P51160 (PDE6C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	858 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat
Ligand	Metal-binding Nucleotide-binding cGMP cGMP-binding
Molecular function	Hydrolase
PTM	Lipoprotein Methylation Prenylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	metabolic process Inferred from electronic annotation. Source: GOC phototransduction, visible light Inferred from electronic annotation. Source: Compara retinal cone cell development Inferred from electronic annotation. Source: Compara visual perception Traceable author statement Ref.3. Source: ProtInc
Cellular_component	plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	3',5'-cyclic-GMP phosphodiesterase activity Inferred from electronic annotation. Source: EC cGMP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 855	855	Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'		PRO_0000198831
	Propeptide	856 – 858	3	Removed in mature form Potential		PRO_0000370788
Regions
	Domain	75 – 224	150	GAF 1
	Domain	256 – 433	178	GAF 2
	Nucleotide binding	169 – 172	4	cGMP By similarity
Sites
	Active site	562	1	Proton donor By similarity
	Metal binding	566	1	Divalent metal cation 1 By similarity
	Metal binding	602	1	Divalent metal cation 1 By similarity
	Metal binding	603	1	Divalent metal cation 1 By similarity
	Metal binding	603	1	Divalent metal cation 2 By similarity
	Metal binding	723	1	Divalent metal cation 1 By similarity
	Binding site	97	1	cGMP By similarity
	Binding site	116	1	cGMP By similarity
	Binding site	176	1	cGMP By similarity
Amino acid modifications
	Modified residue	855	1	Cysteine methyl ester Potential
	Lipidation	855	1	S-geranylgeranyl cysteine By similarity
Natural variations
	Natural variant	29	1	R → W in COD4. Ref.7		VAR_062408
	Natural variant	157	1	D → E Rare polymorphism. Ref.6		VAR_025470
	Natural variant	270	1	S → T. Ref.3 Corresponds to variant rs701865 [ dbSNP | Ensembl ].		VAR_050475
	Natural variant	323	1	Y → N in COD4. Ref.7		VAR_062409
	Natural variant	455	1	M → V in COD4. Ref.7		VAR_062410
	Natural variant	699	1	E → A. Corresponds to variant rs12261131 [ dbSNP | Ensembl ].		VAR_050476
	Natural variant	822	1	K → N Rare polymorphism. Ref.6		VAR_025471
	Natural variant	826	1	I → S Found in a renal cell carcinoma sample; somatic mutation. Ref.8		VAR_064744
	Natural variant	834	1	E → G Rare polymorphism. Ref.6		VAR_025472
Experimental info
	Sequence conflict	116	1	D → V in AAA96392. Ref.1
	Sequence conflict	116	1	D → V in AAA92886. Ref.2
	Sequence conflict	373	1	Q → P in AAA96392. Ref.1
	Sequence conflict	464	1	P → L in AAA96392. Ref.1
	Sequence conflict	565	1	R → Q in AAA96392. Ref.1
	Sequence conflict	565	1	R → Q in AAA92886. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P51160 [UniParc]. Last modified March 7, 2006. Version 2. Checksum: 06FFD025EE5936A5	FASTA	858	99,147
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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 , 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.
IPI	IPI00747459.
PIR	JC4520. S63688.
RefSeq	NP_006195.3. NM_006204.3.
UniGene	Hs.658121.
3D structure databases
ProteinModelPortal	P51160.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000360502.
PTM databases
PhosphoSite	P51160.
Polymorphism databases
DMDM	90111861.
Proteomic databases
PaxDb	P51160.
PRIDE	P51160.
Protocols and materials databases
DNASU	5146.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371447; ENSP00000360502; ENSG00000095464.
GeneID	5146.
KEGG	hsa:5146.
UCSC	uc001kiu.4. human.
Organism-specific databases
CTD	5146.
GeneCards	GC10P095362.
H-InvDB	HIX0035433.
HGNC	HGNC:8787. PDE6C.
MIM	600827. gene. 613093. phenotype.
neXtProt	NX_P51160.
Orphanet	49382. Achromatopsia. 1871. Progressive cone dystrophy.
PharmGKB	PA33135.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG290744.
HOGENOM	HOG000007069.
HOVERGEN	HBG053539.
InParanoid	P51160.
KO	K13757.
OMA	SKYLNFV.
OrthoDB	EOG40GCQ6.
PhylomeDB	P51160.
Enzyme and pathway databases
Pathway_Interaction_DB	cone_pathway. Visual signal transduction: Cones.
Gene expression databases
Bgee	P51160.
CleanEx	HS_PDE6C.
Genevestigator	P51160.
GermOnline	ENSG00000095464. Homo sapiens.
Family and domain databases
Gene3D	1.10.1300.10. 1 hit.
InterPro	IPR003018. GAF. IPR003607. HD/PDEase_dom. IPR023088. PDEase. IPR002073. PDEase_catalytic_dom. IPR023174. PDEase_CS. [Graphical view]
Pfam	PF01590. GAF. 2 hits. PF00233. PDEase_I. 1 hit. [Graphical view]
PRINTS	PR00387. PDIESTERASE1.
SMART	SM00065. GAF. 2 hits. SM00471. HDc. 1 hit. [Graphical view]
PROSITE	PS00126. PDEASE_I. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P51160.
ChEMBL	CHEMBL3977.
GenomeRNAi	5146.
NextBio	19856.
SOURCE	Search...

Entry information

Entry name

PDE6C_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.