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The cGMP Specific Phosphodiesterase Type 5 (PDE5) Enzyme

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Sequence Alignment of the cGMP Specific Phosphodiesterase Type 5 Enzyme  (with Clustalw)a

Species Sequence Alignment of PDE5

humans  MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAE 60
dog     ----MLPFGHQR--------------------------------------REMVNAWFAE 18
cow     MERAGPGSARPQQQ----------WDQDSVEAWLDDHWDFTFSYFVRKGTREMVNAWFAE 50
mouse   MERAGPNSVRSQQQ----------RDPDWVEAWLDDHRDFTFSYFIRKATRDMVNAWFSE 50
rat     MLPFG------------------------------------------DKTRDMVNAWFSE 18
                                                          *:******:*

humans  RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG 120
dog     RVHTIPVCKEGIRGHAESCSCSSQQSSRADSSAPGTPTRKISASEFDRPLRPIVVKDSEG 78
cow     RVHTIPVCKEGIKGHTESCSCPLQPSPRAESSVPGTPTRKISASEFDRPLRPIVIKDSEG 110
mouse   RVHNIPVCKEGIRAHTESCSCSLQQSPHADNTTPGAPARKISASEFDRPLRPIVVKDSEG 110
rat     RVHNIPVCKEGIRAHTESCSCSLPQSPHADNTTPGAPARKISASEFDRPLRPIVVKDSEG 78
        ***.********:.*:*****.   *.:*:.:.**:*:****************:*****

humans  TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI 180
dog     TVSFLADSEKKEQMPLTPPRFDNDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI 138
cow     TVSFLSDSDKKEQMPLTSPRFDNDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI 170
mouse   TVSFLSDSGKKEQMPLTPPRFDSDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI 170
rat     TVSFLSDSGKKEQMPLTSPRFDSDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI 138
        *****:** ********.**** *************************************

humans  SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL 240
dog     SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEASNNCIRLEWNKGIVGHVAALGEPL 198
cow     SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEASNNCIRLEWNKGIVGHVAAFGEPL 230
mouse   SADRYTLFLVCEDSSKDKFLISRLFDVAEGSTLEEASNNCIRLEWNKGIVGHVAAFGEPL 230
rat     SADRYSLFLVCEDSSKDKFLVSRLFDVAEGSTLEEASNNCIRLEWNKGIVGHVAAFGEPL 198
        *****:*********:****:**************.*******************:****

humans  NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE 300
dog     NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE 258
cow     NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE 290
mouse   NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE 290
rat     NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE 258
        ************************************************************

humans  KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS 360
dog     KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS 318
cow     KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS 350
mouse   KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS 350
rat     KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS 318
        ************************************************************

humans  FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME 420
dog     FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKLPDTLTRERDANRINYMYAQYVKNTME 378
cow     FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTRERDANRINYMYAQYVKNTME 410
mouse   FMQVQKCTIFIVDEDCPDSFSRVFHMECEEVGKPSDPLTREQDANKINYMYAQYVKNTME 410
rat     FMQVQKCTIFIVDEDCPDSFSRVFQMEWEEVGKSSEPLTREHDANKINYMYAQYVKNTME 378
        ****************.**** **:** **: * .:.****:***:**************

humans  PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK 480
dog     PLNIPDVSKDKRFPWTNENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK 438
cow     PLNIPDVSKDKRFPWTNENMGNINQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEETTGK 470
mouse   PLNIPDVTKDKRFPWTNENMGHVNTPCIGSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK 470
rat     PLNIPDVTKDNRFPWTNENMGHINTHCIRSLLCTPIKNGKKNKVIGVCQLVNKMEEKTGK 438
        *******:**:*****.** *::*  ** ***************************.***

humans  VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL 540
dog     VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETKEL 498
cow     VKAFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL 530
mouse   IKAFNQNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL 530
rat     IKAFNQNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL 498
        :*.**:***************************************************:**

humans  QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL 600
dog     QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL 558
cow     QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCKWIL 590
mouse   QALSAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL 590
rat     QALAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL 558
        *:*:****************************************************:***

humans  SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV 660
dog     SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV 618
cow     SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQKRLTDLEILALLIAALSHDLDHRGV 650
mouse   SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLETLALLIAALSHDLDHRGV 650
rat     SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLETLALLIAALSHDLDHRGV 618
        ***********************************::***** *****************

humans  NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI 720
dog     NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI 678
cow     NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI 710
mouse   NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIDEYKTTLKIIKQAI 710
rat     NNSYIQRSEHPLAQLYCHSTMEHHHFDQCLMVLNSPGNQILSGLSIEEYKTTLKIIKQAI 678
        ******************* ***********:**************:*************

humans  LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE 780
dog     LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE 738
cow     LATDLALYIKRRGEFFELIMKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE 770
mouse   LATDLALYIKRRGEFFELIRKNQFSFEDPLQKELFLAMLMTACDLSAITKPWPIQQRIAE 770
rat     LATDLALYIKRRGEFFELIRKNEFSFEDPLQKELFLAMLMTACDLSAITKPWPIQQRIAE 738
        ******************* **:*.:*** ******************************

humans  LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF 840
dog     LVATEFFDQGDRERKELNIEPADLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF 798
cow     LVATEFFDQGDRERKELNIEPADLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF 830
mouse   LVAAEFFDQGDRERKELNMEPADLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCL 830
rat     LVAAEFFDQGDRERKELNMEPADLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCL 798
        ***:**************:**:*************************************:

humans  PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN 875
dog     PLLDGCRKNRQKWQALAEQQEKTLINGESSQAKRN 833
cow     PLLDGCRKNRQKWQALAEQQEKTLINGESSQTKRN 865
mouse   PLLDGCRKNRQKWQALAEQQEKMLLNGESSQGKRD 865
rat     PLLDGCRKNRQKWQALADQQEKTLLNGESGQAKRD 833
        *****************:**** *:****.* **:

Accession Numbers of the phosphodiesterase 5 protein sequences used in the protein sequence alignment:  humans (isoform 1) - NP_001074; mouse - NP_700471; rat - NP_598268; dog - NP_001003188; cow - NP_776842

Isoform (Homo sapiens)  Sequence Alignment

PDE5.2  ------------------------------------------MLPFGDKTREMVNAWFAE 18
PDE5.3  ----------------------------------------------------MVNAWFAE 8
PDE5.1  MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAE 60
                                                            ********

PDE5.2  RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG 78
PDE5.3  RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG 68
PDE5.1  RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG 120
        ************************************************************

PDE5.2  TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI 138
PDE5.3  TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI 128
PDE5.1  TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI 180
        ************************************************************

PDE5.2  SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL 198
PDE5.3  SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL 188
PDE5.1  SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL 240
        ************************************************************

PDE5.2  NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE 258
PDE5.3  NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE 248
PDE5.1  NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE 300
        ************************************************************

PDE5.2  KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS 318
PDE5.3  KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS 308
PDE5.1  KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS 360
        ************************************************************

PDE5.2  FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME 378
PDE5.3  FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME 368
PDE5.1  FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME 420
        ************************************************************

PDE5.2  PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK 438
PDE5.3  PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK 428
PDE5.1  PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK 480
        ************************************************************

PDE5.2  VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL 498
PDE5.3  VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL 488
PDE5.1  VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL 540
        ************************************************************

PDE5.2  QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL 558
PDE5.3  QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL 548
PDE5.1  QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL 600
        ************************************************************

PDE5.2  SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV 618
PDE5.3  SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV 608
PDE5.1  SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV 660
        ************************************************************

PDE5.2  NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI 678
PDE5.3  NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI 668
PDE5.1  NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI 720
        ************************************************************

PDE5.2  LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE 738
PDE5.3  LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE 728
PDE5.1  LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE 780
        ************************************************************

PDE5.2  LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF 798
PDE5.3  LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF 788
PDE5.1  LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF 840
        ************************************************************

PDE5.2  PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN 833
PDE5.3  PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN 823
PDE5.1  PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN 875
        ***********************************

Accession Numbers:  phosphodiesterase 5A isoform 1 - NP_001074 ; phosphodiesterase 5A isoform 2 - NP_236914 ; phosphodiesterase 5A isoform - NP_246273

Predicted General Properties of the cGMP Specific Phosphodiesterase Type 5 Enzyme Protein, Isoform 1  (Homo sapiens) - Primary Sequence Analysis (with ProtParam)b

Number of amino acids: 875

Molecular weight: 99984.9

Theoretical pI: 5.74

Total number of negatively charged residues (Asp + Glu): 120

Total number of positively charged residues (Arg + Lys): 99

Atomic composition: Carbon C 4410 Hydrogen H 6961 Nitrogen N 1221 Oxygen O 1337 Sulfur S 47

Formula: C4410H6961N1221O1337S47

Total number of atoms: 13976

Extinction coefficients: Extinction coefficients are in units of M-1 cm-1, at 280 nm measured in water. Ext. coefficient 77820 Abs 0.1% (=1 g/l) 0.778, assuming ALL Cys residues appear as half cystines Ext. coefficient 76320 Abs 0.1% (=1 g/l) 0.763, assuming NO Cys residues appear as half cystines

Estimated half-life: The N-terminal of the sequence considered is M (Met). The estimated half-life is: 30 hours (mammalian reticulocytes, in vitro). >20 hours (yeast, in vivo). >10 hours (Escherichia coli, in vivo).

Instability index: The instability index (II) is computed to be 42.76 This classifies the protein as unstable.

Aliphatic index: 85.06

Grand average of hydropathicity (GRAVY): -0.394

Bioinformatics References

a Higgins D., Thompson J., Gibson T. Thompson J. D., Higgins D. G., Gibson T. J.(1994). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting,position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22:4673-4680.

b Gasteiger E., Hoogland C., Gattiker A., Duvaud S., Wilkins M.R., Appel R.D., Bairoch A.; Protein Identification and Analysis Tools on the ExPASy Server;
(In) John M. Walker (ed): The Proteomics Protocols Handbook, Humana Press (2005). pp. 571-607  Full text - Copyright Humana Press.

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