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Protein

Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'

Gene

PDE6C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.2 Publications

Catalytic activityi

Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.2 Publications

Cofactori

a divalent metal cationBy similarityNote: 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei97cGMPBy similarity1
Binding sitei116cGMPBy similarity1
Binding sitei176cGMPBy similarity1
Active sitei562Proton donorBy similarity1
Metal bindingi566Divalent metal cation 1By similarity1
Metal bindingi602Divalent metal cation 1By similarity1
Metal bindingi603Divalent metal cation 1By similarity1
Metal bindingi603Divalent metal cation 2By similarity1
Metal bindingi723Divalent metal cation 1By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi169 – 172cGMPBy similarity4

GO - Molecular functioni

GO - Biological processi

  • phototransduction, visible light Source: Ensembl
  • retinal cone cell development Source: Ensembl
  • visual perception Source: ProtInc

Keywordsi

Molecular functionHydrolase
Biological processSensory transduction, Vision
LigandcGMP, cGMP-binding, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (EC:3.1.4.352 Publications)
Alternative name(s):
cGMP phosphodiesterase 6C
Gene namesi
Name:PDE6C
Synonyms:PDEA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000095464.9
HGNCiHGNC:8787 PDE6C
MIMi600827 gene
neXtProtiNX_P51160

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Cone dystrophy 4 (COD4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:613093
Achromatopsia 5 (ACHM5)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. ACHM5 inheritance is autosomal recessive.
See also OMIM:613093
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079307104R → W in ACHM5; severely decreases cGMP phosphodiesterase activity. 2 PublicationsCorresponds to variant dbSNP:rs769506319Ensembl.1
Natural variantiVAR_079308276 – 858Missing in ACHM5. 1 PublicationAdd BLAST583
Natural variantiVAR_062409323Y → N in ACHM5; decreases cGMP phosphodiesterase activity. 3 PublicationsCorresponds to variant dbSNP:rs121918538EnsemblClinVar.1
Natural variantiVAR_079309391P → L in ACHM5; severely decreases cGMP phosphodiesterase activity. 2 Publications1
Natural variantiVAR_062410455M → V in ACHM5; decreases cGMP phosphodiesterase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918539EnsemblClinVar.1
Natural variantiVAR_079310602H → L in ACHM5; severely decreases cGMP phosphodiesterase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606934EnsemblClinVar.1
Natural variantiVAR_079311790E → K in ACHM5; decreases cGMP phosphodiesterase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606936EnsemblClinVar.1
Natural variantiVAR_079312819 – 858Missing in ACHM5. 1 PublicationAdd BLAST40

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi858L → V: No effect on cGMP phosphodiesterase activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5146
GeneReviewsiPDE6C
MalaCardsiPDE6C
MIMi613093 phenotype
OpenTargetsiENSG00000095464
Orphaneti49382 Achromatopsia
1871 Progressive cone dystrophy
PharmGKBiPA33135

Chemistry databases

ChEMBLiCHEMBL3977
DrugBankiDB00201 Caffeine
GuidetoPHARMACOLOGYi1314

Polymorphism and mutation databases

BioMutaiPDE6C
DMDMi90111861

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001988311 – 855Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'Add BLAST855
PropeptideiPRO_0000370788856 – 858Removed in mature formSequence analysis3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei855Cysteine methyl esterSequence analysis1
Lipidationi855S-geranylgeranyl cysteineBy similarity1

Keywords - PTMi

Lipoprotein, Methylation, Prenylation

Proteomic databases

PaxDbiP51160
PeptideAtlasiP51160
PRIDEiP51160
ProteomicsDBi56291

PTM databases

iPTMnetiP51160
PhosphoSitePlusiP51160

Expressioni

Gene expression databases

BgeeiENSG00000095464 Expressed in 83 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_PDE6C
GenevisibleiP51160 HS

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9606.ENSP00000360502

Chemistry databases

BindingDBiP51160

Structurei

Secondary structure

1858
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP51160
SMRiP51160
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini75 – 224GAF 1Add BLAST150
Domaini256 – 433GAF 2Add BLAST178
Domaini486 – 819PDEasePROSITE-ProRule annotationAdd BLAST334

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000119066
HOGENOMiHOG000007069
HOVERGENiHBG053539
KOiK13757
OMAiPIVMGKE
OrthoDBiEOG091G01RK
PhylomeDBiP51160
TreeFamiTF316499

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
3.30.450.40, 2 hits
InterProiView protein in InterPro
IPR003018 GAF
IPR029016 GAF-like_dom_sf
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF01590 GAF, 2 hits
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00065 GAF, 2 hits
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P51160-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGEINQVAVE KYLEENPQFA KEYFDRKLRV EVLGEIFKNS QVPVQSSMSF
60 70 80 90 100
SELTQVEESA LCLELLWTVQ EEGGTPEQGV HRALQRLAHL LQADRCSMFL
110 120 130 140 150
CRSRNGIPEV ASRLLDVTPT SKFEDNLVGP DKEVVFPLDI GIVGWAAHTK
160 170 180 190 200
KTHNVPDVKK NSHFSDFMDK QTGYVTKNLL ATPIVVGKEV LAVIMAVNKV
210 220 230 240 250
NASEFSKQDE EVFSKYLNFV SIILRLHHTS YMYNIESRRS QILMWSANKV
260 270 280 290 300
FEELTDVERQ FHKALYTVRS YLNCERYSIG LLDMTKEKEF YDEWPIKLGE
310 320 330 340 350
VEPYKGPKTP DGREVNFYKI IDYILHGKEE IKVIPTPPAD HWTLISGLPT
360 370 380 390 400
YVAENGFICN MMNAPADEYF TFQKGPVDET GWVIKNVLSL PIVNKKEDIV
410 420 430 440 450
GVATFYNRKD GKPFDEHDEY ITETLTQFLG WSLLNTDTYD KMNKLENRKD
460 470 480 490 500
IAQEMLMNQT KATPEEIKSI LKFQEKLNVD VIDDCEEKQL VAILKEDLPD
510 520 530 540 550
PRSAELYEFR FSDFPLTEHG LIKCGIRLFF EINVVEKFKV PVEVLTRWMY
560 570 580 590 600
TVRKGYRAVT YHNWRHGFNV GQTMFTLLMT GRLKKYYTDL EAFAMLAAAF
610 620 630 640 650
CHDIDHRGTN NLYQMKSTSP LARLHGSSIL ERHHLEYSKT LLQDESLNIF
660 670 680 690 700
QNLNKRQFET VIHLFEVAII ATDLALYFKK RTMFQKIVDA CEQMQTEEEA
710 720 730 740 750
IKYVTVDPTK KEIIMAMMMT ACDLSAITKP WEVQSQVALM VANEFWEQGD
760 770 780 790 800
LERTVLQQQP IPMMDRNKRD ELPKLQVGFI DFVCTFVYKE FSRFHKEITP
810 820 830 840 850
MLSGLQNNRV EWKSLADEYD AKMKVIEEEA KKQEGGAEKA AEDSGGGDDK

KSKTCLML
Length:858
Mass (Da):99,147
Last modified:March 7, 2006 - v2
Checksum:i06FFD025EE5936A5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti116D → V in AAA96392 (PubMed:8543163).Curated1
Sequence conflicti116D → V in AAA92886 (PubMed:7490077).Curated1
Sequence conflicti373Q → P in AAA96392 (PubMed:8543163).Curated1
Sequence conflicti464P → L in AAA96392 (PubMed:8543163).Curated1
Sequence conflicti565R → Q in AAA96392 (PubMed:8543163).Curated1
Sequence conflicti565R → Q in AAA92886 (PubMed:7490077).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06240829R → W in COD4 and ACHM5; severely decreases cGMP phosphodiesterase activity. 3 PublicationsCorresponds to variant dbSNP:rs121918537EnsemblClinVar.1
Natural variantiVAR_079307104R → W in ACHM5; severely decreases cGMP phosphodiesterase activity. 2 PublicationsCorresponds to variant dbSNP:rs769506319Ensembl.1
Natural variantiVAR_025470157D → E Rare polymorphism. 1 PublicationCorresponds to variant dbSNP:rs76999928EnsemblClinVar.1
Natural variantiVAR_050475270S → T1 PublicationCorresponds to variant dbSNP:rs701865EnsemblClinVar.1
Natural variantiVAR_079308276 – 858Missing in ACHM5. 1 PublicationAdd BLAST583
Natural variantiVAR_062409323Y → N in ACHM5; decreases cGMP phosphodiesterase activity. 3 PublicationsCorresponds to variant dbSNP:rs121918538EnsemblClinVar.1
Natural variantiVAR_079309391P → L in ACHM5; severely decreases cGMP phosphodiesterase activity. 2 Publications1
Natural variantiVAR_062410455M → V in ACHM5; decreases cGMP phosphodiesterase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918539EnsemblClinVar.1
Natural variantiVAR_079310602H → L in ACHM5; severely decreases cGMP phosphodiesterase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606934EnsemblClinVar.1
Natural variantiVAR_050476699E → A. Corresponds to variant dbSNP:rs12261131EnsemblClinVar.1
Natural variantiVAR_079311790E → K in ACHM5; decreases cGMP phosphodiesterase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606936EnsemblClinVar.1
Natural variantiVAR_079312819 – 858Missing in ACHM5. 1 PublicationAdd BLAST40
Natural variantiVAR_025471822K → N Rare polymorphism. 1 PublicationCorresponds to variant dbSNP:rs79487435Ensembl.1
Natural variantiVAR_064744826I → S Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_025472834E → G Rare polymorphism. 1 PublicationCorresponds to variant dbSNP:rs148661165EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 Genomic DNA No translation available.
AL157396 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW50064.1
CCDSiCCDS7429.1
PIRiS63688 JC4520
RefSeqiNP_006195.3, NM_006204.3
UniGeneiHs.658121

Genome annotation databases

EnsembliENST00000371447; ENSP00000360502; ENSG00000095464
GeneIDi5146
KEGGihsa:5146
UCSCiuc001kiu.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 Genomic DNA No translation available.
AL157396 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW50064.1
CCDSiCCDS7429.1
PIRiS63688 JC4520
RefSeqiNP_006195.3, NM_006204.3
UniGeneiHs.658121

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3JWQX-ray2.87A/B/C/D746-785[»]
3JWRX-ray2.99A/B746-785[»]
5E8FX-ray2.10D/E851-855[»]
ProteinModelPortaliP51160
SMRiP51160
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000360502

Chemistry databases

BindingDBiP51160
ChEMBLiCHEMBL3977
DrugBankiDB00201 Caffeine
GuidetoPHARMACOLOGYi1314

PTM databases

iPTMnetiP51160
PhosphoSitePlusiP51160

Polymorphism and mutation databases

BioMutaiPDE6C
DMDMi90111861

Proteomic databases

PaxDbiP51160
PeptideAtlasiP51160
PRIDEiP51160
ProteomicsDBi56291

Protocols and materials databases

DNASUi5146
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371447; ENSP00000360502; ENSG00000095464
GeneIDi5146
KEGGihsa:5146
UCSCiuc001kiu.5 human

Organism-specific databases

CTDi5146
DisGeNETi5146
EuPathDBiHostDB:ENSG00000095464.9
GeneCardsiPDE6C
GeneReviewsiPDE6C
H-InvDBiHIX0035433
HGNCiHGNC:8787 PDE6C
MalaCardsiPDE6C
MIMi600827 gene
613093 phenotype
neXtProtiNX_P51160
OpenTargetsiENSG00000095464
Orphaneti49382 Achromatopsia
1871 Progressive cone dystrophy
PharmGKBiPA33135
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3689 Eukaryota
ENOG410XRI7 LUCA
GeneTreeiENSGT00760000119066
HOGENOMiHOG000007069
HOVERGENiHBG053539
KOiK13757
OMAiPIVMGKE
OrthoDBiEOG091G01RK
PhylomeDBiP51160
TreeFamiTF316499

Miscellaneous databases

ChiTaRSiPDE6C human
GeneWikiiPDE6C
GenomeRNAii5146
PROiPR:P51160
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000095464 Expressed in 83 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_PDE6C
GenevisibleiP51160 HS

Family and domain databases

CDDicd00077 HDc, 1 hit
Gene3Di1.10.1300.10, 1 hit
3.30.450.40, 2 hits
InterProiView protein in InterPro
IPR003018 GAF
IPR029016 GAF-like_dom_sf
IPR003607 HD/PDEase_dom
IPR023088 PDEase
IPR002073 PDEase_catalytic_dom
IPR036971 PDEase_catalytic_dom_sf
IPR023174 PDEase_CS
PfamiView protein in Pfam
PF01590 GAF, 2 hits
PF00233 PDEase_I, 1 hit
PRINTSiPR00387 PDIESTERASE1
SMARTiView protein in SMART
SM00065 GAF, 2 hits
SM00471 HDc, 1 hit
PROSITEiView protein in PROSITE
PS00126 PDEASE_I_1, 1 hit
PS51845 PDEASE_I_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPDE6C_HUMAN
AccessioniPrimary (citable) accession number: P51160
Secondary accession number(s): A6NCR6, Q5VY29
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 7, 2006
Last modified: November 7, 2018
This is version 171 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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