Conserved Protein Domain Family
HSPA1-2_6-8-like_NBD

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cd10233: HSPA1-2_6-8-like_NBD 
Click on image for an interactive view with Cn3D
Nucleotide-binding domain of HSPA1-A, -B, -L, HSPA-2, -6, -7, -8, and similar proteins
This subfamily includes human HSPA1A (70-kDa heat shock protein 1A, also known as HSP72; HSPA1; HSP70I; HSPA1B; HSP70-1; HSP70-1A), HSPA1B (70-kDa heat shock protein 1B, also known as HSPA1A; HSP70-2; HSP70-1B), and HSPA1L (70-kDa heat shock protein 1-like, also known as HSP70T; hum70t; HSP70-1L; HSP70-HOM). The genes for these three HSPA1 proteins map in close proximity on the major histocompatibility complex (MHC) class III region on chromosome 6, 6p21.3. This subfamily also includes human HSPA8 (heat shock 70kDa protein 8, also known as LAP1; HSC54; HSC70; HSC71; HSP71; HSP73; NIP71; HSPA10; the HSPA8 gene maps to 11q24.1), human HSPA2 (70-kDa heat shock protein 2, also known as HSP70-2; HSP70-3, the HSPA2 gene maps to 14q24.1), human HSPA6 (also known as heat shock 70kDa protein 6 (HSP70B') gi 94717614, the HSPA6 gene maps to 1q23.3), human HSPA7 (heat shock 70kDa protein 7 , also known as HSP70B; the HSPA7 gene maps to 1q23.3) and Saccharmoyces cerevisiae Stress-Seventy subfamily B/Ssb1p. This subfamily belongs to the heat shock protein 70 (HSP70) family of chaperones that assist in protein folding and assembly and can direct incompetent "client" proteins towards degradation. Typically, HSP70s have a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. The two subdomains of each lobe change conformation between ATP-bound, ADP-bound, and nucleotide-free states. ATP binding opens up the substrate-binding site; substrate-binding increases the rate of ATP hydrolysis. HSP70 chaperone activity is regulated by various co-chaperones: J-domain proteins and nucleotide exchange factors (NEFs). Associations of polymorphisms within the MHC-III HSP70 gene locus with longevity, systemic lupus erythematosus, Meniere's disease, noise-induced hearing loss, high-altitude pulmonary edema, and coronary heart disease, have been found. HSPA2 is involved in cancer cell survival, is required for maturation of male gametophytes, and is linked to male infertility. The induction of HSPA6 is a biomarker of cellular stress. HSPA8 participates in the folding and trafficking of client proteins to different subcellular compartments, and in the signal transduction and apoptosis process; it has been shown to protect cardiomyocytes against oxidative stress partly through an interaction with alpha-enolase. S. cerevisiae Ssb1p, is part of the ribosome-associated complex (RAC), it acts as a chaperone for nascent polypeptides, and is important for translation fidelity; Ssb1p is also a [PSI+] prion-curing factor.
BioAssay Targets and Results
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CID: 274127
AID: 1193
GI: 5729877
IC50: 3.98µM
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In Vitro Hsc70 Dose Response Fluorescence Polarization Assay
Chemical Name: NSC119915
IC50: 3.98µM
CID: 16654696
AID: 1193
GI: 5729877
IC50: 0.28µM
more
In Vitro Hsc70 Dose Response Fluorescence Polarization Assay
Chemical Name: Adenosine 5'-diphosphate
IC50: 0.28µM
CID: 54686376
AID: 1193
GI: 5729877
IC50: 2.73µM
more
In Vitro Hsc70 Dose Response Fluorescence Polarization Assay
Chemical Name: AC1NS1JN
IC50: 2.73µM
Statistics
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PSSM-Id: 212675
View PSSM: cd10233
Aligned: 53 rows
Threshold Bit Score: 754.563
Threshold Setting Gi: 225734321
Created: 6-Oct-2006
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
Hierarchy
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Display:
 
Conserved site includes 27 residues -Click on image for an interactive view with Cn3D
Feature 1:nucleotide binding site [chemical binding site]
Evidence:

cd10233 is part of a hierarchy of related CD models.
Use the graphical representation to navigate this hierarchy.
cd10233 is a member of the superfamily cl17037.
cd00012:NBD_sugar-kinase_HSP70_actincd00366:FGGYcd07768:FGGY_RBK_likecd07769:FGGY_GKcd07770:FGGY_GntKcd07771:FGGY_RhuKcd07772:FGGY_NaCK_likecd07773:FGGY_FKcd07774:FGGY_1cd07775:FGGY_AI-2Kcd07776:FGGY_D-XK_eukcd07777:FGGY_SHK_likecd07778:FGGY_L-RBK_likecd07779:FGGY_ygcE_likecd07781:FGGY_RBKcd07782:FGGY_YpCarbK_likecd07783:FGGY_CarbK-RPE_likecd07786:FGGY_EcGK_likecd07789:FGGY_CsGK_likecd07791:FGGY_GK2_bacteriacd07792:FGGY_GK1-3_metazoacd07793:FGGY_GK5_metazoacd07794:FGGY_GK_like_proteobactcd07795:FGGY_ScGut1p_likecd07796:FGGY_NHO1_plantcd07798:FGGY_AI-2K_likecd07802:FGGY_L-XKcd07803:FGGY_D-XKcd07804:FGGY_XK_like_1cd07805:FGGY_XK_like_2cd07808:FGGY_D-XK_EcXK-likecd07809:FGGY_D-XK_1cd07810:FGGY_D-XK_2cd07811:FGGY_D-XK_3cd10170:HSP70_NBDcd10225:MreB_likecd10227:ParM_likecd10228:HSPA4_like_NDBcd10229:HSPA12_like_NBDcd10230:HYOU1-like_NBDcd10231:YegD_likecd10232:ScSsz1p_like_NBDcd10233:HSPA1-2_6-8-like_NBDcd10234:HSPA9-Ssq1-like_NBDcd10235:HscC_like_NBDcd10236:HscA_like_NBDcd10237:HSPA13-like_NBDcd10238:HSPA14-like_NBDcd10241:HSPA5-like_NBDcd10427:FGGY_GK_1cd11732:HSP105-110_like_NBDcd11733:HSPA9-like_NBDcd11734:Ssq1_like_NBDcd11735:HSPA12A_like_NBDcd11736:HSPA12B_like_NBDcd11737:HSPA4_NBDcd11738:HSPA4L_NBDcd11739:HSPH1_NBD3KVG A123598748306841219085853GL1 A1986294115895612363320659811814864684914891069616268900412643273226517932246384601170370220973284256032242585270468014748967444098874249535930581061252928954768176253828513387533214709283A8Y A2E8A A1S3X A14774456511962393212360494717614347848322663083999391564542742162965432154940473I33 A17083072292883333016162572495341453843701YUW A2V7Z A3CQX A3C7N B167417273KVG A123598748306841219085853GL1 A1986294115895612363320659811814864684914891069616268900412643273226517932246384601170370220973284256032242585270468014748967444098874249535930581061252928954768176253828513387533214709283A8Y A2E8A A1S3X A14774456511962393212360494717614347848322663083999391564542742162965432154940473I33 A17083072292883333016162572495341453843701YUW A2V7Z A3CQX A3C7N B16741727
cd10233 Sequence Cluster
cd10233 Sequence Cluster
Sub-family Hierarchy
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 cd10233 Branch
 Whole Hierarchy
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CD Hierarchy
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1            # ####                                                       #              
1YUW_A         6 AVGIDLGTTYSCVGVFQHgKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQS 85
2V7Z_A         6 AVGIDLGTTYSCVGVFQHgKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQS 85
gi 148646849   5 AIGIDLGTTYSCVGLWQHdRVEIIPNEQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPINTVFDAKRLIGRKFSDPTVQH 84
gi 148910696   8 AIGIDLGTTYSCVGVWQHdRVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFSDPTVQN 87
gi 162689004   9 AIGIDLGTTYSCVGVWQHdRVEIIANDQGNRTTPSYVAFTDSERLIGDAAKNQVAMNPINTVFDAKRLIGRRFSDASVQS 88
gi 12643273    9 AIGIDLGTTYSCVGVWQHdRVEIIANDQGNRTTPSYVAFTDSERLIGDAAKNQVAMNPVNTVFDAKRLIGRRFSDSSVQS 88
gi 1170370     8 SVGIDLGTTYSCVGVWQNdRVEIIANDQGNRTTPSYVAFTDSERLIGDAAKNQVAMNPANTVFDAKRLIGRKFNDPATQA 87
gi 226517932   8 AIGIDLGTTYSCVGVWQHdRVEIIANDQGNRTTPSYVAFTDSERLIGDAAKNQTAMNPKNTVFDAKRMIGRKFSDPQIQA 87
gi 256032242  12 SIGIDLGTTYSCVGIWQNdRVEIIANDQGNRTTPSFVAFTDSERLIGDSAKNQVAINATNTVFDAKRMIGRKFSDPSVQQ 91
gi 585270      9 AIGIDLGTTYSCVGVWLHdRVEVIANDQGNRTTPSYVAFTETERLIGDSAKNQVAMNPDNTVFDAKRLIGRRFQDPAVQE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                        #               
1YUW_A        86 DMKHWPFMVVNDAGRPKVQV-EYKGETKSFYPEEVSSMVLTKMKEIAEAYLG--KTVTNAVVTVPAYFNDSQRQATKDAG 162
2V7Z_A        86 DMKHWPFMVVNDAGRPKVQV-EYKGETKSFYPEEVSSMVLTKMKEIAEAYLG--KTVTNAVVTVPAYFNDSQRQAAKDAG 162
gi 148646849  85 DISHWPFKVVSGPGDKPMIQvSHKGEEKTFAPEEISSMVLVKMKEIAQAYVGadKEVKKAVVTVPAYFNDSQRQATKDAG 164
gi 148910696  88 DMKLWPFKVISGPAEKPMIVvSYKGEDKQFAAEEISSMVLTKMKEIAEAYLG--TTIKNAVVTVPAYFNDSQRQATKDAG 165
gi 162689004  89 DMKLWPFKITPGPGEKPMISvQYKGEEKTFAAEEISSMVLIKMKEIAEAYLG--STVKNAVVTVPAYFNDSQRQATKDAG 166
gi 12643273   89 DMKLWPFKIQAGPADKPMIYvEYKGEEKEFAAEEISSMVLIKMREIAEAYLG--VTIKNAVVTVPAYFNDSQRQATKDAG 166
gi 1170370    88 DIKHWPFKVTPGAGDKPQITvEFKGETKTFQPEEISSMVLIKMKEVAEAFIG--TAVNNAVITVPAYFNDSQRQATKDAG 165
gi 226517932  88 DIKDWSYTVVCGEAEKPMIQvEFHGEEKKFSAEEISSMILVKMKEIAEAYLG--KEIKNAVVTVPAYFNDSQRQATKDAA 165
gi 256032242  92 DMKHFSFKVVQKEGDKPVVEvQYKGETKQFSPEEISAMVLSKMREVAESYLG--KEVKTAVVTVPAYFNDSQRLATKDAG 169
gi 585270     89 DVKPFPFKVICKDGDKPAVEvKYKGETKIFAPEEISSMVLLKMKEIAESFLG--KEVKNAVITVPAYFNDSQRQATKDAG 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    #                           ###### #                       ##       
1YUW_A       163 TIAGLNVLRIINEPTAAAIAYGLDKKv----gAERNVLIFDLGGGTFDVSILTIAAGIFEVKSTAGDTHLGGEDFDNRMV 238
2V7Z_A       163 TIAGLNVLRIINEPTAAAIAYGLDKKv----rAERNVLIFDLGGGTFDVSILTTEDGIFEVKSTAGDTHLGGEDFDNRMV 238
gi 148646849 165 VIAGLEVMRIINEPTAAAIAYGLDKKgt--tsGEQNVLIFDLGGGTFDVSLLTIEEGIFEVKATAGDTHLGGEDFDNRLV 242
gi 148910696 166 VISGLNVMRIINEPTAAAIAYGLDKKat--svGEKNVLIFDLGGGTFDVSLLTIEEGIFEVKATAGDTHLGGEDFDNRLV 243
gi 162689004 167 VIAGLNVLRIINEPTAAAIAYGLDKKat--svGEKNVLIFDLGGGTFDVSLLTIEEGIFEVKATAGDTHLGGEDFDNRMV 244
gi 12643273  167 VIAGLNVMRIINEPTAAAIAYGLDKKat--svGEKNVLIFDLGGGTFDVSLLTIEEGIFEVKATAGDTHLGGEDFDNRMV 244
gi 1170370   166 AIAGLNVLRIINEPTRAAIAYGLDKKg-----GERNVLIFDLGGGTFDVSLLTIEEGIFEVKATAGDTHLGGEDFDNRLV 240
gi 226517932 166 VIAGINCMRIINEPTAAAIAYGLDKKdqn-ggAERNVLIFDLGGGTFDVSLLTIEEGIFEVKATAGDTHLGGEDFDQRLM 244
gi 256032242 170 TIAGLHVSRIINEPTAAAIAYGLDRKtagdtaLERTVLIFDLGGGTFDVSLLSIEDGIFEVKATAGDTHLGGEDFDNRLV 249
gi 585270    167 AITGLNVLRIINEPTAAAIAYGLDKKtsg-skSERNVLIFDLGGGTFDVSLLTIEEGIFEVKATAGDTHLGGEDFDSRLV 245
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                     #  ##  #                                           
1YUW_A       239 NHFIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVE 318
2V7Z_A       239 NHFIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVE 318
gi 148646849 243 NFFVQEFKRKHRKDISSNPRALRRLRTSCERAKRTLSSSTQASIEIDSLYEGIDFYSSITRARFEELNMDLFRKCMEPVE 322
gi 148910696 244 NHFTQEFKRKYKKDLSSSARALRRLRTACERAKRTLSSTAQTTIEIDSLYEGIDFYSTITRARFEELNMDLFRKCMEPVE 323
gi 162689004 245 NHFVQEFKRKYKKDIGSNPRALRRLRTAAERAKRTLSSTAQTTIEIDSLYEGVDFYSTITRARFEELNMDMFRKCMEPVE 324
gi 12643273  245 NHFVQEFKRKSKKDITGNPRALRRLRTSCERAKRTLSSTAQTTIEIDSLYEGIDFYSTITRARFEELNMDLFRKCMEPVE 324
gi 1170370   241 DHFTAEFKRKHRKDMTQNQRALRRLRTACERAKRTLSSSAQAYIEIDSLFDGIDFNSTITRARFEDMCGDYFRKTMEPVE 320
gi 226517932 245 NHFVQEFKRKHKKDITGNARALRRLRTSCERAKRTLSSTAQTSIEIDSLFEGVDFYTSITRARFEELNMDLFRKCMEPVE 324
gi 256032242 250 NHFSAEFKRKNKKDMSNNPRSQRRLRTACERAKRTLSSATQTTIEIDSLFEGVDFYSSLSRAKFEELCMDLFRGTLEPVE 329
gi 585270    246 NFFVSEFKRKYKKDVTSNARSLRRLRTACERAKRTLSSGTQTTVEIDSLIDGIDYYASITRAKFEELCMDLFRGTSEPVE 325
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
Feature 1                           ### ##                      #               
1YUW_A       319 KALRDAKLDKSQIHDIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAVQAAILS 381
2V7Z_A       319 KALRDAKLDKSQIHDIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAVQAAILS 381
gi 148646849 323 KVLRDAKMDKGQVNEVVLVGGSTRIPKVQQLLQDFFNGKELCKSINPDEAVAYGAAVQAAILN 385
gi 148910696 324 KCLRDAKMDKSTIHDVVLVGGSTRIPKVQQLLQDFFNGKELCKSINPDEAVAYGAAVQAAILS 386
gi 162689004 325 KCLRDAKMDKSSIHDVVLVGGSTRIPKVQQLLQDFFNGKELCKSINPDEAVAYGAAVQAAILS 387
gi 12643273  325 KCLRDAKMDKSTVHDVVLVGGSTRIPKVQQLLQDFFNGKELCKSINPDEAVAYGAAVQGAILS 387
gi 1170370   321 KVLRDSKLSKSQVHEVVLVGGSTRIPKVQQLLSDFFNGKEPCKSINPDEAVAFGATVQAAILS 383
gi 226517932 325 KCLRDSKIDKSAVHEIVLVGGSTRIPKVQSLLSDFFNGKELCKSINPDEAVAYGAAVQAAILS 387
gi 256032242 330 KVLRDAKAAKGDVDDIVLVGGSTRIPKVQSLLVDFFNGKELSKSINPDEAVAYGAAVQAAILA 392
gi 585270    326 KVLRDSKISKSEIHDVVLVGGSTRIPKVQQLLIDYFNGKELCKNINPDEAVAYGAAVQAAILA 388

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