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Protein

Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta

Gene

PDE6D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Promotes the release of prenylated target proteins from cellular membranes (PubMed:9712853). Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location (PubMed:22002721, PubMed:23698361). Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E (PubMed:24166846). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (By similarity). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate (By similarity).By similarity6 Publications

GO - Molecular functioni

  1. 3',5'-cyclic-nucleotide phosphodiesterase activity Source: InterPro
  2. GTPase inhibitor activity Source: UniProtKB
  3. Rab GTPase binding Source: UniProtKB

GO - Biological processi

  1. organelle organization Source: Reactome
  2. response to stimulus Source: UniProtKB-KW
  3. visual perception Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Sensory transduction, Vision

Keywords - Ligandi

cGMP

Enzyme and pathway databases

ReactomeiREACT_268148. ARL13B-mediated ciliary trafficking of INPP5E.

Names & Taxonomyi

Protein namesi
Recommended name:
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta
Short name:
GMP-PDE delta
Alternative name(s):
Protein p17
Gene namesi
Name:PDE6D
Synonyms:PDED
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:8788. PDE6D.

Subcellular locationi

  1. Cytoplasmcytosol 3 Publications
  2. Cytoplasmic vesicle membrane 1 Publication; Peripheral membrane protein 1 Publication
  3. Cytoplasmcytoskeletoncilium basal body 1 Publication

GO - Cellular componenti

  1. cytoplasmic vesicle Source: UniProtKB
  2. cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  3. cytoskeleton Source: UniProtKB-KW
  4. cytosol Source: UniProtKB
  5. primary cilium Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Joubert syndrome 22 (JBTS22)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly.

See also OMIM:615665

Keywords - Diseasei

Ciliopathy, Joubert syndrome

Organism-specific databases

MIMi615665. phenotype.
Orphaneti2754. Joubert syndrome with orofaciodigital defect.
PharmGKBiPA33136.

Polymorphism and mutation databases

BioMutaiPDE6D.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 150150Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit deltaPRO_0000221208Add
BLAST

Proteomic databases

MaxQBiO43924.
PaxDbiO43924.
PRIDEiO43924.

Expressioni

Tissue specificityi

Widely expressed. Detected in various tissues including spleen, prostate gland, testis, ovary, small intestine, colon, retina, and peripheral blood.1 Publication

Gene expression databases

BgeeiO43924.
CleanExiHS_PDE6D.
ExpressionAtlasiO43924. baseline and differential.
GenevestigatoriO43924.

Organism-specific databases

HPAiHPA037433.
HPA037434.

Interactioni

Subunit structurei

Interacts with the prenylated catalytic subunits of PDE6, an oligomer composed of two catalytic chains (PDE6A and PDE6B) and two inhibitory chains (gamma); has no effect on enzyme activity but promotes the release of the prenylated enzyme from cell membrane (By similarity). Interacts with prenylated GRK1 and GRK7 (By similarity). Interacts with prenylated Ras family members, including RAP2A and RAP2C (By similarity). Interacts with prenylated RHEB and NRAS (PubMed:22002721). Interacts with prenylated HRAS and KRAS. Interacts with RAB13 (prenylated form); dissociates RAB13 from membranes (PubMed:9712853). Interacts with prenylated INPP5E (PubMed:24166846). Interacts with RPGR (PubMed:9990021, PubMed:24166846, PubMed:23559067). Interacts with ARL2 (PubMed:24166846, PubMed:22002721). Interacts with ARL3; the interaction occurs specifically with the GTP-bound form of ARL3 (PubMed:24166846). Interaction with ARL2 and ARL3 promotes release of farnesylated cargo proteins (PubMed:22002721).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARL16Q0P5N65EBI-712685,EBI-10186132
ARL2P3640410EBI-712685,EBI-752365
Arl2Q9D0J46EBI-712685,EBI-1033319From a different organism.
ARL3P364052EBI-712685,EBI-712710
Arl3Q9WUL74EBI-712685,EBI-6860857From a different organism.
RAB13P511532EBI-712685,EBI-1780121
RHEBQ153825EBI-712685,EBI-6860739
RPGRQ928349EBI-712685,EBI-6558417
tirQ7DB773EBI-712685,EBI-6480811From a different organism.

Protein-protein interaction databases

BioGridi111173. 26 interactions.
DIPiDIP-36660N.
IntActiO43924. 15 interactions.
MINTiMINT-236371.
STRINGi9606.ENSP00000287600.

Structurei

Secondary structure

1
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 1311Combined sources
Beta strandi15 – 2410Combined sources
Turni25 – 273Combined sources
Beta strandi30 – 345Combined sources
Beta strandi43 – 508Combined sources
Helixi51 – 555Combined sources
Beta strandi57 – 6913Combined sources
Beta strandi71 – 8212Combined sources
Beta strandi85 – 9713Combined sources
Beta strandi101 – 11010Combined sources
Helixi114 – 1163Combined sources
Helixi120 – 1234Combined sources
Turni124 – 1263Combined sources
Beta strandi127 – 1359Combined sources
Beta strandi138 – 15013Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KSGX-ray2.30B1-150[»]
1KSHX-ray1.80B1-150[»]
1KSJX-ray2.60B1-150[»]
3T5GX-ray1.70B1-150[»]
3T5IX-ray2.10A/B/C/D1-150[»]
4JHPX-ray1.90B1-150[»]
4JV6X-ray1.87B1-150[»]
4JV8X-ray1.45B1-150[»]
4JVBX-ray1.75B1-150[»]
4JVFX-ray2.40B1-150[»]
ProteinModelPortaliO43924.
SMRiO43924. Positions 4-150.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43924.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni144 – 1507Required for association with membranes1 Publication

Sequence similaritiesi

Belongs to the PDE6D/unc-119 family.Curated

Phylogenomic databases

eggNOGiNOG302334.
HOGENOMiHOG000007689.
HOVERGENiHBG053542.
KOiK13758.
OMAiDSTNTWQ.
OrthoDBiEOG7HMS2N.
PhylomeDBiO43924.
TreeFamiTF314474.

Family and domain databases

Gene3Di2.70.50.40. 1 hit.
InterProiIPR008015. GMP_PDE_delta.
IPR014756. Ig_E-set.
IPR017287. Rhodop-sen_GMP-Pdiesterase_dsu.
[Graphical view]
PfamiPF05351. GMP_PDE_delta. 1 hit.
[Graphical view]
PIRSFiPIRSF037825. GMP-Pdiesterase_delta. 1 hit.
SUPFAMiSSF81296. SSF81296. 1 hit.

Sequencei

Sequence statusi: Complete.

O43924-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAKDERARE ILRGFKLNWM NLRDAETGKI LWQGTEDLSV PGVEHEARVP
60 70 80 90 100
KKILKCKAVS RELNFSSTEQ MEKFRLEQKV YFKGQCLEEW FFEFGFVIPN
110 120 130 140 150
STNTWQSLIE AAPESQMMPA SVLTGNVIIE TKFFDDDLLV STSRVRLFYV
Length:150
Mass (Da):17,420
Last modified:June 1, 1998 - v1
Checksum:iAB8D9309C33B4411
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti117 – 1171M → V in CAA04880 (PubMed:9712853).Curated
Sequence conflicti146 – 1461R → G in CAA04880 (PubMed:9712853).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045999 Genomic DNA. Translation: AAC39720.1.
AF022912 mRNA. Translation: AAB87872.1.
AF042835, AF042833, AF042834 Genomic DNA. Translation: AAC25953.1.
AJ001626 mRNA. Translation: CAA04880.1.
BT007278 mRNA. Translation: AAP35942.1.
BC007831 mRNA. Translation: AAH07831.1.
CCDSiCCDS33398.1.
RefSeqiNP_001277947.1. NM_001291018.1.
NP_002592.1. NM_002601.3.
UniGeneiHs.516808.

Genome annotation databases

EnsembliENST00000287600; ENSP00000287600; ENSG00000156973.
GeneIDi5147.
KEGGihsa:5147.
UCSCiuc002vse.1. human.

Polymorphism and mutation databases

BioMutaiPDE6D.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045999 Genomic DNA. Translation: AAC39720.1.
AF022912 mRNA. Translation: AAB87872.1.
AF042835, AF042833, AF042834 Genomic DNA. Translation: AAC25953.1.
AJ001626 mRNA. Translation: CAA04880.1.
BT007278 mRNA. Translation: AAP35942.1.
BC007831 mRNA. Translation: AAH07831.1.
CCDSiCCDS33398.1.
RefSeqiNP_001277947.1. NM_001291018.1.
NP_002592.1. NM_002601.3.
UniGeneiHs.516808.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KSGX-ray2.30B1-150[»]
1KSHX-ray1.80B1-150[»]
1KSJX-ray2.60B1-150[»]
3T5GX-ray1.70B1-150[»]
3T5IX-ray2.10A/B/C/D1-150[»]
4JHPX-ray1.90B1-150[»]
4JV6X-ray1.87B1-150[»]
4JV8X-ray1.45B1-150[»]
4JVBX-ray1.75B1-150[»]
4JVFX-ray2.40B1-150[»]
ProteinModelPortaliO43924.
SMRiO43924. Positions 4-150.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111173. 26 interactions.
DIPiDIP-36660N.
IntActiO43924. 15 interactions.
MINTiMINT-236371.
STRINGi9606.ENSP00000287600.

Chemistry

ChEMBLiCHEMBL2363066.

Polymorphism and mutation databases

BioMutaiPDE6D.

Proteomic databases

MaxQBiO43924.
PaxDbiO43924.
PRIDEiO43924.

Protocols and materials databases

DNASUi5147.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000287600; ENSP00000287600; ENSG00000156973.
GeneIDi5147.
KEGGihsa:5147.
UCSCiuc002vse.1. human.

Organism-specific databases

CTDi5147.
GeneCardsiGC02M232597.
HGNCiHGNC:8788. PDE6D.
HPAiHPA037433.
HPA037434.
MIMi602676. gene.
615665. phenotype.
neXtProtiNX_O43924.
Orphaneti2754. Joubert syndrome with orofaciodigital defect.
PharmGKBiPA33136.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG302334.
HOGENOMiHOG000007689.
HOVERGENiHBG053542.
KOiK13758.
OMAiDSTNTWQ.
OrthoDBiEOG7HMS2N.
PhylomeDBiO43924.
TreeFamiTF314474.

Enzyme and pathway databases

ReactomeiREACT_268148. ARL13B-mediated ciliary trafficking of INPP5E.

Miscellaneous databases

ChiTaRSiPDE6D. human.
EvolutionaryTraceiO43924.
GeneWikiiPDE6D.
GenomeRNAii5147.
NextBioi19860.
PROiO43924.
SOURCEiSearch...

Gene expression databases

BgeeiO43924.
CleanExiHS_PDE6D.
ExpressionAtlasiO43924. baseline and differential.
GenevestigatoriO43924.

Family and domain databases

Gene3Di2.70.50.40. 1 hit.
InterProiIPR008015. GMP_PDE_delta.
IPR014756. Ig_E-set.
IPR017287. Rhodop-sen_GMP-Pdiesterase_dsu.
[Graphical view]
PfamiPF05351. GMP_PDE_delta. 1 hit.
[Graphical view]
PIRSFiPIRSF037825. GMP-Pdiesterase_delta. 1 hit.
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of human and mouse rod cGMP phosphodiesterase delta subunit (PDE6D) and chromosomal localization of the human gene."
    Li N., Florio S.K., Pettenati M.J., Rao P.N., Beavo J.A., Baehr W.
    Genomics 49:76-82(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "cDNA sequence, genomic organization and mapping of PDE6D, the human gene encoding the delta subunit of the cGMP phosphodiesterase of retinal rod cells to chromosome 2q36."
    Erchova G., Derre J., Chatelin S., Nancy V., Berger R., Kaplan J., Munnich A., de Gunzburg J.
    Cytogenet. Cell Genet. 79:139-141(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Cloning and gene structure of the rod cGMP phosphodiesterase delta subunit gene (PDED) in man and mouse."
    Lorenz B., Migliaccio C., Lichtner P., Meyer C., Strom T.M., D'Urso M., Becker J., Ciccodicola A., Meitinger T.
    Eur. J. Hum. Genet. 6:283-290(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "The rod cGMP phosphodiesterase delta subunit dissociates the small GTPase Rab13 from membranes."
    Marzesco A.M., Galli T., Louvard D., Zahraoui A.
    J. Biol. Chem. 273:22340-22345(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH RAB13, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. "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: Placenta.
  7. "The delta subunit of rod specific cyclic GMP phosphodiesterase, PDE delta, interacts with the Arf-like protein Arl3 in a GTP specific manner."
    Linari M., Hanzal-Bayer M., Becker J.
    FEBS Lett. 458:55-59(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARL3.
  8. "The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase."
    Linari M., Ueffing M., Manson F., Wright A., Meitinger T., Becker J.
    Proc. Natl. Acad. Sci. U.S.A. 96:1315-1320(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RPGR.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. Cited for: INVOLVEMENT IN JBTS22, FUNCTION, INTERACTION WITH RPGR; ARL2; ARL3 AND INPP5E, SUBCELLULAR LOCATION.
  11. "The complex of Arl2-GTP and PDE delta: from structure to function."
    Hanzal-Bayer M., Renault L., Roversi P., Wittinghofer A., Hillig R.C.
    EMBO J. 21:2095-2106(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH MOUSE ARL2 AND GTP, INTERACTION WITH HRAS.
  12. "Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo."
    Ismail S.A., Chen Y.X., Rusinova A., Chandra A., Bierbaum M., Gremer L., Triola G., Waldmann H., Bastiaens P.I., Wittinghofer A.
    Nat. Chem. Biol. 7:942-949(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH RHEB, FUNCTION, INTERACTION WITH RHEB; NRAS AND ARL2, SUBCELLULAR LOCATION.
  13. "The interplay between RPGR, PDE? and Arl2/3 regulate the ciliary targeting of farnesylated cargo."
    Watzlich D., Vetter I., Gotthardt K., Miertzschke M., Chen Y.X., Wittinghofer A., Ismail S.
    EMBO Rep. 14:465-472(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH RPGR, FUNCTION, INTERACTION WITH RPGR.
  14. "Small molecule inhibition of the KRAS-PDE? interaction impairs oncogenic KRAS signalling."
    Zimmermann G., Papke B., Ismail S., Vartak N., Chandra A., Hoffmann M., Hahn S.A., Triola G., Wittinghofer A., Bastiaens P.I., Waldmann H.
    Nature 497:638-642(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS), FUNCTION, INTERACTION WITH RHEB AND KRAS, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiPDE6D_HUMAN
AccessioniPrimary (citable) accession number: O43924
Secondary accession number(s): O43250
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: April 29, 2015
This is version 134 of the entry and version 1 of the sequence. [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. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.