ID A0A3B3ISJ6_HUMAN Unreviewed; 791 AA. AC A0A3B3ISJ6; DT 05-DEC-2018, integrated into UniProtKB/TrEMBL. DT 05-DEC-2018, sequence version 1. DT 24-JAN-2024, entry version 24. DE RecName: Full=Phosphodiesterase {ECO:0000256|RuleBase:RU363067}; DE EC=3.1.4.- {ECO:0000256|RuleBase:RU363067}; GN Name=PDE10A {ECO:0000313|Ensembl:ENSP00000497277.1}; GN Synonyms=PDE10A19 {ECO:0000313|EMBL:AMN14870.1}; 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 {ECO:0000313|Ensembl:ENSP00000497277.1, ECO:0000313|Proteomes:UP000005640}; RN [1] {ECO:0000313|Ensembl:ENSP00000497277.1, ECO:0000313|Proteomes:UP000005640} 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., 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 [2] {ECO:0007829|PubMed:18691976} RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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 [3] {ECO:0007829|PubMed:19369195} 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 [4] {ECO:0000313|EMBL:AMN14870.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=Striatum {ECO:0000313|EMBL:AMN14870.1}; RX PubMed=26905414; RA MacMullen C.M., Vick K., Pacifico R., Fallahi-Sichani M., Davis R.L.; RT "Novel, primate-specific PDE10A isoform highlights gene expression RT complexity in human striatum with implications on the molecular pathology RT of bipolar disorder."; RL Transl. Psychiatry 6:e742-e742(2016). RN [5] {ECO:0000313|Ensembl:ENSP00000497277.1} RP IDENTIFICATION. RG Ensembl; RL Submitted (SEP-2023) to UniProtKB. CC -!- COFACTOR: CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; CC Evidence={ECO:0000256|RuleBase:RU363067}; 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:0000256|RuleBase:RU363067}; CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family. CC {ECO:0000256|RuleBase:RU363067}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL117345; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL121789; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL136130; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL160160; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590302; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591962; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KF458352; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KF458359; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KU232567; AMN14870.1; -; mRNA. DR MassIVE; A0A3B3ISJ6; -. DR Antibodypedia; 33512; 284 antibodies from 27 providers. DR Ensembl; ENST00000648917.1; ENSP00000497277.1; ENSG00000112541.19. DR HGNC; HGNC:8772; PDE10A. DR VEuPathDB; HostDB:ENSG00000112541; -. DR GeneTree; ENSGT00940000156543; -. DR ChiTaRS; PDE10A; human. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000112541; Expressed in adrenal tissue and 144 other cell types or tissues. DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR CDD; cd00077; HDc; 1. DR Gene3D; 3.30.450.40; -; 2. DR Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1. 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 PANTHER; PTHR11347:SF111; CAMP AND CAMP-INHIBITED CGMP 3',5'-CYCLIC PHOSPHODIESTERASE 10A; 1. DR PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1. 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 SUPFAM; SSF55781; GAF domain-like; 2. DR SUPFAM; SSF109604; HD-domain/PDEase-like; 1. DR PROSITE; PS00126; PDEASE_I_1; 1. DR PROSITE; PS51845; PDEASE_I_2; 1. PE 1: Evidence at protein level; KW cGMP {ECO:0000256|ARBA:ARBA00022535}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU363067}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, KW ECO:0000256|PIRSR:PIRSR623088-3}; KW Proteomics identification {ECO:0007829|MaxQB:A0A3B3ISJ6, KW ECO:0007829|PeptideAtlas:A0A3B3ISJ6}; KW Reference proteome {ECO:0000313|Proteomes:UP000005640}. FT DOMAIN 454..771 FT /note="PDEase" FT /evidence="ECO:0000259|PROSITE:PS51845" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..16 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 527 FT /note="Proton donor" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-1" FT BINDING 527..531 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2" FT BINDING 531 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 565 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 566 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2" FT BINDING 566 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 566 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 676 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2" FT BINDING 676 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 728 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2" SQ SEQUENCE 791 AA; 89552 MW; 144276319F8DF444 CRC64; MEGSTAWSSE AEPQEGRSQM LQRAGLTDEK VKAYLSLHPQ VLDEFVSESV SAETVEKWLK RKNNKSEDES APKEVSRYQD TNMQGVVYEL NSYIEQRLDT GGDNQLLLYE LSSIIKIATK ADGFALYFLG ECNNSLCIFT PPGIKEGKPR LIPAGPITQG TTVSAYVAKS RKTLLVEDIL GDERFPRGTG LESGTRIQSV LCLPIVTAIG DLIGILELYR HWGKEAFCLS HQEVATANLA WASVAIHQVQ VCRGLAKQTE LNDFLLDVSK TYFDNIVAID SLLEHIMIYA KNLVNADRCA LFQVDHKNKE LYSDLFDIGE EKEGKPVFKK TKEIRFSIEK GIAGQVARTG EVLNIPDAYA DPRFNREVDL YTGYTTRNIL CMPIVSRGSV IGVVQMVNKI SGSAFSKTDE NNFKMFAVFC ALALHCANMY HRIRHSECIY RVTMEKLSYH SICTSEEWQG LMQFTLPVRL CKEIELFHFD IGPFENMWPG IFVYMVHRSC GTSCFELEKL CRFIMSVKKN YRRVPYHNWK HAVTVAHCMY AILQNNHTLF TDLERKGLLI ACLCHDLDHR GFSNSYLQKF DHPLAALYST STMEQHHFSQ TVSILQLEGH NIFSTLSSSE YEQVLEIIRK AIIATDLALY FGNRKQLEEM YQTGSLNLNN QSHRDRVIGL MMTACDLCSV TKLWPVTKLT ANDIYAEFWA EGDEMKKLGI QPIPMMDRDK KDEVPQGQLG FYNAVAIPCY TTLTQILPPT EPLLKACRDN LSQWEKVIRG EETATWISSP SVAQKAAASE D //