P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116063568  149 DLDGLEKALQRAVFGQPAAVSRIVALMRDYLATHVHSRPLLLALHGPSGVGKSHVGRLLARH-FRSVLEdSALVLQYHAR 227
Cdd:pfam06309   8 NYTGLERDLARRLFGQHLVKQLVVRSVKGHWENPKPRKPLVLSFHGWTGTGKNFVAEIIADNlYRDGLR-SDYVHHFVAT 86

                          90       100
                  ....*....|....*....|....*.
gi 116063568  228 HHCPEARAAQDCREELARRVADVVAR 253
Cdd:pfam06309  87 FHFPHPKYVELYKVELKNQIRGTLRA 112

Torsin; This family consists of several eukaryotic torsin proteins. Torsion dystonia is an autosomal dominant movement disorder characterized by involuntary, repetitive muscle contractions and twisted postures. The most severe early-onset form of dystonia has been linked to mutations in the human DYT1 (TOR1A) gene encoding a protein termed torsinA. While causative genetic alterations have been identified, the function of torsin proteins and the molecular mechanism underlying dystonia remain unknown. Phylogenetic analysis of the torsin protein family indicates these proteins share distant sequence similarity with the large and diverse family of (pfam00004) proteins. It has been suggested that torsins play a role in effectively managing protein folding and that possible breakdown in a neuroprotective mechanism that is, in part, mediated by torsins may be responsible for the neuronal dysfunction associated with dystonia.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116063568  149 DLDGLEKALQRAVFGQPAAVSRIVALMRDYLATHVHSRPLLLALHGPSGVGKSHVGRLLARH-FRSVLEdSALVLQYHAR 227
Cdd:pfam06309   8 NYTGLERDLARRLFGQHLVKQLVVRSVKGHWENPKPRKPLVLSFHGWTGTGKNFVAEIIADNlYRDGLR-SDYVHHFVAT 86

                          90       100
                  ....*....|....*....|....*.
gi 116063568  228 HHCPEARAAQDCREELARRVADVVAR 253
Cdd:pfam06309  87 FHFPHPKYVELYKVELKNQIRGTLRA 112

Chaperone protein ClpB/Hsp104 subfamily; Bacterial Caseinolytic peptidase B (ClpB) and eukaryotic Heat shock protein 104 (Hsp104) are ATP-dependent molecular chaperones and essential proteins of the heat-shock response. ClpB/Hsp104 ATPases, in concert with the DnaK/Hsp70 chaperone system, disaggregate and reactivate aggregated proteins. This RecA-like_ClpB_Hsp104_like subfamily belongs to the RecA-like NTPase family which includes the NTP binding domain of F1 and V1 H(+)ATPases, DnaB and related helicases as well as bacterial RecA and related eukaryotic and archaeal recombinases. The RecA-like NTPase family also includes bacterial conjugation proteins and related DNA transfer proteins involved in type II and type IV secretion.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 116063568 149 DLDGLEKALQRAVFGQPAAVSRIVALMRDYLA--THVHSRPLLLALHGPSGVGKSHVGRLLAR 209
Cdd:cd19499    1 KLLNLEERLHERVVGQDEAVKAVSDAIRRARAglSDPNRPIGSFLFLGPTGVGKTELAKALAE 63

Torsin; This family consists of several eukaryotic torsin proteins. Torsion dystonia is an autosomal dominant movement disorder characterized by involuntary, repetitive muscle contractions and twisted postures. The most severe early-onset form of dystonia has been linked to mutations in the human DYT1 (TOR1A) gene encoding a protein termed torsinA. While causative genetic alterations have been identified, the function of torsin proteins and the molecular mechanism underlying dystonia remain unknown. Phylogenetic analysis of the torsin protein family indicates these proteins share distant sequence similarity with the large and diverse family of (pfam00004) proteins. It has been suggested that torsins play a role in effectively managing protein folding and that possible breakdown in a neuroprotective mechanism that is, in part, mediated by torsins may be responsible for the neuronal dysfunction associated with dystonia.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116063568  149 DLDGLEKALQRAVFGQPAAVSRIVALMRDYLATHVHSRPLLLALHGPSGVGKSHVGRLLARH-FRSVLEdSALVLQYHAR 227
Cdd:pfam06309   8 NYTGLERDLARRLFGQHLVKQLVVRSVKGHWENPKPRKPLVLSFHGWTGTGKNFVAEIIADNlYRDGLR-SDYVHHFVAT 86

                          90       100
                  ....*....|....*....|....*.
gi 116063568  228 HHCPEARAAQDCREELARRVADVVAR 253
Cdd:pfam06309  87 FHFPHPKYVELYKVELKNQIRGTLRA 112

ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116063568   186 RPLLLALHGPSGVGKSHVGRLLARHFRSVLEDSALV-----LQYHARHHCPEARAAQDCREELARRVADVVARAEaEEKT 260
Cdd:smart00382   1 PGEVILIVGPPGSGKTTLARALARELGPPGGGVIYIdgediLEEVLDQLLLIIVGGKKASGSGELRLRLALALAR-KLKP 79

                           90       100       110
                   ....*....|....*....|....*....|
gi 116063568   261 PLLVLDDVELMPRPLLDELHGFLQPQRSHH 290
Cdd:smart00382  80 DVLILDEITSLLDAEQEALLLLLEELRLLL 109

The AAA+ (ATPases Associated with a wide variety of cellular Activities) superfamily represents an ancient group of ATPases belonging to the ASCE (for additional strand, catalytic E) division of the P-loop NTPase fold. The ASCE division also includes ABC, RecA-like, VirD4-like, PilT-like, and SF1/2 helicases. Members of the AAA+ ATPases function as molecular chaperons, ATPase subunits of proteases, helicases, or nucleic-acid stimulated ATPases. The AAA+ proteins contain several distinct features in addition to the conserved alpha-beta-alpha core domain structure and the Walker A and B motifs of the P-loop NTPases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116063568 190 LALHGPSGVGKSHVGRLLARHfrsVLEDSALVLQYHARHHCPEARAAQDCREELARRVADVVARAeaeeKTPLLVLDDVE 269
Cdd:cd00009   22 LLLYGPPGTGKTTLARAIANE---LFRPGAPFLYLNASDLLEGLVVAELFGHFLVRLLFELAEKA----KPGVLFIDEID 94

                         90
                 ....*....|....*
gi 116063568 270 LMPRPLLDELHGFLQ 284
Cdd:cd00009   95 SLSRGAQNALLRVLE 109

Clp protease ATP binding subunit

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 116063568 153 LEKALQRAVFGQPAAVSRI-VALMRDYLATHVHSRPL---LLAlhGPSGVGKSHVGRLLARHF 211
Cdd:CHL00095 503 MEETLHKRIIGQDEAVVAVsKAIRRARVGLKNPNRPIasfLFS--GPTGVGKTELTKALASYF 563