PDE6C_HUMAN
ID PDE6C_HUMAN Reviewed; 858 AA.
AC P51160; A6NCR6; Q5VY29;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha';
DE EC=3.1.4.35 {ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373};
DE AltName: Full=cGMP phosphodiesterase 6C;
DE Flags: Precursor;
GN Name=PDE6C; Synonyms=PDEA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=8543163; DOI=10.1016/0378-1119(95)00585-4;
RA Viczian A.S., Piriev N.I., Farber D.B.;
RT "Isolation and characterization of a cDNA encoding the alpha' subunit of
RT human cone cGMP-phosphodiesterase.";
RL Gene 166:205-211(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Retina;
RX PubMed=7490077; DOI=10.1006/geno.1995.1171;
RA Piriev N.I., Viczian A.S., Ye J., Kerner B., Korenberg J.R., Farber D.B.;
RT "Gene structure and amino acid sequence of the human cone photoreceptor
RT cGMP-phosphodiesterase alpha' subunit (PDEA2) and its chromosomal
RT localization to 10q24.";
RL Genomics 28:429-435(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT THR-270.
RC TISSUE=Retina;
RX PubMed=8641425; DOI=10.1016/0014-5793(96)00104-4;
RA Feshchenko E.A., Andreeva S.G., Suslova V.A., Smirnova E.V.,
RA Zagranichny V.E., Lipkin V.M.;
RT "Human cone-specific cGMP phosphodiesterase alpha' subunit: complete cDNA
RT sequence and gene arrangement.";
RL FEBS Lett. 381:149-152(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, INVOLVEMENT IN ACHM5, VARIANTS ACHM5 TRP-29; TRP-104;
RP 276-ARG--LEU-858 DEL; ASN-323; LEU-391; LEU-602; LYS-790 AND
RP 819-TYR--LEU-858 DEL, AND CHARACTERIZATION OF VARIANTS ACHM5 TRP-29;
RP TRP-104; ASN-323; LEU-391; LEU-602 AND LYS-790.
RX PubMed=21127010; DOI=10.1093/hmg/ddq517;
RA Grau T., Artemyev N.O., Rosenberg T., Dollfus H., Haugen O.H.,
RA Cumhur Sener E., Jurklies B., Andreasson S., Kernstock C., Larsen M.,
RA Zrenner E., Wissinger B., Kohl S.;
RT "Decreased catalytic activity and altered activation properties of PDE6C
RT mutants associated with autosomal recessive achromatopsia.";
RL Hum. Mol. Genet. 20:719-730(2011).
RN [7]
RP FUNCTION, CHARACTERIZATION OF VARIANTS ACHM5 TRP-29; TRP-104; ASN-323;
RP LEU-391; VAL-455; LEU-602 AND LYS-790, AND MUTAGENESIS OF LEU-858.
RX PubMed=28583373; DOI=10.1016/j.cellsig.2017.06.002;
RA Gopalakrishna K.N., Boyd K., Artemyev N.O.;
RT "Mechanisms of mutant PDE6 proteins underlying retinal diseases.";
RL Cell. Signal. 37:74-80(2017).
RN [8]
RP VARIANTS GLU-157; ASN-822 AND GLY-834.
RX PubMed=10393054;
RA Gao Y.Q., Danciger M., Longmuir R., Piriev N.I., Zhao D.Y.,
RA Heckenlively J.R., Fishman G.A., Weleber R.G., Jacobson S.G., Stone E.M.,
RA Farber D.B.;
RT "Screening of the gene encoding the alpha'-subunit of cone cGMP-PDE in
RT patients with retinal degenerations.";
RL Invest. Ophthalmol. Vis. Sci. 40:1818-1822(1999).
RN [9]
RP INVOLVEMENT IN COD4, INVOLVEMENT IN ACHM5, VARIANT COD4 TRP-29, AND
RP VARIANTS ACHM5 ASN-323 AND VAL-455.
RX PubMed=19615668; DOI=10.1016/j.ajhg.2009.06.016;
RA Thiadens A.A., den Hollander A.I., Roosing S., Nabuurs S.B.,
RA Zekveld-Vroon R.C., Collin R.W., De Baere E., Koenekoop R.K.,
RA van Schooneveld M.J., Strom T.M., van Lith-Verhoeven J.J., Lotery A.J.,
RA van Moll-Ramirez N., Leroy B.P., van den Born L.I., Hoyng C.B.,
RA Cremers F.P., Klaver C.C.;
RT "Homozygosity mapping reveals PDE6C mutations in patients with early-onset
RT cone photoreceptor disorders.";
RL Am. J. Hum. Genet. 85:240-247(2009).
RN [10]
RP VARIANT SER-826.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: As cone-specific cGMP phosphodiesterase, it plays an
CC essential role in light detection and cone phototransduction by rapidly
CC decreasing intracellular levels of cGMP. {ECO:0000269|PubMed:21127010,
CC ECO:0000269|PubMed:28583373}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746,
CC ChEBI:CHEBI:58115; EC=3.1.4.35;
CC Evidence={ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions, while site 2 has a preference for
CC magnesium and/or manganese ions. {ECO:0000250};
CC -!- SUBUNIT: Composed of two alpha' subunits that are associated with 3
CC smaller proteins of 11, 13, and 15 kDa.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC -!- DISEASE: Cone dystrophy 4 (COD4) [MIM:613093]: An early-onset cone
CC dystrophy. Cone dystrophies are retinal dystrophies characterized by
CC progressive degeneration of the cone photoreceptors with preservation
CC of rod function, as indicated by electroretinogram. However, some rod
CC involvement may be present in some cone dystrophies, particularly at
CC late stage. Affected individuals suffer from photophobia, loss of
CC visual acuity, color vision and central visual field. Another sign is
CC the absence of macular lesions for many years. Cone dystrophies are
CC distinguished from the cone-rod dystrophies in which some loss of
CC peripheral vision also occurs. {ECO:0000269|PubMed:19615668}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Achromatopsia 5 (ACHM5) [MIM:613093]: A form of achromatopsia,
CC an ocular stationary disorder due to the absence of functioning cone
CC photoreceptors in the retina. It is characterized by total
CC colorblindness, low visual acuity, photophobia and nystagmus. ACHM5
CC inheritance is autosomal recessive. {ECO:0000269|PubMed:19615668,
CC ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000305}.
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DR EMBL; U31973; AAA96392.1; -; mRNA.
DR EMBL; U20212; AAA92886.1; -; Genomic_DNA.
DR EMBL; U20196; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20197; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20199; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20200; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20201; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20202; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20203; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20204; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20205; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20206; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20207; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20208; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20209; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20210; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; U20211; AAA92886.1; JOINED; Genomic_DNA.
DR EMBL; X94354; CAA64079.1; -; Genomic_DNA.
DR EMBL; AL356214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157396; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW50064.1; -; Genomic_DNA.
DR CCDS; CCDS7429.1; -.
DR PIR; S63688; JC4520.
DR RefSeq; NP_006195.3; NM_006204.3.
DR PDB; 3JWQ; X-ray; 2.87 A; A/B/C/D=746-785.
DR PDB; 3JWR; X-ray; 2.99 A; A/B=746-785.
DR PDB; 5E8F; X-ray; 2.10 A; D/E=851-855.
DR PDBsum; 3JWQ; -.
DR PDBsum; 3JWR; -.
DR PDBsum; 5E8F; -.
DR AlphaFoldDB; P51160; -.
DR SMR; P51160; -.
DR BioGRID; 111172; 2.
DR STRING; 9606.ENSP00000360502; -.
DR BindingDB; P51160; -.
DR ChEMBL; CHEMBL3977; -.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB09283; Trapidil.
DR DrugCentral; P51160; -.
DR GuidetoPHARMACOLOGY; 1314; -.
DR iPTMnet; P51160; -.
DR PhosphoSitePlus; P51160; -.
DR BioMuta; PDE6C; -.
DR DMDM; 90111861; -.
DR jPOST; P51160; -.
DR MassIVE; P51160; -.
DR PaxDb; P51160; -.
DR PeptideAtlas; P51160; -.
DR PRIDE; P51160; -.
DR ProteomicsDB; 56291; -.
DR Antibodypedia; 30485; 121 antibodies from 21 providers.
DR DNASU; 5146; -.
DR Ensembl; ENST00000371447.4; ENSP00000360502.3; ENSG00000095464.10.
DR GeneID; 5146; -.
DR KEGG; hsa:5146; -.
DR MANE-Select; ENST00000371447.4; ENSP00000360502.3; NM_006204.4; NP_006195.3.
DR UCSC; uc001kiu.5; human.
DR CTD; 5146; -.
DR DisGeNET; 5146; -.
DR GeneCards; PDE6C; -.
DR GeneReviews; PDE6C; -.
DR HGNC; HGNC:8787; PDE6C.
DR HPA; ENSG00000095464; Tissue enriched (retina).
DR MalaCards; PDE6C; -.
DR MIM; 600827; gene.
DR MIM; 613093; phenotype.
DR neXtProt; NX_P51160; -.
DR OpenTargets; ENSG00000095464; -.
DR Orphanet; 49382; Achromatopsia.
DR Orphanet; 1871; Progressive cone dystrophy.
DR PharmGKB; PA33135; -.
DR VEuPathDB; HostDB:ENSG00000095464; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000157825; -.
DR HOGENOM; CLU_006980_2_0_1; -.
DR OMA; MYLNCER; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; P51160; -.
DR TreeFam; TF316499; -.
DR PathwayCommons; P51160; -.
DR BioGRID-ORCS; 5146; 5 hits in 1058 CRISPR screens.
DR ChiTaRS; PDE6C; human.
DR GeneWiki; PDE6C; -.
DR GenomeRNAi; 5146; -.
DR Pharos; P51160; Tclin.
DR PRO; PR:P51160; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P51160; protein.
DR Bgee; ENSG00000095464; Expressed in secondary oocyte and 94 other tissues.
DR Genevisible; P51160; HS.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007603; P:phototransduction, visible light; IEA:Ensembl.
DR GO; GO:0046549; P:retinal cone cell development; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR Gene3D; 3.30.450.40; -; 2.
DR InterPro; IPR003018; GAF.
DR InterPro; IPR029016; GAF-like_dom_sf.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR Pfam; PF01590; GAF; 2.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00065; GAF; 2.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; cGMP; cGMP-binding; Disease variant;
KW Hydrolase; Lipoprotein; Membrane; Metal-binding; Methylation;
KW Nucleotide-binding; Prenylation; Reference proteome; Repeat;
KW Sensory transduction; Vision.
FT CHAIN 1..855
FT /note="Cone cGMP-specific 3',5'-cyclic phosphodiesterase
FT subunit alpha'"
FT /id="PRO_0000198831"
FT PROPEP 856..858
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000370788"
FT DOMAIN 75..224
FT /note="GAF 1"
FT DOMAIN 256..433
FT /note="GAF 2"
FT DOMAIN 486..819
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 830..858
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 830..850
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 562
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 97
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250"
FT BINDING 116
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250"
FT BINDING 169..172
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250"
FT BINDING 176
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000250"
FT BINDING 566
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 602
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 603
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 603
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 723
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT MOD_RES 855
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000255"
FT LIPID 855
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT VARIANT 29
FT /note="R -> W (in COD4 and ACHM5; severely decreases cGMP
FT phosphodiesterase activity; dbSNP:rs121918537)"
FT /evidence="ECO:0000269|PubMed:19615668,
FT ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373"
FT /id="VAR_062408"
FT VARIANT 104
FT /note="R -> W (in ACHM5; severely decreases cGMP
FT phosphodiesterase activity; dbSNP:rs769506319)"
FT /evidence="ECO:0000269|PubMed:21127010,
FT ECO:0000269|PubMed:28583373"
FT /id="VAR_079307"
FT VARIANT 157
FT /note="D -> E (in dbSNP:rs76999928)"
FT /evidence="ECO:0000269|PubMed:10393054"
FT /id="VAR_025470"
FT VARIANT 270
FT /note="S -> T (in dbSNP:rs701865)"
FT /evidence="ECO:0000269|PubMed:8641425"
FT /id="VAR_050475"
FT VARIANT 276..858
FT /note="Missing (in ACHM5)"
FT /evidence="ECO:0000269|PubMed:21127010"
FT /id="VAR_079308"
FT VARIANT 323
FT /note="Y -> N (in ACHM5; decreases cGMP phosphodiesterase
FT activity; dbSNP:rs121918538)"
FT /evidence="ECO:0000269|PubMed:19615668,
FT ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373"
FT /id="VAR_062409"
FT VARIANT 391
FT /note="P -> L (in ACHM5; severely decreases cGMP
FT phosphodiesterase activity)"
FT /evidence="ECO:0000269|PubMed:21127010,
FT ECO:0000269|PubMed:28583373"
FT /id="VAR_079309"
FT VARIANT 455
FT /note="M -> V (in ACHM5; decreases cGMP phosphodiesterase
FT activity; dbSNP:rs121918539)"
FT /evidence="ECO:0000269|PubMed:19615668,
FT ECO:0000269|PubMed:28583373"
FT /id="VAR_062410"
FT VARIANT 602
FT /note="H -> L (in ACHM5; severely decreases cGMP
FT phosphodiesterase activity; dbSNP:rs267606934)"
FT /evidence="ECO:0000269|PubMed:21127010,
FT ECO:0000269|PubMed:28583373"
FT /id="VAR_079310"
FT VARIANT 699
FT /note="E -> A (in dbSNP:rs12261131)"
FT /id="VAR_050476"
FT VARIANT 790
FT /note="E -> K (in ACHM5; decreases cGMP phosphodiesterase
FT activity; dbSNP:rs267606936)"
FT /evidence="ECO:0000269|PubMed:21127010,
FT ECO:0000269|PubMed:28583373"
FT /id="VAR_079311"
FT VARIANT 819..858
FT /note="Missing (in ACHM5)"
FT /evidence="ECO:0000269|PubMed:21127010"
FT /id="VAR_079312"
FT VARIANT 822
FT /note="K -> N (in dbSNP:rs79487435)"
FT /evidence="ECO:0000269|PubMed:10393054"
FT /id="VAR_025471"
FT VARIANT 826
FT /note="I -> S (found in a renal cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064744"
FT VARIANT 834
FT /note="E -> G (in dbSNP:rs148661165)"
FT /evidence="ECO:0000269|PubMed:10393054"
FT /id="VAR_025472"
FT MUTAGEN 858
FT /note="L->V: No effect on cGMP phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:28583373"
FT CONFLICT 116
FT /note="D -> V (in Ref. 1; AAA96392 and 2; AAA92886)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="Q -> P (in Ref. 1; AAA96392)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="P -> L (in Ref. 1; AAA96392)"
FT /evidence="ECO:0000305"
FT CONFLICT 565
FT /note="R -> Q (in Ref. 1; AAA96392 and 2; AAA92886)"
FT /evidence="ECO:0000305"
FT HELIX 746..754
FT /evidence="ECO:0007829|PDB:3JWQ"
FT HELIX 762..764
FT /evidence="ECO:0007829|PDB:3JWQ"
FT HELIX 766..771
FT /evidence="ECO:0007829|PDB:3JWQ"
FT HELIX 772..782
FT /evidence="ECO:0007829|PDB:3JWQ"
SQ SEQUENCE 858 AA; 99147 MW; 06FFD025EE5936A5 CRC64;
MGEINQVAVE KYLEENPQFA KEYFDRKLRV EVLGEIFKNS QVPVQSSMSF SELTQVEESA
LCLELLWTVQ EEGGTPEQGV HRALQRLAHL LQADRCSMFL CRSRNGIPEV ASRLLDVTPT
SKFEDNLVGP DKEVVFPLDI GIVGWAAHTK KTHNVPDVKK NSHFSDFMDK QTGYVTKNLL
ATPIVVGKEV LAVIMAVNKV NASEFSKQDE EVFSKYLNFV SIILRLHHTS YMYNIESRRS
QILMWSANKV FEELTDVERQ FHKALYTVRS YLNCERYSIG LLDMTKEKEF YDEWPIKLGE
VEPYKGPKTP DGREVNFYKI IDYILHGKEE IKVIPTPPAD HWTLISGLPT YVAENGFICN
MMNAPADEYF TFQKGPVDET GWVIKNVLSL PIVNKKEDIV GVATFYNRKD GKPFDEHDEY
ITETLTQFLG WSLLNTDTYD KMNKLENRKD IAQEMLMNQT KATPEEIKSI LKFQEKLNVD
VIDDCEEKQL VAILKEDLPD PRSAELYEFR FSDFPLTEHG LIKCGIRLFF EINVVEKFKV
PVEVLTRWMY TVRKGYRAVT YHNWRHGFNV GQTMFTLLMT GRLKKYYTDL EAFAMLAAAF
CHDIDHRGTN NLYQMKSTSP LARLHGSSIL ERHHLEYSKT LLQDESLNIF QNLNKRQFET
VIHLFEVAII ATDLALYFKK RTMFQKIVDA CEQMQTEEEA IKYVTVDPTK KEIIMAMMMT
ACDLSAITKP WEVQSQVALM VANEFWEQGD LERTVLQQQP IPMMDRNKRD ELPKLQVGFI
DFVCTFVYKE FSRFHKEITP MLSGLQNNRV EWKSLADEYD AKMKVIEEEA KKQEGGAEKA
AEDSGGGDDK KSKTCLML
