magnesium transporting ATPase (MgtA), similar to Escherichia coli MgtA and Salmonella typhimurium MgtA; MgtA is a membrane protein which actively transports Mg(2+) into the cytosol with its electro-chemical gradient rather than against the gradient as other cation transporters do. It may act both as a transporter and as a sensor for Mg(2+). In Salmonella typhimurium and Escherichia coli, the two-component system PhoQ/PhoP regulates the transcription of the mgtA gene by sensing Mg(2+) concentrations in the periplasm. MgtA is activated by cardiolipin and it highly sensitive to free magnesium in vitro. It consists of a transmembrane domain and three cytosolic domains: nucleotide-binding domain, phosphorylation domain and actuator domain, and belongs to the P-type ATPase type III subfamily. The P-type ATPases, are a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  54 GLSIKEAQKRIHVYGKNELSSKR-----------------------AILS---DV----------------MMKLGEMIP 91
Cdd:cd02077    1 GLTNEEAEERLEKYGPNEISHEKfpswfklllkafinpfnivllvlALVSfftDVllapgefdlvgaliilLMVLISGLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  92 GFVkQRVHNENQCEIVTvtvSRVEGCTNVgMNSESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTG 171
Cdd:cd02077   81 DFI-QEIRSLKAAEKLK---KMVKNTATV-IRDGSKYMEIPIDELVPGDIVYLSAGDMIPADVRIIQSKDLFVSQSSLTG 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 507042518 172 KEINVEKFEScyhlerkrfipLKRMKDYNPLQLENVCFKGTHIVNGTAKAVVVSTGKNTYSGLL 235
Cdd:cd02077  156 ESEPVEKHAT-----------AKKTKDESILELENICFMGTNVVSGSALAVVIATGNDTYFGSI 208

magnesium-translocating P-type ATPase; This model describes the magnesium translocating P-type ATPase found in a limited number of bacterial species and best described in Salmonella typhimurium, which contains two isoforms. These transporters are active in low external Mg2+ concentrations and pump the ion into the cytoplasm. The magnesium ATPases have been classified as type IIIB by a phylogenetic analysis. [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518   33 LIEIATRDVKSVFAYFKTTRDGLSIKEAQKRIHVYGKNELSSKR--------------------AILSDV---------- 82
Cdd:TIGR01524  12 LLKESQMGKETLLRKLGVHETGLTNVEVTERLAEFGPNQTVEEKkvpnlrllirafnnpfiyilAMLMGVsyltddleat 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518   83 ----MMKLGEMIPGFVKQRVHNENQCEIVTVTVSRVEGCTNVGMNSESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVY 158
Cdd:TIGR01524  92 viiaLMVLASGLLGFIQESRAERAAYALKNMVKNTATVLRVINENGNGSMDEVPIDALVPGDLIELAAGDIIPADARVIS 171

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 507042518  159 AEDLLVNESVLTGKEINVEKFEScyhlerkrfipLKRMKDYNPLQLENVCFKGTHIVNGTAKAVVVSTGKNTYSGLL 235
Cdd:TIGR01524 172 ARDLFINQSALTGESLPVEKFVE-----------DKRARDPEILERENLCFMGTNVLSGHAQAVVLATGSSTWFGSL 237

Cation transporter/ATPase, N-terminus; This entry represents the conserved N-terminal region found in several classes of cation-transporting P-type ATPases, including those that transport H+, Na+, Ca2+, Na+/K+, and H+/K+. In the H+/K+- and Na+/K+-exchange P-ATPases, this domain is found in the catalytic alpha chain. In gastric H+/K+-ATPases, this domain undergoes reversible sequential phosphorylation inducing conformational changes that may be important for regulating the function of these ATPases.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 507042518    38 TRDVKSVFAYFKTTRD-GLSIKEAQKRIHVYGKNELSSKR 76
Cdd:smart00831   6 ALSLEEVLERLQTDLEkGLSSEEAARRLERYGPNELPPPK 45

magnesium transporting ATPase (MgtA), similar to Escherichia coli MgtA and Salmonella typhimurium MgtA; MgtA is a membrane protein which actively transports Mg(2+) into the cytosol with its electro-chemical gradient rather than against the gradient as other cation transporters do. It may act both as a transporter and as a sensor for Mg(2+). In Salmonella typhimurium and Escherichia coli, the two-component system PhoQ/PhoP regulates the transcription of the mgtA gene by sensing Mg(2+) concentrations in the periplasm. MgtA is activated by cardiolipin and it highly sensitive to free magnesium in vitro. It consists of a transmembrane domain and three cytosolic domains: nucleotide-binding domain, phosphorylation domain and actuator domain, and belongs to the P-type ATPase type III subfamily. The P-type ATPases, are a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  54 GLSIKEAQKRIHVYGKNELSSKR-----------------------AILS---DV----------------MMKLGEMIP 91
Cdd:cd02077    1 GLTNEEAEERLEKYGPNEISHEKfpswfklllkafinpfnivllvlALVSfftDVllapgefdlvgaliilLMVLISGLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  92 GFVkQRVHNENQCEIVTvtvSRVEGCTNVgMNSESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTG 171
Cdd:cd02077   81 DFI-QEIRSLKAAEKLK---KMVKNTATV-IRDGSKYMEIPIDELVPGDIVYLSAGDMIPADVRIIQSKDLFVSQSSLTG 155

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 507042518 172 KEINVEKFEScyhlerkrfipLKRMKDYNPLQLENVCFKGTHIVNGTAKAVVVSTGKNTYSGLL 235
Cdd:cd02077  156 ESEPVEKHAT-----------AKKTKDESILELENICFMGTNVVSGSALAVVIATGNDTYFGSI 208

magnesium-transporting P-type ATPase MgtA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518 108 TVTVSRVEGCTnvgmnSESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTGKEINVEKFESCYHLER 187
Cdd:PRK10517 160 TATVLRVINDK-----GENGWLEIPIDQLVPGDIIKLAAGDMIPADLRILQARDLFVAQASLTGESLPVEKFATTRQPEH 234

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 507042518 188 KrfiplkrmkdyNPLQLENVCFKGTHIVNGTAKAVVVSTGKNTYSGLLHTCCSQT 242
Cdd:PRK10517 235 S-----------NPLECDTLCFMGTNVVSGTAQAVVIATGANTWFGQLAGRVSEQ 278

prokaryotic P-type Ca(2+)-ATPase similar to Synechococcus elongatus sp. strain PCC 7942 PacL and Listeria monocytogenes LMCA1; Ca(2+) transport ATPase is a plasma membrane protein which pumps Ca(2+) ion out of the cytoplasm. This prokaryotic subfamily includes the Ca(2+)-ATPase Synechococcus elongatus PacL, Listeria monocytogenes Ca(2+)-ATPase 1 (LMCA1) which has a low Ca(2+) affinity and a high pH optimum (pH about 9) and may remove Ca(2+) from the microorganism in environmental conditions when e.g. stressed by high Ca(2+) and alkaline pH, and the Bacillus subtilis putative P-type Ca(2+)-transport ATPase encoded by the yloB gene, which is expressed during sporulation. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  54 GLSIKEAQKRIHVYGKNELSSKRAI---------LSDVM-----------MKLGE--------------MIPGFVkQRVH 99
Cdd:cd02089    1 GLSEEEAERRLAKYGPNELVEKKKRspwkkfleqFKDFMvivllaaavisGVLGEyvdaiviiaivilnAVLGFV-QEYK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518 100 NENQCE------IVTVTVSRvegctnvgmnsESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTGKE 173
Cdd:cd02089   80 AEKALAalkkmsAPTAKVLR-----------DGKKQEIPARELVPGDIVLLEAGDYVPADGRLIESASLRVEESSLTGES 148

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 507042518 174 INVEKFescyhlerkrfiPLKRMKDYNPL--QLeNVCFKGTHIVNGTAKAVVVSTGKNT 230
Cdd:cd02089  149 EPVEKD------------ADTLLEEDVPLgdRK-NMVFSGTLVTYGRGRAVVTATGMNT 194

sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), similar to mammalian ATP2A1-3/SERCA1-3; SERCA is a transmembrane (Ca2+)-ATPase and a major regulator of Ca(2+) homeostasis and contractility in cardiac and skeletal muscle. It re-sequesters cytoplasmic Ca(2+) to the sarco/endoplasmic reticulum store, thereby also terminating Ca(2+)-induced signaling such as in muscle contraction. Three genes (ATP2A1-3/SERCA1-3) encode SERCA pumps in mammals, further isoforms exist due to alternative splicing of transcripts. The activity of SERCA is regulated by two small membrane proteins called phospholamban and sarcolipin. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  38 TRDVKSVFAYFKTTRD-GLSIKEAQKRIHVYGKNELSSKR-----------------------AILSDVMMKLG---EMI 90
Cdd:cd02083    2 SKTVEEVLAYFGVDPTrGLSDEQVKRRREKYGPNELPAEEgkslwelvleqfddllvrilllaAIISFVLALFEegeEGV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  91 PGFVKQRV----------------HN---------ENQCEIVTVtvsrvegctnvgMNSESRIMKLPVEELVPGDMVFLS 145
Cdd:cd02083   82 TAFVEPFVillilianavvgvwqeRNaekaiealkEYEPEMAKV------------LRNGKGVQRIRARELVPGDIVEVA 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518 146 AGDTVPADVRIV--YAEDLLVNESVLTGKEINVEKFESCYHLERkrfiPLKRMKdynplqlENVCFKGTHIVNGTAKAVV 223
Cdd:cd02083  150 VGDKVPADIRIIeiKSTTLRVDQSILTGESVSVIKHTDVVPDPR----AVNQDK-------KNMLFSGTNVAAGKARGVV 218

                        250       260
                 ....*....|....*....|
gi 507042518 224 VSTGKNTYSGLLHTCCSQTS 243
Cdd:cd02083  219 VGTGLNTEIGKIRDEMAETE 238

sarco/endoplasmic reticulum calcium-translocating P-type ATPase; This model describes the P-type ATPase responsible for translocating calcium ions across the endoplasmic reticulum membrane of eukaryotes, and is of particular importance in the sarcoplasmic reticulum of skeletal and cardiac muscle in vertebrates. These pumps transfer Ca2+ from the cytoplasm to the lumen of the endoplasmic reticulum. In humans and mice, at least, there are multiple isoforms of the SERCA pump with overlapping but not redundant functions. Defects in SERCA isoforms are associated with diseases in humans. The calcium P-type ATPases have been characterized as Type IIA based on a phylogenetic analysis which distinguishes this group from the Type IIB PMCA calcium pump modelled by TIGR01517. A separate analysis divides Type IIA into sub-types, SERCA and PMR1, the latter of which is modelled by TIGR01522. [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  131 LPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTGKEINVEKFESCYHLERKRFiPLKrmkdynplqlENVCFK 210
Cdd:TIGR01116  86 IKAKDLVPGDIVELAVGDKVPADIRVLSLKTLRVDQSILTGESVSVNKHTESVPDERAVN-QDK----------KNMLFS 154

                          90       100
                  ....*....|....*....|....*.
gi 507042518  211 GTHIVNGTAKAVVVSTGKNTYSGLLH 236
Cdd:TIGR01116 155 GTLVVAGKARGVVVRTGMSTEIGKIR 180

plasma-membrane proton-efflux P-type ATPase; This model describes the plasma membrane proton efflux P-type ATPase found in plants, fungi, protozoa, slime molds and archaea. The best studied representative is from yeast.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518   54 GLSIKEAQKRIHVYGKNELSSKRAILSDV-----------MMKLGEMIPGFVKQRVHNENQCEI--VTVTVSRVEGCT-- 118
Cdd:TIGR01647   1 GLTSAEAKKRLAKYGPNELPEKKVSPLLKflgffwnplswVMEAAAIIAIALENWVDFVIILGLllLNATIGFIEENKag 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  119 NV------GMNSESRIMK------LPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTGKEINVEKfescyhle 186
Cdd:TIGR01647  81 NAvealkqSLAPKARVLRdgkwqeIPASELVPGDVVRLKIGDIVPADCRLFEGDYIQVDQAALTGESLPVTK-------- 152

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 507042518  187 rkrfiplkrmkdynplQLENVCFKGTHIVNGTAKAVVVSTGKNTYSG 233
Cdd:TIGR01647 153 ----------------KTGDIAYSGSTVKQGEAEAVVTATGMNTFFG 183

sodium or proton efflux -- potassium uptake antiporter, P-type ATPase, alpha subunit; This model describes the P-type ATPases responsible for the exchange of either protons or sodium ions for potassium ions across the plasma membranes of eukaryotes. Unlike most other P-type ATPases, members of this subfamily require a beta subunit for activity. This model encompasses eukaryotes and consists of two functional types, a Na/K antiporter found widely distributed in eukaryotes and a H/K antiporter found only in vertebrates. The Na+ or H+/K+ antiporter P-type ATPases have been characterized as Type IIC based on a published phylogenetic analysis. Sequences from Blastocladiella emersonii (GP|6636502, GP|6636502 and PIR|T43025), C. elegans (GP|2315419, GP|6671808 and PIR|T31763) and Drosophila melanogaster (GP|7291424) score below trusted cutoff, apparently due to long branch length (excessive divergence from the last common ancestor) as evidenced by a phylogenetic tree. Experimental evidence is needed to determine whether these sequences represent ATPases with conserved function. Aside from fragments, other sequences between trusted and noise appear to be bacterial ATPases of unclear lineage, but most likely calcium pumps. [Energy metabolism, ATP-proton motive force interconversion]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  125 ESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTGkeinvekfEScyhlerkrfIPLKRMKDY---NP 201
Cdd:TIGR01106 148 DGEKMSINAEQVVVGDLVEVKGGDRIPADLRIISAQGCKVDNSSLTG--------ES---------EPQTRSPEFtheNP 210

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 507042518  202 LQLENVCFKGTHIVNGTAKAVVVSTGKNTYSGLLHTCCS 240
Cdd:TIGR01106 211 LETRNIAFFSTNCVEGTARGIVVNTGDRTVMGRIASLAS 249

fungal-type Na(+)-ATPase, similar to the plasma membrane sodium transporters Saccharomyces cerevisiae Ena1p, Ena2p and Ustilago maydis Ena1, and the endoplasmic reticulum sodium transporter Ustilago maydis Ena2; Fungal-type Na(+)-ATPase (also called ENA ATPases). This subfamily includes the Saccharomyces cerevisiae plasma membrane transporters: Na(+)/Li(+)-exporting ATPase Ena1p which may also extrudes K(+), and Na(+)-exporting P-type ATPase Ena2p. It also includes Ustilago maydis plasma membrane Ena1, an K(+)/Na(+)-ATPase whose chief role is to pump Na(+) and K(+) out of the cytoplasm, especially at high pH values, and endoplasmic reticulum Ena2 ATPase which mediates Na(+) or K(+) fluxes in the ER or in other endomembranes. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518 125 ESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTGKEINVEKfescyHLErkrfIPLKRMKDYNPLQL 204
Cdd:cd02086  100 SGKTETISSKDVVPGDIVLLKVGDTVPADLRLIETKNFETDEALLTGESLPVIK-----DAE----LVFGKEEDVSVGDR 170

                         90       100
                 ....*....|....*....|....*....
gi 507042518 205 ENVCFKGTHIVNGTAKAVVVSTGKNTYSG 233
Cdd:cd02086  171 LNLAYSSSTVTKGRAKGIVVATGMNTEIG 199

golgi-associated secretory pathway Ca(2+) transport ATPases, similar to human ATPase secretory pathway Ca(2+) transporting 1/hSPCA1 and Saccharomyces cerevisiae Ca(2+)/Mn(2+)-transporting P-type ATPase, Pmr1p; SPCAs are Ca(2+) pumps important for the golgi-associated secretion pathway, in addition some function as Mn(2+) pumps in Mn(2+) detoxification. Saccharomyces cerevisiae Pmr1p is a high affinity Ca(2+)/Mn(2+) ATPase which transports Ca(2+) and Mn(2+) from the cytoplasm into the Golgi. Pmr1p also contributes to Cd(2+) detoxification. This subfamily includes human SPCA1 and SPCA2, encoded by the ATP2C1 and ATP2C2 genes; autosomal dominant Hailey-Hailey disease is caused by mutations in the human ATP2C1 gene. It also includes Strongylocentrotus purpuratus testis secretory pathway calcium transporting ATPase SPCA which plays an important role in fertilization. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518 135 ELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTGKEINVEKFESCyhLERKRFIPLKRMKdynplqleNVCFKGTHI 214
Cdd:cd02085  101 ELVPGDLVCLSIGDRIPADLRLFEATDLSIDESSLTGETEPCSKTTEV--IPKASNGDLTTRS--------NIAFMGTLV 170

                         90
                 ....*....|....*....
gi 507042518 215 VNGTAKAVVVSTGKNTYSG 233
Cdd:cd02085  171 RCGHGKGIVIGTGENSEFG 189

ATPase, P-type (transporting), HAD superfamily, subfamily IC; The P-type ATPases are a large family of trans-membrane transporters acting on charged substances. The distinguishing feature of the family is the formation of a phosphorylated intermediate (aspartyl-phosphate) during the course of the reaction. Another common name for these enzymes is the E1-E2 ATPases based on the two isolable conformations: E1 (unphosphorylated) and E2 (phosphorylated). Generally, P-type ATPases consist of only a single subunit encompassing the ATPase and ion translocation pathway, however, in the case of the potassium (TIGR01497) and sodium/potassium (TIGR01106) varieties, these functions are split between two subunits. Additional small regulatory or stabilizing subunits may also exist in some forms. P-type ATPases are nearly ubiquitous in life and are found in numerous copies in higher organisms (at least 45 in Arabidopsis thaliana, for instance). Phylogenetic analyses have revealed that the P-type ATPase subfamily is divided up into groups based on substrate specificities and this is represented in the various subfamily and equivalog models that have been made: IA (K+) TIGR01497, IB (heavy metals) TIGR01525, IIA1 (SERCA-type Ca++) TIGR01116, IIA2 (PMR1-type Ca++) TIGR01522, IIB (PMCA-type Ca++) TIGR01517, IIC (Na+/K+, H+/K+ antiporters) TIGR01106, IID (fungal-type Na+ and K+) TIGR01523, IIIA (H+) TIGR01647, IIIB (Mg++) TIGR01524, IV (phospholipid, flippase) TIGR01652 and V (unknown specificity) TIGR01657. The crystal structure of one calcium-pumping ATPase and an analysis of the fold of the catalytic domain of the P-type ATPases have been published. These reveal that the catalytic core of these enzymes is a haloacid dehalogenase(HAD)-type aspartate-nucleophile hydrolase. The location of the ATP-binding loop in between the first and second HAD conserved catalytic motifs defines these enzymes as members of subfamily I of the HAD superfamily (see also TIGR01493, TIGR01509, TIGR01549, TIGR01544 and TIGR01545). Based on these classifications, the P-type ATPase _superfamily_ corresponds to the IC subfamily of the HAD superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  131 LPVEELVPGDMVFLSAGDTVPADVRIvYAEDLLVNESVLTGKEINVEKFescyhlerkrfiplkrmkdynPLQLENVCFK 210
Cdd:TIGR01494  47 ISSKDLVPGDVVLVKSGDTVPADGVL-LSGSAFVDESSLTGESLPVLKT---------------------ALPDGDAVFA 104

                          90       100
                  ....*....|....*....|
gi 507042518  211 GTHIVNGTAKAVVVSTGKNT 230
Cdd:TIGR01494 105 GTINFGGTLIVKVTATGILT 124

uncharacterized subfamily of P-type ATPase transporter, similar to uncharacterized Streptococcus pneumoniae exported protein 7, Exp7; This subfamily contains P-type ATPase transporters of unknown function, similar to Streptococcus pneumoniae Exp7. The P-type ATPases, are a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids. They are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle. A general characteristic of P-type ATPases is a bundle of transmembrane helices which make up the transport path, and three domains on the cytoplasmic side of the membrane. Members include pumps that transport various light metal ions, such as H(+), Na(+), K(+), Ca(2+), and Mg(2+), pumps that transport indispensable trace elements, such as Zn(2+) and Cu(2+), pumps that remove toxic heavy metal ions, such as Cd(2+), and pumps such as aminophospholipid translocases which transport phosphatidylserine and phosphatidylethanolamine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518 130 KLPVEELVPGDMVFLSAGDTVPADVRIVYAEDLLVNESVLTGKEINVEKfescyhlerkrfiplkrmkdynplQLENVCF 209
Cdd:cd02609  104 KIPPEELVLDDILILKPGEQIPADGEVVEGGGLEVDESLLTGESDLIPK------------------------KAGDKLL 159

                         90       100
                 ....*....|....*....|..
gi 507042518 210 KGTHIVNGTAKAVVVSTGKNTY 231
Cdd:cd02609  160 SGSFVVSGAAYARVTAVGAESY 181

P-type cation-transporting ATPases, similar to human ATPase type 13A2 (ATP13A2) protein and Saccharomyces cerevisiae Ypk9p; Saccharomyces cerevisiae Yph9p localizes to the yeast vacuole and may play a role in sequestering heavy metal ions, its deletion confers sensitivity for growth for cadmium, manganese, nickel or selenium. Human ATP13A2 (PARK9/CLN12) is a lysosomal transporter with zinc as the possible substrate. Mutation in the ATP13A2 gene has been linked to Parkinson's disease and Kufor-Rakeb syndrome, and to neuronal ceroid lipofuscinoses. ATP13A3/AFURS1 is a candidate gene for oculo auriculo vertebral spectrum (OAVS), being one of nine genes included in a 3q29 microduplication in a patient with OAVS. Mutation in the human ATP13A4 may be involved in a speech-language disorder. This subfamily also includes zebrafish ATP13A2 a lysosome-specific transmembrane ATPase protein of unknown function which plays a crucial role during embryonic development, its deletion is lethal. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518  96 QRVHNENQCEIVTVTVSRVEGctnvgmnsesrIMKLPVEELVPGDMVFLSA-GDTVPADVrIVYAEDLLVNESVLTGKEI 174
Cdd:cd07542   76 SKRLREMVHFTCPVRVIRDGE-----------WQTISSSELVPGDILVIPDnGTLLPCDA-ILLSGSCIVNESMLTGESV 143

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 507042518 175 NVEKFescyhlerkrfiPLKRMKDYNPLQLEN-------VCFKGTHIV------NGTAKAVVVSTGKNTYSGLL 235
Cdd:cd07542  144 PVTKT------------PLPDESNDSLWSIYSiedhskhTLFCGTKVIqtrayeGKPVLAVVVRTGFNTTKGQL 205

P-type heavy metal-transporting ATPase, similar to Archaeoglobus fulgidus CopB, a Cu(2+)-ATPase; Archaeoglobus fulgidus CopB transports Cu(2+) from the cytoplasm to the exterior of the cell using ATP as energy source, it transports preferentially Cu(2+) over Cu(+), it is activated by Cu(2+) with high affinity and partially by Cu(+) and Ag(+). This subclass of P-type ATPase is also referred to as CPx-type ATPases because their amino acid sequences contain a characteristic CPC or CPH motif associated with a stretch of hydrophobic amino acids and N-terminal ion-binding sequences. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 507042518 125 ESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVYAEDlLVNESVLTGKEINVEK 178
Cdd:cd07552  138 DGSIEDVPVSELKVGDVVLVRAGEKIPADGTILEGES-SVNESMVTGESKPVEK 190

copper-(or silver)-translocating P-type ATPase; This model describes the P-type ATPase primarily responsible for translocating copper ions accross biological membranes. These transporters are found in prokaryotes and eukaryotes. This model encompasses those species which pump copper ions out of cells or organelles (efflux pumps such as CopA of Escherichia coli) as well as those which pump the ion into cells or organelles either for the purpose of supporting life in extremely low-copper environments (for example CopA of Enterococcus hirae) or for the specific delivery of copper to a biological complex for which it is a necessary component (for example FixI of Bradyrhizobium japonicum, or CtaA and PacS of Synechocystis). The substrate specificity of these transporters may, to a varying degree, include silver ions (for example, CopA from Archaeoglobus fulgidus). Copper transporters from this family are well known as the genes which are mutated in two human disorders of copper metabolism, Wilson's and Menkes' diseases. The sequences contributing to the seed of this model are all experimentally characterized. The copper P-type ATPases have been characterized as Type IB based on a phylogenetic analysis which combines the copper-translocating ATPases with the cadmium-translocating species. This model and that describing the cadmium-ATPases (TIGR01512) are well separated, and thus we further type the copper-ATPases as IB1 (and the cadmium-ATPases as IB2). Several sequences which have not been characterized experimentally fall just below the cutoffs for both of these models (SP|Q9CCL1 from Mycobacterium leprae, GP|13816263 from Sulfolobus solfataricus, OMNI|NTL01CJ01098 from Campylobacter jejuni, OMNI|NTL01HS01687 from Halobacterium sp., GP|6899169 from Ureaplasma urealyticum and OMNI|HP1503 from Helicobacter pylori). Accession PIR|A29576 from Enterococcus faecalis scores very high against this model, but yet is annotated as an "H+/K+ exchanging ATPase". BLAST of this sequence does not hit anything else annotated in this way. This error may come from the characterization paper published in 1987. Accession GP|7415611 from Saccharomyces cerevisiae appears to be mis-annotated as a cadmium resistance protein. Accession OMNI|NTL01HS00542 from Halobacterium which scores above trusted for this model is annotated as "molybdenum-binding protein" although no evidence can be found for this classification. [Cellular processes, Detoxification, Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 507042518  125 ESRIMKLPVEELVPGDMVFLSAGDTVPADVRIVYAEDlLVNESVLTGKEINVEK 178
Cdd:TIGR01511  99 DGSIEEVPVALLQPGDIVKVLPGEKIPVDGTVIEGES-EVDESLVTGESLPVPK 151

Cation transporter/ATPase, N-terminus; Members of this families are involved in Na+/K+, H+/K+, Ca++ and Mg++ transport.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 507042518   36 IATRDVKSVFAYFKTTR-DGLSIKEAQKRIHVYGKNELSSKR 76
Cdd:pfam00690   1 WHALSVEEVLKKLGTDLeKGLTEAEAEKRLKKYGPNELPEKK 42

Cation-transporting P-type ATPase [Inorganic ion transport and metabolism];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 507042518 127 RIMKLPVEELVPGDMVFLSAGDTVPADVRIVyAEDLLVNESVLTGKEINVEK 178
Cdd:COG2217  222 EEVEVPVEELRVGDRVLVRPGERIPVDGVVL-EGESSVDESMLTGESLPVEK 272

P-type cation-transporting ATPases, similar to human cation-transporting ATPase type 13A1 (ATP13A1) and Saccharomyces manganese-transporting ATPase 1 Spf1p; Saccharomyces Spf1p may mediate manganese transport into the endoplasmic reticulum (ER); one consequence of deletion of SPF1 is severe ER stress. This subfamily also includes Arabidopsis thaliana MIA (Male Gametogenesis Impaired Anthers) protein which is highly abundant in the endoplasmic reticulum and small vesicles of developing pollen grains and tapetum cells. The MIA gene functionally complements a mutant in the SPF1 from Saccharomyces cerevisiae. The expression of ATP13A1 has been followed during mouse development, ATP13A1 transcript expression showed an increase as development progressed, with the highest expression at the peak of neurogenesis. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518 130 KLPVEELVPGDMVFLSAG---DTVPADVRIVYAEdLLVNESVLTGkeinvekfESCYHLERkrfiPLKRMKDYNPLQLEN 206
Cdd:cd07543   98 PISSDELLPGDLVSIGRSaedNLVPCDLLLLRGS-CIVNEAMLTG--------ESVPLMKE----PIEDRDPEDVLDDDG 164

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 507042518 207 -----VCFKGTHIVNGTAK-------------AVVVSTGKNTYSG-LLHT 237
Cdd:cd07543  165 ddklhVLFGGTKVVQHTPPgkgglkppdggclAYVLRTGFETSQGkLLRT 214

P-type heavy metal-transporting ATPase, similar to Escherichia coli ZntA which is selective for Pb(2+), Zn(2+), and Cd(2+); Escherichia coli ZntA mediates resistance to toxic levels of selected divalent metal ions. ZntA has the highest selectivity for Pb(2+), followed by Zn(2+) and Cd(2+); it also shows low levels of activity with Cu(2+), Ni(2+), and Co(2+). It is upregulated by the transcription factor ZntR at high zinc concentrations. This subclass of P-type ATPase is also referred to as CPx-type ATPases because their amino acid sequences contain a characteristic CPC or CPH motif associated with a stretch of hydrophobic amino acids and N-terminal ion-binding sequences. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 507042518 132 PVEELVPGDMVFLSAGDTVPADVRIVyAEDLLVNESVLTGKEINVEK 178
Cdd:cd07546  113 PADSLRPGDVIEVAPGGRLPADGELL-SGFASFDESALTGESIPVEK 158

zinc/cadmium/mercury/lead-transporting ATPase; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 507042518 130 KLPVEELVPGDMVFLSAGDTVPADVRIVyAEDLLVNESVLTGKEINVEK 178
Cdd:PRK11033 255 EVAIADLRPGDVIEVAAGGRLPADGKLL-SPFASFDESALTGESIPVER 302

P-type cation-transporting ATPases, similar to human ATPase type 13A1-A4 (ATP13A1-A4) proteins and Saccharomyces cerevisiae Ypk9p and Spf1p; Saccharomyces cerevisiae Yph9p localizes to the yeast vacuole and may play a role in sequestering heavy metal ions, its deletion confers sensitivity for growth for cadmium, manganese, nickel or selenium. Saccharomyces 1 Spf1p may mediate manganese transport into the endoplasmic reticulum. Human ATP13A2 (PARK9/CLN12) is a lysosomal transporter with zinc as the possible substrate. Mutation in the ATP13A2 gene has been linked to Parkinson's disease and Kufor-Rakeb syndrome, and to neuronal ceroid lipofuscinoses. ATP13A3/AFURS1 is a candidate gene for oculo auriculo vertebral spectrum (OAVS), being one of nine genes included in a 3q29 microduplication in a patient with OAVS. Mutation in the human ATP13A4 may be involved in a speech-language disorder. The expression of ATP13A1 has been followed during mouse development, ATP13A1 transcript expression showed an increase as development progressed, with the highest expression at the peak of neurogenesis. This subfamily belongs to the P-type ATPases, a large family of integral membrane transporters that are of critical importance in all kingdoms of life. They generate and maintain (electro-) chemical gradients across cellular membranes, by translocating cations, heavy metals and lipids, and are distinguished from other main classes of transport ATPases (F- , V- , and ABC- type) by the formation of a phosphorylated (P-) intermediate state in the catalytic cycle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507042518 135 ELVPGD-MVFLSAGDTVPADVRIVYAEdLLVNESVLTGKEINVEKFE-SCYHLERKRFIPLKRMKdynplqleNVCFKGT 212
Cdd:cd02082  104 MIVPGDiVLIKRREVTLPCDCVLLEGS-CIVTEAMLTGESVPIGKCQiPTDSHDDVLFKYESSKS--------HTLFQGT 174

                         90       100
                 ....*....|....*....|....*....
gi 507042518 213 HIV------NGTAKAVVVSTGKNTYSGLL 235
Cdd:cd02082  175 QVMqiippeDDILKAIVVRTGFGTSKGQL 203