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 386764745   60 EGDNKVlKLRFDVSQYAPEEIVVKTVDQKLLVHAKHEEKSDTK------SVYREYNREFLLPKGVNPESIRSSLsKDGVL 133
Cdd:pfam00011   4 EDEDAF-EVRLDVPGFKPEELKVKVEDNRLLVKGEHEEEKEDDhglrseRSYGSFSRKFTLPENADPDKVKASL-KDGVL 81

                          90
                  ....*....|....*...
gi 386764745  134 TVDAPLPALTAGETLIPI 151
Cdd:pfam00011  82 TVTVPKLEPEPKERRIQI 99

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386764745  67 KLRFDVSQYAPEEIVVKTVDQKLLVHAKHEEKSDTKS-VYREYNREFLLPKGVNPESIRSSLSKDGVLTVDAPL 139
Cdd:cd06475   13 KVSLDVNHFAPEELVVKTKDGVVEITGKHEEKQDEHGfVSRCFTRKYTLPPGVDPTAVTSSLSPDGILTVEAPI 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386764745  71 DVSQYAPEEIVVKTVDQKLLVHAKHEEKSDTKS-VYREYNREFLLPKGVNPESIRSSLSKDGVLTVDAP 138
Cdd:cd06478   14 DVKHFSPEELSVKVLGDFVEIHGKHEERQDEHGfISREFHRRYRLPPGVDPAAITSSLSADGVLTISGP 82

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 386764745  58 QDEGDNKVLKLRFDVSQYAPEEIVVKTVDQKLLVHAKHEEKSDTKS-VYREYNREFLLPKGVNPESIRSSLSKDGVLTVD 136
Cdd:cd06476    1 QVESEDDKYQVFLDVCHFTPDEITVRTVDNLLEVSARHPQRMDRHGfVSREFTRTYILPMDVDPLLVRASLSHDGILCIQ 80

                 ..
gi 386764745 137 AP 138
Cdd:cd06476   81 AP 82

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386764745  60 EGDNKVlKLRFDVSQYAPEEIVVKTVDQKLLVHAKHEEKSDTKSVYREYNREFLLPKGVNPESIRSSLsKDGVLTVDAP 138
Cdd:cd00298    3 QTDDEV-VVTVDLPGVKKEDIKVEVEDNVLTISGKREEEEERERSYGEFERSFELPEDVDPEKSKASL-ENGVLEITLP 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386764745  62 DNKVLKLRFDVSQYAPEEIVVKTVDQKLLVHAKHEEKSDTKS-VYREYNREFLLPKGVNPESIRSSLSKDGVLTVDAP 138
Cdd:cd06497    8 DRDKFTIYLDVKHFSPEDLTVKVLDDYVEIHGKHSERQDDHGyISREFHRRYRLPSNVDQSAITCSLSADGMLTFSGP 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 386764745  67 KLRFDVSQYAPEEIVVKTVDQKLLVHAKHEEKSDTKS-VYREYNREFLLPKGVNPESIRSSLSKDGVLTVDAPL 139
Cdd:cd06480   18 KVCVNVHSFKPEELTVKTKDGFVEVSGKHEEQQKEGGiVSKNFTKKIQLPPEVDPVTVFASLSPEGLLIIEAPQ 91

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386764745  57 IQDEGDNkvLKLRFDVSQYAPEEIVVKTVDQKLLVHAKHEEKSDTKSV--------YREYNREFLLPKGVNPESIRSSLs 128
Cdd:COG0071    4 IEETDDA--YVITADLPGVDKEDIDVTVEGNVLTISGERKEEEEEEGEnylrrerrYGSFERSFTLPDDVDVDKIEASY- 80

                         90       100
                 ....*....|....*....|...
gi 386764745 129 KDGVLTVDAPLPAlTAGETLIPI 151
Cdd:COG0071   81 ENGVLTITLPKAE-EAKPRKIEI 102