CYTH-like (also known as triphosphate tunnel metalloenzyme (TTM)-like) Phosphatases; CYTH-like superfamily enzymes hydrolyze triphosphate-containing substrates and require metal cations as cofactors. They have a unique active site located at the center of an eight-stranded antiparallel beta barrel tunnel (the triphosphate tunnel). The name CYTH originated from the gene designation for bacterial class IV adenylyl cyclases (CyaB), and from thiamine triphosphatase. Class IV adenylate cyclases catalyze the conversion of ATP to 3',5'-cyclic AMP (cAMP) and PPi. Thiamine triphosphatase is a soluble cytosolic enzyme which converts thiamine triphosphate to thiamine diphosphate. This domain superfamily also contains RNA triphosphatases, membrane-associated polyphosphate polymerases, tripolyphosphatases, nucleoside triphosphatases, nucleoside tetraphosphatases and other proteins with unknown functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 373251209   6 IEVERKFLPGPGTEERLQELGG--TLEYRVTFRDTYYDTPELSLMQADHWLRRREDsGWELKCPGAAGV--LGPHTEYKE 81
Cdd:cd07758    1 LEVERKFRCGPSAEERLRKLGAllELLGRRTFHDTYYDTPDNTLSLNDVWLRQRNG-QWELKIPPGGDPptAGANTRYEE 79

                         90
                 ....*....|....
gi 373251209  82 LTAEPTIVAQLCKV 95
Cdd:cd07758   80 LTGEAAIAAALRKL 93

Thiamine Triphosphatase; ThTPase is a soluble cytosolic enzyme which converts thiamine triphosphate (ThTP) to thiamine diphosphate. This catalytic activity depends on a divalent metal cofactor, for example Mg++. ThTPase regulates the intracellular concentration of ThTP, maintaining it at a low concentration in vivo. ThTP acts as a messenger in cell signaling in response to cellular stress, and in addition, can phosphorylate proteins in certain tissues. There is another class of membrane-associated enzymes in animal tissues which also convert ThTP to thiamine diphosphate, however they do not belong to this subgroup. This subgroup belongs to the CYTH/triphosphate tunnel metalloenzyme (TTM)-like superfamily, whose enzymes have a unique active site located within an eight-stranded beta barrel.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 373251209   6 IEVERKFLPGPGTEERLQELGG--TLEYRVTFRDTYYDTPELSLMQADHWLRRREDsGWELKCPGAAGV--LGPHTEYKE 81
Cdd:cd07758    1 LEVERKFRCGPSAEERLRKLGAllELLGRRTFHDTYYDTPDNTLSLNDVWLRQRNG-QWELKIPPGGDPptAGANTRYEE 79

                         90
                 ....*....|....
gi 373251209  82 LTAEPTIVAQLCKV 95
Cdd:cd07758   80 LTGEAAIAAALRKL 93

Adenylate cyclase class IV, CYTH domain (includes archaeal enzymes of unknown function) [Signal transduction mechanisms, General function prediction only];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 373251209   6 IEVERKF-LPGPGT-EERLQELGGTLEYRVTFRDTYYDTPELSLMQADHWLR-RREDSGWEL 64
Cdd:COG1437    1 IEVEVKVrVIDLEEvRERLEELGAELVGEEHQIDIYYDAPDRDFAETDEALRiRRGGGRATL 62

Thiamine Triphosphatase; ThTPase is a soluble cytosolic enzyme which converts thiamine triphosphate (ThTP) to thiamine diphosphate. This catalytic activity depends on a divalent metal cofactor, for example Mg++. ThTPase regulates the intracellular concentration of ThTP, maintaining it at a low concentration in vivo. ThTP acts as a messenger in cell signaling in response to cellular stress, and in addition, can phosphorylate proteins in certain tissues. There is another class of membrane-associated enzymes in animal tissues which also convert ThTP to thiamine diphosphate, however they do not belong to this subgroup. This subgroup belongs to the CYTH/triphosphate tunnel metalloenzyme (TTM)-like superfamily, whose enzymes have a unique active site located within an eight-stranded beta barrel.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 373251209   6 IEVERKFLPGPGTEERLQELGG--TLEYRVTFRDTYYDTPELSLMQADHWLRRREDsGWELKCPGAAGV--LGPHTEYKE 81
Cdd:cd07758    1 LEVERKFRCGPSAEERLRKLGAllELLGRRTFHDTYYDTPDNTLSLNDVWLRQRNG-QWELKIPPGGDPptAGANTRYEE 79

                         90
                 ....*....|....
gi 373251209  82 LTAEPTIVAQLCKV 95
Cdd:cd07758   80 LTGEAAIAAALRKL 93

CYTH-like (also known as triphosphate tunnel metalloenzyme (TTM)-like) Phosphatases; CYTH-like superfamily enzymes hydrolyze triphosphate-containing substrates and require metal cations as cofactors. They have a unique active site located at the center of an eight-stranded antiparallel beta barrel tunnel (the triphosphate tunnel). The name CYTH originated from the gene designation for bacterial class IV adenylyl cyclases (CyaB), and from thiamine triphosphatase. Class IV adenylate cyclases catalyze the conversion of ATP to 3',5'-cyclic AMP (cAMP) and PPi. Thiamine triphosphatase is a soluble cytosolic enzyme which converts thiamine triphosphate to thiamine diphosphate. This domain superfamily also contains RNA triphosphatases, membrane-associated polyphosphate polymerases, tripolyphosphatases, nucleoside triphosphatases, nucleoside tetraphosphatases and other proteins with unknown functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 373251209   7 EVERKFLPGPGTEERLQE-----LGGTLEYRVTFRDTYYDTPELSLMQADHWLRRRE---DSGWELKCPGAAGvlgphtE 78
Cdd:cd07374    1 EVERKFRVPDDAVLPLLLgvpgvLGVGEPETVQLRAIYFDTPDLRLARAGLRLRRRTggaDAGWHLKLPGGIS------R 74

                         90       100
                 ....*....|....*....|...
gi 373251209  79 YKELTAEPTIVAQLCKVCLHRRQ 101
Cdd:cd07374   75 RTEVRAPLGDAAAVAPLLLAAAL 97

Uncharacterized subgroup of the CYTH-like superfamily having an associated CHAD domain; This subgroup belongs to the CYTH-like (also known as triphosphate tunnel metalloenzyme (TTM)-like) superfamily. Members of this superfamily hydrolyze triphosphate-containing substrates, require metal cations as cofactors, and have a unique active site located at the center of an eight-stranded antiparallel beta barrel tunnel (the triphosphate tunnel). A number of proteins in this subgroup also contain a C-terminal CHAD (Conserved Histidine Alpha-helical Domain) domain which may participate in metal chelation or act as a phosphor-acceptor. The name CYTH originated from the gene designation for bacterial class IV adenylyl cyclases (CyaB) and from thiamine triphosphatase. Class IV adenylate cyclases catalyze the conversion of ATP to 3',5'-cyclic AMP (cAMP) and PPi. Thiamine triphosphatase is a soluble cytosolic enzyme which converts thiamine triphosphate to thiamine diphosphate. This domain superfamily also contains RNA triphosphatases, membrane-associated polyphosphate polymerases, tripolyphosphatases, nucleoside triphosphatases, nucleoside tetraphosphatases and other proteins with unknown functions. Proteins of this subgroup have not been characterized.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 373251209   7 EVERKFLPGPGTEER------LQELGGTLEYRVTFRDTYYDTPELSLMQADHWLR-RREDSGWE--LKCPGAAgVLGPH 76
Cdd:cd07756    1 EIELKLLLPPEDLEAlaahplLAALAAGRAQTRRLHNTYFDTPDLALRRAGIALRvRREGGQWVqtLKTAGSV-VGGLH 78

Adenylyl cyclase (AC) class IV-like, a subgroup of the CYTH-like superfamily; This subgroup contains class IV ACs and similar proteins. AC catalyzes the conversion of ATP to 3',5'-cyclic AMP (cAMP) and PPi. cAMP is a key signaling molecule which conveys a variety of signals in different cell types. In prokaryotes, cAMP is a catabolite derepression signal which triggers the expression of metabolic pathways including the lactose operon. Six non-homologous classes of ACs have been identified (I-VI). Class IV ACs are found in this group. In bacteria, the gene encoding Class IV AC has been designated cyaB and the protein as AC2. AC-IV occurs in addition to AC-I in bacterial pathogens such as Yersinia pestis (plague disease). The role of AC-IV is unknown but it has been speculated that it may be a factor in pathogenesis, perhaps providing cAMP for a secondary internal signaling function, or for secretion and uptake into host cells, where it may disrupt normal cellular processes. This subgroup belongs to the CYTH/triphosphate tunnel metalloenzyme (TTM)-like superfamily, whose enzymes have a unique active site located within an eight-stranded beta barrel.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 373251209   7 EVERKF-LPGPGT-EERLQELGGTLEYRVTFRDTYYDTPELSLMQADHWL--RRREDSG---WELKCPGAAG 71
Cdd:cd07890    1 EVEIKArVDDLEAlRERLAALGGAEGGREFQEDIYFDHPDRDLAATDEALrlRRMGDSGktlLTYKGPKLDG 72