Conserved Protein Domain Family
ACD_HspB4-5-6

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cd06478: ACD_HspB4-5-6 
Alpha-crystallin domain found in alphaA-crystallin (HspB4), alphaB-crystallin (HspB5), and the small heat shock protein (sHsp) HspB6, also known as Hsp20. sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits. Alpha crystallin, an abundant protein in the mammalian lens, is a large (700 kDa) heteropolymer composed of HspB4 and HspB5, generally in a molar ratio of HspB4:HspB5 of 3:1. Only trace amounts of HspB4 are found in tissues other than the lens. HspB5 on the other hand is also expressed constitutively in other tissues including brain, heart, and type I and type IIa skeletal muscle fibers, and in several cancers including gliomas, renal cell carcinomas, basal-like and metaplastic breast carcinomas, and head and neck cancer. HspB5's functions include effects on the apoptotic pathway and on metastasis. Phosphorylation of HspB5 reduces its oligomerization and anti-apoptotic activities. HspB5 is protective in demyelinating disease such as multiple sclerosis (MS), being a negative regulator of inflammation. In early active MS lesions it is the most abundant gene transcript and an autoantigen, the immune response against it would disrupt its function and worsen inflammation and demyelination. Given as therapy for ongoing demyelinating disease it may counteract this effect. It is an autoantigen in the pathogenesis of various other inflammatory disorders including Lens-associated uveitis (LAU), and Behcet's disease. Mutations in HspB5 have been associated with diseases including dominant cataract and desmin-related myopathy. Mutations in HspB4 have been associated with Autosomal Dominant Congenital Cataract (ADCC). HspB6 (Hsp20) is ubiquitous and is involved in diverse functions including regulation of glucose transport and contraction of smooth muscle, in platelet aggregation, in cardioprotection, and in the prevention of apoptosis. It interacts with the universal scaffolding and adaptor protein 14-3-3, and also with the proapoptotic protein Bax.
Statistics
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PSSM-Id: 107233
View PSSM: cd06478
Aligned: 12 rows
Threshold Bit Score: 151.446
Threshold Setting Gi: 47227157
Created: 29-Apr-2008
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
putative dimer
Feature 1:putative dimer interface [polypeptide binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1         #####     # # ##                                    #                    ##    
P02511        67 EMRLEKdRFSVNLDVKHFSPEELKVKVLgDVIEVHGKHeeRQDeHGFISREFHRKYRIPADVDPltITSSLSsdGVLTVN 146 human
P02503        63 EVRSDRdRFVIYLDVKHFSPEDLTVKVLdDYVEIHGKHseRQDdHGYISREFHRRYRLPSNVDQsaISCSLSadGMLTFS 142 North American ...
CAG00519      60 EMRIEKdRYVIYLDVKHFSPDELSVSVSdEFVTIHAKHqdRQDdHGFVSREFLRRYKLPPGVTSadVTSSLSvdGVLTIT 139 spotted green p...
NP_001086479  68 EVKLDKdQFSVLLDVKHFSPEELNVKVVgDSVEVHAKHeeRLDeHGFISREFHRRYKIPPTVNPgaISSALSaeGLLSIQ 147 African clawed ...
NP_001002670  56 EVKMEKdQFSLSLDVKHFAPEELSVKIIgDFIEIHAKHedRQDgHGFVSREFLRKYRVPVGVDPasITSSLSsdGVLTVT 135 zebrafish
O14558        66 QVPTDPgHFSVLLDVKHFSPEEIAVKVVgEHVEVHARHeeRPDeHGFVAREFHRRYRLPPGVDPaaVTSALSpeGVLSIQ 145 human
P97541        66 QVPTDPgYFSVLLDVKHFSPEEISVKVVgDHVEVHARHeeRPDeHGFIAREFHRRYRLPPGVDPaaVTSALSpeGVLSIQ 145 Norway rat
O93591        64 EVRSDRdKFMVYLDVKHFSPEELNVKVAeDYVEIQGKHgeRQDdHGYISREFHRRYRLPSNVDQsaITCTLSadGQLTIC 143 Mexican tetra
Q91311        63 EVRSDRdRFTINLDVKHFSPDDLTVKILdDFVEIHGKHseRQDdHGYISREFHRRYRLPSNLDQssISCSLSadGILTFS 142 bullfrog
P02504        63 EVRSDRdKFTIMLDVKHFSPEDLSVKIIdDFVEIHGKHseRQDdHGYISREFHRRYRLPANVDQsaITCSLSsdGMLTFS 142 chicken
Q91312        65 EMRLEKdKFSINLDVKHFSPEELKVKVSgDFIEIHGKHeeRQDeHGYVSRDFQRRYKIPVDVDPlsITSSLSpdGVLTVC 144 bullfrog
Q05713        66 EMRLEKdKFSVNLDVKHFSPEELKVKVLgDMIEIHGKHeeRQDeHGFIAREFSRKYRIPADVDPltITSSLSldGVLTVS 145 chicken
Feature 1           
P02511       147 GPR 149 human
P02503       143 GPK 145 North American opossum
CAG00519     140 VPR 142 spotted green pufferfish
NP_001086479 148 APV 150 African clawed frog
NP_001002670 136 GPL 138 zebrafish
O14558       146 AAP 148 human
P97541       146 ATP 148 Norway rat
O93591       144 GPK 146 Mexican tetra
Q91311       143 GPK 145 bullfrog
P02504       143 GPK 145 chicken
Q91312       145 GPR 147 bullfrog
Q05713       146 APR 148 chicken

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