alpha-crystallin domain (ACD) found in alpha-crystallin-type small heat shock proteins, and a similar domain found in p23 (a cochaperone for Hsp90) and in other p23-like proteins.; The alpha-crystallin-Hsps_p23-like superfamily includes the alpha-crystallin domain (ACD) of alpha-crystallin-type small heat shock proteins (sHsps) and a similar domain found in p23-like proteins. sHsps are small stress induced proteins with monomeric masses between 12-43 kDa, whose common feature is this 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. p23 is a cochaperone of the Hsp90 chaperoning pathway. It binds Hsp90 and participates in the folding of a number of Hsp90 clients including the progesterone receptor. p23 also has a passive chaperoning activity. p23 in addition may act as the cytosolic prostaglandin E2 synthase. Included in this superfamily is the p23-like C-terminal CHORD-SGT1 (CS) domain of suppressor of G2 allele of Skp1 (Sgt1) and the p23-like domains of human butyrate-induced transcript 1 (hB-ind1), NUD (nuclear distribution) C, Melusin, and NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59799322  60 GISEVRSDRDKFVIFLDVKHFSPEDLTVKVQEDFVEIHGKHNERQDDHGYISREFHRRYRLPSNVDQSALSCSLSADGML 139
Cdd:cd06497   1 GISEVRSDRDKFTIYLDVKHFSPEDLTVKVLDDYVEIHGKHSERQDDHGYISREFHRRYRLPSNVDQSAITCSLSADGML 80

                ....*.
gi 59799322 140 TFSGPK 145
Cdd:cd06497  81 TFSGPK 86

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 59799322  60 GISEVRSDRDKFVIFLDVKHFSPEDLTVKVQEDFVEIHGKHNERQDDHGYISREFHRRYRLPSNVDQSALSCSLSADGML 139
Cdd:cd06497   1 GISEVRSDRDKFTIYLDVKHFSPEDLTVKVLDDYVEIHGKHSERQDDHGYISREFHRRYRLPSNVDQSAITCSLSADGML 80

                ....*.
gi 59799322 140 TFSGPK 145
Cdd:cd06497  81 TFSGPK 86

Alpha crystallin A chain, N terminal;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 59799322     1 MDIAIQHPWFKRALGP-FYPSRLFDQFFGEGLFEYDLLPFLSSTISPYY-RQSLFR 54
Cdd:pfam00525   1 MDVAIQHPWFRRPLFPsFFPSRIFDQRFGEGLLESDLFPFCPPTLSPYYyRPSFFR 56

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 59799322  60 GISEVRSDRDKFVIFLDVKHFSPEDLTVKVQEDFVEIHGKHNERQDDHGYISREFHRRYRLPSNVDQSALSCSLSADGML 139
Cdd:cd06497   1 GISEVRSDRDKFTIYLDVKHFSPEDLTVKVLDDYVEIHGKHSERQDDHGYISREFHRRYRLPSNVDQSAITCSLSADGML 80

                ....*.
gi 59799322 140 TFSGPK 145
Cdd:cd06497  81 TFSGPK 86

Alpha-crystallin domain (ACD) of metazoan 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 59799322  63 EVRSDRDKFVIFLDVKHFSPEDLTVKVQEDFVEIHGKHNERQDDHGYISREFHRRYRLPSNVDQSALSCSLSADGMLTFS 142
Cdd:cd06526   1 VVNDDDEKFQVTLDVKGFKPEELKVKVSDNKLVVEGKHEEREDEHGYVSREFTRRYQLPEGVDPDSVTSSLSSDGVLTIE 80

                ...
gi 59799322 143 GPK 145
Cdd:cd06526  81 APK 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 59799322  60 GISEVRSDRDKFVIFLDVKHFSPEDLTVKVQEDFVEIHGKHNERQDDHGYISREFHRRYRLPSNVDQSALSCSLSADGML 139
Cdd:cd06475   1 GMSEIRQTADRWKVSLDVNHFAPEELVVKTKDGVVEITGKHEEKQDEHGFVSRCFTRKYTLPPGVDPTAVTSSLSPDGIL 80

                ....*
gi 59799322 140 TFSGP 144
Cdd:cd06475  81 TVEAP 85

Alpha crystallin A chain, N terminal;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 59799322     1 MDIAIQHPWFKRALGP-FYPSRLFDQFFGEGLFEYDLLPFLSSTISPYY-RQSLFR 54
Cdd:pfam00525   1 MDVAIQHPWFRRPLFPsFFPSRIFDQRFGEGLLESDLFPFCPPTLSPYYyRPSFFR 56

Alpha crystallin domain (ACD) found in mammalian small heat shock protein (sHsp) HspB2/heat shock 27kDa protein 2 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. HspB2 is preferentially and constitutively expressed in skeletal muscle and heart. HspB2 shows homooligomeric activity and forms aggregates in muscle cytosol. Although its expression is not induced by heat shock, it redistributes to the insoluble fraction in response to heat shock. In the mouse heart, HspB2 plays a role in maintaining energetic balance, by protecting cardiac energetics during ischemia/reperfusion, and allowing for increased work during acute inotropic challenge. hHspB2 [previously also known as myotonic dystrophy protein kinase (DMPK) binding protein (MKBP)] is selectively up-regulated in skeletal muscles from myotonic dystrophy patients. The ACD of hHspB2 binds the DMPK kinase domain. In vitro, hHspB2 enhances the kinase activity of DMPK and confers thermoresistance. The hHspB2 gene lies less than 1kb from the 5 prime end of the related alphaB (HspB4)-crystallin gene, with the opposite transcription direction. These two genes may share regulatory elements for their expression.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59799322  64 VRSDRDKFVIFLDVKHFSPEDLTVKVQEDFVEIHGKHNERQDDHGYISREFHRRYRLPSNVDQSALSCSLSADGMLTFSG 143
Cdd:cd06476   2 VESEDDKYQVFLDVCHFTPDEITVRTVDNLLEVSARHPQRMDRHGFVSREFTRTYILPMDVDPLLVRASLSHDGILCIQA 81

                ..
gi 59799322 144 PK 145
Cdd:cd06476  82 PR 83

Alpha crystallin domain (ACD) found in mammalian small heat shock protein (sHsp) HspB9 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) HspB9 is expressed exclusively in the normal testis and in various tumor samples and is a cancer/testis antigen. hHspB9 interacts with TCTEL1 (T-complex testis expressed protein -1), a subunit of dynein. hHspB9 and TCTEL1 are co-expressed in similar cells within the testis and in tumor cells. Included in this group is Xenopus Hsp30, a developmentally-regulated heat-inducible molecular chaperone.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59799322  69 DKFVIFLDVKHFSPEDLTVKVQEDFVEIHGKHNERQDDHG----YISREFHRRYRLPSNVDQSALSCSLSADGMLTFSGP 144
Cdd:cd06481   7 EGFSLKLDVRGFSPEDLSVRVDGRKLVVTGKREKKNEDEKgsfsYEYQEFVREAQLPEHVDPEAVTCSLSPSGHLHIRAP 86

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 59799322  75 LDVKHFSPEDLTVKVQEDFVEIHGKHNERQDDHGYISREFHRRYRLPSNVDQSALSCSLSADGMLTFSGPK 145
Cdd:cd06480  21 VNVHSFKPEELTVKTKDGFVEVSGKHEEQQKEGGIVSKNFTKKIQLPPEVDPVTVFASLSPEGLLIIEAPQ 91

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 59799322  64 VRSDRDKFVIFLDVKHFSPEDLTVKVQEDFVEIHGkhnERQDDHGYISREFHRRYRLPSNVDQSALSCSLSADGMLTFS 142
Cdd:cd06479   3 VKTLGDTYQFAVDVSDFSPEDIIVTTSNNQIEVHA---EKLASDGTVMNTFTHKCQLPEDVDPTSVSSSLGEDGTLTIK 78

Alpha crystallin domain (ACD) found in Saccharomyces cerevisiae (Sc) small heat shock protein (Hsp)26 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. ScHsp26 is temperature-regulated, it switches from an inactive to a chaperone-active form upon elevation in temperature. It associates into large 24-mers storage forms which upon heat shock disassociate into dimers. These dimers initiate the interaction with non-native substrate proteins and re-assemble into large globular assemblies having one monomer of substrate bound per dimer. This group also contains Arabidopsis thaliana (Ath) Hsp15.7, a peroxisomal matrix protein which can complement the morphological phenotype of S. cerevisiae mutants deficient in Hsps26. AthHsp15.7 is minimally expressed under normal conditions and is strongly induced by heat and oxidative stress. Also belonging to this group is wheat HSP16.9 which differs in quaternary structure from the shell-type particles of ScHsp26, it assembles as a dodecameric double disc, with each disc organized as a trimer of dimers.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59799322  69 DKFVIFLDVKHFSPEDLTVKVQEDFV-EIHG---KHNERQDDHGYISR----EFHRRYRLPSNVDQSALSCSLSaDGMLT 140
Cdd:cd06472   9 EAHVFKADVPGVKKEDVKVEVEDGRVlRISGerkKEEEKKGDDWHRVErssgRFVRRFRLPENADADEVKAFLE-NGVLT 87

                ....*
gi 59799322 141 FSGPK 145
Cdd:cd06472  88 VTVPK 92