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P16499 (PDE6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha

Short name=GMP-PDE alpha
EC=3.1.4.35
Alternative name(s):
PDE V-B1
Gene names
Name:PDE6A
Synonyms:PDEA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length860 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This protein participates in processes of transmission and amplification of the visual signal.

Catalytic activity

Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.

Cofactor

Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions By similarity.

Subunit structure

Oligomer composed of two catalytic chains (alpha and beta), an inhibitory chain (gamma) and the delta chain.

Subcellular location

Cell membrane; Lipid-anchor; Cytoplasmic side Potential.

Involvement in disease

Retinitis pigmentosa 43 (RP43) [MIM:613810]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Contains 2 GAF domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 857856Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha
PRO_0000198828
Propeptide858 – 8603Removed in mature form By similarity
PRO_0000396697

Regions

Domain73 – 222150GAF 1
Domain254 – 431178GAF 2

Sites

Active site5591Proton donor By similarity
Metal binding5631Divalent metal cation 1 By similarity
Metal binding5991Divalent metal cation 1 By similarity
Metal binding6001Divalent metal cation 1 By similarity
Metal binding6001Divalent metal cation 2 By similarity
Metal binding7201Divalent metal cation 1 By similarity

Amino acid modifications

Modified residue21N-acetylglycine By similarity
Modified residue8571Cysteine methyl ester By similarity
Lipidation8571S-farnesyl cysteine By similarity

Natural variations

Natural variant1021R → H in RP43. Ref.6
VAR_025460
Natural variant1021R → S in RP43. Ref.6
VAR_025461
Natural variant1451A → T.
Corresponds to variant rs35431421 [ dbSNP | Ensembl ].
VAR_047730
Natural variant2161N → S. Ref.6
Corresponds to variant rs10057110 [ dbSNP | Ensembl ].
VAR_025462
Natural variant2771V → A. Ref.6
VAR_025463
Natural variant2931P → L. Ref.6
Corresponds to variant rs114973968 [ dbSNP | Ensembl ].
VAR_025464
Natural variant3441S → R in RP43. Ref.5
VAR_006049
Natural variant3911V → M. Ref.6
Corresponds to variant rs61732059 [ dbSNP | Ensembl ].
VAR_025465
Natural variant4921Q → H.
Corresponds to variant rs17711594 [ dbSNP | Ensembl ].
VAR_047731
Natural variant5691Q → K in RP43. Ref.6
VAR_025466
Natural variant5731S → P in RP43. Ref.6
VAR_025467
Natural variant8271K → Q. Ref.6
VAR_025468
Natural variant8501G → V. Ref.6
Corresponds to variant rs138315990 [ dbSNP | Ensembl ].
VAR_025469

Experimental info

Sequence conflict2241V → W in AAB69155. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P16499 [UniParc].

Last modified November 25, 2008. Version 4.
Checksum: 7EEA48A234C1FE59

FASTA86099,547
        10         20         30         40         50         60 
MGEVTAEEVE KFLDSNIGFA KQYYNLHYRA KLISDLLGAK EAAVDFSNYH SPSSMEESEI 

        70         80         90        100        110        120 
IFDLLRDFQE NLQTEKCIFN VMKKLCFLLQ ADRMSLFMYR TRNGIAELAT RLFNVHKDAV 

       130        140        150        160        170        180 
LEDCLVMPDQ EIVFPLDMGI VGHVAHSKKI ANVPNTEEDE HFCDFVDILT EYKTKNILAS 

       190        200        210        220        230        240 
PIMNGKDVVA IIMAVNKVDG SHFTKRDEEI LLKYLNFANL IMKVYHLSYL HNCETRRGQI 

       250        260        270        280        290        300 
LLWSGSKVFE ELTDIERQFH KALYTVRAFL NCDRYSVGLL DMTKQKEFFD VWPVLMGEVP 

       310        320        330        340        350        360 
PYSGPRTPDG REINFYKVID YILHGKEDIK VIPNPPPDHW ALVSGLPAYV AQNGLICNIM 

       370        380        390        400        410        420 
NAPAEDFFAF QKEPLDESGW MIKNVLSMPI VNKKEEIVGV ATFYNRKDGK PFDEMDETLM 

       430        440        450        460        470        480 
ESLTQFLGWS VLNPDTYESM NKLENRKDIF QDIVKYHVKC DNEEIQKILK TREVYGKEPW 

       490        500        510        520        530        540 
ECEEEELAEI LQAELPDADK YEINKFHFSD LPLTELELVK CGIQMYYELK VVDKFHIPQE 

       550        560        570        580        590        600 
ALVRFMYSLS KGYRKITYHN WRHGFNVGQT MFSLLVTGKL KRYFTDLEAL AMVTAAFCHD 

       610        620        630        640        650        660 
IDHRGTNNLY QMKSQNPLAK LHGSSILERH HLEFGKTLLR DESLNIFQNL NRRQHEHAIH 

       670        680        690        700        710        720 
MMDIAIIATD LALYFKKRTM FQKIVDQSKT YESEQEWTQY MMLEQTRKEI VMAMMMTACD 

       730        740        750        760        770        780 
LSAITKPWEV QSQVALLVAA EFWEQGDLER TVLQQNPIPM MDRNKADELP KLQVGFIDFV 

       790        800        810        820        830        840 
CTFVYKEFSR FHEEITPMLD GITNNRKEWK ALADEYDAKM KVQEEKKQKQ QSAKSAAAGN 

       850        860 
QPGGNPSPGG ATTSKSCCIQ 

« Hide

References

« Hide 'large scale' references
[1]"Molecular characterization of human and bovine rod photoreceptor cGMP phosphodiesterase alpha-subunit and chromosomal localization of the human gene."
Pittler S.J., Baehr W., Wasmuth J.J., McConnell D.G., Champagne M.S., VanTuinen P., Ledbetter D., Davis R.L.
Genomics 6:272-283(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Pittler S.J., Baehr W., Wasmuth J.J., McConnell D.G., Champagne M.S., Vantuinen P., Ledbetter D., Davis R.L.
Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 846-849.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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].
Tissue: Eye.
[5]"Autosomal recessive retinitis pigmentosa caused by mutations in the alpha subunit of rod cGMP phosphodiesterase."
Huang S.H., Pittler S.J., Huang X., Oliveira L., Berson E.L., Dryja T.P.
Nat. Genet. 11:468-471(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RP43 ARG-344.
[6]"Frequency of mutations in the gene encoding the alpha subunit of rod cGMP-phosphodiesterase in autosomal recessive retinitis pigmentosa."
Dryja T.P., Rucinski D.E., Chen S.H., Berson E.L.
Invest. Ophthalmol. Vis. Sci. 40:1859-1865(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS RP43 HIS-102; SER-102; LYS-569 AND PRO-573, VARIANTS SER-216; ALA-277; LEU-293; MET-391; GLN-827 AND VAL-850.
+Additional computationally mapped references.

Web resources

Mutations of the PDE6A/B/G genes

Retina International's Scientific Newsletter

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M26061 mRNA. Translation: AAB69155.1.
CH471062 Genomic DNA. Translation: EAW61757.1.
BC035909 mRNA. Translation: AAH35909.1.
CCDSCCDS4299.1.
PIRB34611.
RefSeqNP_000431.2. NM_000440.2.
UniGeneHs.567314.

3D structure databases

ProteinModelPortalP16499.
SMRP16499. Positions 31-816.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111171. 1 interaction.
STRING9606.ENSP00000255266.

Chemistry

BindingDBP16499.
ChEMBLCHEMBL2097163.

PTM databases

PhosphoSiteP16499.

Polymorphism databases

DMDM215274230.

Proteomic databases

PaxDbP16499.
PRIDEP16499.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000255266; ENSP00000255266; ENSG00000132915.
GeneID5145.
KEGGhsa:5145.
UCSCuc003lrg.4. human.

Organism-specific databases

CTD5145.
GeneCardsGC05M149220.
GeneReviewsPDE6A.
HGNCHGNC:8785. PDE6A.
HPAHPA016970.
MIM180071. gene.
613810. phenotype.
neXtProtNX_P16499.
Orphanet791. Retinitis pigmentosa.
PharmGKBPA33133.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG242608.
HOGENOMHOG000007069.
HOVERGENHBG053539.
InParanoidP16499.
KOK08718.
OMAQMYYELK.
OrthoDBEOG7BGHK1.
PhylomeDBP16499.
TreeFamTF316499.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpressP16499.
BgeeP16499.
CleanExHS_PDE6A.
GenevestigatorP16499.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
3.30.450.40. 3 hits.
InterProIPR003018. GAF.
IPR029016. GAF_dom_like.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSPR00387. PDIESTERASE1.
SMARTSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
SUPFAMSSF55781. SSF55781. 3 hits.
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPDE6A.
GenomeRNAi5145.
NextBio19852.
PMAP-CutDBP16499.
PROP16499.
SOURCESearch...

Entry information

Entry namePDE6A_HUMAN
AccessionPrimary (citable) accession number: P16499
Secondary accession number(s): Q0P638
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 25, 2008
Last modified: July 9, 2014
This is version 143 of the entry and version 4 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

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 5

Human chromosome 5: entries, gene names and cross-references to MIM