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Conserved domains on  [gi|255304960|ref|NP_001157286|]
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twinkle mtDNA helicase isoform D [Homo sapiens]

Protein Classification

P-loop NTPase family protein( domain architecture ID 1562424)

P-loop NTPase (nucleoside triphosphate hydrolase) family protein contains two conserved sequence signatures, the Walker A motif (the P-loop proper) and Walker B motif which bind, respectively, the beta and gamma phosphate moieties of the bound nucleotide (typically ATP or GTP), and a Mg(2+) cation

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
P-loop_NTPase super family cl38936
P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain ...
 1-126 8.22e-79

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.


The actual alignment was detected with superfamily member cd01122:

Pssm-ID: 476819  Cd Length: 266  Bit Score: 232.90  E-value: 8.22e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960   1 MLTQFAEGRLEDQLDKYDHWADRFEDLPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAA 80
Cdd:cd01122   90 MLTQFAGKNLEDNLREFDEWADKFELLPMYFMKFHGSTDIDEVLDAMEHAVYVYDIQHIVIDNLQFMMGTQASGSDRFEL 169

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 255304960  81 QDYIIGVFRKFATDNNCHVTLVIHPRKEDDDKELQTASIFGSAKVS 126
Cdd:cd01122  170 QDLIIGKFRRFATNNNVHITLVIHPRKEDDDNELTTSSIFGSAKAT 215
 
Name Accession Description Interval E-value
Twinkle_C cd01122
C-terminal domain of Twinkle; Twinkle ( T7 gp4-like protein with intramitochondrial nucleoid ...
 1-126 8.22e-79

C-terminal domain of Twinkle; Twinkle ( T7 gp4-like protein with intramitochondrial nucleoid localization, also known as C10orf2, PEO1, SCA8, ATXN8, IOSCA, PEOA3 or SANDO) is a homohexameric DNA helicases which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. Mutations in the human gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. This group also contains viral GP4-like and related bacterial helicases.


Pssm-ID: 410867  Cd Length: 266  Bit Score: 232.90  E-value: 8.22e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960   1 MLTQFAEGRLEDQLDKYDHWADRFEDLPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAA 80
Cdd:cd01122   90 MLTQFAGKNLEDNLREFDEWADKFELLPMYFMKFHGSTDIDEVLDAMEHAVYVYDIQHIVIDNLQFMMGTQASGSDRFEL 169

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 255304960  81 QDYIIGVFRKFATDNNCHVTLVIHPRKEDDDKELQTASIFGSAKVS 126
Cdd:cd01122  170 QDLIIGKFRRFATNNNVHITLVIHPRKEDDDNELTTSSIFGSAKAT 215
AAA_25 pfam13481
AAA domain; This AAA domain is found in a wide variety of presumed DNA repair proteins.
 9-110 1.48e-12

AAA domain; This AAA domain is found in a wide variety of presumed DNA repair proteins.


Pssm-ID: 463892 [Multi-domain]  Cd Length: 193  Bit Score: 61.24  E-value: 1.48e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960    9 RLEDQLDKYDHWA-----DRFEDLPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAAqdy 83
Cdd:pfam13481  90 RLRAAGADLDLPArllflSLVESLPLFFLDRGGPLLDADVDALEAALEEVEDPDLVVIDPLARALGGDENSNSDVGR--- 166

                          90       100
                  ....*....|....*....|....*..
gi 255304960   84 IIGVFRKFATDNNCHVTLVIHPRKEDD 110
Cdd:pfam13481 167 LVKALDRLARRTGATVLLVHHVGKDGA 193
RepA COG3598
RecA-family ATPase [Replication, recombination and repair];
9-122 1.01e-06

RecA-family ATPase [Replication, recombination and repair];


Pssm-ID: 442817 [Multi-domain]  Cd Length: 313  Bit Score: 46.05  E-value: 1.01e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960   9 RLEDQLDKYDHWADRFEDlPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAAqdyIIGVF 88
Cdd:COG3598   68 RLKALGADLGLPFADLDG-RLRLLSLAGDLDDTDDLEALERAIEEEGPDLVVIDPLARVFGGDENDAEEMRA---FLNPL 143

                         90       100       110
                 ....*....|....*....|....*....|....
gi 255304960  89 RKFATDNNCHVTLVIHPRKeDDDKELQTASIFGS 122
Cdd:COG3598  144 DRLAERTGAAVLLVHHTGK-GGAGKDSGDRARGS 176
 
Name Accession Description Interval E-value
Twinkle_C cd01122
C-terminal domain of Twinkle; Twinkle ( T7 gp4-like protein with intramitochondrial nucleoid ...
 1-126 8.22e-79

C-terminal domain of Twinkle; Twinkle ( T7 gp4-like protein with intramitochondrial nucleoid localization, also known as C10orf2, PEO1, SCA8, ATXN8, IOSCA, PEOA3 or SANDO) is a homohexameric DNA helicases which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. Mutations in the human gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. This group also contains viral GP4-like and related bacterial helicases.


Pssm-ID: 410867  Cd Length: 266  Bit Score: 232.90  E-value: 8.22e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960   1 MLTQFAEGRLEDQLDKYDHWADRFEDLPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAA 80
Cdd:cd01122   90 MLTQFAGKNLEDNLREFDEWADKFELLPMYFMKFHGSTDIDEVLDAMEHAVYVYDIQHIVIDNLQFMMGTQASGSDRFEL 169

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 255304960  81 QDYIIGVFRKFATDNNCHVTLVIHPRKEDDDKELQTASIFGSAKVS 126
Cdd:cd01122  170 QDLIIGKFRRFATNNNVHITLVIHPRKEDDDNELTTSSIFGSAKAT 215
AAA_25 pfam13481
AAA domain; This AAA domain is found in a wide variety of presumed DNA repair proteins.
 9-110 1.48e-12

AAA domain; This AAA domain is found in a wide variety of presumed DNA repair proteins.


Pssm-ID: 463892 [Multi-domain]  Cd Length: 193  Bit Score: 61.24  E-value: 1.48e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960    9 RLEDQLDKYDHWA-----DRFEDLPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAAqdy 83
Cdd:pfam13481  90 RLRAAGADLDLPArllflSLVESLPLFFLDRGGPLLDADVDALEAALEEVEDPDLVVIDPLARALGGDENSNSDVGR--- 166

                          90       100
                  ....*....|....*....|....*..
gi 255304960   84 IIGVFRKFATDNNCHVTLVIHPRKEDD 110
Cdd:pfam13481 167 LVKALDRLARRTGATVLLVHHVGKDGA 193
RecA-like_superfamily cd01120
RecA-like_NTPases; RecA-like NTPases. This superfamily includes the NTP binding domain of F1 ...
 44-125 1.76e-11

RecA-like_NTPases; RecA-like NTPases. This superfamily 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. This group also includes bacterial conjugation proteins and related DNA transfer proteins involved in type II and type IV secretion.


Pssm-ID: 410865 [Multi-domain]  Cd Length: 119  Bit Score: 56.74  E-value: 1.76e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960  44 IDTMQHAVYV----YDICHVIIDNLQFMMGHEQlsTDRIAAQDYIIGVFRKFATDNNCHVTLVIHPRKEDDDKELQTASI 119
Cdd:cd01120   35 LDTILEAIEDlieeKKLDIIIIDSLSSLARASQ--GDRSSELLEDLAKLLRAARNTGITVIATIHSDKFDIDRGGSSNDE 112


                 ....*.
gi 255304960 120 FGSAKV 125
Cdd:cd01120  113 RLLKSL 118
RepA COG3598
RecA-family ATPase [Replication, recombination and repair];
9-122 1.01e-06

RecA-family ATPase [Replication, recombination and repair];


Pssm-ID: 442817 [Multi-domain]  Cd Length: 313  Bit Score: 46.05  E-value: 1.01e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960   9 RLEDQLDKYDHWADRFEDlPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAAqdyIIGVF 88
Cdd:COG3598   68 RLKALGADLGLPFADLDG-RLRLLSLAGDLDDTDDLEALERAIEEEGPDLVVIDPLARVFGGDENDAEEMRA---FLNPL 143

                         90       100       110
                 ....*....|....*....|....*....|....
gi 255304960  89 RKFATDNNCHVTLVIHPRKeDDDKELQTASIFGS 122
Cdd:COG3598  144 DRLAERTGAAVLLVHHTGK-GGAGKDSGDRARGS 176
RecA-like_Gp4D_helicase cd19483
RecA-like domain of Escherichia coli bacteriophage T7 Gp4D helicase; This family includes the ...
 29-112 2.86e-03

RecA-like domain of Escherichia coli bacteriophage T7 Gp4D helicase; This family includes the RecA-like domain of the Gp4D fragment of the Gene4 helicase-primase (Gp4) from bacteriophage T7. Gp4D (residues 241-566) is the minimal fragment of the Gp4 that forms hexameric rings, it contains the helicase domain and the linker connecting the helicase and primase domains. Helicases are ring-shaped oligomeric enzymes that unwind DNA at the replication fork; they couple NTP hydrolysis to the unwinding of nucleic acid duplexes into their component strands. This family belongs to the RecA-like NTPase superfamily 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.


Pssm-ID: 410891 [Multi-domain]  Cd Length: 231  Bit Score: 36.01  E-value: 2.86e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255304960  29 LYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQfMMGHEQLSTDRIAAQDYIIGVFRKFATDNNCHVTLVIHPRKE 108
Cdd:cd19483   82 FFLYDHFGSLDWDNLKEKIRYMVKVLGCKVIVLDHLT-ILVSGLDSSDERKELDEIMTELAALVKELGVTIILVSHLRRP 160


                 ....
gi 255304960 109 DDDK 112
Cdd:cd19483  161 GGGK 164
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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