PDE10_HUMAN
ID PDE10_HUMAN Reviewed; 779 AA.
AC Q9Y233; Q6FHX1; Q9HCP9; Q9NTV4; Q9ULW9; Q9Y5T1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A;
DE EC=3.1.4.17 {ECO:0000269|PubMed:10373451, ECO:0000269|PubMed:10393245, ECO:0000269|PubMed:17389385, ECO:0000269|PubMed:27058447};
GN Name=PDE10A;
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] (ISOFORM PDE10A2), SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION AT THR-16 (ISOFORM PDE10A2) BY PKA.
RC TISSUE=Fetal lung;
RX PubMed=10441464; DOI=10.1006/bbrc.1999.1013;
RA Kotera J., Fujishige K., Yuasa K., Omori K.;
RT "Characterization and phosphorylation of PDE10A2, a novel alternative
RT splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP.";
RL Biochem. Biophys. Res. Commun. 261:551-557(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE10A1), FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, AND SUBCELLULAR LOCATION.
RC TISSUE=Fetal lung;
RX PubMed=10373451; DOI=10.1074/jbc.274.26.18438;
RA Fujishige K., Kotera J., Michibata H., Yuasa K., Takebayashi S.,
RA Okumura K., Omori K.;
RT "Cloning and characterization of a novel human phosphodiesterase that
RT hydrolyzes both cAMP and cGMP (PDE10A).";
RL J. Biol. Chem. 274:18438-18445(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE10A1 AND PDE10A2), FUNCTION,
RP CATALYTIC ACTIVITY, AND PATHWAY.
RC TISSUE=Fetal brain;
RX PubMed=10393245; DOI=10.1016/s0378-1119(99)00171-7;
RA Loughney K., Snyder P.B., Uher L., Rosman G.J., Ferguson K., Florio V.A.;
RT "Isolation and characterization of PDE10A, a novel human 3',5'-cyclic
RT nucleotide phosphodiesterase.";
RL Gene 234:109-117(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE10A1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE10A1).
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 66-779, AND ALTERNATIVE SPLICING.
RX PubMed=10998054; DOI=10.1046/j.1432-1327.2000.01661.x;
RA Fujishige K., Kotera J., Yuasa K., Omori K.;
RT "The human phosphodiesterase PDE10A gene genomic organization and
RT evolutionary relatedness with other PDEs containing GAF domains.";
RL Eur. J. Biochem. 267:5943-5951(2000).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DOMAIN, AND ACTIVITY REGULATION.
RX PubMed=16330539; DOI=10.1074/jbc.m511468200;
RA Gross-Langenhoff M., Hofbauer K., Weber J., Schultz A., Schultz J.E.;
RT "cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10
RT and cGMP for the tandem GAF domain of phosphodiesterase 11.";
RL J. Biol. Chem. 281:2841-2846(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [11]
RP INVOLVEMENT IN IOLOD, VARIANTS IOLOD CYS-97 AND PRO-106, AND
RP CHARACTERIZATION OF VARIANTS IOLOD CYS-97 AND PRO-106.
RX PubMed=27058446; DOI=10.1016/j.ajhg.2016.03.015;
RA Diggle C.P., Sukoff Rizzo S.J., Popiolek M., Hinttala R., Schuelke J.P.,
RA Kurian M.A., Carr I.M., Markham A.F., Bonthron D.T., Watson C.,
RA Sharif S.M., Reinhart V., James L.C., Vanase-Frawley M.A., Charych E.,
RA Allen M., Harms J., Schmidt C.J., Ng J., Pysden K., Strick C., Vieira P.,
RA Mankinen K., Kokkonen H., Kallioinen M., Sormunen R., Rinne J.O.,
RA Johansson J., Alakurtti K., Huilaja L., Hurskainen T., Tasanen K.,
RA Anttila E., Marques T.R., Howes O., Politis M., Fahiminiya S., Nguyen K.Q.,
RA Majewski J., Uusimaa J., Sheridan E., Brandon N.J.;
RT "Biallelic mutations in PDE10A Lead to loss of striatal PDE10A and a
RT hyperkinetic movement disorder with onset in infancy.";
RL Am. J. Hum. Genet. 98:735-743(2016).
RN [12]
RP TISSUE SPECIFICITY, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INVOLVEMENT IN
RP ADSD2, VARIANTS ADSD2 LEU-290 AND LEU-324, AND CHARACTERIZATION OF VARIANTS
RP ADSD2 LEU-290 AND LEU-324.
RX PubMed=27058447; DOI=10.1016/j.ajhg.2016.02.015;
RA Mencacci N.E., Kamsteeg E.J., Nakashima K., R'Bibo L., Lynch D.S.,
RA Balint B., Willemsen M.A., Adams M.E., Wiethoff S., Suzuki K., Davies C.H.,
RA Ng J., Meyer E., Veneziano L., Giunti P., Hughes D., Raymond F.L.,
RA Carecchio M., Zorzi G., Nardocci N., Barzaghi C., Garavaglia B.,
RA Salpietro V., Hardy J., Pittman A.M., Houlden H., Kurian M.A., Kimura H.,
RA Vissers L.E., Wood N.W., Bhatia K.P.;
RT "De novo mutations in PDE10A cause childhood-onset chorea with bilateral
RT striatal lesions.";
RL Am. J. Hum. Genet. 98:763-771(2016).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 436-766 IN COMPLEXES WITH AMP;
RP CAMP; GMP; CGMP AND MAGNESIUM, MUTAGENESIS OF ASP-554, FUNCTION, CATALYTIC
RP ACTIVITY, PATHWAY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17389385; DOI=10.1073/pnas.0700279104;
RA Wang H., Liu Y., Hou J., Zheng M., Robinson H., Ke H.;
RT "Structural insight into substrate specificity of phosphodiesterase 10.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:5782-5787(2007).
RN [14] {ECO:0007744|PDB:2ZMF}
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 242-427 IN COMPLEX WITH CAMP,
RP DOMAIN, AND SUBUNIT.
RX PubMed=18477562; DOI=10.1074/jbc.m800595200;
RA Handa N., Mizohata E., Kishishita S., Toyama M., Morita S.,
RA Uchikubo-Kamo T., Akasaka R., Omori K., Kotera J., Terada T., Shirouzu M.,
RA Yokoyama S.;
RT "Crystal structure of the GAF-B domain from human phosphodiesterase 10A
RT complexed with its ligand, cAMP.";
RL J. Biol. Chem. 283:19657-19664(2008).
CC -!- FUNCTION: Plays a role in signal transduction by regulating the
CC intracellular concentration of cyclic nucleotides (PubMed:10373451,
CC PubMed:10393245, PubMed:16330539, PubMed:27058447, PubMed:17389385).
CC Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and
CC is more efficient with cAMP as substrate (PubMed:10373451,
CC PubMed:10393245, PubMed:27058447, PubMed:17389385). May play a critical
CC role in regulating cAMP and cGMP levels in the striatum, a region of
CC the brain that contributes to the control of movement and cognition
CC (PubMed:27058447). {ECO:0000269|PubMed:10373451,
CC ECO:0000269|PubMed:10393245, ECO:0000269|PubMed:16330539,
CC ECO:0000269|PubMed:17389385, ECO:0000269|PubMed:27058447}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-
CC phosphate + H(+); Xref=Rhea:RHEA:14653, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57867, ChEBI:CHEBI:58464; EC=3.1.4.17;
CC Evidence={ECO:0000269|PubMed:10373451, ECO:0000269|PubMed:10393245,
CC ECO:0000269|PubMed:17389385, ECO:0000269|PubMed:27058447};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:10373451,
CC ECO:0000269|PubMed:10393245, ECO:0000269|PubMed:16330539,
CC ECO:0000269|PubMed:17389385, ECO:0000269|PubMed:27058447};
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; Evidence={ECO:0000269|PubMed:10373451,
CC ECO:0000269|PubMed:10393245, ECO:0000269|PubMed:17389385,
CC ECO:0000269|PubMed:27058447};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:17389385};
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:0000269|PubMed:17389385};
CC -!- ACTIVITY REGULATION: Inhibited by dipyridamole and moderately by IBMX.
CC cGMP acts as an allosteric activator. {ECO:0000269|PubMed:16330539}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.26 uM for cAMP {ECO:0000269|PubMed:10373451};
CC KM=7.2 uM for cGMP {ECO:0000269|PubMed:10373451};
CC KM=56 nM for cAMP {ECO:0000269|PubMed:17389385};
CC KM=4.4 uM for cGMP {ECO:0000269|PubMed:17389385};
CC Vmax=507 nmol/min/mg enzyme for cAMP {ECO:0000269|PubMed:17389385};
CC Vmax=1860 nmol/min/mg enzyme for cGMP {ECO:0000269|PubMed:17389385};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1. {ECO:0000269|PubMed:10373451,
CC ECO:0000269|PubMed:10393245, ECO:0000269|PubMed:16330539,
CC ECO:0000269|PubMed:17389385, ECO:0000269|PubMed:27058447}.
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from
CC 3',5'-cyclic GMP: step 1/1. {ECO:0000269|PubMed:10373451,
CC ECO:0000269|PubMed:10393245, ECO:0000269|PubMed:17389385,
CC ECO:0000269|PubMed:27058447}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18477562}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10373451,
CC ECO:0000269|PubMed:10441464}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Isoforms differ in their N-terminal region.;
CC Name=PDE10A1;
CC IsoId=Q9Y233-1; Sequence=Displayed;
CC Name=PDE10A2;
CC IsoId=Q9Y233-2; Sequence=VSP_004601;
CC -!- TISSUE SPECIFICITY: Abundant in the putamen and caudate nucleus regions
CC of brain and testis, moderately expressed in the thyroid gland,
CC pituitary gland, thalamus and cerebellum. {ECO:0000269|PubMed:10373451,
CC ECO:0000269|PubMed:27058447}.
CC -!- DOMAIN: The tandem GAF domains bind cAMP, and regulate enzyme activity.
CC The binding of cAMP stimulates enzyme activity.
CC {ECO:0000269|PubMed:16330539}.
CC -!- DOMAIN: Composed of a C-terminal catalytic domain containing two
CC divalent metal sites and an N-terminal regulatory domain which contains
CC one cyclic nucleotide-binding region. {ECO:0000269|PubMed:17389385,
CC ECO:0000269|PubMed:18477562}.
CC -!- PTM: [Isoform PDE10A2]: Phosphorylated on Thr-16.
CC {ECO:0000269|PubMed:10441464}.
CC -!- DISEASE: Dyskinesia, limb and orofacial, infantile-onset (IOLOD)
CC [MIM:616921]: An autosomal recessive, early-onset hyperkinetic movement
CC disorder characterized by axial hypotonia, dyskinesia of the limbs and
CC trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of
CC the hyperkinesis is variable. {ECO:0000269|PubMed:27058446}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Striatal degeneration, autosomal dominant 2 (ADSD2)
CC [MIM:616922]: An autosomal dominant disorder characterized by striatal
CC degeneration and dysfunction of basal ganglia, resulting in
CC hyperkinesis. {ECO:0000269|PubMed:27058447}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD32596.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB026816; BAA84467.1; -; mRNA.
DR EMBL; AB020593; BAA78034.1; -; mRNA.
DR EMBL; AF127479; AAD32595.1; -; mRNA.
DR EMBL; AF127480; AAD32596.1; ALT_INIT; mRNA.
DR EMBL; CR536567; CAG38804.1; -; mRNA.
DR EMBL; AL117345; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136130; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160160; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC104858; AAI04859.1; -; mRNA.
DR EMBL; BC104860; AAI04861.1; -; mRNA.
DR EMBL; AB041798; BAB16383.1; -; Genomic_DNA.
DR CCDS; CCDS47513.1; -. [Q9Y233-2]
DR CCDS; CCDS5289.1; -. [Q9Y233-1]
DR RefSeq; NP_001124162.1; NM_001130690.2. [Q9Y233-2]
DR RefSeq; NP_006652.1; NM_006661.3. [Q9Y233-1]
DR RefSeq; XP_011533690.1; XM_011535388.2. [Q9Y233-1]
DR PDB; 2OUN; X-ray; 1.56 A; A/B=439-766.
DR PDB; 2OUP; X-ray; 1.56 A; A/B=439-766.
DR PDB; 2OUQ; X-ray; 1.90 A; A/B=439-766.
DR PDB; 2OUR; X-ray; 1.45 A; A/B=439-766.
DR PDB; 2OUS; X-ray; 1.45 A; A/B=439-766.
DR PDB; 2OUU; X-ray; 1.52 A; A/B=439-766.
DR PDB; 2OUV; X-ray; 1.56 A; A/B=439-766.
DR PDB; 2OUY; X-ray; 1.90 A; A/B=439-766.
DR PDB; 2WEY; X-ray; 2.80 A; A/B=439-779.
DR PDB; 2Y0J; X-ray; 2.43 A; A/B=432-764.
DR PDB; 2ZMF; X-ray; 2.10 A; A/B=246-427.
DR PDB; 3SN7; X-ray; 1.82 A; A/B=439-779.
DR PDB; 3SNI; X-ray; 1.90 A; A/B=439-779.
DR PDB; 3SNL; X-ray; 2.40 A; A/B=439-779.
DR PDB; 3UI7; X-ray; 2.28 A; A/B=432-760.
DR PDB; 3UUO; X-ray; 2.11 A; A/B=432-760.
DR PDB; 3WI2; X-ray; 2.26 A; A/B=439-779.
DR PDB; 3WS8; X-ray; 2.60 A; A/B=439-779.
DR PDB; 3WS9; X-ray; 2.99 A; A/B=439-779.
DR PDB; 3WYK; X-ray; 2.50 A; A/B=442-779.
DR PDB; 3WYL; X-ray; 2.68 A; A/B=442-779.
DR PDB; 3WYM; X-ray; 2.00 A; A/B=442-779.
DR PDB; 4AEL; X-ray; 2.20 A; A/B=439-779.
DR PDB; 4AJD; X-ray; 2.30 A; A/D=439-764.
DR PDB; 4AJF; X-ray; 1.90 A; A/D=439-764.
DR PDB; 4AJG; X-ray; 2.30 A; A/D=439-764.
DR PDB; 4AJM; X-ray; 2.40 A; A/D=439-764.
DR PDB; 4BBX; X-ray; 2.50 A; A/B=443-769.
DR PDB; 4DDL; X-ray; 2.07 A; A/B=442-779.
DR PDB; 4DFF; X-ray; 2.11 A; A/B=432-779.
DR PDB; 4FCB; X-ray; 2.10 A; A/B=439-779.
DR PDB; 4FCD; X-ray; 2.02 A; A/B=439-779.
DR PDB; 4HEU; X-ray; 2.00 A; A/B=442-759.
DR PDB; 4HF4; X-ray; 2.00 A; A/B=442-759.
DR PDB; 4LKQ; X-ray; 1.62 A; A/B=439-779.
DR PDB; 4LLJ; X-ray; 1.56 A; A/B=439-779.
DR PDB; 4LLK; X-ray; 1.55 A; A/B=439-779.
DR PDB; 4LLP; X-ray; 1.75 A; A/B=439-779.
DR PDB; 4LLX; X-ray; 1.75 A; A/B=439-779.
DR PDB; 4LM0; X-ray; 1.66 A; A/B=439-779.
DR PDB; 4LM1; X-ray; 1.60 A; A/B=439-779.
DR PDB; 4LM2; X-ray; 1.55 A; A/B=439-779.
DR PDB; 4LM3; X-ray; 1.49 A; A/B=439-779.
DR PDB; 4LM4; X-ray; 1.48 A; A/B=439-779.
DR PDB; 4MRW; X-ray; 1.96 A; A/B=439-779.
DR PDB; 4MRZ; X-ray; 1.58 A; A/B=439-779.
DR PDB; 4MS0; X-ray; 1.79 A; A/B=439-779.
DR PDB; 4MSA; X-ray; 1.62 A; A/B=439-779.
DR PDB; 4MSC; X-ray; 2.47 A; A/B=439-779.
DR PDB; 4MSE; X-ray; 2.81 A; A/B=439-779.
DR PDB; 4MSH; X-ray; 2.30 A; A/B=439-779.
DR PDB; 4MSN; X-ray; 2.30 A; A/B=439-779.
DR PDB; 4MUW; X-ray; 2.64 A; A/B=442-779.
DR PDB; 4MVH; X-ray; 2.50 A; A/B=442-779.
DR PDB; 4P0N; X-ray; 2.08 A; A/B=442-779.
DR PDB; 4P1R; X-ray; 2.24 A; A/B=442-779.
DR PDB; 4PHW; X-ray; 2.50 A; A/B=442-779.
DR PDB; 4TPM; X-ray; 2.77 A; A/B=442-779.
DR PDB; 4TPP; X-ray; 2.65 A; A/B=442-779.
DR PDB; 4WN1; X-ray; 3.13 A; A/B=439-779.
DR PDB; 4XY2; X-ray; 2.03 A; A/B=439-779.
DR PDB; 4YQH; X-ray; 2.31 A; A/B=439-759.
DR PDB; 4YS7; X-ray; 2.50 A; A/B=439-759.
DR PDB; 4ZO5; X-ray; 2.50 A; A/B=439-759.
DR PDB; 5AXP; X-ray; 1.95 A; A/B=442-779.
DR PDB; 5AXQ; X-ray; 1.77 A; A/B=442-779.
DR PDB; 5B4K; X-ray; 2.90 A; A/B=442-779.
DR PDB; 5B4L; X-ray; 2.40 A; A/B=442-779.
DR PDB; 5C1W; X-ray; 1.70 A; A/B=439-779.
DR PDB; 5C28; X-ray; 1.56 A; A/B=439-779.
DR PDB; 5C29; X-ray; 2.05 A; A/B=439-779.
DR PDB; 5C2A; X-ray; 2.00 A; A/B=439-779.
DR PDB; 5C2E; X-ray; 2.10 A; A/B=439-779.
DR PDB; 5C2H; X-ray; 2.09 A; A/B=439-779.
DR PDB; 5DH4; X-ray; 2.20 A; A/B=439-779.
DR PDB; 5DH5; X-ray; 2.00 A; A/B=439-779.
DR PDB; 5EDE; X-ray; 2.20 A; A/C/D=447-760, B=448-760.
DR PDB; 5EDG; X-ray; 2.30 A; A/B/C/D=447-760.
DR PDB; 5EDH; X-ray; 2.03 A; A/B/C/D=448-760.
DR PDB; 5EDI; X-ray; 2.20 A; A/B/C/D=442-760.
DR PDB; 5I2R; X-ray; 2.50 A; A/B/C/D=447-763.
DR PDB; 5K9R; X-ray; 2.70 A; A/B=448-759.
DR PDB; 5UWF; X-ray; 1.87 A; C/D=439-779.
DR PDB; 5XUI; X-ray; 2.77 A; A/B=439-779.
DR PDB; 5XUJ; X-ray; 2.44 A; A/B=439-779.
DR PDB; 5ZNL; X-ray; 2.80 A; A/B=439-760.
DR PDB; 6IJH; X-ray; 2.60 A; A/B=439-779.
DR PDB; 6IJI; X-ray; 2.70 A; A/B=439-760.
DR PDB; 6KDX; X-ray; 2.44 A; A/B=439-779.
DR PDB; 6KDZ; X-ray; 3.10 A; A/B=439-779.
DR PDB; 6KE0; X-ray; 2.95 A; A/B=439-779.
DR PDB; 6KO0; X-ray; 2.60 A; A/B=439-759.
DR PDB; 6KO1; X-ray; 2.70 A; A/B=439-759.
DR PDB; 6KZE; X-ray; 2.50 A; A/B=439-760.
DR PDB; 6MSA; X-ray; 2.06 A; A/B=439-766.
DR PDB; 6MSC; X-ray; 2.36 A; A/B=439-766.
DR PDB; 7BPI; X-ray; 2.40 A; A/B=439-760.
DR PDBsum; 2OUN; -.
DR PDBsum; 2OUP; -.
DR PDBsum; 2OUQ; -.
DR PDBsum; 2OUR; -.
DR PDBsum; 2OUS; -.
DR PDBsum; 2OUU; -.
DR PDBsum; 2OUV; -.
DR PDBsum; 2OUY; -.
DR PDBsum; 2WEY; -.
DR PDBsum; 2Y0J; -.
DR PDBsum; 2ZMF; -.
DR PDBsum; 3SN7; -.
DR PDBsum; 3SNI; -.
DR PDBsum; 3SNL; -.
DR PDBsum; 3UI7; -.
DR PDBsum; 3UUO; -.
DR PDBsum; 3WI2; -.
DR PDBsum; 3WS8; -.
DR PDBsum; 3WS9; -.
DR PDBsum; 3WYK; -.
DR PDBsum; 3WYL; -.
DR PDBsum; 3WYM; -.
DR PDBsum; 4AEL; -.
DR PDBsum; 4AJD; -.
DR PDBsum; 4AJF; -.
DR PDBsum; 4AJG; -.
DR PDBsum; 4AJM; -.
DR PDBsum; 4BBX; -.
DR PDBsum; 4DDL; -.
DR PDBsum; 4DFF; -.
DR PDBsum; 4FCB; -.
DR PDBsum; 4FCD; -.
DR PDBsum; 4HEU; -.
DR PDBsum; 4HF4; -.
DR PDBsum; 4LKQ; -.
DR PDBsum; 4LLJ; -.
DR PDBsum; 4LLK; -.
DR PDBsum; 4LLP; -.
DR PDBsum; 4LLX; -.
DR PDBsum; 4LM0; -.
DR PDBsum; 4LM1; -.
DR PDBsum; 4LM2; -.
DR PDBsum; 4LM3; -.
DR PDBsum; 4LM4; -.
DR PDBsum; 4MRW; -.
DR PDBsum; 4MRZ; -.
DR PDBsum; 4MS0; -.
DR PDBsum; 4MSA; -.
DR PDBsum; 4MSC; -.
DR PDBsum; 4MSE; -.
DR PDBsum; 4MSH; -.
DR PDBsum; 4MSN; -.
DR PDBsum; 4MUW; -.
DR PDBsum; 4MVH; -.
DR PDBsum; 4P0N; -.
DR PDBsum; 4P1R; -.
DR PDBsum; 4PHW; -.
DR PDBsum; 4TPM; -.
DR PDBsum; 4TPP; -.
DR PDBsum; 4WN1; -.
DR PDBsum; 4XY2; -.
DR PDBsum; 4YQH; -.
DR PDBsum; 4YS7; -.
DR PDBsum; 4ZO5; -.
DR PDBsum; 5AXP; -.
DR PDBsum; 5AXQ; -.
DR PDBsum; 5B4K; -.
DR PDBsum; 5B4L; -.
DR PDBsum; 5C1W; -.
DR PDBsum; 5C28; -.
DR PDBsum; 5C29; -.
DR PDBsum; 5C2A; -.
DR PDBsum; 5C2E; -.
DR PDBsum; 5C2H; -.
DR PDBsum; 5DH4; -.
DR PDBsum; 5DH5; -.
DR PDBsum; 5EDE; -.
DR PDBsum; 5EDG; -.
DR PDBsum; 5EDH; -.
DR PDBsum; 5EDI; -.
DR PDBsum; 5I2R; -.
DR PDBsum; 5K9R; -.
DR PDBsum; 5UWF; -.
DR PDBsum; 5XUI; -.
DR PDBsum; 5XUJ; -.
DR PDBsum; 5ZNL; -.
DR PDBsum; 6IJH; -.
DR PDBsum; 6IJI; -.
DR PDBsum; 6KDX; -.
DR PDBsum; 6KDZ; -.
DR PDBsum; 6KE0; -.
DR PDBsum; 6KO0; -.
DR PDBsum; 6KO1; -.
DR PDBsum; 6KZE; -.
DR PDBsum; 6MSA; -.
DR PDBsum; 6MSC; -.
DR PDBsum; 7BPI; -.
DR AlphaFoldDB; Q9Y233; -.
DR SMR; Q9Y233; -.
DR BioGRID; 116057; 7.
DR IntAct; Q9Y233; 2.
DR STRING; 9606.ENSP00000438284; -.
DR BindingDB; Q9Y233; -.
DR ChEMBL; CHEMBL4409; -.
DR DrugBank; DB08384; 2-({4-[4-(pyridin-4-ylmethyl)-1H-pyrazol-3-yl]phenoxy}methyl)quinoline.
DR DrugBank; DB08386; 2-{[4-(4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy]methyl}quinoline.
DR DrugBank; DB08383; 4,5-bis(4-methoxyphenyl)-2-thiophen-2-yl-1H-imidazole.
DR DrugBank; DB08389; 6,7-DIMETHOXY-4-[(3R)-3-(2-NAPHTHYLOXY)PYRROLIDIN-1-YL]QUINAZOLINE.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB00975; Dipyridamole.
DR DrugBank; DB08387; Mardepodect.
DR DrugBank; DB01113; Papaverine.
DR DrugBank; DB08391; PQ-10.
DR DrugBank; DB08811; Tofisopam.
DR DrugBank; DB09283; Trapidil.
DR DrugBank; DB08814; Triflusal.
DR DrugCentral; Q9Y233; -.
DR GuidetoPHARMACOLOGY; 1310; -.
DR GlyGen; Q9Y233; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y233; -.
DR PhosphoSitePlus; Q9Y233; -.
DR SwissPalm; Q9Y233; -.
DR BioMuta; PDE10A; -.
DR DMDM; 7993747; -.
DR EPD; Q9Y233; -.
DR jPOST; Q9Y233; -.
DR MassIVE; Q9Y233; -.
DR MaxQB; Q9Y233; -.
DR PaxDb; Q9Y233; -.
DR PeptideAtlas; Q9Y233; -.
DR PRIDE; Q9Y233; -.
DR ProteomicsDB; 85625; -. [Q9Y233-1]
DR ProteomicsDB; 85626; -. [Q9Y233-2]
DR Antibodypedia; 33512; 232 antibodies from 27 providers.
DR DNASU; 10846; -.
DR Ensembl; ENST00000366882.7; ENSP00000355847.3; ENSG00000112541.19.
DR GeneID; 10846; -.
DR KEGG; hsa:10846; -.
DR UCSC; uc003quo.4; human. [Q9Y233-1]
DR CTD; 10846; -.
DR DisGeNET; 10846; -.
DR GeneCards; PDE10A; -.
DR HGNC; HGNC:8772; PDE10A.
DR HPA; ENSG00000112541; Tissue enriched (brain).
DR MalaCards; PDE10A; -.
DR MIM; 610652; gene.
DR MIM; 616921; phenotype.
DR MIM; 616922; phenotype.
DR neXtProt; NX_Q9Y233; -.
DR Orphanet; 494541; Childhood-onset benign chorea with striatal involvement.
DR Orphanet; 494526; Infantile-onset generalized dyskinesia with orofacial involvement.
DR PharmGKB; PA33120; -.
DR VEuPathDB; HostDB:ENSG00000112541; -.
DR eggNOG; KOG3689; Eukaryota.
DR HOGENOM; CLU_006980_1_0_1; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; Q9Y233; -.
DR TreeFam; TF316499; -.
DR BRENDA; 3.1.4.17; 2681.
DR PathwayCommons; Q9Y233; -.
DR Reactome; R-HSA-418457; cGMP effects.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR SABIO-RK; Q9Y233; -.
DR SignaLink; Q9Y233; -.
DR SIGNOR; Q9Y233; -.
DR UniPathway; UPA00762; UER00747.
DR UniPathway; UPA00763; UER00748.
DR BioGRID-ORCS; 10846; 7 hits in 1071 CRISPR screens.
DR ChiTaRS; PDE10A; human.
DR EvolutionaryTrace; Q9Y233; -.
DR GeneWiki; PDE10A; -.
DR GenomeRNAi; 10846; -.
DR Pharos; Q9Y233; Tclin.
DR PRO; PR:Q9Y233; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9Y233; protein.
DR Bgee; ENSG00000112541; Expressed in adrenal tissue and 142 other tissues.
DR ExpressionAtlas; Q9Y233; baseline and differential.
DR Genevisible; Q9Y233; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IEA:RHEA.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:RHEA.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0030552; F:cAMP binding; IDA:UniProtKB.
DR GO; GO:0030553; F:cGMP binding; NAS:UniProtKB.
DR GO; GO:0004118; F:cGMP-stimulated cyclic-nucleotide phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046069; P:cGMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; 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; Allosteric enzyme; Alternative splicing; cAMP; cAMP-binding;
KW cGMP; cGMP-binding; Cytoplasm; Disease variant; Hydrolase; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..779
FT /note="cAMP and cAMP-inhibited cGMP 3',5'-cyclic
FT phosphodiesterase 10A"
FT /id="PRO_0000198843"
FT DOMAIN 91..234
FT /note="GAF 1"
FT DOMAIN 266..412
FT /note="GAF 2"
FT DOMAIN 442..759
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT ACT_SITE 515
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O76083"
FT BINDING 286..287
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:18477562,
FT ECO:0007744|PDB:2ZMF"
FT BINDING 330..331
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:18477562,
FT ECO:0007744|PDB:2ZMF"
FT BINDING 364
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:18477562,
FT ECO:0007744|PDB:2ZMF"
FT BINDING 383
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:18477562,
FT ECO:0007744|PDB:2ZMF"
FT BINDING 515
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:17389385"
FT BINDING 515
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000269|PubMed:17389385"
FT BINDING 519
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17389385"
FT BINDING 553
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17389385"
FT BINDING 554
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17389385"
FT BINDING 554
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17389385"
FT BINDING 664
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17389385"
FT BINDING 716
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:17389385"
FT BINDING 716
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /evidence="ECO:0000269|PubMed:17389385"
FT VAR_SEQ 1..13
FT /note="MRIEERKSQHLTG -> MEDGPSNNASCFRRLTECFLSPS (in isoform
FT PDE10A2)"
FT /evidence="ECO:0000303|PubMed:10393245,
FT ECO:0000303|PubMed:10441464"
FT /id="VSP_004601"
FT VARIANT 97
FT /note="Y -> C (in IOLOD; decreased protein abundance;
FT dbSNP:rs778899140)"
FT /evidence="ECO:0000269|PubMed:27058446"
FT /id="VAR_076798"
FT VARIANT 106
FT /note="A -> P (in IOLOD; decreased protein abundance;
FT dbSNP:rs875989839)"
FT /evidence="ECO:0000269|PubMed:27058446"
FT /id="VAR_076799"
FT VARIANT 290
FT /note="F -> L (in ADSD2; no effect on basal 3',5'-cyclic-
FT nucleotide phosphodiesterase activity; the mutation
FT severely disrupts the stimulatory effect on the enzyme
FT activity mediated by cAMP binding; dbSNP:rs875989841)"
FT /evidence="ECO:0000269|PubMed:27058447"
FT /id="VAR_076800"
FT VARIANT 303
FT /note="L -> P"
FT /id="VAR_008797"
FT VARIANT 324
FT /note="F -> L (in ADSD2; no effect on basal 3',5'-cyclic-
FT nucleotide phosphodiesterase activity; the mutation
FT severely disrupts the stimulatory effect on the enzyme
FT activity mediated by cAMP binding; dbSNP:rs875989840)"
FT /evidence="ECO:0000269|PubMed:27058447"
FT /id="VAR_076801"
FT VARIANT 706
FT /note="R -> K (in dbSNP:rs2224252)"
FT /id="VAR_047822"
FT VARIANT 707
FT /note="D -> N (in dbSNP:rs2860112)"
FT /id="VAR_047823"
FT MUTAGEN 554
FT /note="D->A: Loss of activity and of zinc binding."
FT /evidence="ECO:0000269|PubMed:17389385"
FT MUTAGEN 554
FT /note="D->N: Reduces activity 1000-fold."
FT /evidence="ECO:0000269|PubMed:17389385"
FT CONFLICT 657
FT /note="G -> S (in Ref. 4; CAG38804)"
FT /evidence="ECO:0000305"
FT HELIX 247..262
FT /evidence="ECO:0007829|PDB:2ZMF"
FT HELIX 267..282
FT /evidence="ECO:0007829|PDB:2ZMF"
FT STRAND 284..293
FT /evidence="ECO:0007829|PDB:2ZMF"
FT TURN 294..297
FT /evidence="ECO:0007829|PDB:2ZMF"
FT STRAND 298..304
FT /evidence="ECO:0007829|PDB:2ZMF"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:2ZMF"
FT HELIX 329..337
FT /evidence="ECO:0007829|PDB:2ZMF"
FT STRAND 341..344
FT /evidence="ECO:0007829|PDB:2ZMF"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:2ZMF"
FT HELIX 355..360
FT /evidence="ECO:0007829|PDB:2ZMF"
FT STRAND 367..374
FT /evidence="ECO:0007829|PDB:2ZMF"
FT STRAND 377..387
FT /evidence="ECO:0007829|PDB:2ZMF"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:2ZMF"
FT HELIX 395..419
FT /evidence="ECO:0007829|PDB:2ZMF"
FT HELIX 443..449
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 456..461
FT /evidence="ECO:0007829|PDB:2OUR"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:3UI7"
FT HELIX 470..475
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 476..488
FT /evidence="ECO:0007829|PDB:2OUR"
FT TURN 490..492
FT /evidence="ECO:0007829|PDB:3SNI"
FT HELIX 495..507
FT /evidence="ECO:0007829|PDB:2OUR"
FT STRAND 513..516
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 517..532
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 533..537
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 540..552
FT /evidence="ECO:0007829|PDB:2OUR"
FT TURN 553..556
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 562..567
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 571..575
FT /evidence="ECO:0007829|PDB:2OUR"
FT STRAND 577..579
FT /evidence="ECO:0007829|PDB:2OUS"
FT HELIX 580..593
FT /evidence="ECO:0007829|PDB:2OUR"
FT TURN 596..598
FT /evidence="ECO:0007829|PDB:3SN7"
FT TURN 600..603
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 606..622
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 625..640
FT /evidence="ECO:0007829|PDB:2OUR"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:3WI2"
FT HELIX 649..664
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 666..669
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 672..695
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 702..704
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 706..711
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 712..722
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 724..734
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 736..738
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 739..757
FT /evidence="ECO:0007829|PDB:2OUR"
FT HELIX 762..765
FT /evidence="ECO:0007829|PDB:5C28"
FT MOD_RES Q9Y233-2:16
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:10441464"
SQ SEQUENCE 779 AA; 88412 MW; C5651BBB524A32B7 CRC64;
MRIEERKSQH LTGLTDEKVK AYLSLHPQVL DEFVSESVSA ETVEKWLKRK NNKSEDESAP
KEVSRYQDTN MQGVVYELNS YIEQRLDTGG DNQLLLYELS SIIKIATKAD GFALYFLGEC
NNSLCIFTPP GIKEGKPRLI PAGPITQGTT VSAYVAKSRK TLLVEDILGD ERFPRGTGLE
SGTRIQSVLC LPIVTAIGDL IGILELYRHW GKEAFCLSHQ EVATANLAWA SVAIHQVQVC
RGLAKQTELN DFLLDVSKTY FDNIVAIDSL LEHIMIYAKN LVNADRCALF QVDHKNKELY
SDLFDIGEEK EGKPVFKKTK EIRFSIEKGI AGQVARTGEV LNIPDAYADP RFNREVDLYT
GYTTRNILCM PIVSRGSVIG VVQMVNKISG SAFSKTDENN FKMFAVFCAL ALHCANMYHR
IRHSECIYRV TMEKLSYHSI CTSEEWQGLM QFTLPVRLCK EIELFHFDIG PFENMWPGIF
VYMVHRSCGT SCFELEKLCR FIMSVKKNYR RVPYHNWKHA VTVAHCMYAI LQNNHTLFTD
LERKGLLIAC LCHDLDHRGF SNSYLQKFDH PLAALYSTST MEQHHFSQTV SILQLEGHNI
FSTLSSSEYE QVLEIIRKAI IATDLALYFG NRKQLEEMYQ TGSLNLNNQS HRDRVIGLMM
TACDLCSVTK LWPVTKLTAN DIYAEFWAEG DEMKKLGIQP IPMMDRDKKD EVPQGQLGFY
NAVAIPCYTT LTQILPPTEP LLKACRDNLS QWEKVIRGEE TATWISSPSV AQKAAASED
