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

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gi 1576727526  56 SFQIKVDAQGFAPEDLVVRIDGQNLTVTGQRQHESNDPSRGRYRMEQ---SVHRQMQLPPTLDPAAMTCSL 123
Cdd:COG0071    10 AYVITADLPGVDKEDIDVTVEGNVLTISGERKEEEEEEGENYLRRERrygSFERSFTLPDDVDVDKIEASY 80

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1576727526  57 FQIKVDAQGFAPEDLVVRIDGQNLTVTGqrQHESNDPSRGRYRMEqsVHRQMQLPPTLDPAAMTCSLTPSGHLWLRGQN 135
Cdd:cd06526     9 FQVTLDVKGFKPEELKVKVSDNKLVVEG--KHEEREDEHGYVSRE--FTRRYQLPEGVDPDSVTSSLSSDGVLTIEAPK 83

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).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1576727526  56 SFQIKVDAQGFAPEDLVVRIDGQNLTVTGQRQHESndpsrGRYRMEQSVHRQMQLPPTLDPAAMTCSLTPsGHLWLR 132
Cdd:cd00298     7 EVVVTVDLPGVKKEDIKVEVEDNVLTISGKREEEE-----ERERSYGEFERSFELPEDVDPEKSKASLEN-GVLEIT 77

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.

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gi 1576727526  53 EQPSFQIKVDAQGFAPEDLVVRIDGQNLTVTG---QRQHESNDPSRgryrmeqSVHRQMQLPPTLDPAAMTCSLTPSGHL 129
Cdd:cd06478     5 DKDRFSVNLDVKHFSPEELSVKVLGDFVEIHGkheERQDEHGFISR-------EFHRRYRLPPGVDPAAITSSLSADGVL 77

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gi 1576727526 130 WLRG 133
Cdd:cd06478    78 TISG 81

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.

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gi 1576727526  53 EQPSFQIKVDAQGFAPEDLVVRIDGQNLTVTGqrQHESNDPSRGryRMEQSVHRQMQLPPTLDPAAMTCSLTPSGHLWLR 132
Cdd:cd06498     5 EKDKFSVNLDVKHFSPEELKVKVLGDFIEIHG--KHEERQDEHG--FISREFQRKYRIPADVDPLTITSSLSPDGVLTVC 80

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gi 1576727526 133 GQNK 136
Cdd:cd06498    81 GPRK 84

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.

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gi 1576727526  54 QPSFQIKVDAQGFAPEDLVVRIDGQNLTVTGQrqHESNDPSRGRyrMEQSVHRQMQLPPTLDPAAMTCSLTPSGHL 129
Cdd:cd06475     9 ADRWKVSLDVNHFAPEELVVKTKDGVVEITGK--HEEKQDEHGF--VSRCFTRKYTLPPGVDPTAVTSSLSPDGIL 80

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.

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gi 1576727526  57 FQIKVDAQGFAPEDLVVRIDGQNLTVTGQRQHESND 92
Cdd:cd06470    13 YRITLAVAGFSEDDLEIEVENNQLTVTGKKADEENE 48