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Protein

Carboxypeptidase A4

Gene

CPA4

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

Functioni

Metalloprotease that could be involved in the histone hyperacetylation pathway (PubMed:10383164). Releases a C-terminal amino acid, with preference for -Phe, -Leu, -Ile, -Met, -Tyr and -Val (PubMed:20385563).2 Publications

Cofactori

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

Activity regulationi

Inhibited by interaction with the metallocarboxypeptidase inhibitor (MCPI) from N.versicolor that binds to the catalytic zinc ion.1 Publication

Kineticsi

  1. KM=55.6 µM for 3-(2-furyl)acryloyl-Phe-Phe1 Publication
  2. KM=19.4 µM for 3-(2-furyl)acryloyl-Phe-Leu1 Publication
  3. KM=23.3 µM for 3-(2-furyl)acryloyl-Phe-Ile1 Publication
  4. KM=40.4 µM for 3-(2-furyl)acryloyl-Phe-Met1 Publication
  5. KM=57.3 µM for 3-(2-furyl)acryloyl-Phe-Val1 Publication
  6. KM=0.329 µM for neurotensin1 Publication
  7. KM=9.23 µM for Met-enkephalin-Arg-Phe1 Publication

    pH dependencei

    Optimum pH is 8.5-9.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi181Zinc; catalytic1 Publication1
    Metal bindingi184Zinc; catalytic1 Publication1
    Binding sitei239SubstrateBy similarity1
    Metal bindingi308Zinc; catalytic1 Publication1
    Binding sitei360SubstrateBy similarity1
    Active sitei382Proton donor/acceptorBy similarity1

    GO - Molecular functioni

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

    GO - Biological processi

    • histone acetylation Source: UniProtKB
    • proteolysis Source: GO_Central

    Keywordsi

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

    Enzyme and pathway databases

    BRENDAi3.4.17.1 2681

    Protein family/group databases

    MEROPSiM14.017

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carboxypeptidase A4 (EC:3.4.17.-)
    Alternative name(s):
    Carboxypeptidase A3
    Gene namesi
    Name:CPA4
    Synonyms:CPA3
    ORF Names:UNQ694/PRO1339
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000128510.10
    HGNCiHGNC:15740 CPA4
    MIMi607635 gene
    neXtProtiNX_Q9UI42

    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

    Organism-specific databases

    DisGeNETi51200
    OpenTargetsiENSG00000128510
    PharmGKBiPA26819

    Polymorphism and mutation databases

    BioMutaiCPA4
    DMDMi61252703

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 16Sequence analysisAdd BLAST16
    PropeptideiPRO_000000435717 – 113Activation peptideSequence analysisAdd BLAST97
    ChainiPRO_0000004358114 – 421Carboxypeptidase A4Add BLAST308

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi250 ↔ 2733 Publications
    Glycosylationi260N-linked (GlcNAc...) asparagine2 Publications1

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    EPDiQ9UI42
    PaxDbiQ9UI42
    PeptideAtlasiQ9UI42
    PRIDEiQ9UI42
    ProteomicsDBi84471
    84472 [Q9UI42-2]

    PTM databases

    GlyConnecti1065
    iPTMnetiQ9UI42
    PhosphoSitePlusiQ9UI42
    SwissPalmiQ9UI42

    Expressioni

    Tissue specificityi

    Fetal expression in the adrenal gland, brain, heart, intestine, kidney, liver and lung. Except for fetal brain that shows no imprinting, expression was found preferentially from the maternal allele.

    Inductioni

    Up-regulated by inhibitors of histone dacetylation.1 Publication

    Gene expression databases

    BgeeiENSG00000128510 Expressed in 70 organ(s), highest expression level in ectocervix
    CleanExiHS_CPA3
    HS_CPA4
    ExpressionAtlasiQ9UI42 baseline and differential

    Organism-specific databases

    HPAiHPA021030

    Interactioni

    Subunit structurei

    Monomer. Interacts with LXN.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    P848753EBI-16060275,EBI-16060264From Sabellastarte magnifica.

    Protein-protein interaction databases

    BioGridi119373, 38 interactors
    DIPiDIP-60558N
    IntActiQ9UI42, 1 interactor
    STRINGi9606.ENSP00000222482

    Structurei

    Secondary structure

    1421
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ9UI42
    SMRiQ9UI42
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UI42

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni181 – 184Substrate binding4
    Regioni256 – 257Substrate bindingBy similarity2
    Regioni275 – 276Substrate binding2
    Regioni309 – 310Substrate bindingBy similarity2

    Sequence similaritiesi

    Belongs to the peptidase M14 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG2650 Eukaryota
    COG2866 LUCA
    GeneTreeiENSGT00760000119103
    HOGENOMiHOG000252967
    HOVERGENiHBG050815
    InParanoidiQ9UI42
    KOiK08637
    OMAiWKSPSTF
    OrthoDBiEOG091G0HUI
    PhylomeDBiQ9UI42
    TreeFamiTF317197

    Family and domain databases

    CDDicd03870 M14_CPA, 1 hit
    Gene3Di3.30.70.340, 1 hit
    InterProiView protein in InterPro
    IPR034248 CPA_M14_CPD
    IPR036990 M14A-like_propep
    IPR003146 M14A_act_pep
    IPR000834 Peptidase_M14
    PfamiView protein in Pfam
    PF00246 Peptidase_M14, 1 hit
    PF02244 Propep_M14, 1 hit
    PRINTSiPR00765 CRBOXYPTASEA
    SMARTiView protein in SMART
    SM00631 Zn_pept, 1 hit
    PROSITEiView protein in PROSITE
    PS00132 CARBOXYPEPT_ZN_1, 1 hit
    PS00133 CARBOXYPEPT_ZN_2, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q9UI42-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MRWILFIGAL IGSSICGQEK FFGDQVLRIN VRNGDEISKL SQLVNSNNLK
    60 70 80 90 100
    LNFWKSPSSF NRPVDVLVPS VSLQAFKSFL RSQGLEYAVT IEDLQALLDN
    110 120 130 140 150
    EDDEMQHNEG QERSSNNFNY GAYHSLEAIY HEMDNIAADF PDLARRVKIG
    160 170 180 190 200
    HSFENRPMYV LKFSTGKGVR RPAVWLNAGI HSREWISQAT AIWTARKIVS
    210 220 230 240 250
    DYQRDPAITS ILEKMDIFLL PVANPDGYVY TQTQNRLWRK TRSRNPGSSC
    260 270 280 290 300
    IGADPNRNWN ASFAGKGASD NPCSEVYHGP HANSEVEVKS VVDFIQKHGN
    310 320 330 340 350
    FKGFIDLHSY SQLLMYPYGY SVKKAPDAEE LDKVARLAAK ALASVSGTEY
    360 370 380 390 400
    QVGPTCTTVY PASGSSIDWA YDNGIKFAFT FELRDTGTYG FLLPANQIIP
    410 420
    TAEETWLGLK TIMEHVRDNL Y
    Length:421
    Mass (Da):47,351
    Last modified:March 15, 2005 - v2
    Checksum:i52750CC50B470EC9
    GO
    Isoform 2 (identifier: Q9UI42-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         96-128: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:388
    Mass (Da):43,570
    Checksum:i088297ACC9D70264
    GO

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    C9J3P4C9J3P4_HUMAN
    Carboxypeptidase A4
    CPA4
    171Annotation score:
    C9J6N7C9J6N7_HUMAN
    Carboxypeptidase A4
    CPA4
    177Annotation score:
    B7Z5J4B7Z5J4_HUMAN
    Carboxypeptidase A4
    CPA4
    317Annotation score:
    C9J7D6C9J7D6_HUMAN
    Carboxypeptidase A4
    CPA4
    29Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti18Q → R in AAF23230 (PubMed:10383164).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04859427L → F. Corresponds to variant dbSNP:rs34587586Ensembl.1
    Natural variantiVAR_020393157P → T. Corresponds to variant dbSNP:rs3735051Ensembl.1
    Natural variantiVAR_048595183R → L. Corresponds to variant dbSNP:rs3735053Ensembl.1
    Natural variantiVAR_020394303G → C. Corresponds to variant dbSNP:rs2171492Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_04289496 – 128Missing in isoform 2. 1 PublicationAdd BLAST33

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF095719 mRNA Translation: AAF23230.1
    AY358699 mRNA Translation: AAQ89062.1
    AK298550 mRNA Translation: BAH12812.1
    AC024085 Genomic DNA No translation available.
    BC052289 mRNA Translation: AAH52289.1
    CCDSiCCDS55163.1 [Q9UI42-2]
    CCDS5818.1 [Q9UI42-1]
    RefSeqiNP_001156918.1, NM_001163446.1 [Q9UI42-2]
    NP_057436.2, NM_016352.3 [Q9UI42-1]
    UniGeneiHs.93764

    Genome annotation databases

    EnsembliENST00000222482; ENSP00000222482; ENSG00000128510 [Q9UI42-1]
    ENST00000445470; ENSP00000412947; ENSG00000128510 [Q9UI42-2]
    GeneIDi51200
    KEGGihsa:51200
    UCSCiuc003vpr.4 human [Q9UI42-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF095719 mRNA Translation: AAF23230.1
    AY358699 mRNA Translation: AAQ89062.1
    AK298550 mRNA Translation: BAH12812.1
    AC024085 Genomic DNA No translation available.
    BC052289 mRNA Translation: AAH52289.1
    CCDSiCCDS55163.1 [Q9UI42-2]
    CCDS5818.1 [Q9UI42-1]
    RefSeqiNP_001156918.1, NM_001163446.1 [Q9UI42-2]
    NP_057436.2, NM_016352.3 [Q9UI42-1]
    UniGeneiHs.93764

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2BO9X-ray1.60A/C114-421[»]
    2BOAX-ray2.20A/B19-421[»]
    2PCUX-ray1.60A116-420[»]
    4A94X-ray1.70A/B112-421[»]
    4BD9X-ray2.20A112-421[»]
    ProteinModelPortaliQ9UI42
    SMRiQ9UI42
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi119373, 38 interactors
    DIPiDIP-60558N
    IntActiQ9UI42, 1 interactor
    STRINGi9606.ENSP00000222482

    Protein family/group databases

    MEROPSiM14.017

    PTM databases

    GlyConnecti1065
    iPTMnetiQ9UI42
    PhosphoSitePlusiQ9UI42
    SwissPalmiQ9UI42

    Polymorphism and mutation databases

    BioMutaiCPA4
    DMDMi61252703

    Proteomic databases

    EPDiQ9UI42
    PaxDbiQ9UI42
    PeptideAtlasiQ9UI42
    PRIDEiQ9UI42
    ProteomicsDBi84471
    84472 [Q9UI42-2]

    Protocols and materials databases

    DNASUi51200
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000222482; ENSP00000222482; ENSG00000128510 [Q9UI42-1]
    ENST00000445470; ENSP00000412947; ENSG00000128510 [Q9UI42-2]
    GeneIDi51200
    KEGGihsa:51200
    UCSCiuc003vpr.4 human [Q9UI42-1]

    Organism-specific databases

    CTDi51200
    DisGeNETi51200
    EuPathDBiHostDB:ENSG00000128510.10
    GeneCardsiCPA4
    HGNCiHGNC:15740 CPA4
    HPAiHPA021030
    MIMi607635 gene
    neXtProtiNX_Q9UI42
    OpenTargetsiENSG00000128510
    PharmGKBiPA26819
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2650 Eukaryota
    COG2866 LUCA
    GeneTreeiENSGT00760000119103
    HOGENOMiHOG000252967
    HOVERGENiHBG050815
    InParanoidiQ9UI42
    KOiK08637
    OMAiWKSPSTF
    OrthoDBiEOG091G0HUI
    PhylomeDBiQ9UI42
    TreeFamiTF317197

    Enzyme and pathway databases

    BRENDAi3.4.17.1 2681

    Miscellaneous databases

    ChiTaRSiCPA4 human
    EvolutionaryTraceiQ9UI42
    GeneWikiiCPA4_(gene)
    GenomeRNAii51200
    PROiPR:Q9UI42
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000128510 Expressed in 70 organ(s), highest expression level in ectocervix
    CleanExiHS_CPA3
    HS_CPA4
    ExpressionAtlasiQ9UI42 baseline and differential

    Family and domain databases

    CDDicd03870 M14_CPA, 1 hit
    Gene3Di3.30.70.340, 1 hit
    InterProiView protein in InterPro
    IPR034248 CPA_M14_CPD
    IPR036990 M14A-like_propep
    IPR003146 M14A_act_pep
    IPR000834 Peptidase_M14
    PfamiView protein in Pfam
    PF00246 Peptidase_M14, 1 hit
    PF02244 Propep_M14, 1 hit
    PRINTSiPR00765 CRBOXYPTASEA
    SMARTiView protein in SMART
    SM00631 Zn_pept, 1 hit
    PROSITEiView protein in PROSITE
    PS00132 CARBOXYPEPT_ZN_1, 1 hit
    PS00133 CARBOXYPEPT_ZN_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCBPA4_HUMAN
    AccessioniPrimary (citable) accession number: Q9UI42
    Secondary accession number(s): B7Z576, Q86UY9
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 13, 2001
    Last sequence update: March 15, 2005
    Last modified: November 7, 2018
    This is version 159 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, 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 7
      Human chromosome 7: entries, gene names and cross-references to MIM
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