ID HSPB8_HUMAN Reviewed; 196 AA. AC Q9UJY1; B2R6A6; Q6FIH3; Q9UKS3; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 28-JAN-2026, entry version 214. DE RecName: Full=Heat shock protein beta-8; DE Short=HspB8; DE AltName: Full=Alpha-crystallin C chain; DE AltName: Full=E2-induced gene 1 protein; DE AltName: Full=Heat shock protein family B member 8; DE AltName: Full=Protein kinase H11; DE AltName: Full=Small stress protein-like protein HSP22; GN Name=HSPB8; Synonyms=CRYAC, E2IG1, HSP22; ORFNames=PP1629; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=11085516; RA Charpentier A.H., Bednarek A.K., Daniel R.L., Hawkins K.A., Laflin K.J., RA Gaddis S., MacLeod M.C., Aldaz C.M.; RT "Effects of estrogen on global gene expression: identification of novel RT targets of estrogen action."; RL Cancer Res. 60:5977-5983(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH HSPB1. RX PubMed=11342557; DOI=10.1074/jbc.m103001200; RA Benndorf R., Sun X., Gilmont R.R., Biederman K.J., Molloy M.P., RA Goodmurphy C.W., Cheng H., Andrews P.C., Welsh M.J.; RT "HSP22, a new member of the small heat shock protein superfamily, interacts RT with mimic of phosphorylated HSP27 (3DHSP27)."; RL J. Biol. Chem. 276:26753-26761(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Melanoma; RX PubMed=10833516; DOI=10.1074/jbc.m002140200; RA Smith C.C., Yu Y.X., Kulka M., Aurelian L.; RT "A novel human gene similar to the protein kinase (PK) coding domain of the RT large subunit of herpes simplex virus type 2 ribonucleotide reductase RT (ICP10) codes for a serine-threonine PK and is expressed in melanoma RT cells."; RL J. Biol. Chem. 275:25690-25699(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP PHOSPHORYLATION AT THR-63, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11816564; DOI=10.1021/ac0104227; RA Molloy M.P., Andrews P.C.; RT "Phosphopeptide derivatization signatures to identify serine and threonine RT phosphorylated peptides by mass spectrometry."; RL Anal. Chem. 73:5387-5394(2001). RN [12] RP TISSUE SPECIFICITY. RX PubMed=11470154; DOI=10.1016/s0167-4781(01)00237-8; RA Kappe G., Verschuure P., Philipsen R.L.A., Staalduinen A.A., RA Van de Boogaart P., Boelens W.C., de Jong W.W.; RT "Characterization of two novel human small heat shock proteins: protein RT kinase-related HspB8 and testis-specific HspB9."; RL Biochim. Biophys. Acta 1520:1-6(2001). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP SUBCELLULAR LOCATION. RX PubMed=19464326; DOI=10.1016/j.bbamcr.2009.05.005; RA Vos M.J., Kanon B., Kampinga H.H.; RT "HSPB7 is a SC35 speckle resident small heat shock protein."; RL Biochim. Biophys. Acta 1793:1343-1353(2009). RN [16] RP INTERACTION WITH BAG3; HSPA8 AND STUB1 IN CASA COMPLEX. RX PubMed=20060297; DOI=10.1016/j.cub.2009.11.022; RA Arndt V., Dick N., Tawo R., Dreiseidler M., Wenzel D., Hesse M., RA Fuerst D.O., Saftig P., Saint R., Fleischmann B.K., Hoch M., Hoehfeld J.; RT "Chaperone-assisted selective autophagy is essential for muscle RT maintenance."; RL Curr. Biol. 20:143-148(2010). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP INTERACTION WITH DNAJB6. RX PubMed=22366786; DOI=10.1038/ng.1103; RA Sarparanta J., Jonson P.H., Golzio C., Sandell S., Luque H., Screen M., RA McDonald K., Stajich J.M., Mahjneh I., Vihola A., Raheem O., Penttila S., RA Lehtinen S., Huovinen S., Palmio J., Tasca G., Ricci E., Hackman P., RA Hauser M., Katsanis N., Udd B.; RT "Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 RT cause limb-girdle muscular dystrophy."; RL Nat. Genet. 44:450-455(2012). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP INTERACTION WITH BAG3 AND HSPA1A. RX PubMed=27884606; DOI=10.1016/j.jmb.2016.11.013; RA Rauch J.N., Tse E., Freilich R., Mok S.A., Makley L.N., Southworth D.R., RA Gestwicki J.E.; RT "BAG3 is a modular, scaffolding protein that physically links heat shock RT protein 70 (Hsp70) to the small heat shock proteins."; RL J. Mol. Biol. 429:128-141(2017). RN [21] RP VARIANTS HMND2 GLU-141 AND ASN-141, INVOLVEMENT IN HMND2, AND RP CHARACTERIZATION OF VARIANTS HMND2 GLU-141 AND ASN-141. RX PubMed=15122253; DOI=10.1038/ng1328; RA Irobi J., Van Impe K., Seeman P., Jordanova A., Dierick I., Verpoorten N., RA Michalik A., De Vriendt E., Jacobs A., Van Gerwen V., Vennekens K., RA Mazanec R., Tournev I., Hilton-Jones D., Talbot K., Kremensky I., RA Van Den Bosch L., Robberecht W., Van Vandekerckhove J., Broeckhoven C., RA Gettemans J., De Jonghe P., Timmerman V.; RT "Hot-spot residue in small heat-shock protein 22 causes distal motor RT neuropathy."; RL Nat. Genet. 36:597-601(2004). RN [22] RP VARIANT CMT2L ASN-141, AND INVOLVEMENT IN CMT2L. RX PubMed=15565283; DOI=10.1007/s00439-004-1218-3; RA Tang B.-S., Zhao G.-H., Luo W., Xia K., Cai F., Pan Q., Zhang R.-X., RA Zhang F.F., Liu X.-M., Chen B., Zhang C., Shen L., Jiang H., Long Z.G., RA Dai H.-P.; RT "Small heat-shock protein 22 mutated in autosomal dominant Charcot-Marie- RT Tooth disease type 2L."; RL Hum. Genet. 116:222-224(2005). RN [23] RP VARIANTS [LARGE SCALE ANALYSIS] SER-67 AND MET-78. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [24] RP VARIANT CMT2L THR-141, AND INVOLVEMENT IN CMT2L. RX PubMed=23796487; DOI=10.1016/j.nmd.2013.05.009; RA Nakhro K., Park J.M., Kim Y.J., Yoon B.R., Yoo J.H., Koo H., Choi B.O., RA Chung K.W.; RT "A novel Lys141Thr mutation in small heat shock protein 22 (HSPB8) gene in RT Charcot-Marie-Tooth disease type 2L."; RL Neuromuscul. Disord. 23:656-663(2013). RN [25] RP VARIANT MFM13 GLU-141, INVOLVEMENT IN MFM13, AND CHARACTERIZATION OF RP VARIANT MFM13 GLU-141. RX PubMed=26718575; DOI=10.1212/wnl.0000000000002324; RA Ghaoui R., Palmio J., Brewer J., Lek M., Needham M., Evilae A., Hackman P., RA Jonson P.H., Penttilae S., Vihola A., Huovinen S., Lindfors M., Davis R.L., RA Waddell L., Kaur S., Yiannikas C., North K., Clarke N., MacArthur D.G., RA Sue C.M., Udd B.; RT "Mutations in HSPB8 causing a new phenotype of distal myopathy and motor RT neuropathy."; RL Neurology 86:391-398(2016). RN [26] RP INVOLVEMENT IN MFM13. RX PubMed=28501893; DOI=10.1007/s00401-017-1724-8; RA Echaniz-Laguna A., Lornage X., Lannes B., Schneider R., Bierry G., RA Dondaine N., Boland A., Deleuze J.F., Boehm J., Thompson J., Laporte J., RA Biancalana V.; RT "HSPB8 haploinsufficiency causes dominant adult-onset axial and distal RT myopathy."; RL Acta Neuropathol. 134:163-165(2017). RN [27] RP VARIANTS HMND2 LEU-90; THR-138; ASN-141 AND MET-141, INVOLVEMENT IN HMND2, RP INTERACTION WITH BAG3, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF RP VARIANTS HMND2 LEU-90; THR-138; ASN-141 AND MET-141. RX PubMed=28144995; DOI=10.1002/humu.23189; RA Echaniz-Laguna A., Geuens T., Petiot P., Pereon Y., Adriaenssens E., RA Haidar M., Capponi S., Maisonobe T., Fournier E., Dubourg O., Degos B., RA Salachas F., Lenglet T., Eymard B., Delmont E., Pouget J., RA Juntas Morales R., Goizet C., Latour P., Timmerman V., Stojkovic T.; RT "Axonal Neuropathies due to Mutations in Small Heat Shock Proteins: RT Clinical, Genetic, and Functional Insights into Novel Mutations."; RL Hum. Mutat. 38:556-568(2017). RN [28] RP VARIANT HMND2 GLU-141, AND INVOLVEMENT IN HMND2. RX PubMed=29029362; DOI=10.1111/ene.13478; RA Cortese A., Laura M., Casali C., Nishino I., Hayashi Y.K., Magri S., RA Taroni F., Stuani C., Saveri P., Moggio M., Ripolone M., Prelle A., RA Pisciotta C., Sagnelli A., Pichiecchio A., Reilly M.M., Buratti E., RA Pareyson D.; RT "Altered TDP-43-dependent splicing in HSPB8-related distal hereditary motor RT neuropathy and myofibrillar myopathy."; RL Eur. J. Neurol. 25:154-163(2018). RN [29] RP INVOLVEMENT IN MFM13. RX PubMed=31403083; DOI=10.1212/nxg.0000000000000349; RA Al-Tahan S., Weiss L., Yu H., Tang S., Saporta M., Vihola A., Mozaffar T., RA Udd B., Kimonis V.; RT "New family with HSPB8-associated autosomal dominant rimmed vacuolar RT myopathy."; RL Neurol. Genet. 5:e349-e349(2019). RN [30] RP INVOLVEMENT IN MFM13. RX PubMed=32165108; DOI=10.1016/j.nmd.2020.02.005; RA Nicolau S., Liewluck T., Elliott J.L., Engel A.G., Milone M.; RT "A novel heterozygous mutation in the C-terminal region of HSPB8 leads to RT limb-girdle rimmed vacuolar myopathy."; RL Neuromuscul. Disord. 30:236-240(2020). RN [31] RP INVOLVEMENT IN MFM13. RX PubMed=33744911; DOI=10.1038/s10038-021-00916-y; RA Inoue-Shibui A., Niihori T., Kobayashi M., Suzuki N., Izumi R., Warita H., RA Hara K., Shirota M., Funayama R., Nakayama K., Nishino I., Aoki M., RA Aoki Y.; RT "A novel deletion in the C-terminal region of HSPB8 in a family with rimmed RT vacuolar myopathy."; RL J. Hum. Genet. 66:965-972(2021). RN [32] RP INVOLVEMENT IN MFM13. RX PubMed=39548192; DOI=10.1038/s10038-024-01305-x; RA Yang G., Lv X., Yang M., Feng Y., Wang G., Yan C., Lin P.; RT "Expanding the spectrum of HSPB8-related myopathy: a novel mutation causing RT atypical pediatric-onset axial and limb-girdle involvement with autophagy RT abnormalities and molecular dynamics studies."; RL J. Hum. Genet. 70:159-165(2025). CC -!- FUNCTION: Involved in the chaperone-assisted selective autophagy CC (CASA), a crucial process for protein quality control, particularly in CC mechanical strained cells and tissues such as muscle. Displays CC temperature-dependent chaperone activity. CC {ECO:0000250|UniProtKB:Q9JK92}. CC -!- SUBUNIT: Monomer. Forms a ternary complex with BAG3 and HSPA1A CC (PubMed:27884606). Component of the chaperone-assisted selective CC autophagy (CASA) complex consisting of BAG3, HSPA8/HSC70, HSPB8 and CC STUB1/CHIP (PubMed:20060297). Interacts with HSPB1 (PubMed:11342557). CC Interacts with DNAJB6 (PubMed:22366786). Interacts with BAG3 CC (PubMed:28144995). {ECO:0000269|PubMed:11342557, CC ECO:0000269|PubMed:22366786, ECO:0000269|PubMed:27884606, CC ECO:0000269|PubMed:28144995}. CC -!- INTERACTION: CC Q9UJY1; Q7L5A3: ATOSB; NbExp=3; IntAct=EBI-739074, EBI-745689; CC Q9UJY1; O95817: BAG3; NbExp=13; IntAct=EBI-739074, EBI-747185; CC Q9UJY1; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-739074, EBI-739879; CC Q9UJY1; Q9UNI6: DUSP12; NbExp=3; IntAct=EBI-739074, EBI-715161; CC Q9UJY1; P04792: HSPB1; NbExp=3; IntAct=EBI-739074, EBI-352682; CC Q9UJY1; Q16082: HSPB2; NbExp=3; IntAct=EBI-739074, EBI-739395; CC Q9UJY1; Q9UBY9: HSPB7; NbExp=11; IntAct=EBI-739074, EBI-739361; CC Q9UJY1; Q9UJY1: HSPB8; NbExp=6; IntAct=EBI-739074, EBI-739074; CC Q9UJY1; Q8IVT2: MISP; NbExp=3; IntAct=EBI-739074, EBI-2555085; CC Q9UJY1; Q15773: MLF2; NbExp=3; IntAct=EBI-739074, EBI-1051875; CC Q9UJY1; Q9HC29-1: NOD2; NbExp=2; IntAct=EBI-739074, EBI-21496213; CC Q9UJY1; Q2TAL8: QRICH1; NbExp=7; IntAct=EBI-739074, EBI-2798044; CC Q9UJY1; P49247: RPIA; NbExp=3; IntAct=EBI-739074, EBI-744831; CC Q9UJY1; O15375: SLC16A5; NbExp=3; IntAct=EBI-739074, EBI-12874738; CC Q9UJY1; O14512: SOCS7; NbExp=3; IntAct=EBI-739074, EBI-1539606; CC Q9UJY1; O75865-2: TRAPPC6A; NbExp=3; IntAct=EBI-739074, EBI-8451480; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19464326, CC ECO:0000269|PubMed:28144995}. Nucleus {ECO:0000269|PubMed:19464326}. CC Note=Translocates to nuclear foci during heat shock. CC -!- TISSUE SPECIFICITY: Predominantly expressed in skeletal muscle and CC heart. {ECO:0000269|PubMed:11470154}. CC -!- INDUCTION: By 17-beta-estradiol. CC -!- DISEASE: Neuronopathy, distal hereditary motor, autosomal dominant 2 CC (HMND2) [MIM:158590]: A form of distal hereditary motor neuronopathy, a CC heterogeneous group of neuromuscular disorders caused by selective CC degeneration of motor neurons in the anterior horn of the spinal cord, CC without sensory deficit in the posterior horn. The overall clinical CC picture consists of a classical distal muscular atrophy syndrome in the CC legs without clinical sensory loss. The disease starts with weakness CC and wasting of distal muscles of the anterior tibial and peroneal CC compartments of the legs. Later on, weakness and atrophy may expand to CC the proximal muscles of the lower limbs and/or to the distal upper CC limbs. {ECO:0000269|PubMed:15122253, ECO:0000269|PubMed:28144995, CC ECO:0000269|PubMed:29029362}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, type 2L (CMT2L) CC [MIM:608673]: An autosomal dominant, axonal form of Charcot-Marie-Tooth CC disease, a disorder of the peripheral nervous system, characterized by CC progressive weakness and atrophy, initially of the peroneal muscles and CC later of the distal muscles of the arms. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathies (designated CMT1 when they are dominantly inherited) and CC primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 CC group are characterized by signs of axonal degeneration in the absence CC of obvious myelin alterations, normal or slightly reduced nerve CC conduction velocities, and progressive distal muscle weakness and CC atrophy. {ECO:0000269|PubMed:15565283, ECO:0000269|PubMed:23796487}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Myopathy, myofibrillar, 13, with rimmed vacuoles (MFM13) CC [MIM:621078]: A form of myofibrillar myopathy, a group of chronic CC neuromuscular disorders characterized at ultrastructural level by CC disintegration of the sarcomeric Z disk and myofibrils, and replacement CC of the normal myofibrillar markings by small dense granules, or larger CC hyaline masses, or amorphous material. MFM13 is an autosomal dominant CC form characterized by progressive distal and proximal muscle weakness, CC muscle atrophy, and unsteady gait and walking difficulties. Symptoms CC usually begin in adulthood, although earlier disease onset has been CC reported in some cases. Muscle biopsy shows myofibrillar changes and CC rimmed vacuoles. Some patients have features of a peripheral motor or CC sensorimotor neuropathy. {ECO:0000269|PubMed:26718575, CC ECO:0000269|PubMed:28501893, ECO:0000269|PubMed:31403083, CC ECO:0000269|PubMed:32165108, ECO:0000269|PubMed:33744911, CC ECO:0000269|PubMed:39548192}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the small heat shock protein (HSP20) family. CC {ECO:0000255|PROSITE-ProRule:PRU00285}. CC -!- CAUTION: Was reported to have a protein kinase activity and to act as a CC Mn(2+)-dependent serine-threonine-specific protein kinase. CC {ECO:0000305|PubMed:10833516}. CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="https://uantwerpen.vib.be/CMTMutations"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF191017; AAF09481.1; -; mRNA. DR EMBL; AF250138; AAF65562.1; -; mRNA. DR EMBL; AF133207; AAD55359.1; -; mRNA. DR EMBL; AL136936; CAB66870.1; -; mRNA. DR EMBL; AF217987; AAG17230.1; -; mRNA. DR EMBL; BT006876; AAP35522.1; -; mRNA. DR EMBL; CR533453; CAG38484.1; -; mRNA. DR EMBL; AK312501; BAG35403.1; -; mRNA. DR EMBL; CH471054; EAW98144.1; -; Genomic_DNA. DR EMBL; BC002673; AAH02673.1; -; mRNA. DR CCDS; CCDS9189.1; -. DR RefSeq; NP_055180.1; NM_014365.3. DR PDB; 8S7A; X-ray; 1.95 A; A=87-168. DR PDBsum; 8S7A; -. DR AlphaFoldDB; Q9UJY1; -. DR SMR; Q9UJY1; -. DR BioGRID; 117689; 191. DR CORUM; Q9UJY1; -. DR ELM; Q9UJY1; -. DR FunCoup; Q9UJY1; 487. DR IntAct; Q9UJY1; 158. DR MINT; Q9UJY1; -. DR STRING; 9606.ENSP00000281938; -. DR GlyGen; Q9UJY1; 3 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9UJY1; -. DR PhosphoSitePlus; Q9UJY1; -. DR BioMuta; HSPB8; -. DR DMDM; 13431576; -. DR jPOST; Q9UJY1; -. DR MassIVE; Q9UJY1; -. DR PaxDb; 9606-ENSP00000281938; -. DR PeptideAtlas; Q9UJY1; -. DR ProteomicsDB; 84690; -. DR Pumba; Q9UJY1; -. DR Antibodypedia; 18895; 603 antibodies from 42 providers. DR DNASU; 26353; -. DR Ensembl; ENST00000281938.7; ENSP00000281938.3; ENSG00000152137.8. DR GeneID; 26353; -. DR KEGG; hsa:26353; -. DR MANE-Select; ENST00000281938.7; ENSP00000281938.3; NM_014365.3; NP_055180.1. DR UCSC; uc001txb.4; human. DR AGR; HGNC:30171; -. DR ClinPGx; PA134900173; -. DR CTD; 26353; -. DR DisGeNET; 26353; -. DR GeneCards; HSPB8; -. DR GeneReviews; HSPB8; -. DR HGNC; HGNC:30171; HSPB8. DR HPA; ENSG00000152137; Tissue enhanced (skeletal). DR MalaCards; HSPB8; -. DR MIM; 158590; phenotype. DR MIM; 608014; gene. DR MIM; 608673; phenotype. DR MIM; 621078; phenotype. DR OpenTargets; ENSG00000152137; -. DR Orphanet; 99945; Autosomal dominant Charcot-Marie-Tooth disease type 2L. DR Orphanet; 476093; Autosomal dominant distal axonal motor neuropathy-myofibrillar myopathy syndrome. DR Orphanet; 139525; Distal hereditary motor neuropathy type 2. DR VEuPathDB; HostDB:ENSG00000152137; -. DR eggNOG; KOG3591; Eukaryota. DR GeneTree; ENSGT00940000160605; -. DR HOGENOM; CLU_095001_0_1_1; -. DR InParanoid; Q9UJY1; -. DR OMA; PCHYPSR; -. DR OrthoDB; 10060792at2759; -. DR PAN-GO; Q9UJY1; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q9UJY1; -. DR PathwayCommons; Q9UJY1; -. DR Reactome; R-HSA-3371571; HSF1-dependent transactivation. DR SignaLink; Q9UJY1; -. DR SIGNOR; Q9UJY1; -. DR Agora; ENSG00000152137; -. DR BioGRID-ORCS; 26353; 17 hits in 1155 CRISPR screens. DR ChiTaRS; HSPB8; human. DR GeneWiki; HSPB8; -. DR GenomeRNAi; 26353; -. DR Pharos; Q9UJY1; Tbio. DR PRO; PR:Q9UJY1; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9UJY1; protein. DR Bgee; ENSG00000152137; Expressed in skeletal muscle tissue of rectus abdominis and 196 other cell types or tissues. DR ExpressionAtlas; Q9UJY1; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0101031; C:protein folding chaperone complex; IDA:ARUK-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0042803; F:protein homodimerization activity; IPI:ARUK-UCL. DR GO; GO:0034620; P:cellular response to unfolded protein; IMP:ARUK-UCL. DR GO; GO:1905337; P:positive regulation of aggrephagy; IMP:ARUK-UCL. DR CDD; cd06480; ACD_HspB8_like; 1. DR DisProt; DP04309; -. DR FunFam; 2.60.40.790:FF:000028; Heat shock protein beta-8; 1. DR Gene3D; 2.60.40.790; -; 1. DR InterPro; IPR002068; A-crystallin/Hsp20_dom. DR InterPro; IPR001436; Alpha-crystallin/sHSP_animal. DR InterPro; IPR008978; HSP20-like_chaperone. DR InterPro; IPR043254; HSPB8. DR InterPro; IPR042790; HspB8_ACD. DR PANTHER; PTHR46906; HEAT SHOCK PROTEIN BETA-8; 1. DR PANTHER; PTHR46906:SF1; HEAT SHOCK PROTEIN BETA-8; 1. DR Pfam; PF00011; HSP20; 1. DR PRINTS; PR00299; ACRYSTALLIN. DR SUPFAM; SSF49764; HSP20-like chaperones; 1. DR PROSITE; PS01031; SHSP; 1. PE 1: Evidence at protein level; KW 3D-structure; Chaperone; Charcot-Marie-Tooth disease; Cytoplasm; KW Disease variant; Methylation; Myofibrillar myopathy; Neurodegeneration; KW Neuropathy; Nucleus; Phosphoprotein; Proteomics identification; KW Reference proteome; Stress response. FT CHAIN 1..196 FT /note="Heat shock protein beta-8" FT /id="PRO_0000125945" FT DOMAIN 74..185 FT /note="sHSP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00285" FT REGION 176..196 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 177..196 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 24 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 57 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9EPX0" FT MOD_RES 63 FT /note="Phosphothreonine; by PKC; in vitro" FT /evidence="ECO:0000269|PubMed:11816564" FT MOD_RES 71 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9JK92" FT MOD_RES 78 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9JK92" FT VARIANT 67 FT /note="G -> S (in a glioblastoma multiforme sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042244" FT VARIANT 78 FT /note="R -> M (in dbSNP:rs55826713)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042245" FT VARIANT 90 FT /note="P -> L (in HMND2; uncertain significance; no effect FT on cytoskeleton architecture; no effect on cytoplasmic FT location; no effect on interaction with BAG3; FT dbSNP:rs1565927080)" FT /evidence="ECO:0000269|PubMed:28144995" FT /id="VAR_078133" FT VARIANT 138 FT /note="N -> T (in HMND2; uncertain significance; no effect FT on cytoskeleton architecture; no effect on cytoplasmic FT location; no effect on interaction with BAG3; FT dbSNP:rs1565929080)" FT /evidence="ECO:0000269|PubMed:28144995" FT /id="VAR_078134" FT VARIANT 141 FT /note="K -> E (in HMND2 and MFM13; pathogenic; MFM13 FT patients display concomitant neuropathy features; affects FT chaperone function and results in increased protein FT aggregation and accumulation of cytoplasmic aggregates; FT increased interaction with HSPB1; dbSNP:rs104894351)" FT /evidence="ECO:0000269|PubMed:15122253, FT ECO:0000269|PubMed:26718575, ECO:0000269|PubMed:29029362" FT /id="VAR_018504" FT VARIANT 141 FT /note="K -> M (in HMND2; likely pathogenic; increased FT interaction with BAG3; no effect on cytoskeleton FT architecture; no effect on cytoplasmic location; FT dbSNP:rs1565929090)" FT /evidence="ECO:0000269|PubMed:28144995" FT /id="VAR_078135" FT VARIANT 141 FT /note="K -> N (in CMT2L and HMND2; pathogenic; affects FT chaperone function and results in increased protein FT aggregation and accumulation of cytoplasmic aggregates; FT increased interaction with HSPB1; no effect on cytoskeleton FT architecture; no effect on cytoplasmic location; increased FT interaction with BAG3; dbSNP:rs104894345)" FT /evidence="ECO:0000269|PubMed:15122253, FT ECO:0000269|PubMed:15565283, ECO:0000269|PubMed:28144995" FT /id="VAR_018505" FT VARIANT 141 FT /note="K -> T (in CMT2L; pathogenic; dbSNP:rs1565929090)" FT /evidence="ECO:0000269|PubMed:23796487" FT /id="VAR_090397" FT CONFLICT 51 FT /note="W -> C (in Ref. 3; AAD55359)" FT /evidence="ECO:0000305" SQ SEQUENCE 196 AA; 21604 MW; B76058CED52292CB CRC64; MADGQMPFSC HYPSRLRRDP FRDSPLSSRL LDDGFGMDPF PDDLTASWPD WALPRLSSAW PGTLRSGMVP RGPTATARFG VPAEGRTPPP FPGEPWKVCV NVHSFKPEEL MVKTKDGYVE VSGKHEEKQQ EGGIVSKNFT KKIQLPAEVD PVTVFASLSP EGLLIIEAPQ VPPYSTFGES SFNNELPQDS QEVTCT //