HS71B_MOUSE
ID HS71B_MOUSE Reviewed; 642 AA.
AC P17879; Q61689; Q925V6;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Heat shock 70 kDa protein 1B;
DE AltName: Full=Heat shock 70 kDa protein 1;
DE Short=HSP70.1;
GN Name=Hspa1b; Synonyms=Hcp70.1, Hsp70-1, Hsp70a1, Hspa1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=A/J;
RX PubMed=2332169; DOI=10.1016/0378-1119(90)90302-8;
RA Hunt C., Calderwood S.;
RT "Characterization and sequence of a mouse hsp70 gene and its expression in
RT mouse cell lines.";
RL Gene 87:199-204(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=129;
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [3]
RP IDENTIFICATION IN A COMPLEX WITH CATSPER1 AND CATSPERB.
RX PubMed=17478420; DOI=10.1074/jbc.m701083200;
RA Liu J., Xia J., Cho K.-H., Clapham D.E., Ren D.;
RT "CatSperbeta, a novel transmembrane protein in the CatSper channel
RT complex.";
RL J. Biol. Chem. 282:18945-18952(2007).
RN [4]
RP IDENTIFICATION IN A COMPLEX WITH CATSPER1; CATSPERB AND CATSPERG2.
RX PubMed=19516020; DOI=10.1095/biolreprod.109.077107;
RA Wang H., Liu J., Cho K.-H., Ren D.;
RT "A novel, single, transmembrane protein CATSPERG is associated with
RT CATSPER1 channel protein.";
RL Biol. Reprod. 81:539-544(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH FOXP3.
RX PubMed=23973223; DOI=10.1016/j.immuni.2013.08.006;
RA Chen Z., Barbi J., Bu S., Yang H.Y., Li Z., Gao Y., Jinasena D., Fu J.,
RA Lin F., Chen C., Zhang J., Yu N., Li X., Shan Z., Nie J., Gao Z., Tian H.,
RA Li Y., Yao Z., Zheng Y., Park B.V., Pan Z., Zhang J., Dang E., Li Z.,
RA Wang H., Luo W., Li L., Semenza G.L., Zheng S.G., Loser K., Tsun A.,
RA Greene M.I., Pardoll D.M., Pan F., Li B.;
RT "The ubiquitin ligase Stub1 negatively modulates regulatory T cell
RT suppressive activity by promoting degradation of the transcription factor
RT Foxp3.";
RL Immunity 39:272-285(2013).
CC -!- FUNCTION: Molecular chaperone implicated in a wide variety of cellular
CC processes, including protection of the proteome from stress, folding
CC and transport of newly synthesized polypeptides, activation of
CC proteolysis of misfolded proteins and the formation and dissociation of
CC protein complexes. Plays a pivotal role in the protein quality control
CC system, ensuring the correct folding of proteins, the re-folding of
CC misfolded proteins and controlling the targeting of proteins for
CC subsequent degradation. This is achieved through cycles of ATP binding,
CC ATP hydrolysis and ADP release, mediated by co-chaperones. The co-
CC chaperones have been shown to not only regulate different steps of the
CC ATPase cycle, but they also have an individual specificity such that
CC one co-chaperone may promote folding of a substrate while another may
CC promote degradation. The affinity for polypeptides is regulated by its
CC nucleotide bound state. In the ATP-bound form, it has a low affinity
CC for substrate proteins. However, upon hydrolysis of the ATP to ADP, it
CC undergoes a conformational change that increases its affinity for
CC substrate proteins. It goes through repeated cycles of ATP hydrolysis
CC and nucleotide exchange, which permits cycles of substrate binding and
CC release. The co-chaperones are of three types: J-domain co-chaperones
CC such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide
CC exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70
CC from the ADP-bound to the ATP-bound state thereby promoting substrate
CC release), and the TPR domain chaperones such as HOPX and STUB1.
CC Maintains protein homeostasis during cellular stress through two
CC opposing mechanisms: protein refolding and degradation. Its
CC acetylation/deacetylation state determines whether it functions in
CC protein refolding or protein degradation by controlling the competitive
CC binding of co-chaperones HOPX and STUB1. During the early stress
CC response, the acetylated form binds to HOPX which assists in chaperone-
CC mediated protein refolding, thereafter, it is deacetylated and binds to
CC ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein
CC degradation. Regulates centrosome integrity during mitosis, and is
CC required for the maintenance of a functional mitotic centrosome that
CC supports the assembly of a bipolar mitotic spindle. Enhances STUB1-
CC mediated SMAD3 ubiquitination and degradation and facilitates STUB1-
CC mediated inhibition of TGF-beta signaling. Essential for STUB1-mediated
CC ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg)
CC during inflammation. {ECO:0000250|UniProtKB:P0DMV9}.
CC -!- SUBUNIT: May be an auxiliary component of the CatSper complex
CC (PubMed:17478420, PubMed:19516020). Identified in a IGF2BP1-dependent
CC mRNP granule complex containing untranslated mRNAs (By similarity).
CC Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2 (By
CC similarity). Interacts with TERT; the interaction occurs in the absence
CC of the RNA component, TERC, and dissociates once the TERT complex has
CC formed (By similarity). Interacts with TRIM5 (via B30.2/SPRY domain)
CC (By similarity). Interacts with METTL21A (By similarity). Interacts
CC with PRKN (By similarity). Interacts with FOXP3 (PubMed:23973223).
CC Interacts with NOD2; the interaction enhances NOD2 stability (By
CC similarity). Interacts with DNAJC9 (via J domain) (By similarity).
CC Interacts with ATF5; the interaction protects ATF5 from degradation via
CC proteasome-dependent and caspase-dependent processes. Interacts with
CC NAA10, HSP40, HSP90 and HDAC4. The acetylated form and the non-
CC acetylated form interact with HOPX and STUB1 respectively. Interacts
CC with NEDD1 and SMAD3. Interacts (via NBD) with BAG1, BAG2, BAG3 and
CC HSPH1/HSP105. Interacts with DNAJC8 (By similarity).
CC {ECO:0000250|UniProtKB:P0DMV9, ECO:0000269|PubMed:17478420,
CC ECO:0000269|PubMed:19516020, ECO:0000269|PubMed:23973223}.
CC -!- INTERACTION:
CC P17879; P28301: Lox; NbExp=2; IntAct=EBI-397360, EBI-642911;
CC P17879; P70196: Traf6; NbExp=3; IntAct=EBI-397360, EBI-448028;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P0DMV9}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:P0DMV9}. Note=Localized in cytoplasmic mRNP
CC granules containing untranslated mRNAs. {ECO:0000250|UniProtKB:P0DMV9}.
CC -!- TISSUE SPECIFICITY: Testis-specific.
CC -!- DOMAIN: The N-terminal nucleotide binding domain (NBD) (also known as
CC the ATPase domain) is responsible for binding and hydrolyzing ATP. The
CC C-terminal substrate-binding domain (SBD) (also known as peptide-
CC binding domain) binds to the client/substrate proteins. The two domains
CC are allosterically coupled so that, when ATP is bound to the NBD, the
CC SBD binds relatively weakly to clients. When ADP is bound in the NBD, a
CC conformational change enhances the affinity of the SBD for client
CC proteins. {ECO:0000250|UniProtKB:P0DMV9}.
CC -!- PTM: In response to cellular stress, acetylated at Lys-77 by NA110 and
CC then gradually deacetylated by HDAC4 at later stages. Acetylation
CC enhances its chaperone activity and also determines whether it will
CC function as a chaperone for protein refolding or degradation by
CC controlling its binding to co-chaperones HOPX and STUB1. The acetylated
CC form and the non-acetylated form bind to HOPX and STUB1 respectively.
CC Acetylation also protects cells against various types of cellular
CC stress. {ECO:0000250|UniProtKB:P0DMV9}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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; M35021; AAA37864.1; -; Genomic_DNA.
DR EMBL; AF109906; AAC84168.1; -; Genomic_DNA.
DR CCDS; CCDS37592.1; -.
DR PIR; JH0095; JH0095.
DR RefSeq; NP_034608.2; NM_010478.2.
DR AlphaFoldDB; P17879; -.
DR SMR; P17879; -.
DR BioGRID; 200452; 44.
DR CORUM; P17879; -.
DR DIP; DIP-31549N; -.
DR IntAct; P17879; 11.
DR MINT; P17879; -.
DR STRING; 10090.ENSMUSP00000133815; -.
DR jPOST; P17879; -.
DR MaxQB; P17879; -.
DR PaxDb; P17879; -.
DR PeptideAtlas; P17879; -.
DR PRIDE; P17879; -.
DR ProteomicsDB; 267065; -.
DR DNASU; 15511; -.
DR Ensembl; ENSMUST00000172753; ENSMUSP00000133815; ENSMUSG00000090877.
DR GeneID; 15511; -.
DR KEGG; mmu:15511; -.
DR UCSC; uc008ceo.1; mouse.
DR CTD; 3304; -.
DR MGI; MGI:99517; Hspa1b.
DR VEuPathDB; HostDB:ENSMUSG00000090877; -.
DR eggNOG; KOG0101; Eukaryota.
DR GeneTree; ENSGT00940000161215; -.
DR HOGENOM; CLU_005965_3_0_1; -.
DR InParanoid; P17879; -.
DR OMA; SHIHEIV; -.
DR OrthoDB; 288077at2759; -.
DR PhylomeDB; P17879; -.
DR TreeFam; TF105042; -.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-MMU-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-MMU-3371568; Attenuation phase.
DR Reactome; R-MMU-3371571; HSF1-dependent transactivation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 15511; 5 hits in 70 CRISPR screens.
DR ChiTaRS; Hspa1a; mouse.
DR PRO; PR:P17879; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P17879; protein.
DR Bgee; ENSMUSG00000090877; Expressed in tail skin and 237 other tissues.
DR Genevisible; P17879; MM.
DR GO; GO:0016235; C:aggresome; ISO:MGI.
DR GO; GO:0044297; C:cell body; IDA:MGI.
DR GO; GO:0005814; C:centriole; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016234; C:inclusion body; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISO:MGI.
DR GO; GO:0002199; C:zona pellucida receptor complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0140545; F:ATP-dependent protein disaggregase activity; ISO:MGI.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
DR GO; GO:0044183; F:protein folding chaperone; IDA:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0051082; F:unfolded protein binding; ISO:MGI.
DR GO; GO:0046034; P:ATP metabolic process; ISO:MGI.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; IDA:MGI.
DR GO; GO:0070370; P:cellular heat acclimation; ISO:MGI.
DR GO; GO:0034605; P:cellular response to heat; ISO:MGI.
DR GO; GO:0034620; P:cellular response to unfolded protein; IBA:GO_Central.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central.
DR GO; GO:0006402; P:mRNA catabolic process; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:MGI.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; ISO:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; ISS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0070434; P:positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; ISO:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:0006457; P:protein folding; IDA:UniProtKB.
DR GO; GO:0042026; P:protein refolding; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:1901673; P:regulation of mitotic spindle assembly; ISS:UniProtKB.
DR GO; GO:0031396; P:regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0009408; P:response to heat; IDA:MGI.
DR GO; GO:0006986; P:response to unfolded protein; ISO:MGI.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 1.20.1270.10; -; 1.
DR Gene3D; 2.60.34.10; -; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR029048; HSP70_C_sf.
DR InterPro; IPR029047; HSP70_peptide-bd_sf.
DR InterPro; IPR013126; Hsp_70_fam.
DR PANTHER; PTHR19375; PTHR19375; 1.
DR Pfam; PF00012; HSP70; 1.
DR SUPFAM; SSF100920; SSF100920; 1.
DR SUPFAM; SSF100934; SSF100934; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
DR PROSITE; PS00297; HSP70_1; 1.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Chaperone; Cytoplasm; Cytoskeleton; Methylation;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Stress response.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT CHAIN 2..642
FT /note="Heat shock 70 kDa protein 1B"
FT /id="PRO_0000078251"
FT REGION 2..386
FT /note="Nucleotide-binding domain (NBD)"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT REGION 394..509
FT /note="Substrate-binding domain (SBD)"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT REGION 617..642
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 12..15
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 202..204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 268..275
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 339..342
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 77
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 108
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 246
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 348
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 469
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 561
FT /note="N6,N6,N6-trimethyllysine; by METTL21A; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 561
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 634
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
FT MOD_RES 637
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV9"
SQ SEQUENCE 642 AA; 70176 MW; 4BB9B0B130C23D8B CRC64;
MAKNTAIGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
LNPQNTVFDA KRLIGRKFGD AVVQSDMKHW PFQVVNDGDK PKVQVNYKGE SRSFFPEEIS
SMVLTKMKEI AEAYLGHPVT NAVITVPAYF NDSQRQATKD AGVIAGLNVL RIINEPTAAA
IAYGLDRTGK GERNVLIFDL GGGTFDVSIL TIDDGIFEVK ATAGDTHLGG EDFDNRLVSH
FVEEFKRKHK KDISQNKRAV RRLRTACERA KRTLSSSTQA SLEIDSLFEG IDFYTSITRA
RFEELCSDLF RGTLEPVEKA LRDAKMDKAQ IHDLVLVGGS TRIPKVQKLL QDFFNGRDLN
KSINPDEAVA YGAAVQAAIL MGDKSENVQD LLLLDVAPLS LGLETAGGVM TALIKRNSTI
PTKQTQTFTT YSDNQPGVLI QVYEGERAMT RDNNLLGRFE LSGIPPAPRG VPQIEVTFDI
DANGILNVTA TDKSTGKANK ITITNDKGRL SKEEIERMVQ EAERYKAEDE VQRDRVAAKN
ALESYAFNMK SAVEDEGLKG KLSEADKKKV LDKCQEVISW LDSNTLADKE EFVHKREELE
RVCSPIISGL YQGAGAPGAG GFGAQAPPKG ASGSGPTIEE VD
