPKEHR IGIPEFKYVA NMHGDETVGR ELLLHLIDYL
    110 120 130 140 150
    VTSDGKDPEI TNLINSTRIH IMPSMNPDGF EAVKKPDCYY SIGRENYNQY
    160 170 180 190 200
    DLNRNFPDAF EYNNVSRQPE TVAVMKWLKT ETFVLSANLH GGALVASYPF
    210 220 230 240 250
    DNGVQATGAL YSRSLTPDDD VFQYLAHTYA SRNPNMKKGD ECKNKMNFPN
    260 270 280 290 300
    GVTNGYSWYP LQGGMQDYNY IWAQCFEITL ELSCCKYPRE EKLPSFWNNN
    310 320 330 340 350
    KASLIEYIKQ VHLGVKGQVF DQNGNPLPNV IVEVQDRKHI CPYRTNKYGE
    360 370 380 390 400
    YYLLLLPGSY IINVTVPGHD PHITKVIIPE KSQNFSALKK DILLPFQGQL
    410 420 430 440
    DSIPVSNPSC PMIPLYRNLP DHSAATKPSL FLFLVSLLHI FFK
    Length:443
    Mass (Da):50,514
    Last modified:July 11, 2001 - v2
    Checksum:i98EB0C94E201B901
    GO

    Computationally mapped potential isoform sequencesi

    There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    F8W111F8W111_HUMAN
    Carboxypeptidase M
    CPM
    249Annotation score:
    F8VVI6F8VVI6_HUMAN
    Carboxypeptidase M
    CPM
    136Annotation score:
    H0YHG6H0YHG6_HUMAN
    Carboxypeptidase M
    CPM
    35Annotation score:
    H0YHN7H0YHN7_HUMAN
    Carboxypeptidase M
    CPM
    198Annotation score:
    F8VR29F8VR29_HUMAN
    Carboxypeptidase M
    CPM
    64Annotation score:
    F8VU13F8VU13_HUMAN
    Carboxypeptidase M
    CPM
    72Annotation score:

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04860024R → H. Corresponds to variant dbSNP:rs7978197Ensembl.1
    Natural variantiVAR_048601133V → I. Corresponds to variant dbSNP:rs7309831Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J04970 mRNA Translation: AAA35651.2
    AF262947
    , AF262940, AF262941, AF262942, AF262943, AF262944, AF262945, AF262946 Genomic DNA Translation: AAG47641.1
    AF368463 mRNA Translation: AAK69717.1
    AK313180 mRNA Translation: BAG35997.1
    BC022276 mRNA Translation: AAH22276.1
    CCDSiCCDS8987.1
    PIRiA32619
    RefSeqiNP_001005502.1, NM_001005502.2
    NP_001865.1, NM_001874.4
    NP_938079.1, NM_198320.3
    UniGeneiHs.654387

    Genome annotation databases

    EnsembliENST00000338356; ENSP00000339157; ENSG00000135678
    ENST00000546373; ENSP00000447255; ENSG00000135678
    ENST00000551568; ENSP00000448517; ENSG00000135678
    GeneIDi1368
    KEGGihsa:1368
    UCSCiuc001sup.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J04970 mRNA Translation: AAA35651.2
    AF262947
    , AF262940, AF262941, AF262942, AF262943, AF262944, AF262945, AF262946 Genomic DNA Translation: AAG47641.1
    AF368463 mRNA Translation: AAK69717.1
    AK313180 mRNA Translation: BAG35997.1
    BC022276 mRNA Translation: AAH22276.1
    CCDSiCCDS8987.1
    PIRiA32619
    RefSeqiNP_001005502.1, NM_001005502.2
    NP_001865.1, NM_001874.4
    NP_938079.1, NM_198320.3
    UniGeneiHs.654387

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1UWYX-ray3.00A18-443[»]
    ProteinModelPortaliP14384
    SMRiP14384
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107760, 35 interactors
    IntActiP14384, 31 interactors
    STRINGi9606.ENSP00000339157

    Chemistry databases

    BindingDBiP14384
    ChEMBLiCHEMBL3038
    GuidetoPHARMACOLOGYi1596

    Protein family/group databases

    MEROPSiM14.006

    PTM databases

    iPTMnetiP14384
    PhosphoSitePlusiP14384

    Polymorphism and mutation databases

    BioMutaiCPM
    DMDMi14916957

    Proteomic databases

    EPDiP14384
    MaxQBiP14384
    PaxDbiP14384
    PeptideAtlasiP14384
    PRIDEiP14384
    ProteomicsDBi53049

    Protocols and materials databases

    DNASUi1368
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000338356; ENSP00000339157; ENSG00000135678
    ENST00000546373; ENSP00000447255; ENSG00000135678
    ENST00000551568; ENSP00000448517; ENSG00000135678
    GeneIDi1368
    KEGGihsa:1368
    UCSCiuc001sup.4 human

    Organism-specific databases

    CTDi1368
    DisGeNETi1368
    EuPathDBiHostDB:ENSG00000135678.11
    GeneCardsiCPM
    HGNCiHGNC:2311 CPM
    HPAiHPA002657
    HPA077243
    MIMi114860 gene
    neXtProtiNX_P14384
    OpenTargetsiENSG00000135678
    PharmGKBiPA26828
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2649 Eukaryota
    ENOG410XX0H LUCA
    GeneTreeiENSGT00760000119124
    HOGENOMiHOG000232185
    HOVERGENiHBG003410
    InParanoidiP14384
    KOiK01296
    OMAiYSNGREN
    OrthoDBiEOG091G06A9
    PhylomeDBiP14384
    TreeFamiTF315592

    Enzyme and pathway databases

    BRENDAi3.4.17.12 2681
    ReactomeiR-HSA-163125 Post-translational modification: synthesis of GPI-anchored proteins
    SABIO-RKiP14384

    Miscellaneous databases

    ChiTaRSiCPM human
    EvolutionaryTraceiP14384
    GeneWikiiCPM_(gene)
    GenomeRNAii1368
    PROiPR:P14384
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000135678 Expressed in 202 organ(s), highest expression level in upper lobe of lung
    CleanExiHS_CPM
    ExpressionAtlasiP14384 baseline and differential
    GenevisibleiP14384 HS

    Family and domain databases

    CDDicd03866 M14_CPM, 1 hit
    InterProiView protein in InterPro
    IPR008969 CarboxyPept-like_regulatory
    IPR033842 CPM_N
    IPR000834 Peptidase_M14
    PfamiView protein in Pfam
    PF00246 Peptidase_M14, 1 hit
    PRINTSiPR00765 CRBOXYPTASEA
    SMARTiView protein in SMART
    SM00631 Zn_pept, 1 hit
    SUPFAMiSSF49464 SSF49464, 1 hit
    PROSITEiView protein in PROSITE
    PS00132 CARBOXYPEPT_ZN_1, 1 hit
    PS00133 CARBOXYPEPT_ZN_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCBPM_HUMAN
    AccessioniPrimary (citable) accession number: P14384
    Secondary accession number(s): B2R800, Q9H2K9
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
    Last sequence update: July 11, 2001
    Last modified: November 7, 2018
    This is version 186 of the entry and version 2 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, Direct protein sequencing, 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
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