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Protein

Carboxypeptidase A6

Gene

CPA6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May be involved in the proteolytic inactivation of enkephalins and neurotensin in some brain areas. May convert inactive angiotensin I into the biologically active angiotensin II.1 Publication

Catalytic activityi

Release of a C-terminal amino acid, with preference for large hydrophobic C-terminal amino acids and only very weak activity toward small amino acids and histidine.1 Publication

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Kineticsi

  1. KM=266 µM for 3-(2-furyl)acryloyl-Phe-Phe1 Publication
  2. KM=100 µM for 3-(2-furyl)acryloyl-Phe-Tyr1 Publication
  3. KM=386 µM for 3-(2-furyl)acryloyl-Phe-Leu1 Publication
  4. KM=339 µM for 3-(2-furyl)acryloyl-Phe-Trp1 Publication
  5. KM=786 µM for 3-(2-furyl)acryloyl-Phe-Met1 Publication

    pH dependencei

    Optimum pH is 8.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi196Zinc; catalyticBy similarity1
    Metal bindingi199Zinc; catalyticBy similarity1
    Binding sitei254SubstrateBy similarity1
    Metal bindingi324Zinc; catalyticBy similarity1
    Binding sitei376SubstrateBy similarity1
    Active sitei398Proton donor/acceptorBy similarity1

    GO - Molecular functioni

    • metallocarboxypeptidase activity Source: UniProtKB
    • zinc ion binding Source: InterPro
    Complete GO annotation...

    Keywords - Molecular functioni

    Carboxypeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciZFISH:HS09181-MONOMER.

    Protein family/group databases

    MEROPSiM14.018.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carboxypeptidase A6 (EC:3.4.17.-)
    Gene namesi
    Name:CPA6
    Synonyms:CPAH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:17245. CPA6.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    A chromosomal aberration involving CPA6 was found in a patient with Duane retraction syndrome. Translocation t(6;8)(q26;q13).

    Epilepsy, familial temporal lobe, 5 (ETL5)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature.
    See also OMIM:614417
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_066946267G → R in ETL5; affects protein secretion presumably by altering protein folding or stability. 1 PublicationCorresponds to variant rs61738009dbSNPEnsembl.1
    Febrile seizures, familial, 11 (FEB11)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionSeizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy.
    See also OMIM:614418
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_066947270A → V in FEB11; affects protein secretion presumably by altering protein folding or stability. 1 PublicationCorresponds to variant rs114402678dbSNPEnsembl.1

    Keywords - Diseasei

    Disease mutation, Epilepsy

    Organism-specific databases

    DisGeNETi57094.
    MalaCardsiCPA6.
    MIMi614417. phenotype.
    614418. phenotype.
    OpenTargetsiENSG00000165078.
    Orphaneti165805. Familial mesial temporal lobe epilepsy with febrile seizures.
    PharmGKBiPA38444.

    Polymorphism and mutation databases

    BioMutaiCPA6.
    DMDMi85683250.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 30Sequence analysisAdd BLAST30
    PropeptideiPRO_000000436531 – 129Activation peptideBy similarityAdd BLAST99
    ChainiPRO_0000004366130 – 437Carboxypeptidase A6Add BLAST308

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi89N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi153N-linked (GlcNAc...)Sequence analysis1
    Disulfide bondi265 ↔ 288By similarity
    Glycosylationi427N-linked (GlcNAc...)Sequence analysis1

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PaxDbiQ8N4T0.
    PeptideAtlasiQ8N4T0.
    PRIDEiQ8N4T0.

    PTM databases

    iPTMnetiQ8N4T0.
    PhosphoSitePlusiQ8N4T0.

    Expressioni

    Tissue specificityi

    Expressed in the hippocampus, nucleus raphe, and cortex.1 Publication

    Gene expression databases

    BgeeiENSG00000165078.
    CleanExiHS_CPA6.
    ExpressionAtlasiQ8N4T0. baseline and differential.
    GenevisibleiQ8N4T0. HS.

    Interactioni

    Protein-protein interaction databases

    BioGridi121362. 11 interactors.
    STRINGi9606.ENSP00000297770.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8N4T0.
    SMRiQ8N4T0.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni196 – 199Substrate bindingBy similarity4
    Regioni271 – 272Substrate bindingBy similarity2
    Regioni325 – 326Substrate bindingBy similarity2

    Sequence similaritiesi

    Belongs to the peptidase M14 family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG2650. Eukaryota.
    COG2866. LUCA.
    GeneTreeiENSGT00760000119103.
    HOGENOMiHOG000252968.
    HOVERGENiHBG050815.
    InParanoidiQ8N4T0.
    KOiK08782.
    OMAiRKHIRAY.
    OrthoDBiEOG091G0HUI.
    PhylomeDBiQ8N4T0.
    TreeFamiTF317197.

    Family and domain databases

    CDDicd03872. M14_CPA6. 1 hit.
    Gene3Di3.30.70.340. 1 hit.
    InterProiIPR033843. CPAH.
    IPR003146. M14A_act_pep.
    IPR000834. Peptidase_M14.
    IPR009020. Propept_inh.
    [Graphical view]
    PfamiPF00246. Peptidase_M14. 1 hit.
    PF02244. Propep_M14. 1 hit.
    [Graphical view]
    PRINTSiPR00765. CRBOXYPTASEA.
    SMARTiSM00631. Zn_pept. 1 hit.
    [Graphical view]
    SUPFAMiSSF54897. SSF54897. 1 hit.
    PROSITEiPS00133. CARBOXYPEPT_ZN_2. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q8N4T0-1) [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
    MKCLGKRRGQ AAAFLPLCWL FLKILQPGHS HLYNNRYAGD KVIRFIPKTE
    60 70 80 90 100
    EEAYALKKIS YQLKVDLWQP SSISYVSEGT VTDVHIPQNG SRALLAFLQE
    110 120 130 140 150
    ANIQYKVLIE DLQKTLEKGS SLHTQRNRRS LSGYNYEVYH SLEEIQNWMH
    160 170 180 190 200
    HLNKTHSGLI HMFSIGRSYE GRSLFILKLG RRSRLKRAVW IDCGIHAREW
    210 220 230 240 250
    IGPAFCQWFV KEALLTYKSD PAMRKMLNHL YFYIMPVFNV DGYHFSWTND
    260 270 280 290 300
    RFWRKTRSRN SRFRCRGVDA NRNWKVKWCD EGASMHPCDD TYCGPFPESE
    310 320 330 340 350
    PEVKAVANFL RKHRKHIRAY LSFHAYAQML LYPYSYKYAT IPNFRCVESA
    360 370 380 390 400
    AYKAVNALQS VYGVRYRYGP ASTTLYVSSG SSMDWAYKNG IPYAFAFELR
    410 420 430
    DTGYFGFLLP EMLIKPTCTE TMLAVKNITM HLLKKCP
    Length:437
    Mass (Da):51,008
    Last modified:January 24, 2006 - v2
    Checksum:i9C21780D4B7D0A98
    GO
    Isoform 2 (identifier: Q8N4T0-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         280-437: DEGASMHPCD...ITMHLLKKCP → GKFGTNWDPD...SHGRLMFFCM

    Note: May be due to intron retention. No experimental confirmation available.
    Show »
    Length:315
    Mass (Da):37,070
    Checksum:iECAA4B2F7F822684
    GO
    Isoform 3 (identifier: Q8N4T0-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         65-92: VDLWQPSSISYVSEGTVTDVHIPQNGSR → GPHRRSSENTGEGKQLAHPEKPKIPLWI
         93-437: Missing.

    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
    Show »
    Length:92
    Mass (Da):10,612
    Checksum:iAEBBD1313BB8F61C
    GO

    Sequence cautioni

    The sequence AAK84941 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02424145F → L.Corresponds to variant rs10957393dbSNPEnsembl.1
    Natural variantiVAR_025003173S → C.2 PublicationsCorresponds to variant rs17853192dbSNPEnsembl.1
    Natural variantiVAR_048597249N → S.Corresponds to variant rs17343819dbSNPEnsembl.1
    Natural variantiVAR_066946267G → R in ETL5; affects protein secretion presumably by altering protein folding or stability. 1 PublicationCorresponds to variant rs61738009dbSNPEnsembl.1
    Natural variantiVAR_066947270A → V in FEB11; affects protein secretion presumably by altering protein folding or stability. 1 PublicationCorresponds to variant rs114402678dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_05837565 – 92VDLWQ…QNGSR → GPHRRSSENTGEGKQLAHPE KPKIPLWI in isoform 3. 1 PublicationAdd BLAST28
    Alternative sequenceiVSP_05837693 – 437Missing in isoform 3. 1 PublicationAdd BLAST345
    Alternative sequenceiVSP_008808280 – 437DEGAS…LKKCP → GKFGTNWDPDPKVSAGFTLQ NMSPEDSHGRLMFFCM in isoform 2. 1 PublicationAdd BLAST158

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF466284 Genomic DNA. Translation: AAM19307.1.
    BK000188 mRNA. Translation: DAA00037.1.
    AY044833 mRNA. Translation: AAK84941.1. Sequence problems.
    AF221594 mRNA. Translation: AAF91231.1.
    BC033684 mRNA. Translation: AAH33684.1.
    CCDSiCCDS6200.1. [Q8N4T0-1]
    RefSeqiNP_065094.3. NM_020361.4. [Q8N4T0-1]
    UniGeneiHs.658850.

    Genome annotation databases

    EnsembliENST00000297770; ENSP00000297770; ENSG00000165078. [Q8N4T0-1]
    ENST00000479862; ENSP00000419016; ENSG00000165078. [Q8N4T0-3]
    ENST00000518549; ENSP00000431112; ENSG00000165078. [Q8N4T0-2]
    GeneIDi57094.
    KEGGihsa:57094.
    UCSCiuc003xxq.5. human. [Q8N4T0-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF466284 Genomic DNA. Translation: AAM19307.1.
    BK000188 mRNA. Translation: DAA00037.1.
    AY044833 mRNA. Translation: AAK84941.1. Sequence problems.
    AF221594 mRNA. Translation: AAF91231.1.
    BC033684 mRNA. Translation: AAH33684.1.
    CCDSiCCDS6200.1. [Q8N4T0-1]
    RefSeqiNP_065094.3. NM_020361.4. [Q8N4T0-1]
    UniGeneiHs.658850.

    3D structure databases

    ProteinModelPortaliQ8N4T0.
    SMRiQ8N4T0.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi121362. 11 interactors.
    STRINGi9606.ENSP00000297770.

    Protein family/group databases

    MEROPSiM14.018.

    PTM databases

    iPTMnetiQ8N4T0.
    PhosphoSitePlusiQ8N4T0.

    Polymorphism and mutation databases

    BioMutaiCPA6.
    DMDMi85683250.

    Proteomic databases

    PaxDbiQ8N4T0.
    PeptideAtlasiQ8N4T0.
    PRIDEiQ8N4T0.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000297770; ENSP00000297770; ENSG00000165078. [Q8N4T0-1]
    ENST00000479862; ENSP00000419016; ENSG00000165078. [Q8N4T0-3]
    ENST00000518549; ENSP00000431112; ENSG00000165078. [Q8N4T0-2]
    GeneIDi57094.
    KEGGihsa:57094.
    UCSCiuc003xxq.5. human. [Q8N4T0-1]

    Organism-specific databases

    CTDi57094.
    DisGeNETi57094.
    GeneCardsiCPA6.
    H-InvDBHIX0007565.
    HGNCiHGNC:17245. CPA6.
    MalaCardsiCPA6.
    MIMi609562. gene.
    614417. phenotype.
    614418. phenotype.
    neXtProtiNX_Q8N4T0.
    OpenTargetsiENSG00000165078.
    Orphaneti165805. Familial mesial temporal lobe epilepsy with febrile seizures.
    PharmGKBiPA38444.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2650. Eukaryota.
    COG2866. LUCA.
    GeneTreeiENSGT00760000119103.
    HOGENOMiHOG000252968.
    HOVERGENiHBG050815.
    InParanoidiQ8N4T0.
    KOiK08782.
    OMAiRKHIRAY.
    OrthoDBiEOG091G0HUI.
    PhylomeDBiQ8N4T0.
    TreeFamiTF317197.

    Enzyme and pathway databases

    BioCyciZFISH:HS09181-MONOMER.

    Miscellaneous databases

    GeneWikiiCarboxypeptidase_A6.
    GenomeRNAii57094.
    PROiQ8N4T0.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000165078.
    CleanExiHS_CPA6.
    ExpressionAtlasiQ8N4T0. baseline and differential.
    GenevisibleiQ8N4T0. HS.

    Family and domain databases

    CDDicd03872. M14_CPA6. 1 hit.
    Gene3Di3.30.70.340. 1 hit.
    InterProiIPR033843. CPAH.
    IPR003146. M14A_act_pep.
    IPR000834. Peptidase_M14.
    IPR009020. Propept_inh.
    [Graphical view]
    PfamiPF00246. Peptidase_M14. 1 hit.
    PF02244. Propep_M14. 1 hit.
    [Graphical view]
    PRINTSiPR00765. CRBOXYPTASEA.
    SMARTiSM00631. Zn_pept. 1 hit.
    [Graphical view]
    SUPFAMiSSF54897. SSF54897. 1 hit.
    PROSITEiPS00133. CARBOXYPEPT_ZN_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCBPA6_HUMAN
    AccessioniPrimary (citable) accession number: Q8N4T0
    Secondary accession number(s): Q8NEX8, Q8TDE8, Q9NRI9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 7, 2003
    Last sequence update: January 24, 2006
    Last modified: November 30, 2016
    This is version 139 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: 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. Peptidase families
      Classification of peptidase families and list of entries
    6. 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.