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Conserved domains on  [gi|594591577|ref|NP_001277584|]
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activator of 90 kDa heat shock protein ATPase homolog 2 isoform 3 [Mus musculus]

Protein Classification

activator of 90 kDa heat shock protein ATPase homolog( domain architecture ID 10659696)

activator of 90 kDa heat shock protein ATPase homolog is a co-chaperone that regulates the dimeric chaperone Hsp90, and may act as either a negative or positive regulator of chaperone-dependent activation

Gene Ontology:  GO:0051087|GO:0032781|GO:0006457|GO:0001671|GO:0051879
PubMed:  12504007|12604615

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Aha1_N smart01000
Activator of Hsp90 ATPase, N-terminal; This domain is predominantly found in the protein ...
 29-158 3.11e-53

Activator of Hsp90 ATPase, N-terminal; This domain is predominantly found in the protein 'Activator of Hsp90 ATPase', it adopts a secondary structure consisting of an N-terminal alpha-helix leading into a four-stranded meandering antiparallel beta-sheet, followed by a C-terminal alpha-helix. The two helices are packed together, with the beta-sheet curving around them. They bind to the molecular chaperone HSP82 and stimulate its ATPase activity.


:

Pssm-ID: 214964  Cd Length: 134  Bit Score: 169.75  E-value: 3.11e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594591577    29 ERDATIWSKGKLRELLVGIA--MENEAGRCEISELKQVEGEASCNSRKGKLIFFYEWNIKLAWKGTVKESGAKHKGLIEI 106
Cdd:smart01000   1 EKDCTPWAKEYLKELLVGLKisSEDEEGKIEISSVSSVSGDASVSQRKGKLICLYDLKITLKWSGTVAKDGKKVKGSIEI 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 594591577   107 PSLSEENEINDTEVNVSKKKGDGEI--LKDLMRTTGTAKVREALGEYLKALKTE 158
Cdd:smart01000  81 PELSHDNEEDDYQFEISITKDKEEKleLKDLVRKKGVPKLREALGKFQKELLTE 134
SRPBCC super family cl14643
START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily; SRPBCC ...
 202-274 6.26e-34

START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily; SRPBCC domains have a deep hydrophobic ligand-binding pocket; they bind diverse ligands. Included in this superfamily are the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD1-STARD15, and the C-terminal catalytic domains of the alpha oxygenase subunit of Rieske-type non-heme iron aromatic ring-hydroxylating oxygenases (RHOs_alpha_C), as well as the SRPBCC domains of phosphatidylinositol transfer proteins (PITPs), Bet v 1 (the major pollen allergen of white birch, Betula verrucosa), CoxG, CalC, and related proteins. Other members of this superfamily include PYR/PYL/RCAR plant proteins, the aromatase/cyclase (ARO/CYC) domains of proteins such as Streptomyces glaucescens tetracenomycin, and the SRPBCC domains of Streptococcus mutans Smu.440 and related proteins.


The actual alignment was detected with superfamily member cd08892:

Pssm-ID: 472699 [Multi-domain]  Cd Length: 126  Bit Score: 119.97  E-value: 6.26e-34
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 594591577 202 LHLTELFDTTVEQLYSIFTVKELVQKFSKSPAVLEAERGGKFQMFDGNISGEYVELVTNRKIIMKWRCRNWPE 274
Cdd:cd08892    2 ISLTETFQVPAEELYEALTDEERVQAFTRSPAKVDAKVGGKFSLFGGNITGEFVELVPGKKIVQKWRFKSWPE 74
 
Name Accession Description Interval E-value
Aha1_N smart01000
Activator of Hsp90 ATPase, N-terminal; This domain is predominantly found in the protein ...
 29-158 3.11e-53

Activator of Hsp90 ATPase, N-terminal; This domain is predominantly found in the protein 'Activator of Hsp90 ATPase', it adopts a secondary structure consisting of an N-terminal alpha-helix leading into a four-stranded meandering antiparallel beta-sheet, followed by a C-terminal alpha-helix. The two helices are packed together, with the beta-sheet curving around them. They bind to the molecular chaperone HSP82 and stimulate its ATPase activity.


Pssm-ID: 214964  Cd Length: 134  Bit Score: 169.75  E-value: 3.11e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594591577    29 ERDATIWSKGKLRELLVGIA--MENEAGRCEISELKQVEGEASCNSRKGKLIFFYEWNIKLAWKGTVKESGAKHKGLIEI 106
Cdd:smart01000   1 EKDCTPWAKEYLKELLVGLKisSEDEEGKIEISSVSSVSGDASVSQRKGKLICLYDLKITLKWSGTVAKDGKKVKGSIEI 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 594591577   107 PSLSEENEINDTEVNVSKKKGDGEI--LKDLMRTTGTAKVREALGEYLKALKTE 158
Cdd:smart01000  81 PELSHDNEEDDYQFEISITKDKEEKleLKDLVRKKGVPKLREALGKFQKELLTE 134
Aha1_N pfam09229
Activator of Hsp90 ATPase, N-terminal; Members of this family, which are predominantly found ...
 29-159 1.79e-45

Activator of Hsp90 ATPase, N-terminal; Members of this family, which are predominantly found in the protein 'Activator of Hsp90 ATPase' adopt a secondary structure consisting of an N-terminal alpha-helix leading into a four-stranded meandering antiparallel beta-sheet, followed by a C-terminal alpha-helix. The two helices are packed together, with the beta-sheet curving around them. They bind to the molecular chaperone HSP82 and stimulate its ATPase activity.


Pssm-ID: 462716  Cd Length: 134  Bit Score: 150.01  E-value: 1.79e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594591577   29 ERDATIWSKGKLRELLVGIAMEN-EAGRCEISELKQVEGEASCNSRKGKLIFFYEWNIKLAWKGTVKESGAKHKGLIEIP 107
Cdd:pfam09229   1 EKNCTPWAKEYLKELLLGLEIEGdEGKSVKITEVSSVEGDASVNQRKGKVITIYDLKLTLEWEGTTKEDGEEVKGTITIP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 594591577  108 SLSEENEINDTEVNVS--KKKGDGEILKDLMRTTGTAKVREALGEYLKALKTEF 159
Cdd:pfam09229  81 ELSHDNEDDEYEFEVSvyDESKEKDKLKDLVRKKLVPKLREKLAKFVKELIEEH 134
SRPBCC_Aha1 cd08892
Putative hydrophobic ligand-binding SRPBCC domain of the Hsp90 co-chaperone Aha1 and related ...
 202-274 6.26e-34

Putative hydrophobic ligand-binding SRPBCC domain of the Hsp90 co-chaperone Aha1 and related proteins; This subfamily includes the C-terminal SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain of Aha1, and related domains. Proteins in this group belong to the SRPBCC domain superfamily of proteins which bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. Aha1 is one of several co-chaperones, which regulate the dimeric chaperone Hsp90. Hsp90, Aha1, and other accessory proteins interact in a chaperone cycle driven by ATP binding and hydrolysis. Aha1 promotes dimerization of the N-terminal domains of Hsp90, and stimulates its low intrinsic ATPase activity. One Aha1 molecule binds per Hsp90 dimer. The N- and C- terminal domains of Aha1 cooperatively bind across the dimer interface of Hsp90. The C-terminal domain of Aha1 binds the N-terminal Hsp90 ATPase domain. Aha1 may regulate the dwell time of Hsp90 with client proteins. Aha1 may act as either a negative or positive regulator of chaperone-dependent activation, depending on the client protein; for example, it acts as a negative regulator in the case of Saccharomyces cerevisiae MAL63 MAL-activator, and acts as a positive regulator in the case of glucocorticoid receptor and v-Src kinase. The mechanisms by which these opposing functions are achieved are unclear. Aha1 is upregulated in a number of tumor lines co-incident with the activation of several signaling kinases.


Pssm-ID: 176901 [Multi-domain]  Cd Length: 126  Bit Score: 119.97  E-value: 6.26e-34
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 594591577 202 LHLTELFDTTVEQLYSIFTVKELVQKFSKSPAVLEAERGGKFQMFDGNISGEYVELVTNRKIIMKWRCRNWPE 274
Cdd:cd08892    2 ISLTETFQVPAEELYEALTDEERVQAFTRSPAKVDAKVGGKFSLFGGNITGEFVELVPGKKIVQKWRFKSWPE 74
PTZ00220 PTZ00220
Activator of HSP-90 ATPase; Provisional
 213-274 6.68e-11

Activator of HSP-90 ATPase; Provisional


Pssm-ID: 173484  Cd Length: 132  Bit Score: 58.68  E-value: 6.68e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 594591577 213 EQLYSIFTVKELVQKFSK-SPAVLEAERGGKFQMFDGNISGEYVELVTNRKIIMKWRCRNWPE 274
Cdd:PTZ00220   6 EVLYNAFLDAYTLTRLSLgSPAEMDAKVGGKFSLFNGSVEGEFTELEKPKKIVQKWRFRDWEE 68
AHSA1 pfam08327
Activator of Hsp90 ATPase homolog 1-like protein; This family includes eukaryotic, prokaryotic ...
 209-274 1.97e-09

Activator of Hsp90 ATPase homolog 1-like protein; This family includes eukaryotic, prokaryotic and archaeal proteins that bear similarity to a C-terminal region of human activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1/p38). This protein is known to interact with the middle domain of Hsp90, and stimulate its ATPase activity. It is probably a general upregulator of Hsp90 function, particularly contributing to its efficiency in conditions of increased stress. p38 is also known to interact with the cytoplasmic domain of the VSV G protein, and may thus be involved in protein transport. It has also been reported as being underexpressed in Down's syndrome. This region is found repeated in two members of this family (Swiss:Q8XY04 and Swiss:Q6MH87). The structure of YndB from Bacillus subtilis showed the helix-grip fold consisting of a beta-sheet with two small and one long alpha-helix which form a hydrophobic cavity that preferentially binds lipid-like molecules. This structure confirms its similarity with the eukaryote protein Aha1 and its classification as a member of the AHSA1 family).


Pssm-ID: 429921 [Multi-domain]  Cd Length: 125  Bit Score: 54.63  E-value: 1.97e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 594591577  209 DTTVEQLYSIFTVKELVQK-FSKSPAVLEAERGGKFQMFDGN------ISGEYVELVTNRKIIMKWRCRNWPE 274
Cdd:pfam08327   1 DAPPERVFRALTDPELLARwFTRTVAEMDLRPGGKFRFMRGPdgeefgGNGTYLELVPPKRIVYTWRLDDWPE 73
YndB COG3832
Chalcone/flavanone-binding protein YndB, AHSA1/START/SRPBCC domain [Lipid transport and ...
 202-275 5.36e-03

Chalcone/flavanone-binding protein YndB, AHSA1/START/SRPBCC domain [Lipid transport and metabolism];


Pssm-ID: 443044 [Multi-domain]  Cd Length: 142  Bit Score: 36.55  E-value: 5.36e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594591577 202 LHLTELFDTTVEQLYSIFTVKELVQKF-----SKSPAVLEAERGGKFQM----FDGN---ISGEYVELVTNRKIIMKWRC 269
Cdd:COG3832    8 ITIEREIDAPPERVWRAWTDPELLARWfgpkgWATVAEFDLRVGGRFRFrmrgPDGEefgFEGEVLEVEPPERLVFTWGF 87


                 ....*.
gi 594591577 270 RNWPEA 275
Cdd:COG3832   88 EDDPEG 93
 
Name Accession Description Interval E-value
Aha1_N smart01000
Activator of Hsp90 ATPase, N-terminal; This domain is predominantly found in the protein ...
 29-158 3.11e-53

Activator of Hsp90 ATPase, N-terminal; This domain is predominantly found in the protein 'Activator of Hsp90 ATPase', it adopts a secondary structure consisting of an N-terminal alpha-helix leading into a four-stranded meandering antiparallel beta-sheet, followed by a C-terminal alpha-helix. The two helices are packed together, with the beta-sheet curving around them. They bind to the molecular chaperone HSP82 and stimulate its ATPase activity.


Pssm-ID: 214964  Cd Length: 134  Bit Score: 169.75  E-value: 3.11e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594591577    29 ERDATIWSKGKLRELLVGIA--MENEAGRCEISELKQVEGEASCNSRKGKLIFFYEWNIKLAWKGTVKESGAKHKGLIEI 106
Cdd:smart01000   1 EKDCTPWAKEYLKELLVGLKisSEDEEGKIEISSVSSVSGDASVSQRKGKLICLYDLKITLKWSGTVAKDGKKVKGSIEI 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 594591577   107 PSLSEENEINDTEVNVSKKKGDGEI--LKDLMRTTGTAKVREALGEYLKALKTE 158
Cdd:smart01000  81 PELSHDNEEDDYQFEISITKDKEEKleLKDLVRKKGVPKLREALGKFQKELLTE 134
Aha1_N pfam09229
Activator of Hsp90 ATPase, N-terminal; Members of this family, which are predominantly found ...
 29-159 1.79e-45

Activator of Hsp90 ATPase, N-terminal; Members of this family, which are predominantly found in the protein 'Activator of Hsp90 ATPase' adopt a secondary structure consisting of an N-terminal alpha-helix leading into a four-stranded meandering antiparallel beta-sheet, followed by a C-terminal alpha-helix. The two helices are packed together, with the beta-sheet curving around them. They bind to the molecular chaperone HSP82 and stimulate its ATPase activity.


Pssm-ID: 462716  Cd Length: 134  Bit Score: 150.01  E-value: 1.79e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594591577   29 ERDATIWSKGKLRELLVGIAMEN-EAGRCEISELKQVEGEASCNSRKGKLIFFYEWNIKLAWKGTVKESGAKHKGLIEIP 107
Cdd:pfam09229   1 EKNCTPWAKEYLKELLLGLEIEGdEGKSVKITEVSSVEGDASVNQRKGKVITIYDLKLTLEWEGTTKEDGEEVKGTITIP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 594591577  108 SLSEENEINDTEVNVS--KKKGDGEILKDLMRTTGTAKVREALGEYLKALKTEF 159
Cdd:pfam09229  81 ELSHDNEDDEYEFEVSvyDESKEKDKLKDLVRKKLVPKLREKLAKFVKELIEEH 134
SRPBCC_Aha1 cd08892
Putative hydrophobic ligand-binding SRPBCC domain of the Hsp90 co-chaperone Aha1 and related ...
 202-274 6.26e-34

Putative hydrophobic ligand-binding SRPBCC domain of the Hsp90 co-chaperone Aha1 and related proteins; This subfamily includes the C-terminal SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain of Aha1, and related domains. Proteins in this group belong to the SRPBCC domain superfamily of proteins which bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. Aha1 is one of several co-chaperones, which regulate the dimeric chaperone Hsp90. Hsp90, Aha1, and other accessory proteins interact in a chaperone cycle driven by ATP binding and hydrolysis. Aha1 promotes dimerization of the N-terminal domains of Hsp90, and stimulates its low intrinsic ATPase activity. One Aha1 molecule binds per Hsp90 dimer. The N- and C- terminal domains of Aha1 cooperatively bind across the dimer interface of Hsp90. The C-terminal domain of Aha1 binds the N-terminal Hsp90 ATPase domain. Aha1 may regulate the dwell time of Hsp90 with client proteins. Aha1 may act as either a negative or positive regulator of chaperone-dependent activation, depending on the client protein; for example, it acts as a negative regulator in the case of Saccharomyces cerevisiae MAL63 MAL-activator, and acts as a positive regulator in the case of glucocorticoid receptor and v-Src kinase. The mechanisms by which these opposing functions are achieved are unclear. Aha1 is upregulated in a number of tumor lines co-incident with the activation of several signaling kinases.


Pssm-ID: 176901 [Multi-domain]  Cd Length: 126  Bit Score: 119.97  E-value: 6.26e-34
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 594591577 202 LHLTELFDTTVEQLYSIFTVKELVQKFSKSPAVLEAERGGKFQMFDGNISGEYVELVTNRKIIMKWRCRNWPE 274
Cdd:cd08892    2 ISLTETFQVPAEELYEALTDEERVQAFTRSPAKVDAKVGGKFSLFGGNITGEFVELVPGKKIVQKWRFKSWPE 74
PTZ00220 PTZ00220
Activator of HSP-90 ATPase; Provisional
 213-274 6.68e-11

Activator of HSP-90 ATPase; Provisional


Pssm-ID: 173484  Cd Length: 132  Bit Score: 58.68  E-value: 6.68e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 594591577 213 EQLYSIFTVKELVQKFSK-SPAVLEAERGGKFQMFDGNISGEYVELVTNRKIIMKWRCRNWPE 274
Cdd:PTZ00220   6 EVLYNAFLDAYTLTRLSLgSPAEMDAKVGGKFSLFNGSVEGEFTELEKPKKIVQKWRFRDWEE 68
AHSA1 pfam08327
Activator of Hsp90 ATPase homolog 1-like protein; This family includes eukaryotic, prokaryotic ...
 209-274 1.97e-09

Activator of Hsp90 ATPase homolog 1-like protein; This family includes eukaryotic, prokaryotic and archaeal proteins that bear similarity to a C-terminal region of human activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1/p38). This protein is known to interact with the middle domain of Hsp90, and stimulate its ATPase activity. It is probably a general upregulator of Hsp90 function, particularly contributing to its efficiency in conditions of increased stress. p38 is also known to interact with the cytoplasmic domain of the VSV G protein, and may thus be involved in protein transport. It has also been reported as being underexpressed in Down's syndrome. This region is found repeated in two members of this family (Swiss:Q8XY04 and Swiss:Q6MH87). The structure of YndB from Bacillus subtilis showed the helix-grip fold consisting of a beta-sheet with two small and one long alpha-helix which form a hydrophobic cavity that preferentially binds lipid-like molecules. This structure confirms its similarity with the eukaryote protein Aha1 and its classification as a member of the AHSA1 family).


Pssm-ID: 429921 [Multi-domain]  Cd Length: 125  Bit Score: 54.63  E-value: 1.97e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 594591577  209 DTTVEQLYSIFTVKELVQK-FSKSPAVLEAERGGKFQMFDGN------ISGEYVELVTNRKIIMKWRCRNWPE 274
Cdd:pfam08327   1 DAPPERVFRALTDPELLARwFTRTVAEMDLRPGGKFRFMRGPdgeefgGNGTYLELVPPKRIVYTWRLDDWPE 73
YndB COG3832
Chalcone/flavanone-binding protein YndB, AHSA1/START/SRPBCC domain [Lipid transport and ...
 202-275 5.36e-03

Chalcone/flavanone-binding protein YndB, AHSA1/START/SRPBCC domain [Lipid transport and metabolism];


Pssm-ID: 443044 [Multi-domain]  Cd Length: 142  Bit Score: 36.55  E-value: 5.36e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 594591577 202 LHLTELFDTTVEQLYSIFTVKELVQKF-----SKSPAVLEAERGGKFQM----FDGN---ISGEYVELVTNRKIIMKWRC 269
Cdd:COG3832    8 ITIEREIDAPPERVWRAWTDPELLARWfgpkgWATVAEFDLRVGGRFRFrmrgPDGEefgFEGEVLEVEPPERLVFTWGF 87


                 ....*.
gi 594591577 270 RNWPEA 275
Cdd:COG3832   88 EDDPEG 93
 
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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