Reviewed, UniProtKB/Swiss-Prot P16499 (PDE6A_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	860 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)

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	Defects in PDE6A are a cause of retinitis pigmentosa autosomal recessive (ARRP) [MIM:268000]. RP leads to degeneration of retinal photoreceptor cells. 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. Ref.5 Ref.6
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 Retinitis pigmentosa
Domain	Repeat
Ligand	Metal-binding cGMP
Molecular function	Hydrolase
PTM	Acetylation Lipoprotein Prenylation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Inferred from electronic annotation. Source: InterPro visual perception Ref.5 Traceable author statement. Source: ProtInc
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	3',5'-cyclic-GMP phosphodiesterase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 860	859	Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha		PRO_0000198828
Regions
	Domain	73 – 222	150	GAF 1
	Domain	254 – 431	178	GAF 2
Sites
	Active site	559	1	Proton donor By similarity
	Metal binding	563	1	Divalent metal cation 1 By similarity
	Metal binding	599	1	Divalent metal cation 1 By similarity
	Metal binding	600	1	Divalent metal cation 1 By similarity
	Metal binding	600	1	Divalent metal cation 2 By similarity
	Metal binding	720	1	Divalent metal cation 1 By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylglycine By similarity
	Lipidation	857	1	S-farnesyl cysteine By similarity
Natural variations
	Natural variant	102	1	R → H in ARRP. Ref.6		VAR_025460
	Natural variant	102	1	R → S in ARRP. Ref.6		VAR_025461
	Natural variant	145	1	A → T: dbSNP rs35431421.		VAR_047730
	Natural variant	216	1	N → S: dbSNP rs10057110. Ref.6		VAR_025462
	Natural variant	277	1	V → A		VAR_025463
	Natural variant	293	1	P → L		VAR_025464
	Natural variant	344	1	S → R in ARRP. Ref.5		VAR_006049
	Natural variant	391	1	V → M		VAR_025465
	Natural variant	492	1	Q → H: dbSNP rs17711594.		VAR_047731
	Natural variant	569	1	Q → K in ARRP. Ref.6		VAR_025466
	Natural variant	573	1	S → P in ARRP. Ref.6		VAR_025467
	Natural variant	827	1	K → Q		VAR_025468
	Natural variant	850	1	G → V		VAR_025469
Experimental info
	Sequence conflict	224	1	V → W in AAB69155. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P16499-1 [UniParc]. Last modified November 25, 2008. Version 4. Checksum: 7EEA48A234C1FE59	FASTA	860	99,547
	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

References

	« Hide 'large scale' referencesShow '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: 2155175] [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. , 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: 15489334] [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: 7493036] [Abstract] Cited for: VARIANT ARRP 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: 10393062] [Abstract] Cited for: VARIANTS ARRP 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

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M26061 mRNA. Translation: AAB69155.1. CH471062 Genomic DNA. Translation: EAW61757.1. BC035909 mRNA. Translation: AAH35909.1.
IPI	IPI00218730.
PIR	B34611.
RefSeq	NP_000431.2.
UniGene	Hs.567314
3D structure databases
SMR	P16499. Positions 64-444, 483-815.
ModBase	Search...
Protein-protein interaction databases
STRING	P16499.
Proteomic databases
PRIDE	P16499.
Genome annotation databases
Ensembl	ENST00000255266; ENSP00000255266; ENSG00000132915; Homo sapiens. [Genome view]
GeneID	5145.
KEGG	hsa:5145.
Organism-specific databases
CTD	5145.
GeneCards	GC05M149220.
H-InvDB	HIX0024840.
HGNC	HGNC:8785. PDE6A.
HPA	HPA016970.
MIM	180071. gene. 268000. phenotype.
Orphanet	791. Retinitis pigmentosa.
PharmGKB	PA33133.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG445272.
HOVERGEN	P16499.
InParanoid	P16499.
OMA	LIMKVFH.
OrthoDB	EOG97Q0R3.
PhylomeDB	P16499.
Enzyme and pathway databases
BRENDA	3.1.4.35. 247.
Pathway_Interaction_DB	rhodopsin_pathway. Visual signal transduction: Rods.
Gene expression databases
ArrayExpress	P16499.
Bgee	P16499.
CleanEx	HS_PDE6A.
Genevestigator	P16499.
GermOnline	ENSG00000132915. Homo sapiens.
Family and domain databases
InterPro	IPR003018. GAF. IPR003607. Metal-dep_PHydrolase_HD_dom. IPR002073. PDEase. [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 Resources
NextBio	19852.
PMAP-CutDB	P16499.
SOURCE	Search...

Entry information

Entry name

PDE6A_HUMAN

Accession

Primary (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:	February 9, 2010
This is version 101 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.