ID   HSPB3_HUMAN             Reviewed;         150 AA.
AC   Q12988;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 2.
DT   28-JAN-2026, entry version 165.
DE   RecName: Full=Heat shock protein beta-3;
DE            Short=HspB3;
DE   AltName: Full=Heat shock 17 kDa protein;
DE            Short=HSP 17;
DE   AltName: Full=Heat shock protein family B member 3;
DE   AltName: Full=Protein 3;
GN   Name=HSPB3; Synonyms=HSP27, HSPL27;
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].
RC   TISSUE=Heart;
RX   PubMed=9858786; DOI=10.1016/s0167-4838(98)00215-5;
RA   Boelens W.C., van Boekel M.A., de Jong W.W.;
RT   "HspB3, the most deviating of the six known human small heat shock
RT   proteins.";
RL   Biochim. Biophys. Acta 1388:513-516(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Heart;
RX   PubMed=8972725; DOI=10.1016/s0167-4889(96)00121-8;
RA   Lam W.Y., Wing Tsui S.K.W., Law P.T.W., Luk S.C., Fung K.P., Lee C.Y.,
RA   Waye M.M.Y.;
RT   "Isolation and characterization of a human heart cDNA encoding a new member
RT   of the small heat shock protein family -- HSPL27.";
RL   Biochim. Biophys. Acta 1314:120-124(1996).
RN   [3]
RP   SEQUENCE REVISION.
RA   Waye M.M.Y.;
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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   [5]
RP   VARIANT HMND4 SER-7.
RX   PubMed=20142617; DOI=10.1212/wnl.0b013e3181cef84a;
RA   Kolb S.J., Snyder P.J., Poi E.J., Renard E.A., Bartlett A., Gu S.,
RA   Sutton S., Arnold W.D., Freimer M.L., Lawson V.H., Kissel J.T., Prior T.W.;
RT   "Mutant small heat shock protein B3 causes motor neuropathy: utility of a
RT   candidate gene approach.";
RL   Neurology 74:502-506(2010).
CC   -!- FUNCTION: Inhibitor of actin polymerization.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19464326}. Nucleus
CC       {ECO:0000269|PubMed:19464326}. Note=Translocates to nuclear foci during
CC       heat shock.
CC   -!- DISEASE: Neuronopathy, distal hereditary motor, autosomal dominant 4
CC       (HMND4) [MIM:613376]: 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:20142617}. Note=The disease is caused by
CC       variants 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   ---------------------------------------------------------------------------
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; U15590; AAD05360.1; -; mRNA.
DR   EMBL; Y17782; CAA76848.1; -; mRNA.
DR   CCDS; CCDS3961.1; -.
DR   RefSeq; NP_006299.1; NM_006308.3.
DR   PDB; 6F2R; X-ray; 3.90 A; Q/T/V=1-149.
DR   PDBsum; 6F2R; -.
DR   AlphaFoldDB; Q12988; -.
DR   SMR; Q12988; -.
DR   BioGRID; 114470; 19.
DR   FunCoup; Q12988; 140.
DR   IntAct; Q12988; 19.
DR   STRING; 9606.ENSP00000303394; -.
DR   GlyGen; Q12988; 1 site.
DR   iPTMnet; Q12988; -.
DR   PhosphoSitePlus; Q12988; -.
DR   BioMuta; HSPB3; -.
DR   DMDM; 6016270; -.
DR   MassIVE; Q12988; -.
DR   PaxDb; 9606-ENSP00000303394; -.
DR   PeptideAtlas; Q12988; -.
DR   ProteomicsDB; 59085; -.
DR   Antibodypedia; 23356; 49 antibodies from 13 providers.
DR   DNASU; 8988; -.
DR   Ensembl; ENST00000302005.3; ENSP00000303394.1; ENSG00000169271.3.
DR   GeneID; 8988; -.
DR   KEGG; hsa:8988; -.
DR   MANE-Select; ENST00000302005.3; ENSP00000303394.1; NM_006308.3; NP_006299.1.
DR   AGR; HGNC:5248; -.
DR   ClinPGx; PA29513; -.
DR   CTD; 8988; -.
DR   DisGeNET; 8988; -.
DR   GeneCards; HSPB3; -.
DR   GeneReviews; HSPB3; -.
DR   HGNC; HGNC:5248; HSPB3.
DR   HPA; ENSG00000169271; Group enriched (heart muscle, skeletal muscle, tongue).
DR   MalaCards; HSPB3; -.
DR   MIM; 604624; gene.
DR   MIM; 613376; phenotype.
DR   OpenTargets; ENSG00000169271; -.
DR   Orphanet; 139525; Distal hereditary motor neuropathy type 2.
DR   VEuPathDB; HostDB:ENSG00000169271; -.
DR   eggNOG; KOG3591; Eukaryota.
DR   GeneTree; ENSGT00940000161247; -.
DR   HOGENOM; CLU_151649_0_0_1; -.
DR   InParanoid; Q12988; -.
DR   OMA; HGPRMDE; -.
DR   OrthoDB; 1431247at2759; -.
DR   PAN-GO; Q12988; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; Q12988; -.
DR   PathwayCommons; Q12988; -.
DR   SignaLink; Q12988; -.
DR   Agora; ENSG00000169271; -.
DR   BioGRID-ORCS; 8988; 11 hits in 1153 CRISPR screens.
DR   CD-CODE; 462A97B5; Leucocyte nuclear body.
DR   GenomeRNAi; 8988; -.
DR   Pharos; Q12988; Tbio.
DR   PRO; PR:Q12988; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q12988; protein.
DR   Bgee; ENSG00000169271; Expressed in heart right ventricle and 126 other cell types or tissues.
DR   ExpressionAtlas; Q12988; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0006986; P:response to unfolded protein; TAS:ProtInc.
DR   CDD; cd06477; ACD_HspB3_Like; 1.
DR   FunFam; 2.60.40.790:FF:000046; Heat shock protein beta-3; 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; IPR033894; HSPB3.
DR   PANTHER; PTHR47097; HEAT SHOCK PROTEIN BETA-3; 1.
DR   PANTHER; PTHR47097:SF1; HEAT SHOCK PROTEIN BETA-3; 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; Cytoplasm; Disease variant; Neurodegeneration; Neuropathy;
KW   Nucleus; Proteomics identification; Reference proteome; Stress response.
FT   CHAIN           1..150
FT                   /note="Heat shock protein beta-3"
FT                   /id="PRO_0000125936"
FT   DOMAIN          47..150
FT                   /note="sHSP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00285"
FT   VARIANT         7
FT                   /note="R -> S (in HMND4; dbSNP:rs139382018)"
FT                   /evidence="ECO:0000269|PubMed:20142617"
FT                   /id="VAR_063773"
FT   VARIANT         67
FT                   /note="G -> S (in dbSNP:rs35258119)"
FT                   /id="VAR_061271"
SQ   SEQUENCE   150 AA;  16966 MW;  CE5A4DF34CD38715 CRC64;
     MAKIILRHLI EIPVRYQEEF EARGLEDCRL DHALYALPGP TIVDLRKTRA AQSPPVDSAA
     ETPPREGKSH FQILLDVVQF LPEDIIIQTF EGWLLIKAQH GTRMDEHGFI SRSFTRQYKL
     PDGVEIKDLS AVLCHDGILV VEVKDPVGTK
//