Alpha-crystallin domain found in the small heat shock protein (sHsp) alphaB-crystallin (HspB5, 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. HspB4 does not belong to this group. HspB5 shows increased synthesis in response to stress. HspB5 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. Its 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1886642037 170 EMRLEKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDEHGFISREFHRKYRIPADVDPLAITSSLSSDGVLSVN 249
Cdd:cd06498     1 EMRLEKDKFSVNLDVKHFSPEELKVKVLGDFIEIHGKHEERQDEHGFISREFQRKYRIPADVDPLTITSSLSPDGVLTVC 80

                  ....
gi 1886642037 250 GPRK 253
Cdd:cd06498    81 GPRK 84

Alpha-crystallin domain found in the small heat shock protein (sHsp) alphaB-crystallin (HspB5, 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. HspB4 does not belong to this group. HspB5 shows increased synthesis in response to stress. HspB5 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. Its 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1886642037 170 EMRLEKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDEHGFISREFHRKYRIPADVDPLAITSSLSSDGVLSVN 249
Cdd:cd06498     1 EMRLEKDKFSVNLDVKHFSPEELKVKVLGDFIEIHGKHEERQDEHGFISREFQRKYRIPADVDPLTITSSLSPDGVLTVC 80

                  ....
gi 1886642037 250 GPRK 253
Cdd:cd06498    81 GPRK 84

Alpha crystallin A chain, N terminal;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1886642037  94 MDIAIHHPWIRRPFFPFHSPSRLFDQFFGEHLLESDLFPA-STSLSPFYLRPsSFFR 149
Cdd:pfam00525   1 MDVAIQHPWFRRPLFPSFFPSRIFDQRFGEGLLESDLFPFcPPTLSPYYYRP-SFFR 56

Alpha-crystallin domain found in the small heat shock protein (sHsp) alphaB-crystallin (HspB5, 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. HspB4 does not belong to this group. HspB5 shows increased synthesis in response to stress. HspB5 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. Its 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1886642037 170 EMRLEKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDEHGFISREFHRKYRIPADVDPLAITSSLSSDGVLSVN 249
Cdd:cd06498     1 EMRLEKDKFSVNLDVKHFSPEELKVKVLGDFIEIHGKHEERQDEHGFISREFQRKYRIPADVDPLTITSSLSPDGVLTVC 80

                  ....
gi 1886642037 250 GPRK 253
Cdd:cd06498    81 GPRK 84

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1886642037 174 EKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDEHGFISREFHRKYRIPADVDPLAITSSLSSDGVLSVNGPR 252
Cdd:cd06526     5 DDEKFQVTLDVKGFKPEELKVKVSDNKLVVEGKHEEREDEHGYVSREFTRRYQLPEGVDPDSVTSSLSSDGVLTIEAPK 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 1886642037 167 GLSEMRLEKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDEHGFISREFHRKYRIPADVDPLAITSSLSSDGVL 246
Cdd:cd06475     1 GMSEIRQTADRWKVSLDVNHFAPEELVVKTKDGVVEITGKHEEKQDEHGFVSRCFTRKYTLPPGVDPTAVTSSLSPDGIL 80

                  ....*
gi 1886642037 247 SVNGP 251
Cdd:cd06475    81 TVEAP 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1886642037 174 EKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDEHGFISREFHRKYRIPADVDPLAITSSLSSDGVLSVNGPR 252
Cdd:cd06476     5 EDDKYQVFLDVCHFTPDEITVRTVDNLLEVSARHPQRMDRHGFVSREFTRTYILPMDVDPLLVRASLSHDGILCIQAPR 83

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 1886642037 174 EKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDE------HGFISREFHRKYRIPADVDPLAITSSLsSDGVLS 247
Cdd:cd06464     5 TDDAYVVEADLPGFKKEDIKVEVEDGVLTISGEREEEEEEeenylrRERSYGSFSRSFRLPEDVDPDKIKASL-ENGVLT 83

                  ....*
gi 1886642037 248 VNGPR 252
Cdd:cd06464    84 ITLPK 88

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 1886642037 178 FSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDEHGFISREFHRKYRIPADVDPLAITSSLSSDGVLSVNGPR 252
Cdd:cd06480    17 WKVCVNVHSFKPEELTVKTKDGFVEVSGKHEEQQKEGGIVSKNFTKKIQLPPEVDPVTVFASLSPEGLLIIEAPQ 91

Small heat shock protein IbpA, HSP20 family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1886642037 176 DRFSVNLDVKHFSPEELKVKVLGDVIEVHG--KHEERQDEHGFISRE-----FHRKYRIPADVDPLAITSSLsSDGVLSV 248
Cdd:COG0071     9 DAYVITADLPGVDKEDIDVTVEGNVLTISGerKEEEEEEGENYLRRErrygsFERSFTLPDDVDVDKIEASY-ENGVLTI 87

                          90
                  ....*....|....*....
gi 1886642037 249 NGPRKQASGPeRTIPITRE 267
Cdd:COG0071    88 TLPKAEEAKP-RKIEIKAG 105

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 1886642037 176 DRFSVNLDVKHFSPEELKVKVLGDVIEVHGkheERQDEHGFISREFHRKYRIPADVDPLAITSSLSSDGVLSVNGPR 252
Cdd:cd06479     8 DTYQFAVDVSDFSPEDIIVTTSNNQIEVHA---EKLASDGTVMNTFTHKCQLPEDVDPTSVSSSLGEDGTLTIKARR 81

Alpha-crystallin domain (ACD) found in Escherichia coli inclusion body-associated proteins IbpA and IbpB, and similar proteins. IbpA and IbpB are 16 kDa small heat shock proteins (sHsps). sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits. IbpA and IbpB are produced during high-level production of various heterologous proteins, specifically human prorenin, renin and bovine insulin-like growth factor 2 (bIGF-2), and are strongly associated with inclusion bodies containing these heterologous proteins. IbpA and IbpB work as an integrated system to stabilize thermally aggregated proteins in a disaggregation competent state. The chaperone activity of IbpB is also significantly elevated as the temperature increases from normal to heat shock. The high temperature results in the disassociation of 2-3-MDa IbpB oligomers into smaller approximately 600-kDa structures. This elevated activity seen under heat shock conditions is retained for an extended period of time after the temperature is returned to normal. IbpA also forms multimers.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1886642037 172 RLEKDRFSVNLDVKHFSPEELKVKVLGDVIEVHGKHEERQDE-----H-GFISREFHRKYRIPADV 231
Cdd:cd06470     7 KTGENNYRITLAVAGFSEDDLEIEVENNQLTVTGKKADEENEereylHrGIAKRAFERSFNLADHV 72