Hsp20/alpha crystallin family; Not only do small heat-shock-proteins occur in eukaryotes and prokaryotes but they have also now been shown to occur in cyanobacterial phages as well as their bacterial hosts.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24660381    51 VIVGKDGFEANVDVHLFKPYEISVKTSGDTVVVEAKHEKRRDGDTFV-----GRHIVKRFVLPRGYYPNDVRSELsSDGI 125
Cdd:pfam00011   2 IKEDEDAFEVRLDVPGFKPEELKVKVEDNRLLVKGEHEEEKEDDHGLrsersYGSFSRKFTLPENADPDKVKASL-KDGV 80

                  ....*..
gi 24660381   126 LTVKCPP 132
Cdd:pfam00011  81 LTVTVPK 87

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24660381  55 KDGFEANVDVHLFKPYEISVKTSGDTVVVEAKHEKRRDGDTFVGRHIVKRFVLPRGYYPNDVRSELSSDGILTVKCPP 132
Cdd:cd06478   6 KDRFSVNLDVKHFSPEELSVKVLGDFVEIHGKHEERQDEHGFISREFHRRYRLPPGVDPAAITSSLSADGVLTISGPR 83

Alpha crystallin domain (ACD) found in mammalian small (s)heat shock protein (Hsp)-27 (also denoted HspB1 in human) and similar proteins. sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits. Hsp27 shows enhanced synthesis in response to stress. It is a molecular chaperone which interacts with a large number of different proteins. It is found in many types of human cells including breast, uterus, cervix, platelets and cancer cells. Hsp27 has diverse cellular functions including, chaperoning, regulation of actin polymerization, keratinocyte differentiation, regulation of inflammatory pathways in keratinocytes, and protection from oxidative stress through modulating glutathione levels. It is also a subunit of AUF1-containing protein complexes. It has been linked to several transduction pathways regulating cellular functions including differentiation, cell growth, development, and apoptosis. Its activity can be regulated by phosphorylation. Its unphosphorylated state is a high molecular weight aggregated form (100-800kDa) composed of up to 24 subunits, which forms as a result of multiple interactions within the ACD, and is required for chaperone function and resistance to oxidative stress. Upon phosphorylation these large aggregates rapidly disassociate to smaller oligomers and chaperone activity is modified. High constitutive levels of Hsp27 have been detected in various cancer cells, in particular those of carcinoma origin. Over-expression of Hsp27 has a protective effect against various diseases-processes, including Huntington's disease. Mutations in Hsp27 have been associated with a form of distal hereditary motor neuropathy type II and Charcot-Marie-Tooth disease type 2.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24660381  48 LSRVIVGKDGFEANVDVHLFKPYEISVKTSGDTVVVEAKHEKRRDGDTFVGRHIVKRFVLPRGYYPNDVRSELSSDGILT 127
Cdd:cd06475   2 MSEIRQTADRWKVSLDVNHFAPEELVVKTKDGVVEITGKHEEKQDEHGFVSRCFTRKYTLPPGVDPTAVTSSLSPDGILT 81

                ....
gi 24660381 128 VKCP 131
Cdd:cd06475  82 VEAP 85

Alpha-crystallin domain (ACD) of alpha-crystallin-type small(s) heat shock proteins (Hsps). sHsps are small stress induced proteins with monomeric masses between 12 -43 kDa, whose common feature is the Alpha-crystallin domain (ACD). sHsps are generally active as large oligomers consisting of multiple subunits, and are believed to be ATP-independent chaperones that prevent aggregation and are important in refolding in combination with other Hsps.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24660381  51 VIVGKDGFEANVDVHLFKPYEISVKTSGDTVVVEAKHEKRRDGDT------FVGRHIVKRFVLPRGYYPNDVRSELsSDG 124
Cdd:cd06464   2 VYETDDAYVVEADLPGFKKEDIKVEVEDGVLTISGEREEEEEEEEnylrreRSYGSFSRSFRLPEDVDPDKIKASL-ENG 80

                ....*..
gi 24660381 125 ILTVKCP 131
Cdd:cd06464  81 VLTITLP 87

Alpha-crystallin domain found in the small heat shock protein (sHsp) alphaA-crystallin (HspB4, 20kDa). 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 does not belong to this group. Mutations inHspB4 have been associated with Autosomal Dominant Congenital Cataract (ADCC). The chaperone-like functions of HspB4 are considered important for maintaining lens transparency and preventing cataract.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24660381  48 LSRVIVGKDGFEANVDVHLFKPYEISVKTSGDTVVVEAKHEKRRDGDTFVGRHIVKRFVLPRGYYPNDVRSELSSDGILT 127
Cdd:cd06497   2 ISEVRSDRDKFTIYLDVKHFSPEDLTVKVLDDYVEIHGKHSERQDDHGYISREFHRRYRLPSNVDQSAITCSLSADGMLT 81

                ....
gi 24660381 128 VKCP 131
Cdd:cd06497  82 FSGP 85

Alpha-crystallin domain (ACD) found in mammalian 21.6 KDa small heat shock protein (sHsp) HspB8, also denoted as Hsp22 in humans, and similar proteins. sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits. A chaperone complex formed of HspB8 and Bag3 stimulates degradation of protein complexes by macroautophagy. HspB8 also forms complexes with Hsp27 (HspB1), MKBP (HspB2), HspB3, alphaB-crystallin (HspB5), Hsp20 (HspB6), and cvHsp (HspB7). These latter interactions may depend on phosphorylation of the respective partner sHsp. HspB8 may participate in the regulation of cell proliferation, cardiac hypertrophy, apoptosis, and carcinogenesis. Point mutations in HspB8 have been correlated with the development of several congenital neurological diseases, including Charcot Marie tooth disease and distal motor neuropathy type II.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24660381  62 VDVHLFKPYEISVKTSGDTVVVEAKHEKRRDGDTFVGRHIVKRFVLPRGYYPNDVRSELSSDGILTVKCP 131
Cdd:cd06480  21 VNVHSFKPEELTVKTKDGFVEVSGKHEEQQKEGGIVSKNFTKKIQLPPEVDPVTVFASLSPEGLLIIEAP 90

Alpha crystallin domain (ACD) found in mammalian small heat shock protein (sHsp) HspB7, also known as cardiovascular small heat shock protein (cvHsp), and similar proteins. sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits. HspB7 is a 25-kDa protein, preferentially expressed in heart and skeletal muscle. It binds the cytoskeleton protein alpha-filamin (also known as actin-binding protein 280). The expression of HspB7 is increased during rat muscle aging. Its expression is also modulated in obesity implicating this protein in this and related metabolic disorders. As the human gene encoding HspB7 is mapped to chromosome 1p36.23-p34.3 it is a positional candidate for several dystrophies and myopathies.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24660381  56 DGFEANVDVHLFKPYEISVKTSGDTVVVeakHEKRRDGDTFVGRHIVKRFVLPRGYYPNDVRSELSSDGILTVK 129
Cdd:cd06479   8 DTYQFAVDVSDFSPEDIIVTTSNNQIEV---HAEKLASDGTVMNTFTHKCQLPEDVDPTSVSSSLGEDGTLTIK 78

Alpha crystallin domain (ACD) found in mammalian small heat shock protein (sHsp) HspB10, also known as sperm outer dense fiber protein (ODFP), and similar proteins. sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits. Human (h) HspB10 occurs exclusively in the axoneme of sperm cells and may have a cytoskeletal role.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24660381  60 ANVDVHLFKPYEISVKTSGDTVVVEAKHEKRRD---GDTFVGRHIVKRFVLPRGYYPNDVRSELSSDGILTVKCP 131
Cdd:cd06482  12 ASVDVCGFEPDQVKVKVKDGKVQVSAERENRYDclgSKKYSYMNICKEFSLPPGVDEKDVTYSYGLGSVVKIETP 86