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P51160 (PDE6C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

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

EC=3.1.4.35
Alternative name(s):
cGMP phosphodiesterase 6C
Gene names
Name:PDE6C
Synonyms:PDEA2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length858 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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

Composed of two alpha' subunits that are associated with 3 smaller proteins of 11, 13, and 15 kDa.

Subcellular location

Cell membrane; Lipid-anchor; Cytoplasmic side Potential.

Involvement in disease

Cone dystrophy 4 (COD4) [MIM:613093]: An early-onset cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the cyclic nucleotide phosphodiesterase family.

Contains 2 GAF domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 855855Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'
PRO_0000198831
Propeptide856 – 8583Removed in mature form Potential
PRO_0000370788

Regions

Domain75 – 224150GAF 1
Domain256 – 433178GAF 2
Nucleotide binding169 – 1724cGMP By similarity

Sites

Active site5621Proton donor By similarity
Metal binding5661Divalent metal cation 1 By similarity
Metal binding6021Divalent metal cation 1 By similarity
Metal binding6031Divalent metal cation 1 By similarity
Metal binding6031Divalent metal cation 2 By similarity
Metal binding7231Divalent metal cation 1 By similarity
Binding site971cGMP By similarity
Binding site1161cGMP By similarity
Binding site1761cGMP By similarity

Amino acid modifications

Modified residue8551Cysteine methyl ester Potential
Lipidation8551S-geranylgeranyl cysteine By similarity

Natural variations

Natural variant291R → W in COD4. Ref.7
VAR_062408
Natural variant1571D → E Rare polymorphism. Ref.6
Corresponds to variant rs76999928 [ dbSNP | Ensembl ].
VAR_025470
Natural variant2701S → T. Ref.3
Corresponds to variant rs701865 [ dbSNP | Ensembl ].
VAR_050475
Natural variant3231Y → N in COD4. Ref.7
VAR_062409
Natural variant4551M → V in COD4. Ref.7
VAR_062410
Natural variant6991E → A.
Corresponds to variant rs12261131 [ dbSNP | Ensembl ].
VAR_050476
Natural variant8221K → N Rare polymorphism. Ref.6
Corresponds to variant rs79487435 [ dbSNP | Ensembl ].
VAR_025471
Natural variant8261I → S Found in a renal cell carcinoma sample; somatic mutation. Ref.8
VAR_064744
Natural variant8341E → G Rare polymorphism. Ref.6
VAR_025472

Experimental info

Sequence conflict1161D → V in AAA96392. Ref.1
Sequence conflict1161D → V in AAA92886. Ref.2
Sequence conflict3731Q → P in AAA96392. Ref.1
Sequence conflict4641P → L in AAA96392. Ref.1
Sequence conflict5651R → Q in AAA96392. Ref.1
Sequence conflict5651R → Q in AAA92886. Ref.2

Secondary structure

...................... 858
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P51160 [UniParc].

Last modified March 7, 2006. Version 2.
Checksum: 06FFD025EE5936A5

FASTA85899,147
        10         20         30         40         50         60 
MGEINQVAVE KYLEENPQFA KEYFDRKLRV EVLGEIFKNS QVPVQSSMSF SELTQVEESA 

        70         80         90        100        110        120 
LCLELLWTVQ EEGGTPEQGV HRALQRLAHL LQADRCSMFL CRSRNGIPEV ASRLLDVTPT 

       130        140        150        160        170        180 
SKFEDNLVGP DKEVVFPLDI GIVGWAAHTK KTHNVPDVKK NSHFSDFMDK QTGYVTKNLL 

       190        200        210        220        230        240 
ATPIVVGKEV LAVIMAVNKV NASEFSKQDE EVFSKYLNFV SIILRLHHTS YMYNIESRRS 

       250        260        270        280        290        300 
QILMWSANKV FEELTDVERQ FHKALYTVRS YLNCERYSIG LLDMTKEKEF YDEWPIKLGE 

       310        320        330        340        350        360 
VEPYKGPKTP DGREVNFYKI IDYILHGKEE IKVIPTPPAD HWTLISGLPT YVAENGFICN 

       370        380        390        400        410        420 
MMNAPADEYF TFQKGPVDET GWVIKNVLSL PIVNKKEDIV GVATFYNRKD GKPFDEHDEY 

       430        440        450        460        470        480 
ITETLTQFLG WSLLNTDTYD KMNKLENRKD IAQEMLMNQT KATPEEIKSI LKFQEKLNVD 

       490        500        510        520        530        540 
VIDDCEEKQL VAILKEDLPD PRSAELYEFR FSDFPLTEHG LIKCGIRLFF EINVVEKFKV 

       550        560        570        580        590        600 
PVEVLTRWMY TVRKGYRAVT YHNWRHGFNV GQTMFTLLMT GRLKKYYTDL EAFAMLAAAF 

       610        620        630        640        650        660 
CHDIDHRGTN NLYQMKSTSP LARLHGSSIL ERHHLEYSKT LLQDESLNIF QNLNKRQFET 

       670        680        690        700        710        720 
VIHLFEVAII ATDLALYFKK RTMFQKIVDA CEQMQTEEEA IKYVTVDPTK KEIIMAMMMT 

       730        740        750        760        770        780 
ACDLSAITKP WEVQSQVALM VANEFWEQGD LERTVLQQQP IPMMDRNKRD ELPKLQVGFI 

       790        800        810        820        830        840 
DFVCTFVYKE FSRFHKEITP MLSGLQNNRV EWKSLADEYD AKMKVIEEEA KKQEGGAEKA 

       850 
AEDSGGGDDK KSKTCLML 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of a cDNA encoding the alpha' subunit of human cone cGMP-phosphodiesterase."
Viczian A.S., Piriev N.I., Farber D.B.
Gene 166:205-211(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Retina.
[2]"Gene structure and amino acid sequence of the human cone photoreceptor cGMP-phosphodiesterase alpha' subunit (PDEA2) and its chromosomal localization to 10q24."
Piriev N.I., Viczian A.S., Ye J., Kerner B., Korenberg J.R., Farber D.B.
Genomics 28:429-435(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Retina.
[3]"Human cone-specific cGMP phosphodiesterase alpha' subunit: complete cDNA sequence and gene arrangement."
Feshchenko E.A., Andreeva S.G., Suslova V.A., Smirnova E.V., Zagranichny V.E., Lipkin V.M.
FEBS Lett. 381:149-152(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT THR-270.
Tissue: Retina.
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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].
[6]"Screening of the gene encoding the alpha'-subunit of cone cGMP-PDE in patients with retinal degenerations."
Gao Y.Q., Danciger M., Longmuir R., Piriev N.I., Zhao D.Y., Heckenlively J.R., Fishman G.A., Weleber R.G., Jacobson S.G., Stone E.M., Farber D.B.
Invest. Ophthalmol. Vis. Sci. 40:1818-1822(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLU-157; ASN-822 AND GLY-834.
[7]"Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders."
Thiadens A.A., den Hollander A.I., Roosing S., Nabuurs S.B., Zekveld-Vroon R.C., Collin R.W., De Baere E., Koenekoop R.K., van Schooneveld M.J., Strom T.M., van Lith-Verhoeven J.J., Lotery A.J., van Moll-Ramirez N., Leroy B.P., van den Born L.I., Hoyng C.B., Cremers F.P., Klaver C.C.
Am. J. Hum. Genet. 85:240-247(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS COD4 TRP-29; ASN-323 AND VAL-455.
[8]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-826.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U31973 mRNA. Translation: AAA96392.1.
U20212 expand/collapse EMBL AC list , U20196, U20197, U20199, U20200, U20201, U20202, U20203, U20204, U20205, U20206, U20207, U20208, U20209, U20210, U20211 Genomic DNA. Translation: AAA92886.1.
X94354 Genomic DNA. Translation: CAA64079.1.
AL356214, AL157396 Genomic DNA. Translation: CAH72330.1.
AL157396, AL356214 Genomic DNA. Translation: CAH73839.1.
CH471066 Genomic DNA. Translation: EAW50064.1.
PIRJC4520. S63688.
RefSeqNP_006195.3. NM_006204.3.
UniGeneHs.658121.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3JWQX-ray2.87A/B/C/D684-788[»]
3JWRX-ray2.99A/B746-785[»]
ProteinModelPortalP51160.
SMRP51160. Positions 24-820.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000360502.

Chemistry

BindingDBP51160.
ChEMBLCHEMBL3977.

PTM databases

PhosphoSiteP51160.

Polymorphism databases

DMDM90111861.

Proteomic databases

PaxDbP51160.
PRIDEP51160.

Protocols and materials databases

DNASU5146.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000371447; ENSP00000360502; ENSG00000095464.
GeneID5146.
KEGGhsa:5146.
UCSCuc001kiu.4. human.

Organism-specific databases

CTD5146.
GeneCardsGC10P095362.
H-InvDBHIX0035433.
HGNCHGNC:8787. PDE6C.
MIM600827. gene.
613093. phenotype.
neXtProtNX_P51160.
Orphanet49382. Achromatopsia.
1871. Progressive cone dystrophy.
PharmGKBPA33135.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG290744.
HOGENOMHOG000007069.
HOVERGENHBG053539.
InParanoidP51160.
KOK13757.
OMAIVMGKEV.
OrthoDBEOG7BGHK1.
PhylomeDBP51160.
TreeFamTF316499.

Gene expression databases

BgeeP51160.
CleanExHS_PDE6C.
GenevestigatorP51160.

Family and domain databases

Gene3D1.10.1300.10. 1 hit.
InterProIPR003018. GAF.
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]
PROSITEPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPDE6C.
GenomeRNAi5146.
NextBio19856.
PROP51160.
SOURCESearch...

Entry information

Entry namePDE6C_HUMAN
AccessionPrimary (citable) accession number: P51160
Secondary accession number(s): A6NCR6, Q5VY29
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 7, 2006
Last modified: April 16, 2014
This is version 131 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 10

Human chromosome 10: entries, gene names and cross-references to MIM