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Protein

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

Gene

PDE10A

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

Functioni

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.1 Publication

Catalytic activityi

Nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate.
Guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate.

Cofactori

a divalent metal cation1 PublicationNote: 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.1 Publication

Enzyme regulationi

Inhibited by dipyridamole and moderately by IBMX. cAMP acts as an allosteric activator.1 Publication

Kineticsi

  1. KM=56 nM for cAMP1 Publication
  2. KM=4.4 µM for cGMP1 Publication
  1. Vmax=507 nmol/min/mg enzyme for cAMP1 Publication
  2. Vmax=1860 nmol/min/mg enzyme for cGMP1 Publication

Pathway:i3',5'-cyclic AMP degradation

This protein is involved in step 1 of the subpathway that synthesizes AMP from 3',5'-cyclic AMP.
Proteins known to be involved in this subpathway in this organism are:
  1. cAMP-specific 3',5'-cyclic phosphodiesterase 4C (PDE4C), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A), cAMP-specific 3',5'-cyclic phosphodiesterase 4A (PDE4A), High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A (PDE7A), cAMP-specific 3',5'-cyclic phosphodiesterase 7B (PDE7B), cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B), cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A), High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (PDE8B)
This subpathway is part of the pathway 3',5'-cyclic AMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from 3',5'-cyclic AMP, the pathway 3',5'-cyclic AMP degradation and in Purine metabolism.

Pathway:i3',5'-cyclic GMP degradation

This protein is involved in step 1 of the subpathway that synthesizes GMP from 3',5'-cyclic GMP.
Proteins known to be involved in this subpathway in this organism are:
  1. cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A), High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (PDE9A), cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A)
This subpathway is part of the pathway 3',5'-cyclic GMP degradation, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes GMP from 3',5'-cyclic GMP, the pathway 3',5'-cyclic GMP degradation and in Purine metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei364 – 3641Allosteric effector
Binding sitei383 – 3831Allosteric effector
Active sitei515 – 5151Proton donorBy similarity
Binding sitei515 – 5151Substrate
Metal bindingi519 – 5191Divalent metal cation 1
Metal bindingi553 – 5531Divalent metal cation 1
Metal bindingi554 – 5541Divalent metal cation 1
Metal bindingi554 – 5541Divalent metal cation 2
Metal bindingi664 – 6641Divalent metal cation 1
Binding sitei716 – 7161Substrate

GO - Molecular functioni

  • 3',5'-cyclic-GMP phosphodiesterase activity Source: UniProtKB-EC
  • 3',5'-cyclic-nucleotide phosphodiesterase activity Source: ProtInc
  • cAMP binding Source: UniProtKB
  • cGMP binding Source: UniProtKB
  • cGMP-stimulated cyclic-nucleotide phosphodiesterase activity Source: UniProtKB
  • drug binding Source: Ensembl
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

cAMP, cAMP-binding, cGMP, cGMP-binding, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.1.4.17. 2681.
ReactomeiREACT_19327. G alpha (s) signalling events.
REACT_23767. cGMP effects.
UniPathwayiUPA00762; UER00747.
UPA00763; UER00748.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (EC:3.1.4.17, EC:3.1.4.35)
Gene namesi
Name:PDE10A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:8772. PDE10A.

Subcellular locationi

  • Cytoplasm

  • Note: Located mostly to soluble cellular fractions.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi554 – 5541D → A: Loss of activity and of zinc binding. 1 Publication
Mutagenesisi554 – 5541D → N: Reduces activity 1000-fold. 1 Publication

Organism-specific databases

PharmGKBiPA33120.

Chemistry

DrugBankiDB00201. Caffeine.
DB00975. Dipyridamole.
DB01113. Papaverine.
DB08811. Tofisopam.
DB08814. Triflusal.

Polymorphism and mutation databases

BioMutaiPDE10A.
DMDMi7993747.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 779779cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10APRO_0000198843Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Isoform PDE10A2 (identifier: Q9Y233-2)
Modified residuei16 – 161Phosphothreonine

Post-translational modificationi

Isoform PDE10A1: Phosphorylated on Thr-16.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Y233.
PaxDbiQ9Y233.
PRIDEiQ9Y233.

PTM databases

PhosphoSiteiQ9Y233.

Expressioni

Tissue specificityi

Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum.

Gene expression databases

BgeeiQ9Y233.
CleanExiHS_PDE10A.
ExpressionAtlasiQ9Y233. baseline and differential.
GenevisibleiQ9Y233. HS.

Organism-specific databases

HPAiCAB045998.
HPA047200.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi116057. 2 interactions.
IntActiQ9Y233. 1 interaction.
MINTiMINT-1401257.
STRINGi9606.ENSP00000438284.

Structurei

Secondary structure

1
779
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi247 – 26216Combined sources
Helixi267 – 28216Combined sources
Beta strandi284 – 29310Combined sources
Turni294 – 2974Combined sources
Beta strandi298 – 3047Combined sources
Beta strandi323 – 3253Combined sources
Helixi329 – 3379Combined sources
Beta strandi341 – 3444Combined sources
Helixi346 – 3483Combined sources
Helixi355 – 3606Combined sources
Beta strandi367 – 3748Combined sources
Beta strandi377 – 38711Combined sources
Beta strandi390 – 3923Combined sources
Helixi395 – 41925Combined sources
Helixi443 – 4497Combined sources
Helixi456 – 4616Combined sources
Beta strandi464 – 4663Combined sources
Helixi470 – 4756Combined sources
Helixi476 – 48813Combined sources
Turni490 – 4923Combined sources
Helixi495 – 50713Combined sources
Beta strandi513 – 5164Combined sources
Helixi517 – 53216Combined sources
Helixi533 – 5375Combined sources
Helixi540 – 55213Combined sources
Turni553 – 5564Combined sources
Helixi562 – 5676Combined sources
Helixi571 – 5755Combined sources
Beta strandi577 – 5793Combined sources
Helixi580 – 59314Combined sources
Turni596 – 5983Combined sources
Turni600 – 6034Combined sources
Helixi606 – 62217Combined sources
Helixi625 – 64016Combined sources
Beta strandi646 – 6483Combined sources
Helixi649 – 66416Combined sources
Helixi666 – 6694Combined sources
Helixi672 – 69524Combined sources
Helixi702 – 7043Combined sources
Helixi706 – 7116Combined sources
Helixi712 – 72211Combined sources
Helixi724 – 73411Combined sources
Helixi736 – 7383Combined sources
Helixi739 – 75719Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LRBmodel-A501-757[»]
2OUNX-ray1.56A/B439-766[»]
2OUPX-ray1.56A/B439-766[»]
2OUQX-ray1.90A/B439-766[»]
2OURX-ray1.45A/B439-766[»]
2OUSX-ray1.45A/B439-766[»]
2OUUX-ray1.52A/B439-766[»]
2OUVX-ray1.56A/B439-766[»]
2OUYX-ray1.90A/B439-766[»]
2WEYX-ray2.80A/B439-779[»]
2Y0JX-ray2.43A/B432-764[»]
2ZMFX-ray2.10A/B246-427[»]
3SN7X-ray1.82A/B439-779[»]
3SNIX-ray1.90A/B439-779[»]
3SNLX-ray2.40A/B439-779[»]
3UI7X-ray2.28A/B432-760[»]
3UUOX-ray2.11A/B432-760[»]
3WI2X-ray2.26A/B439-779[»]
3WS8X-ray2.60A/B439-779[»]
3WS9X-ray2.99A/B439-779[»]
3WYKX-ray2.50A/B442-779[»]
3WYLX-ray2.68A/B442-779[»]
3WYMX-ray2.00A/B442-779[»]
4AELX-ray2.20A/B439-779[»]
4AJDX-ray2.30A/D439-764[»]
4AJFX-ray1.90A/D439-764[»]
4AJGX-ray2.30A/D439-764[»]
4AJMX-ray2.40A/D439-764[»]
4BBXX-ray2.50A/B443-769[»]
4DDLX-ray2.07A/B442-779[»]
4DFFX-ray2.11A/B432-779[»]
4FCBX-ray2.10A/B439-779[»]
4FCDX-ray2.02A/B439-779[»]
4HEUX-ray2.00A/B442-759[»]
4HF4X-ray2.00A/B442-759[»]
4LKQX-ray1.62A/B439-779[»]
4LLJX-ray1.56A/B439-779[»]
4LLKX-ray1.55A/B439-779[»]
4LLPX-ray1.75A/B439-779[»]
4LLXX-ray1.75A/B439-779[»]
4LM0X-ray1.66A/B439-779[»]
4LM1X-ray1.60A/B439-779[»]
4LM2X-ray1.55A/B439-779[»]
4LM3X-ray1.49A/B439-779[»]
4LM4X-ray1.48A/B439-779[»]
4MRWX-ray1.96A/B439-779[»]
4MRZX-ray1.58A/B439-779[»]
4MS0X-ray1.79A/B439-779[»]
4MSAX-ray1.62A/B439-779[»]
4MSCX-ray2.47A/B439-779[»]
4MSEX-ray2.81A/B439-779[»]
4MSHX-ray2.30A/B439-779[»]
4MSNX-ray2.30A/B439-779[»]
4MUWX-ray2.64A/B442-779[»]
4MVHX-ray2.50A/B442-779[»]
4P0NX-ray2.08A/B442-779[»]
4P1RX-ray2.24A/B442-779[»]
4PHWX-ray2.50A/B442-779[»]
4TPMX-ray2.77A/B442-779[»]
4TPPX-ray2.65A/B442-779[»]
4WN1X-ray3.13A/B439-779[»]
4YQHX-ray2.31A/B439-759[»]
4YS7X-ray2.50A/B439-759[»]
ProteinModelPortaliQ9Y233.
SMRiQ9Y233. Positions 155-765.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y233.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini91 – 234144GAF 1Add
BLAST
Domaini266 – 412147GAF 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni286 – 2872Allosteric effector binding
Regioni330 – 3312Allosteric effector binding

Domaini

The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity.
Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region.

Sequence similaritiesi

Contains 2 GAF domains.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG270709.
GeneTreeiENSGT00760000119066.
HOGENOMiHOG000007068.
HOVERGENiHBG082113.
KOiK18438.
OMAiCRFTMSV.
OrthoDBiEOG7WQ7RN.
PhylomeDBiQ9Y233.
TreeFamiTF316499.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
3.30.450.40. 2 hits.
InterProiIPR003018. GAF.
IPR029016. GAF_dom-like.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
SUPFAMiSSF55781. SSF55781. 2 hits.
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Isoforms differ in their N-terminal region.

Isoform PDE10A1 (identifier: Q9Y233-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRIEERKSQH LTGLTDEKVK AYLSLHPQVL DEFVSESVSA ETVEKWLKRK
60 70 80 90 100
NNKSEDESAP KEVSRYQDTN MQGVVYELNS YIEQRLDTGG DNQLLLYELS
110 120 130 140 150
SIIKIATKAD GFALYFLGEC NNSLCIFTPP GIKEGKPRLI PAGPITQGTT
160 170 180 190 200
VSAYVAKSRK TLLVEDILGD ERFPRGTGLE SGTRIQSVLC LPIVTAIGDL
210 220 230 240 250
IGILELYRHW GKEAFCLSHQ EVATANLAWA SVAIHQVQVC RGLAKQTELN
260 270 280 290 300
DFLLDVSKTY FDNIVAIDSL LEHIMIYAKN LVNADRCALF QVDHKNKELY
310 320 330 340 350
SDLFDIGEEK EGKPVFKKTK EIRFSIEKGI AGQVARTGEV LNIPDAYADP
360 370 380 390 400
RFNREVDLYT GYTTRNILCM PIVSRGSVIG VVQMVNKISG SAFSKTDENN
410 420 430 440 450
FKMFAVFCAL ALHCANMYHR IRHSECIYRV TMEKLSYHSI CTSEEWQGLM
460 470 480 490 500
QFTLPVRLCK EIELFHFDIG PFENMWPGIF VYMVHRSCGT SCFELEKLCR
510 520 530 540 550
FIMSVKKNYR RVPYHNWKHA VTVAHCMYAI LQNNHTLFTD LERKGLLIAC
560 570 580 590 600
LCHDLDHRGF SNSYLQKFDH PLAALYSTST MEQHHFSQTV SILQLEGHNI
610 620 630 640 650
FSTLSSSEYE QVLEIIRKAI IATDLALYFG NRKQLEEMYQ TGSLNLNNQS
660 670 680 690 700
HRDRVIGLMM TACDLCSVTK LWPVTKLTAN DIYAEFWAEG DEMKKLGIQP
710 720 730 740 750
IPMMDRDKKD EVPQGQLGFY NAVAIPCYTT LTQILPPTEP LLKACRDNLS
760 770
QWEKVIRGEE TATWISSPSV AQKAAASED
Length:779
Mass (Da):88,412
Last modified:November 1, 1999 - v1
Checksum:iC5651BBB524A32B7
GO
Isoform PDE10A2 (identifier: Q9Y233-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MRIEERKSQHLTG → MEDGPSNNASCFRRLTECFLSPS

Show »
Length:789
Mass (Da):89,390
Checksum:i7CC35F16735FB3C2
GO

Sequence cautioni

The sequence AAD32596.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti657 – 6571G → S in CAG38804 (Ref. 4) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti303 – 3031L → P.
VAR_008797
Natural varianti706 – 7061R → K.
Corresponds to variant rs2224252 [ dbSNP | Ensembl ].
VAR_047822
Natural varianti707 – 7071D → N.
Corresponds to variant rs2860112 [ dbSNP | Ensembl ].
VAR_047823

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1313MRIEE…QHLTG → MEDGPSNNASCFRRLTECFL SPS in isoform PDE10A2. 2 PublicationsVSP_004601Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB026816 mRNA. Translation: BAA84467.1.
AB020593 mRNA. Translation: BAA78034.1.
AF127479 mRNA. Translation: AAD32595.1.
AF127480 mRNA. Translation: AAD32596.1. Different initiation.
CR536567 mRNA. Translation: CAG38804.1.
AL117345, AL136130, AL160160 Genomic DNA. Translation: CAB92797.2.
AL136130, AL117345, AL160160 Genomic DNA. Translation: CAI20436.1.
AL160160, AL117345, AL136130 Genomic DNA. Translation: CAH72023.1.
BC104858 mRNA. Translation: AAI04859.1.
BC104860 mRNA. Translation: AAI04861.1.
AB041798 Genomic DNA. Translation: BAB16383.1.
CCDSiCCDS47513.1. [Q9Y233-2]
RefSeqiNP_001124162.1. NM_001130690.2. [Q9Y233-2]
NP_006652.1. NM_006661.3. [Q9Y233-1]
XP_011533690.1. XM_011535388.1. [Q9Y233-1]
XP_011533691.1. XM_011535389.1. [Q9Y233-1]
UniGeneiHs.348762.

Genome annotation databases

EnsembliENST00000366882; ENSP00000355847; ENSG00000112541.
ENST00000539869; ENSP00000438284; ENSG00000112541. [Q9Y233-2]
GeneIDi10846.
KEGGihsa:10846.
UCSCiuc003qun.3. human. [Q9Y233-1]
uc003quo.3. human. [Q9Y233-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB026816 mRNA. Translation: BAA84467.1.
AB020593 mRNA. Translation: BAA78034.1.
AF127479 mRNA. Translation: AAD32595.1.
AF127480 mRNA. Translation: AAD32596.1. Different initiation.
CR536567 mRNA. Translation: CAG38804.1.
AL117345, AL136130, AL160160 Genomic DNA. Translation: CAB92797.2.
AL136130, AL117345, AL160160 Genomic DNA. Translation: CAI20436.1.
AL160160, AL117345, AL136130 Genomic DNA. Translation: CAH72023.1.
BC104858 mRNA. Translation: AAI04859.1.
BC104860 mRNA. Translation: AAI04861.1.
AB041798 Genomic DNA. Translation: BAB16383.1.
CCDSiCCDS47513.1. [Q9Y233-2]
RefSeqiNP_001124162.1. NM_001130690.2. [Q9Y233-2]
NP_006652.1. NM_006661.3. [Q9Y233-1]
XP_011533690.1. XM_011535388.1. [Q9Y233-1]
XP_011533691.1. XM_011535389.1. [Q9Y233-1]
UniGeneiHs.348762.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LRBmodel-A501-757[»]
2OUNX-ray1.56A/B439-766[»]
2OUPX-ray1.56A/B439-766[»]
2OUQX-ray1.90A/B439-766[»]
2OURX-ray1.45A/B439-766[»]
2OUSX-ray1.45A/B439-766[»]
2OUUX-ray1.52A/B439-766[»]
2OUVX-ray1.56A/B439-766[»]
2OUYX-ray1.90A/B439-766[»]
2WEYX-ray2.80A/B439-779[»]
2Y0JX-ray2.43A/B432-764[»]
2ZMFX-ray2.10A/B246-427[»]
3SN7X-ray1.82A/B439-779[»]
3SNIX-ray1.90A/B439-779[»]
3SNLX-ray2.40A/B439-779[»]
3UI7X-ray2.28A/B432-760[»]
3UUOX-ray2.11A/B432-760[»]
3WI2X-ray2.26A/B439-779[»]
3WS8X-ray2.60A/B439-779[»]
3WS9X-ray2.99A/B439-779[»]
3WYKX-ray2.50A/B442-779[»]
3WYLX-ray2.68A/B442-779[»]
3WYMX-ray2.00A/B442-779[»]
4AELX-ray2.20A/B439-779[»]
4AJDX-ray2.30A/D439-764[»]
4AJFX-ray1.90A/D439-764[»]
4AJGX-ray2.30A/D439-764[»]
4AJMX-ray2.40A/D439-764[»]
4BBXX-ray2.50A/B443-769[»]
4DDLX-ray2.07A/B442-779[»]
4DFFX-ray2.11A/B432-779[»]
4FCBX-ray2.10A/B439-779[»]
4FCDX-ray2.02A/B439-779[»]
4HEUX-ray2.00A/B442-759[»]
4HF4X-ray2.00A/B442-759[»]
4LKQX-ray1.62A/B439-779[»]
4LLJX-ray1.56A/B439-779[»]
4LLKX-ray1.55A/B439-779[»]
4LLPX-ray1.75A/B439-779[»]
4LLXX-ray1.75A/B439-779[»]
4LM0X-ray1.66A/B439-779[»]
4LM1X-ray1.60A/B439-779[»]
4LM2X-ray1.55A/B439-779[»]
4LM3X-ray1.49A/B439-779[»]
4LM4X-ray1.48A/B439-779[»]
4MRWX-ray1.96A/B439-779[»]
4MRZX-ray1.58A/B439-779[»]
4MS0X-ray1.79A/B439-779[»]
4MSAX-ray1.62A/B439-779[»]
4MSCX-ray2.47A/B439-779[»]
4MSEX-ray2.81A/B439-779[»]
4MSHX-ray2.30A/B439-779[»]
4MSNX-ray2.30A/B439-779[»]
4MUWX-ray2.64A/B442-779[»]
4MVHX-ray2.50A/B442-779[»]
4P0NX-ray2.08A/B442-779[»]
4P1RX-ray2.24A/B442-779[»]
4PHWX-ray2.50A/B442-779[»]
4TPMX-ray2.77A/B442-779[»]
4TPPX-ray2.65A/B442-779[»]
4WN1X-ray3.13A/B439-779[»]
4YQHX-ray2.31A/B439-759[»]
4YS7X-ray2.50A/B439-759[»]
ProteinModelPortaliQ9Y233.
SMRiQ9Y233. Positions 155-765.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116057. 2 interactions.
IntActiQ9Y233. 1 interaction.
MINTiMINT-1401257.
STRINGi9606.ENSP00000438284.

Chemistry

BindingDBiQ9Y233.
ChEMBLiCHEMBL4409.
DrugBankiDB00201. Caffeine.
DB00975. Dipyridamole.
DB01113. Papaverine.
DB08811. Tofisopam.
DB08814. Triflusal.

PTM databases

PhosphoSiteiQ9Y233.

Polymorphism and mutation databases

BioMutaiPDE10A.
DMDMi7993747.

Proteomic databases

MaxQBiQ9Y233.
PaxDbiQ9Y233.
PRIDEiQ9Y233.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366882; ENSP00000355847; ENSG00000112541.
ENST00000539869; ENSP00000438284; ENSG00000112541. [Q9Y233-2]
GeneIDi10846.
KEGGihsa:10846.
UCSCiuc003qun.3. human. [Q9Y233-1]
uc003quo.3. human. [Q9Y233-2]

Organism-specific databases

CTDi10846.
GeneCardsiGC06M165714.
HGNCiHGNC:8772. PDE10A.
HPAiCAB045998.
HPA047200.
MIMi610652. gene.
neXtProtiNX_Q9Y233.
PharmGKBiPA33120.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG270709.
GeneTreeiENSGT00760000119066.
HOGENOMiHOG000007068.
HOVERGENiHBG082113.
KOiK18438.
OMAiCRFTMSV.
OrthoDBiEOG7WQ7RN.
PhylomeDBiQ9Y233.
TreeFamiTF316499.

Enzyme and pathway databases

UniPathwayiUPA00762; UER00747.
UPA00763; UER00748.
BRENDAi3.1.4.17. 2681.
ReactomeiREACT_19327. G alpha (s) signalling events.
REACT_23767. cGMP effects.

Miscellaneous databases

EvolutionaryTraceiQ9Y233.
GeneWikiiPDE10A.
GenomeRNAii10846.
NextBioi41178.
PROiQ9Y233.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y233.
CleanExiHS_PDE10A.
ExpressionAtlasiQ9Y233. baseline and differential.
GenevisibleiQ9Y233. HS.

Family and domain databases

Gene3Di1.10.1300.10. 1 hit.
3.30.450.40. 2 hits.
InterProiIPR003018. GAF.
IPR029016. GAF_dom-like.
IPR003607. HD/PDEase_dom.
IPR023088. PDEase.
IPR002073. PDEase_catalytic_dom.
IPR023174. PDEase_CS.
[Graphical view]
PfamiPF01590. GAF. 2 hits.
PF00233. PDEase_I. 1 hit.
[Graphical view]
PRINTSiPR00387. PDIESTERASE1.
SMARTiSM00065. GAF. 2 hits.
SM00471. HDc. 1 hit.
[Graphical view]
SUPFAMiSSF55781. SSF55781. 2 hits.
PROSITEiPS00126. PDEASE_I. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP."
    Kotera J., Fujishige K., Yuasa K., Omori K.
    Biochem. Biophys. Res. Commun. 261:551-557(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE10A2), PHOSPHORYLATION AT THR-16 (ISOFORM PDE10A2) BY PKA.
    Tissue: Fetal lung.
  2. "Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A)."
    Fujishige K., Kotera J., Michibata H., Yuasa K., Takebayashi S., Okumura K., Omori K.
    J. Biol. Chem. 274:18438-18445(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE10A1).
    Tissue: Fetal lung.
  3. "Isolation and characterization of PDE10A, a novel human 3',5'-cyclic nucleotide phosphodiesterase."
    Loughney K., Snyder P.B., Uher L., Rosman G.J., Ferguson K., Florio V.A.
    Gene 234:109-117(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE10A1 AND PDE10A2).
    Tissue: Fetal brain.
  4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE10A1).
  5. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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] (ISOFORM PDE10A1).
    Tissue: Colon.
  7. "The human phosphodiesterase PDE10A gene genomic organization and evolutionary relatedness with other PDEs containing GAF domains."
    Fujishige K., Kotera J., Yuasa K., Omori K.
    Eur. J. Biochem. 267:5943-5951(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 66-779, ALTERNATIVE SPLICING.
  8. "cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10 and cGMP for the tandem GAF domain of phosphodiesterase 11."
    Gross-Langenhoff M., Hofbauer K., Weber J., Schultz A., Schultz J.E.
    J. Biol. Chem. 281:2841-2846(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN, ENZYME REGULATION.
  9. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. "Structural insight into substrate specificity of phosphodiesterase 10."
    Wang H., Liu Y., Hou J., Zheng M., Robinson H., Ke H.
    Proc. Natl. Acad. Sci. U.S.A. 104:5782-5787(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 436-766 IN COMPLEXES WITH AMP; CAMP; GMP; CGMP AND MAGNESIUM, MUTAGENESIS OF ASP-554, FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.
  12. "Crystal structure of the GAF-B domain from human phosphodiesterase 10A complexed with its ligand, cAMP."
    Handa N., Mizohata E., Kishishita S., Toyama M., Morita S., Uchikubo-Kamo T., Akasaka R., Omori K., Kotera J., Terada T., Shirouzu M., Yokoyama S.
    J. Biol. Chem. 283:19657-19664(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 242-427 IN COMPLEX WITH CAMP, DOMAIN, SUBUNIT.

Entry informationi

Entry nameiPDE10_HUMAN
AccessioniPrimary (citable) accession number: Q9Y233
Secondary accession number(s): Q6FHX1
, Q9HCP9, Q9NTV4, Q9ULW9, Q9Y5T1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: July 22, 2015
This is version 151 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, Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.