Reviewed, UniProtKB/Swiss-Prot O76083 (PDE9A_HUMAN)

Names and origin

Protein names

Recommended name:
    High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
    EC=3.1.4.35

Gene names

Name:

PDE9A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	593 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase has a high affinity for cGMP.
Catalytic activity	Guanosine 3',5'-cyclic phosphate + H(2)O = guanosine 5'-phosphate.
Cofactor	Divalent cations. Preferably manganese.
Enzyme regulation	Inhibited by zaprinast.
Tissue specificity	Expressed in all tissues examined (testis, brain, small intestine, skeletal muscle, heart, lung, thymus, spleen, placenta, kidney, liver, pancreas, ovary and prostate) except blood. Highest levels in brain, heart, kidney, spleen, prostate and colon. Isoform PDE9A12 is found in prostate.
Domain	Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.
Involvement in disease	May be involved in affective bipolar disorder.
Sequence similarities	Belongs to the cyclic nucleotide phosphodiesterase family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	Manganese Metal-binding cGMP
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	signal transduction Ref.2 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	3',5'-cyclic-nucleotide phosphodiesterase activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 15 isoforms produced by alternative splicing. [Align] [Select]

Isoform PDE9A1 (identifier: O76083-1)

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.

Isoform PDE9A2 (identifier: O76083-2)

The sequence of this isoform differs from the canonical sequence as follows:
     88-147: Missing.

Isoform PDE9A3 (identifier: O76083-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGSGSSSYRP...DPTMPANSER → MDAFRS
     88-147: Missing.

Isoform PDE9A4 (identifier: O76083-4)

The sequence of this isoform differs from the canonical sequence as follows:
     24-165: VIFSKYCNSS...VLAQVAEQFS → HSVQSETCGHQATL

Isoform PDE9A5 (identifier: O76083-5)

The sequence of this isoform differs from the canonical sequence as follows:
     74-165: TPYKVRPVAI...VLAQVAEQFS → NELILYTSLR...SETCGHQATL

Isoform PDE9A6 (identifier: O76083-6)

Also known as: PDE9A5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR
     88-147: Missing.

Isoform PDE9A7/A8/A14/A19/A20 (identifier: O76083-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-207: Missing.

Isoform PDE9A9 (identifier: O76083-8)

The sequence of this isoform differs from the canonical sequence as follows:
     48-73: Missing.
     88-147: Missing.

Isoform PDE9A10 (identifier: O76083-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: Missing.
     161-165: AEQFS → MDAFR

Isoform PDE9A11/A15 (identifier: O76083-10)

The sequence of this isoform differs from the canonical sequence as follows:
     1-217: Missing.
     218-218: R → M

Isoform PDE9A12 (identifier: O76083-11)

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR
     73-165: Missing.

Isoform PDE9A13 (identifier: O76083-12)

The sequence of this isoform differs from the canonical sequence as follows:
     24-165: VIFSKYCNSS...VLAQVAEQFS → EHDHLPADHR...SETCGHQATL

Isoform PDE9A16 (identifier: O76083-13)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MGSGSSSYRP...DPTMPANSER → MDAFRS

Isoform PDE9A17 (identifier: O76083-14)

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLP → MDAFR

Isoform PDE9A18 (identifier: O76083-15)

The sequence of this isoform differs from the canonical sequence as follows:
     48-73: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 593

593

High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A

Regions

Region

288 – 550

263

Catalytic By similarity

Sites

Metal binding

312

1

Manganese 1 Potential

Metal binding

316

1

Manganese 1 Potential

Metal binding

341

1

Manganese 1 Potential

Metal binding

352

1

Manganese 2 Potential

Metal binding

356

1

Manganese 2 Potential

Metal binding

382

1

Manganese 2 Potential

Amino acid modifications

Modified residue

29

1

Phosphotyrosine

Natural variations

Alternative sequence

1 – 217

217

Missing in isoform PDE9A11/A15.

Alternative sequence

1 – 207

207

Missing in isoform PDE9A7/A8/A14/A19/A20.

Alternative sequence

1 – 160

160

Missing in isoform PDE9A10.

Alternative sequence

1 – 73

73

MGSGS…ANSER → MDAFRS in isoform PDE9A3 and isoform PDE9A16.

Alternative sequence

1 – 46

46

MGSGS…ATGLP → MDAFR in isoform PDE9A6, isoform PDE9A12 and isoform PDE9A17.

Alternative sequence

24 – 165

142

VIFSK…AEQFS → EHDHLPADHRRRHGLHRPHH AREFRTHSVQSETCGHQATL in isoform PDE9A13.

Alternative sequence

24 – 165

142

VIFSK…AEQFS → HSVQSETCGHQATL in isoform PDE9A4.

Alternative sequence

48 – 73

26

Missing in isoform PDE9A9 and isoform PDE9A18.

Alternative sequence

73 – 165

93

Missing in isoform PDE9A12.

Alternative sequence

74 – 165

92

TPYKV…AEQFS → NELILYTSLRNLLFLPSKES WASHQHSVQSETCGHQATL in isoform PDE9A5.

Alternative sequence

88 – 147

60

Missing in isoform PDE9A2, isoform PDE9A3, isoform PDE9A6 and isoform PDE9A9.

Alternative sequence

161 – 165

5

AEQFS → MDAFR in isoform PDE9A10.

Alternative sequence

218

1

R → M in isoform PDE9A11/A15.

Secondary structure

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593

Helix Strand Turn

Details...

Helix

250 – 255

6

Helix

268 – 281

14

Helix

284 – 287

4

Helix

292 – 304

13

Beta strand

310 – 313

4

Helix

314 – 330

17

Helix

333 – 336

4

Helix

339 – 351

13

Turn

352 – 355

4

Helix

361 – 366

6

Helix

370 – 374

5

Turn

375 – 377

3

Helix

380 – 393

14

Helix

396 – 398

3

Turn

400 – 403

4

Helix

406 – 421

16

Helix

425 – 427

3

Helix

428 – 438

11

Helix

439 – 441

3

Helix

447 – 462

16

Helix

465 – 467

3

Helix

470 – 493

24

Helix

500 – 502

3

Turn

504 – 506

3

Helix

509 – 519

11

Helix

521 – 531

11

Helix

535 – 560

26

Sequences

	Sequence		Length	Mass (Da)
	Isoform PDE9A1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: E2731C7C828C0994	FASTA	593	68,493
	10 20 30 40 50 60 MGSGSSSYRP KAIYLDIDGR IQKVIFSKYC NSSDIMDLFC IATGLPRNTT ISLLTTDDAM 70 80 90 100 110 120 VSIDPTMPAN SERTPYKVRP VAIKQLSAGV EDKRTTSRGQ SAERPLRDRR VVGLEQPRRE 130 140 150 160 170 180 GAFESGQVEP RPREPQGCYQ EGQRIPPERE ELIQSVLAQV AEQFSRAFKI NELKAEVANH 190 200 210 220 230 240 LAVLEKRVEL EGLKVVEIEK CKSDIKKMRE ELAARSSRTN CPCKYSFLDN HKKLTPRRDV 250 260 270 280 290 300 PTYPKYLLSP ETIEALRKPT FDVWLWEPNE MLSCLEHMYH DLGLVRDFSI NPVTLRRWLF 310 320 330 340 350 360 CVHDNYRNNP FHNFRHCFCV AQMMYSMVWL CSLQEKFSQT DILILMTAAI CHDLDHPGYN 370 380 390 400 410 420 NTYQINARTE LAVRYNDISP LENHHCAVAF QILAEPECNI FSNIPPDGFK QIRQGMITLI 430 440 450 460 470 480 LATDMARHAE IMDSFKEKME NFDYSNEEHM TLLKMILIKC CDISNEVRPM EVAEPWVDCL 490 500 510 520 530 540 LEEYFMQSDR EKSEGLPVAP FMDRDKVTKA TAQIGFIKFV LIPMFETVTK LFPMVEEIML 550 560 570 580 590 QPLWESRDRY EELKRIDDAM KELQKKTDSL TSGATEKSRE RSRDVKNSEG DCA
	Isoform PDE9A2 [UniParc]. Checksum: 728ADAAACE0E4D29		533	61,709
	10 20 30 40 50 60 MGSGSSSYRP KAIYLDIDGR IQKVIFSKYC NSSDIMDLFC IATGLPRNTT ISLLTTDDAM 70 80 90 100 110 120 VSIDPTMPAN SERTPYKVRP VAIKQLSERE ELIQSVLAQV AEQFSRAFKI NELKAEVANH 130 140 150 160 170 180 LAVLEKRVEL EGLKVVEIEK CKSDIKKMRE ELAARSSRTN CPCKYSFLDN HKKLTPRRDV 190 200 210 220 230 240 PTYPKYLLSP ETIEALRKPT FDVWLWEPNE MLSCLEHMYH DLGLVRDFSI NPVTLRRWLF 250 260 270 280 290 300 CVHDNYRNNP FHNFRHCFCV AQMMYSMVWL CSLQEKFSQT DILILMTAAI CHDLDHPGYN 310 320 330 340 350 360 NTYQINARTE LAVRYNDISP LENHHCAVAF QILAEPECNI FSNIPPDGFK QIRQGMITLI 370 380 390 400 410 420 LATDMARHAE IMDSFKEKME NFDYSNEEHM TLLKMILIKC CDISNEVRPM EVAEPWVDCL 430 440 450 460 470 480 LEEYFMQSDR EKSEGLPVAP FMDRDKVTKA TAQIGFIKFV LIPMFETVTK LFPMVEEIML 490 500 510 520 530 QPLWESRDRY EELKRIDDAM KELQKKTDSL TSGATEKSRE RSRDVKNSEG DCA
	Isoform PDE9A3 [UniParc]. Checksum: DE087DD09AAF4794		466	54,440
	10 20 30 40 50 60 MDAFRSTPYK VRPVAIKQLS EREELIQSVL AQVAEQFSRA FKINELKAEV ANHLAVLEKR 70 80 90 100 110 120 VELEGLKVVE IEKCKSDIKK MREELAARSS RTNCPCKYSF LDNHKKLTPR RDVPTYPKYL 130 140 150 160 170 180 LSPETIEALR KPTFDVWLWE PNEMLSCLEH MYHDLGLVRD FSINPVTLRR WLFCVHDNYR 190 200 210 220 230 240 NNPFHNFRHC FCVAQMMYSM VWLCSLQEKF SQTDILILMT AAICHDLDHP GYNNTYQINA 250 260 270 280 290 300 RTELAVRYND ISPLENHHCA VAFQILAEPE CNIFSNIPPD GFKQIRQGMI TLILATDMAR 310 320 330 340 350 360 HAEIMDSFKE KMENFDYSNE EHMTLLKMIL IKCCDISNEV RPMEVAEPWV DCLLEEYFMQ 370 380 390 400 410 420 SDREKSEGLP VAPFMDRDKV TKATAQIGFI KFVLIPMFET VTKLFPMVEE IMLQPLWESR 430 440 450 460 DRYEELKRID DAMKELQKKT DSLTSGATEK SRERSRDVKN SEGDCA
	Isoform PDE9A4 [UniParc]. Checksum: BDD6A8F85E591A67		465	54,096
	10 20 30 40 50 60 MGSGSSSYRP KAIYLDIDGR IQKHSVQSET CGHQATLRAF KINELKAEVA NHLAVLEKRV 70 80 90 100 110 120 ELEGLKVVEI EKCKSDIKKM REELAARSSR TNCPCKYSFL DNHKKLTPRR DVPTYPKYLL 130 140 150 160 170 180 SPETIEALRK PTFDVWLWEP NEMLSCLEHM YHDLGLVRDF SINPVTLRRW LFCVHDNYRN 190 200 210 220 230 240 NPFHNFRHCF CVAQMMYSMV WLCSLQEKFS QTDILILMTA AICHDLDHPG YNNTYQINAR 250 260 270 280 290 300 TELAVRYNDI SPLENHHCAV AFQILAEPEC NIFSNIPPDG FKQIRQGMIT LILATDMARH 310 320 330 340 350 360 AEIMDSFKEK MENFDYSNEE HMTLLKMILI KCCDISNEVR PMEVAEPWVD CLLEEYFMQS 370 380 390 400 410 420 DREKSEGLPV APFMDRDKVT KATAQIGFIK FVLIPMFETV TKLFPMVEEI MLQPLWESRD 430 440 450 460 RYEELKRIDD AMKELQKKTD SLTSGATEKS RERSRDVKNS EGDCA
	Isoform PDE9A5 [UniParc]. Checksum: 612A2ECEE7F656B4		540	62,491
	10 20 30 40 50 60 MGSGSSSYRP KAIYLDIDGR IQKVIFSKYC NSSDIMDLFC IATGLPRNTT ISLLTTDDAM 70 80 90 100 110 120 VSIDPTMPAN SERNELILYT SLRNLLFLPS KESWASHQHS VQSETCGHQA TLRAFKINEL 130 140 150 160 170 180 KAEVANHLAV LEKRVELEGL KVVEIEKCKS DIKKMREELA ARSSRTNCPC KYSFLDNHKK 190 200 210 220 230 240 LTPRRDVPTY PKYLLSPETI EALRKPTFDV WLWEPNEMLS CLEHMYHDLG LVRDFSINPV 250 260 270 280 290 300 TLRRWLFCVH DNYRNNPFHN FRHCFCVAQM MYSMVWLCSL QEKFSQTDIL ILMTAAICHD 310 320 330 340 350 360 LDHPGYNNTY QINARTELAV RYNDISPLEN HHCAVAFQIL AEPECNIFSN IPPDGFKQIR 370 380 390 400 410 420 QGMITLILAT DMARHAEIMD SFKEKMENFD YSNEEHMTLL KMILIKCCDI SNEVRPMEVA 430 440 450 460 470 480 EPWVDCLLEE YFMQSDREKS EGLPVAPFMD RDKVTKATAQ IGFIKFVLIP MFETVTKLFP 490 500 510 520 530 540 MVEEIMLQPL WESRDRYEEL KRIDDAMKEL QKKTDSLTSG ATEKSRERSR DVKNSEGDCA
	Isoform PDE9A6 (PDE9A5) [UniParc]. Checksum: 1FE4F709AD50C0E6		492	57,285
	10 20 30 40 50 60 MDAFRRNTTI SLLTTDDAMV SIDPTMPANS ERTPYKVRPV AIKQLSEREE LIQSVLAQVA 70 80 90 100 110 120 EQFSRAFKIN ELKAEVANHL AVLEKRVELE GLKVVEIEKC KSDIKKMREE LAARSSRTNC 130 140 150 160 170 180 PCKYSFLDNH KKLTPRRDVP TYPKYLLSPE TIEALRKPTF DVWLWEPNEM LSCLEHMYHD 190 200 210 220 230 240 LGLVRDFSIN PVTLRRWLFC VHDNYRNNPF HNFRHCFCVA QMMYSMVWLC SLQEKFSQTD 250 260 270 280 290 300 ILILMTAAIC HDLDHPGYNN TYQINARTEL AVRYNDISPL ENHHCAVAFQ ILAEPECNIF 310 320 330 340 350 360 SNIPPDGFKQ IRQGMITLIL ATDMARHAEI MDSFKEKMEN FDYSNEEHMT LLKMILIKCC 370 380 390 400 410 420 DISNEVRPME VAEPWVDCLL EEYFMQSDRE KSEGLPVAPF MDRDKVTKAT AQIGFIKFVL 430 440 450 460 470 480 IPMFETVTKL FPMVEEIMLQ PLWESRDRYE ELKRIDDAMK ELQKKTDSLT SGATEKSRER 490 SRDVKNSEGD CA
	Isoform PDE9A7/A8/A14/A19/A20 [UniParc]. Checksum: 4120AB778B9746B9		386	45,290
	10 20 30 40 50 60 MREELAARSS RTNCPCKYSF LDNHKKLTPR RDVPTYPKYL LSPETIEALR KPTFDVWLWE 70 80 90 100 110 120 PNEMLSCLEH MYHDLGLVRD FSINPVTLRR WLFCVHDNYR NNPFHNFRHC FCVAQMMYSM 130 140 150 160 170 180 VWLCSLQEKF SQTDILILMT AAICHDLDHP GYNNTYQINA RTELAVRYND ISPLENHHCA 190 200 210 220 230 240 VAFQILAEPE CNIFSNIPPD GFKQIRQGMI TLILATDMAR HAEIMDSFKE KMENFDYSNE 250 260 270 280 290 300 EHMTLLKMIL IKCCDISNEV RPMEVAEPWV DCLLEEYFMQ SDREKSEGLP VAPFMDRDKV 310 320 330 340 350 360 TKATAQIGFI KFVLIPMFET VTKLFPMVEE IMLQPLWESR DRYEELKRID DAMKELQKKT 370 380 DSLTSGATEK SRERSRDVKN SEGDCA
	Isoform PDE9A9 [UniParc]. Checksum: E211E0EB8B67F284		507	58,933
	10 20 30 40 50 60 MGSGSSSYRP KAIYLDIDGR IQKVIFSKYC NSSDIMDLFC IATGLPRTPY KVRPVAIKQL 70 80 90 100 110 120 SEREELIQSV LAQVAEQFSR AFKINELKAE VANHLAVLEK RVELEGLKVV EIEKCKSDIK 130 140 150 160 170 180 KMREELAARS SRTNCPCKYS FLDNHKKLTP RRDVPTYPKY LLSPETIEAL RKPTFDVWLW 190 200 210 220 230 240 EPNEMLSCLE HMYHDLGLVR DFSINPVTLR RWLFCVHDNY RNNPFHNFRH CFCVAQMMYS 250 260 270 280 290 300 MVWLCSLQEK FSQTDILILM TAAICHDLDH PGYNNTYQIN ARTELAVRYN DISPLENHHC 310 320 330 340 350 360 AVAFQILAEP ECNIFSNIPP DGFKQIRQGM ITLILATDMA RHAEIMDSFK EKMENFDYSN 370 380 390 400 410 420 EEHMTLLKMI LIKCCDISNE VRPMEVAEPW VDCLLEEYFM QSDREKSEGL PVAPFMDRDK 430 440 450 460 470 480 VTKATAQIGF IKFVLIPMFE TVTKLFPMVE EIMLQPLWES RDRYEELKRI DDAMKELQKK 490 500 TDSLTSGATE KSRERSRDVK NSEGDCA
	Isoform PDE9A10 [UniParc]. Checksum: D6036BB3CA9FB7B2		433	50,713
	10 20 30 40 50 60 MDAFRRAFKI NELKAEVANH LAVLEKRVEL EGLKVVEIEK CKSDIKKMRE ELAARSSRTN 70 80 90 100 110 120 CPCKYSFLDN HKKLTPRRDV PTYPKYLLSP ETIEALRKPT FDVWLWEPNE MLSCLEHMYH 130 140 150 160 170 180 DLGLVRDFSI NPVTLRRWLF CVHDNYRNNP FHNFRHCFCV AQMMYSMVWL CSLQEKFSQT 190 200 210 220 230 240 DILILMTAAI CHDLDHPGYN NTYQINARTE LAVRYNDISP LENHHCAVAF QILAEPECNI 250 260 270 280 290 300 FSNIPPDGFK QIRQGMITLI LATDMARHAE IMDSFKEKME NFDYSNEEHM TLLKMILIKC 310 320 330 340 350 360 CDISNEVRPM EVAEPWVDCL LEEYFMQSDR EKSEGLPVAP FMDRDKVTKA TAQIGFIKFV 370 380 390 400 410 420 LIPMFETVTK LFPMVEEIML QPLWESRDRY EELKRIDDAM KELQKKTDSL TSGATEKSRE 430 RSRDVKNSEG DCA
	Isoform PDE9A11/A15 [UniParc]. Checksum: BF896546AED87831		376	44,134
	10 20 30 40 50 60 MTNCPCKYSF LDNHKKLTPR RDVPTYPKYL LSPETIEALR KPTFDVWLWE PNEMLSCLEH 70 80 90 100 110 120 MYHDLGLVRD FSINPVTLRR WLFCVHDNYR NNPFHNFRHC FCVAQMMYSM VWLCSLQEKF 130 140 150 160 170 180 SQTDILILMT AAICHDLDHP GYNNTYQINA RTELAVRYND ISPLENHHCA VAFQILAEPE 190 200 210 220 230 240 CNIFSNIPPD GFKQIRQGMI TLILATDMAR HAEIMDSFKE KMENFDYSNE EHMTLLKMIL 250 260 270 280 290 300 IKCCDISNEV RPMEVAEPWV DCLLEEYFMQ SDREKSEGLP VAPFMDRDKV TKATAQIGFI 310 320 330 340 350 360 KFVLIPMFET VTKLFPMVEE IMLQPLWESR DRYEELKRID DAMKELQKKT DSLTSGATEK 370 SRERSRDVKN SEGDCA
	Isoform PDE9A12 [UniParc].