Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Carboxypeptidase M

Gene

CPM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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: ProtInc
    • serine-type carboxypeptidase activity Source: GO_Central
    • zinc ion binding Source: InterPro

    GO - Biological processi

    • anatomical structure morphogenesis Source: ProtInc
    • peptide metabolic process Source: GO_Central
    • protein processing Source: GO_Central
    Complete GO annotation...

    Keywords - Molecular functioni

    Carboxypeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciZFISH:HS06047-MONOMER.
    BRENDAi3.4.17.12. 2681.
    SABIO-RKP14384.

    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

    HGNCiHGNC:2311. CPM.

    Subcellular locationi

    • Cell membrane 1 Publication; Lipid-anchorGPI-anchor 1 Publication

    GO - Cellular componenti

    • anchored component of membrane Source: UniProtKB-KW
    • cell surface Source: UniProtKB
    • extracellular exosome Source: UniProtKB
    • extracellular space Source: GO_Central
    • plasma membrane Source: ProtInc
    Complete GO annotation...

    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...)1 Publication1
    Glycosylationi115N-linked (GlcNAc...)Combined sources2 Publications1
    Disulfide bondi138 ↔ 285Combined sources1 Publication
    Glycosylationi164N-linked (GlcNAc...)1 Publication1
    Disulfide bondi242 ↔ 284Combined sources1 Publication
    Disulfide bondi341 ↔ 410Combined sources1 Publication
    Glycosylationi363N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi384N-linked (GlcNAc...)Sequence analysis1
    Lipidationi423GPI-anchor amidated serine1 Publication1

    Keywords - PTMi

    Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

    Proteomic databases

    MaxQBiP14384.
    PaxDbiP14384.
    PeptideAtlasiP14384.
    PRIDEiP14384.

    PTM databases

    iPTMnetiP14384.
    PhosphoSitePlusiP14384.

    Expressioni

    Gene expression databases

    BgeeiENSG00000135678.
    CleanExiHS_CPM.
    ExpressionAtlasiP14384. baseline and differential.
    GenevisibleiP14384. HS.

    Organism-specific databases

    HPAiHPA002657.

    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
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi25 – 38Combined sources14
    Turni39 – 41Combined sources3
    Beta strandi42 – 50Combined sources9
    Beta strandi56 – 65Combined sources10
    Beta strandi75 – 80Combined sources6
    Helixi88 – 103Combined sources16
    Turni104 – 106Combined sources3
    Helixi108 – 116Combined sources9
    Beta strandi118 – 123Combined sources6
    Helixi127 – 132Combined sources6
    Beta strandi159 – 161Combined sources3
    Helixi169 – 180Combined sources12
    Beta strandi183 – 185Combined sources3
    Beta strandi188 – 190Combined sources3
    Beta strandi192 – 199Combined sources8
    Helixi205 – 207Combined sources3
    Helixi209 – 211Combined sources3
    Helixi219 – 231Combined sources13
    Turni234 – 238Combined sources5
    Beta strandi243 – 245Combined sources3
    Beta strandi252 – 255Combined sources4
    Turni256 – 258Combined sources3
    Helixi265 – 271Combined sources7
    Beta strandi279 – 287Combined sources9
    Helixi290 – 292Combined sources3
    Helixi293 – 298Combined sources6
    Helixi301 – 308Combined sources8
    Helixi309 – 312Combined sources4
    Beta strandi314 – 320Combined sources7
    Beta strandi331 – 334Combined sources4
    Beta strandi350 – 353Combined sources4
    Beta strandi357 – 365Combined sources9
    Beta strandi367 – 369Combined sources3
    Beta strandi372 – 378Combined sources7
    Beta strandi383 – 386Combined sources4
    Turni415 – 418Combined sources4

    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...

    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.
    OMAiFYSNGRE.
    OrthoDBiEOG091G06A9.
    PhylomeDBiP14384.
    TreeFamiTF315592.

    Family and domain databases

    CDDicd03866. M14_CPM. 1 hit.
    Gene3Di2.60.40.1120. 1 hit.
    InterProiIPR008969. CarboxyPept-like_regulatory.
    IPR014766. CarboxyPept_regulatory_dom.
    IPR027062. CPM.
    IPR033842. CPM_N.
    IPR000834. Peptidase_M14.
    [Graphical view]
    PANTHERiPTHR11532:SF40. PTHR11532:SF40. 1 hit.
    PfamiPF00246. Peptidase_M14. 1 hit.
    [Graphical view]
    PRINTSiPR00765. CRBOXYPTASEA.
    SMARTiSM00631. Zn_pept. 1 hit.
    [Graphical view]
    SUPFAMiSSF49464. SSF49464. 1 hit.
    PROSITEiPS00132. CARBOXYPEPT_ZN_1. 1 hit.
    PS00133. CARBOXYPEPT_ZN_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    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

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04860024R → H.Corresponds to variant rs7978197dbSNPEnsembl.1
    Natural variantiVAR_048601133V → I.Corresponds to variant rs7309831dbSNPEnsembl.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

    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

    MaxQBiP14384.
    PaxDbiP14384.
    PeptideAtlasiP14384.
    PRIDEiP14384.

    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.
    GeneCardsiCPM.
    HGNCiHGNC:2311. CPM.
    HPAiHPA002657.
    MIMi114860. gene.
    neXtProtiNX_P14384.
    OpenTargetsiENSG00000135678.
    PharmGKBiPA26828.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    BioCyciZFISH:HS06047-MONOMER.
    BRENDAi3.4.17.12. 2681.
    SABIO-RKP14384.

    Miscellaneous databases

    ChiTaRSiCPM. human.
    EvolutionaryTraceiP14384.
    GeneWikiiCPM_(gene).
    GenomeRNAii1368.
    PROiP14384.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000135678.
    CleanExiHS_CPM.
    ExpressionAtlasiP14384. baseline and differential.
    GenevisibleiP14384. HS.

    Family and domain databases

    CDDicd03866. M14_CPM. 1 hit.
    Gene3Di2.60.40.1120. 1 hit.
    InterProiIPR008969. CarboxyPept-like_regulatory.
    IPR014766. CarboxyPept_regulatory_dom.
    IPR027062. CPM.
    IPR033842. CPM_N.
    IPR000834. Peptidase_M14.
    [Graphical view]
    PANTHERiPTHR11532:SF40. PTHR11532:SF40. 1 hit.
    PfamiPF00246. Peptidase_M14. 1 hit.
    [Graphical view]
    PRINTSiPR00765. CRBOXYPTASEA.
    SMARTiSM00631. Zn_pept. 1 hit.
    [Graphical view]
    SUPFAMiSSF49464. SSF49464. 1 hit.
    PROSITEiPS00132. CARBOXYPEPT_ZN_1. 1 hit.
    PS00133. CARBOXYPEPT_ZN_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCBPM_HUMAN
    AccessioniPrimary (citable) accession number: P14384
    Secondary accession number(s): B2R800, Q9H2K9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1990
    Last sequence update: July 11, 2001
    Last modified: November 30, 2016
    This is version 171 of the entry and version 2 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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: 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

    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 one 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.