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 1928924     27 VLDDDDHFEVGLEAHNFLPKEIEVKNIGELLEIHMEH-NVKKDSFGDVS----RNITRCYKLPKNVDMKTIKSNLDShGI 101
Cdd:pfam00011   2 IKEDEDAFEVRLDVPGFKPEELKVKVEDNRLLVKGEHeEEKEDDHGLRSersyGSFSRKFTLPENADPDKVKASLKD-GV 80

                  ....*..
gi 1928924    102 LHIEARK 108
Cdd:pfam00011  81 LTVTVPK 87

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 1928924   23 GVVNVLDDDDHFEVGLEAHNFLPKEIEVKNIGELLEIHMEHNVKKDSFGDVSRNITRCYKLPKNVDMKTIKSNLDSHGIL 102
Cdd:cd06475   1 GMSEIRQTADRWKVSLDVNHFAPEELVVKTKDGVVEITGKHEEKQDEHGFVSRCFTRKYTLPPGVDPTAVTSSLSPDGIL 80

                ....
gi 1928924  103 HIEA 106
Cdd:cd06475  81 TVEA 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1928924   30 DDDHFEVGLEAHNFLPKEIEVKNIGELLEIHMEHNVKKDSFGDVSRNITRCYKLPKNVDMKTIKSNLDSHGILHIEA 106
Cdd:cd06498   5 EKDKFSVNLDVKHFSPEELKVKVLGDFIEIHGKHEERQDEHGFISREFQRKYRIPADVDPLTITSSLSPDGVLTVCG 81

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 1928924   27 VLDDDDHFEVGLEAHNFLPKEIEVKNIGELLEIHMEHNVKKDSFGDVSRNITRCYKLPKNVDMKTIKSNLDSHGILHIEA 106
Cdd:cd06476   2 VESEDDKYQVFLDVCHFTPDEITVRTVDNLLEVSARHPQRMDRHGFVSREFTRTYILPMDVDPLLVRASLSHDGILCIQA 81

This domain family 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 family 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 1928924   27 VLDDDDHFEVGLEAHNFLPKEIEVKNIGELLEIHMEHNVKKDSfGDVSRNITRCYKLPKNVDMKTIKSNLDsHGILHIEA 106
Cdd:cd00298   1 WYQTDDEVVVTVDLPGVKKEDIKVEVEDNVLTISGKREEEEER-ERSYGEFERSFELPEDVDPEKSKASLE-NGVLEITL 78

                ..
gi 1928924  107 RK 108
Cdd:cd00298  79 PK 80

Alpha crystallin domain (ACD) found in mammalian HspB3, also known as heat-shock protein 27-like protein (HSPL27, 17-kDa) 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. HspB3 is expressed in adult skeletal muscle, smooth muscle, and heart, and in several other fetal tissues. In muscle cells HspB3 forms an oligomeric 150 kDa complex with myotonic dystrophy protein kinase-binding protein (MKBP/ HspB2), this complex may comprise one of two independent muscle-cell specific chaperone systems. The expression of HspB3 is induced during muscle differentiation controlled by the myogenic factor MyoD. HspB3 may also interact with Hsp22 (HspB8).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1928924   29 DDDDHFEVGLEAHNFLPKEIEVKNIGELLEIHMEHNVKKDSFGDVSRNITRCYKLPKNVDMKTIKSNLDSHGILHIEAR 107
Cdd:cd06477   4 EGKPMFQILLDVVQFRPEDIIIQVFEGWLLIKGQHGVRMDEHGFISRSFTRQYQLPDGVEHKDLSAMLCHDGILVVETK 82

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 1928924   29 DDDDHFEVGLEAHNFLPKEIEVKNIGELLEIHMEHNVK-KDSFGDVS---RNITRCYKLPKNVDMKTIKSNLDSHGILHI 104
Cdd:cd06481   4 DGKEGFSLKLDVRGFSPEDLSVRVDGRKLVVTGKREKKnEDEKGSFSyeyQEFVREAQLPEHVDPEAVTCSLSPSGHLHI 83

                ..
gi 1928924  105 EA 106
Cdd:cd06481  84 RA 85

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928924   25 VNVLDDDDHFEVGLEAHNFLPKEIEVKNIGELLEIHMEHNVKKD-----------SFGDVSRNITrcykLPKNVDMKTIK 93
Cdd:COG0071   2 VDIEETDDAYVITADLPGVDKEDIDVTVEGNVLTISGERKEEEEeegenylrrerRYGSFERSFT----LPDDVDVDKIE 77

                        90
                ....*....|....*
gi 1928924   94 SNLDsHGILHIEARK 108
Cdd:COG0071  78 ASYE-NGVLTITLPK 91