GAF domain; The GAF domain is named after some of the proteins it is found in, including cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA. It is also found in guanylyl cyclases and phytochromes. The structure of a GAF domain shows that the domain shares a similar fold with the PAS domain. This domain can bind O2, CO and NO (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 614662505  206 ILRTQTLLCDMLMR--DAPLGIVSQSPNIMDLVKCDGAALLYKDKVWKLG*TP*EFHLQEIASWLCEYH*DSTGLSTDSL 283
Cdd:pfam00360   1 LRRIQDRLVEAMARadDLVDGLVDQSPNLLDLVKADGAALCFGGNLLTLGETPPEEAIRDLAQWLGRNH-DSEVFSTDSL 79

                          90
                  ....*....|....
gi 614662505  284 HDAgFPRALALGDS 297
Cdd:pfam00360  80 SQA-YPEAAALADV 92

Phytochrome region; Phytochromes are red/far-red photochromic biliprotein photoreceptors which regulate plant development. They are widely represented in both photosynthetic and non-photosynthetic bacteria and are known in a variety of fungi. Although sequence similarities are low, this domain is structurally related to pfam01590, which is generally located immediately N-terminal to this domain. Compared with pfam01590, this domain carries an additional tongue-like hairpin loop between the fifth beta-sheet and the sixth alpha-helix which functions to seal the chromophore pocket and stabilize the photoactivated far-red-absorbing state (Pfr). The tongue carries a conserved PRxSF motif, from which an arginine finger points into the chromophore pocket close to ring D forming a salt bridge with a conserved aspartate residue.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 614662505  206 ILRTQTLLCDMLMR--DAPLGIVSQSPNIMDLVKCDGAALLYKDKVWKLG*TP*EFHLQEIASWLCEYH*DSTGLSTDSL 283
Cdd:pfam00360   1 LRRIQDRLVEAMARadDLVDGLVDQSPNLLDLVKADGAALCFGGNLLTLGETPPEEAIRDLAQWLGRNH-DSEVFSTDSL 79

                          90
                  ....*....|....
gi 614662505  284 HDAgFPRALALGDS 297
Cdd:pfam00360  80 SQA-YPEAAALADV 92

GAF domain; This domain is present in cGMP-specific phosphodiesterases, adenylyl and guanylyl cyclases, phytochromes, FhlA and NifA. Adenylyl and guanylyl cyclases catalyze ATP and GTP to the second messengers cAMP and cGMP, respectively, these products up-regulating catalytic activity by binding to the regulatory GAF domain(s). The opposite hydrolysis reaction is catalyzed by phosphodiesterase. cGMP-dependent 3',5'-cyclic phosphodiesterase catalyzes the conversion of guanosine 3',5'-cyclic phosphate to guanosine 5'-phosphate. Here too, cGMP regulates catalytic activity by GAF-domain binding. Phytochromes are regulatory photoreceptors in plants and bacteria which exist in two thermally-stable states that are reversibly inter-convertible by light: the Pr state absorbs maximally in the red region of the spectrum, while the Pfr state absorbs maximally in the far-red region. This domain is also found in FhlA (formate hydrogen lyase transcriptional activator) and NifA, a transcriptional activator which is required for activation of most Nif operons which are directly involved in nitrogen fixation. NifA interacts with sigma-54. This domain can bind biliverdine and phycocyanobilin (Matilla et al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 614662505   12 SMERLCDTMVQEVFELTGYDRVMAYkfh*ddhgevvsevtk*gLEPYLGLHYpatdIPQAARFLfmknKVRMIVDCNAKH 91
Cdd:pfam01590   1 DLEEILQTILEELRELLGADRCALY------------------LPDADGLEY----LPPGARWL----KAAGLEIPPGTG 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 614662505   92 VRVLQDEKlsfDLTLCGStlrAPHSCHLQ---YMANMDSIASLVMAVVVNEedgegdapdsttpqkrkRLWGLVVCHNTT 168
Cdd:pfam01590  55 VTVLRTGR---PLVVPDA---AGDPRFLDpllLLRNFGIRSLLAVPIIDDG-----------------ELLGVLVLHHPR 111

                         170       180
                  ....*....|....*....|....*..
gi 614662505  169 PRFvpfpLRYACEFLaQVFAIHVNKEV 195
Cdd:pfam01590 112 PPF----TEEELELL-EVLADQVAIAL 133

Phytochrome region; Phytochromes are red/far-red photochromic biliprotein photoreceptors which regulate plant development. They are widely represented in both photosynthetic and non-photosynthetic bacteria and are known in a variety of fungi. Although sequence similarities are low, this domain is structurally related to pfam01590, which is generally located immediately N-terminal to this domain. Compared with pfam01590, this domain carries an additional tongue-like hairpin loop between the fifth beta-sheet and the sixth alpha-helix which functions to seal the chromophore pocket and stabilize the photoactivated far-red-absorbing state (Pfr). The tongue carries a conserved PRxSF motif, from which an arginine finger points into the chromophore pocket close to ring D forming a salt bridge with a conserved aspartate residue.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 614662505  206 ILRTQTLLCDMLMR--DAPLGIVSQSPNIMDLVKCDGAALLYKDKVWKLG*TP*EFHLQEIASWLCEYH*DSTGLSTDSL 283
Cdd:pfam00360   1 LRRIQDRLVEAMARadDLVDGLVDQSPNLLDLVKADGAALCFGGNLLTLGETPPEEAIRDLAQWLGRNH-DSEVFSTDSL 79

                          90
                  ....*....|....
gi 614662505  284 HDAgFPRALALGDS 297
Cdd:pfam00360  80 SQA-YPEAAALADV 92

GAF domain; This domain is present in cGMP-specific phosphodiesterases, adenylyl and guanylyl cyclases, phytochromes, FhlA and NifA. Adenylyl and guanylyl cyclases catalyze ATP and GTP to the second messengers cAMP and cGMP, respectively, these products up-regulating catalytic activity by binding to the regulatory GAF domain(s). The opposite hydrolysis reaction is catalyzed by phosphodiesterase. cGMP-dependent 3',5'-cyclic phosphodiesterase catalyzes the conversion of guanosine 3',5'-cyclic phosphate to guanosine 5'-phosphate. Here too, cGMP regulates catalytic activity by GAF-domain binding. Phytochromes are regulatory photoreceptors in plants and bacteria which exist in two thermally-stable states that are reversibly inter-convertible by light: the Pr state absorbs maximally in the red region of the spectrum, while the Pfr state absorbs maximally in the far-red region. This domain is also found in FhlA (formate hydrogen lyase transcriptional activator) and NifA, a transcriptional activator which is required for activation of most Nif operons which are directly involved in nitrogen fixation. NifA interacts with sigma-54. This domain can bind biliverdine and phycocyanobilin (Matilla et al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 614662505   12 SMERLCDTMVQEVFELTGYDRVMAYkfh*ddhgevvsevtk*gLEPYLGLHYpatdIPQAARFLfmknKVRMIVDCNAKH 91
Cdd:pfam01590   1 DLEEILQTILEELRELLGADRCALY------------------LPDADGLEY----LPPGARWL----KAAGLEIPPGTG 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 614662505   92 VRVLQDEKlsfDLTLCGStlrAPHSCHLQ---YMANMDSIASLVMAVVVNEedgegdapdsttpqkrkRLWGLVVCHNTT 168
Cdd:pfam01590  55 VTVLRTGR---PLVVPDA---AGDPRFLDpllLLRNFGIRSLLAVPIIDDG-----------------ELLGVLVLHHPR 111

                         170       180
                  ....*....|....*....|....*..
gi 614662505  169 PRFvpfpLRYACEFLaQVFAIHVNKEV 195
Cdd:pfam01590 112 PPF----TEEELELL-EVLADQVAIAL 133