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 399894425  106 KLRYDLSQYKPEEIVVKTVDNKLFIHAKHEEKTD------SKSVYREYNREFMLPSGTNPEAIRSSLsKDGVLTVEAP-L 178
Cdd:pfam00011  10 EVRLDVPGFKPEELKVKVEDNRLLVKGEHEEEKEddhglrSERSYGSFSRKFTLPENADPDKVKASL-KDGVLTVTVPkL 88

                          90
                  ....*....|..
gi 399894425  179 PAIAGEKLIPIQ 190
Cdd:pfam00011  89 EPEPKERRIQIQ 100

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 399894425 106 KLRYDLSQYKPEEIVVKTVDNKLFIHAKHEEKTDSKS-VYREYNREFMLPSGTNPEAIRSSLSKDGVLTVEAPL 178
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 399894425 110 DLSQYKPEEIVVKTVDNKLFIHAKHEEKTDSKS-VYREYNREFMLPSGTNPEAIRSSLSKDGVLTVEAP 177
Cdd:cd06478   14 DVKHFSPEELSVKVLGDFVEIHGKHEERQDEHGfISREFHRRYRLPPGVDPAAITSSLSADGVLTISGP 82

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 399894425  96 IQEDGEKklLKLRYDLSQYKPEEIVVKTVDNKLFIHAKHEEKTDSKS-------VYREYNREFMLPSGTNPEAIRSSLsK 168
Cdd:cd06464    2 VYETDDA--YVVEADLPGFKKEDIKVEVEDGVLTISGEREEEEEEEEnylrrerSYGSFSRSFRLPEDVDPDKIKASL-E 78

                 ....*....
gi 399894425 169 DGVLTVEAP 177
Cdd:cd06464   79 NGVLTITLP 87

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 399894425  96 IQEDGEKklLKLRYDLSQYKPEEIVVKTVDNKLFIHAKHEEKTDSKSVYREYNREFMLPSGTNPEAIRSSLsKDGVLTVE 175
Cdd:cd00298    1 WYQTDDE--VVVTVDLPGVKKEDIKVEVEDNVLTISGKREEEEERERSYGEFERSFELPEDVDPEKSKASL-ENGVLEIT 77

                 ..
gi 399894425 176 AP 177
Cdd:cd00298   78 LP 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 399894425  96 IQEDGEKKLLKLryDLSQYKPEEIVVKTVDNKLFIHAKHEEKTDSKS-VYREYNREFMLPSGTNPEAIRSSLSKDGVLTV 174
Cdd:cd06497    5 VRSDRDKFTIYL--DVKHFSPEDLTVKVLDDYVEIHGKHSERQDDHGyISREFHRRYRLPSNVDQSAITCSLSADGMLTF 82

                 ...
gi 399894425 175 EAP 177
Cdd:cd06497   83 SGP 85

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 399894425  96 IQEDGEKklLKLRYDLSQYKPEEIVVKTVDNKLFIHAKHEEKTDSKSV--------YREYNREFMLPSGTNPEAIRSSLs 167
Cdd:COG0071    4 IEETDDA--YVITADLPGVDKEDIDVTVEGNVLTISGERKEEEEEEGEnylrrerrYGSFERSFTLPDDVDVDKIEASY- 80

                         90       100
                 ....*....|....*....|...
gi 399894425 168 KDGVLTVEAPLPAIAGEKLIPIQ 190
Cdd:COG0071   81 ENGVLTITLPKAEEAKPRKIEIK 103

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 399894425 110 DLSQYKPEEIVVKTVDNKLFIHAkheEKTDSK-SVYREYNREFMLPSGTNPEAIRSSLSKDGVLTVEA 176
Cdd:cd06479   15 DVSDFSPEDIIVTTSNNQIEVHA---EKLASDgTVMNTFTHKCQLPEDVDPTSVSSSLGEDGTLTIKA 79

Group of bacterial proteins containing an alpha crystallin domain (ACD) similar to Lactobacillus plantarum (Lp) small heat shock proteins (sHsp) HSP 18.5, HSP 18.55 and HSP 19.3. sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits. Transcription of the genes encoding Lp HSP 18.5, 18.55 and 19.3 is regulated by a variety of stresses including heat, cold and ethanol. Early growing L. plantarum cells contain elevated levels of these mRNAs which rapidly fall of as the cells enter stationary phase. Also belonging to this group is Bifidobacterium breve (Bb) HSP20 and Oenococcus oenis (syn. Leuconostoc oenos) (Oo) HSP18. Transcription of the gene encoding BbHSP20 is strongly induced following heat or osmotic shock, and that of the gene encoding OoHSP18 following heat, ethanol or acid shock. OoHSP18 is peripherally associated with the cytoplasmic membrane.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 399894425  96 IQEDGEKKLLKLryDLSQYKPEEIVVKTVDNKLFIHAKHEEKTDSKS-----VYRE-----YNREFMLPsGTNPEAIRSS 165
Cdd:cd06471    5 IKETDDEYIVEA--DLPGFKKEDIKLDYKDGYLTISAKRDESKDEKDkkgnyIRREryygsFSRSFYLP-NVDEEEIKAK 81

                         90
                 ....*....|..
gi 399894425 166 LsKDGVLTVEAP 177
Cdd:cd06471   82 Y-ENGVLKITLP 92