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Q8N4T0 (CBPA6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carboxypeptidase A6

EC=3.4.17.-
Gene names
Name:CPA6
Synonyms:CPAH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length437 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5

Catalytic activity

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. Ref.6

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subcellular location

Secretedextracellular spaceextracellular matrix Ref.5.

Tissue specificity

Expressed in the hippocampus, nucleus raphe, and cortex. Ref.7

Involvement in disease

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) [MIM:614417]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Febrile seizures, familial, 11 (FEB11) [MIM:614418]: Seizures 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the peptidase M14 family.

Biophysicochemical properties

Kinetic parameters:

KM=266 µM for 3-(2-furyl)acryloyl-Phe-Phe Ref.6

KM=100 µM for 3-(2-furyl)acryloyl-Phe-Tyr

KM=386 µM for 3-(2-furyl)acryloyl-Phe-Leu

KM=339 µM for 3-(2-furyl)acryloyl-Phe-Trp

KM=786 µM for 3-(2-furyl)acryloyl-Phe-Met

pH dependence:

Optimum pH is 8.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N4T0-1)

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.
Isoform 2 (identifier: Q8N4T0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     280-437: DEGASMHPCD...ITMHLLKKCP → GKFGTNWDPD...SHGRLMFFCM
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8N4T0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-148: Missing.
     281-376: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Propeptide31 – 12999Activation peptide By similarity
PRO_0000004365
Chain130 – 437308Carboxypeptidase A6
PRO_0000004366

Regions

Region196 – 1994Substrate binding By similarity
Region271 – 2722Substrate binding By similarity
Region325 – 3262Substrate binding By similarity

Sites

Active site3981Nucleophile By similarity
Metal binding1961Zinc; catalytic By similarity
Metal binding1991Zinc; catalytic By similarity
Metal binding3241Zinc; catalytic By similarity
Binding site2541Substrate By similarity

Amino acid modifications

Glycosylation891N-linked (GlcNAc...) Potential
Glycosylation1531N-linked (GlcNAc...) Potential
Glycosylation4271N-linked (GlcNAc...) Potential
Disulfide bond265 ↔ 288 By similarity

Natural variations

Alternative sequence1 – 148148Missing in isoform 3.
VSP_017079
Alternative sequence280 – 437158DEGAS…LKKCP → GKFGTNWDPDPKVSAGFTLQ NMSPEDSHGRLMFFCM in isoform 2.
VSP_008808
Alternative sequence281 – 37696Missing in isoform 3.
VSP_017080
Natural variant451F → L.
Corresponds to variant rs10957393 [ dbSNP | Ensembl ].
VAR_024241
Natural variant1731S → C. Ref.3 Ref.4
Corresponds to variant rs17853192 [ dbSNP | Ensembl ].
VAR_025003
Natural variant2491N → S.
Corresponds to variant rs17343819 [ dbSNP | Ensembl ].
VAR_048597
Natural variant2671G → R in ETL5; affects protein secretion presumably by altering protein folding or stability. Ref.7
VAR_066946
Natural variant2701A → V in FEB11; affects protein secretion presumably by altering protein folding or stability. Ref.7
Corresponds to variant rs114402678 [ dbSNP | Ensembl ].
VAR_066947

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 24, 2006. Version 2.
Checksum: 9C21780D4B7D0A98

FASTA43751,008
        10         20         30         40         50         60 
MKCLGKRRGQ AAAFLPLCWL FLKILQPGHS HLYNNRYAGD KVIRFIPKTE EEAYALKKIS 

        70         80         90        100        110        120 
YQLKVDLWQP SSISYVSEGT VTDVHIPQNG SRALLAFLQE ANIQYKVLIE DLQKTLEKGS 

       130        140        150        160        170        180 
SLHTQRNRRS LSGYNYEVYH SLEEIQNWMH HLNKTHSGLI HMFSIGRSYE GRSLFILKLG 

       190        200        210        220        230        240 
RRSRLKRAVW IDCGIHAREW IGPAFCQWFV KEALLTYKSD PAMRKMLNHL YFYIMPVFNV 

       250        260        270        280        290        300 
DGYHFSWTND RFWRKTRSRN SRFRCRGVDA NRNWKVKWCD EGASMHPCDD TYCGPFPESE 

       310        320        330        340        350        360 
PEVKAVANFL RKHRKHIRAY LSFHAYAQML LYPYSYKYAT IPNFRCVESA AYKAVNALQS 

       370        380        390        400        410        420 
VYGVRYRYGP ASTTLYVSSG SSMDWAYKNG IPYAFAFELR DTGYFGFLLP EMLIKPTCTE 

       430 
TMLAVKNITM HLLKKCP 

« Hide

Isoform 2 [UniParc].

Checksum: ECAA4B2F7F822684
Show »

FASTA31537,070
Isoform 3 [UniParc].

Checksum: 3E8C11586C557024
Show »

FASTA19322,889

References

« Hide 'large scale' references
[1]"Identification and characterization of three members of the human metallocarboxypeptidase gene family."
Wei S., Segura S., Vendrell J., Aviles F.X., Lanoue E., Day R., Feng Y., Fricker L.D.
J. Biol. Chem. 277:14954-14964(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]"A peptidase gene in chromosome 8q is disrupted by a balanced translocation in a duane syndrome patient."
Pizzuti A., Calabrese G., Bozzali M., Telvi L., Morizio E., Guida V., Gatta V., Stuppia L., Ion A., Palka G., Dallapiccola B.
Invest. Ophthalmol. Vis. Sci. 43:3609-3612(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), CHROMOSOMAL TRANSLOCATION.
Tissue: Retina.
[3]"Novel genes expressed in hematopoietic stem/progenitor cells from myelodysplastic syndrome patients."
Gu J., Huang Q., Yu Y., Xu S., Han Z., Fu G., Chen Z.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT CYS-173.
Tissue: Hematopoietic stem cell.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT CYS-173.
Tissue: Brain.
[5]"Characterization of carboxypeptidase A6, an extracellular matrix peptidase."
Lyons P.J., Callaway M.B., Fricker L.D.
J. Biol. Chem. 283:7054-7063(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, SUBSTRATE SPECIFICITY.
[6]"Substrate specificity of human carboxypeptidase A6."
Lyons P.J., Fricker L.D.
J. Biol. Chem. 285:38234-38242(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
[7]"Carboxypeptidase A6 gene (CPA6) mutations in a recessive familial form of febrile seizures and temporal lobe epilepsy and in sporadic temporal lobe epilepsy."
Salzmann A., Guipponi M., Lyons P.J., Fricker L.D., Sapio M., Lambercy C., Buresi C., Bencheikh B.O., Lahjouji F., Ouazzani R., Crespel A., Chaigne D., Malafosse A.
Hum. Mutat. 33:124-135(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANT ETL5 ARG-267, VARIANT FEB11 VAL-270, CHARACTERIZATION OF VARIANT ETL5 ARG-267, CHARACTERIZATION OF VARIANT FEB11 VAL-270.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF466284 Genomic DNA. Translation: AAM19307.1.
BK000188 mRNA. Translation: DAA00037.1.
AY044833 mRNA. Translation: AAK84941.1.
AF221594 mRNA. Translation: AAF91231.1.
BC033684 mRNA. Translation: AAH33684.1.
RefSeqNP_065094.3. NM_020361.4.
UniGeneHs.658850.

3D structure databases

ProteinModelPortalQ8N4T0.
SMRQ8N4T0. Positions 37-433.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000297770.

Chemistry

BindingDBQ8N4T0.

Protein family/group databases

MEROPSM14.018.

PTM databases

PhosphoSiteQ8N4T0.

Polymorphism databases

DMDM85683250.

Proteomic databases

PaxDbQ8N4T0.
PRIDEQ8N4T0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297769; ENSP00000297769; ENSG00000165078. [Q8N4T0-3]
ENST00000297770; ENSP00000297770; ENSG00000165078. [Q8N4T0-1]
ENST00000518549; ENSP00000431112; ENSG00000165078. [Q8N4T0-2]
GeneID57094.
KEGGhsa:57094.
UCSCuc003xxq.4. human. [Q8N4T0-1]
uc003xxr.4. human. [Q8N4T0-3]
uc003xxs.2. human. [Q8N4T0-2]

Organism-specific databases

CTD57094.
GeneCardsGC08M068384.
H-InvDBHIX0007565.
HGNCHGNC:17245. CPA6.
MIM609562. gene.
614417. phenotype.
614418. phenotype.
neXtProtNX_Q8N4T0.
Orphanet165805. Familial mesial temporal lobe epilepsy with febrile seizures.
PharmGKBPA38444.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2866.
HOGENOMHOG000252968.
HOVERGENHBG050815.
InParanoidQ8N4T0.
KOK08782.
OMARKHIRAY.
PhylomeDBQ8N4T0.
TreeFamTF317197.

Gene expression databases

ArrayExpressQ8N4T0.
BgeeQ8N4T0.
CleanExHS_CPA6.
GenevestigatorQ8N4T0.

Family and domain databases

Gene3D3.30.70.340. 1 hit.
InterProIPR000834. Peptidase_M14.
IPR003146. Prot_inh_M14A.
IPR009020. Prot_inh_propept.
[Graphical view]
PfamPF00246. Peptidase_M14. 1 hit.
PF02244. Propep_M14. 1 hit.
[Graphical view]
PRINTSPR00765. CRBOXYPTASEA.
SMARTSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMSSF54897. SSF54897. 1 hit.
PROSITEPS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCarboxypeptidase_A6.
GenomeRNAi57094.
NextBio62909.
PROQ8N4T0.
SOURCESearch...

Entry information

Entry nameCBPA6_HUMAN
AccessionPrimary (citable) accession number: Q8N4T0
Secondary accession number(s): Q8NEX8, Q8TDE8, Q9NRI9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: January 24, 2006
Last modified: April 16, 2014
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM