ID HS71A_PIG Reviewed; 641 AA.
AC P34930;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 27-MAR-2024, entry version 117.
DE RecName: Full=Heat shock 70 kDa protein 1A;
DE AltName: Full=Heat shock 70 kDa protein 1;
DE Short=HSP70.1;
GN Name=HSPA1A; Synonyms=HSPA1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1339404; DOI=10.1007/bf00166836;
RA Peelman L.J., de Weghe A.R., Coppieters W.R., van Zeveren A.J.,
RA Bouquet Y.H.;
RT "Complete nucleotide sequence of a porcine HSP70 gene.";
RL Immunogenetics 35:286-289(1992).
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. Required as a co-chaperone for optimal STUB1/CHIP
CC ubiquitination of NFATC3 (By similarity). Negatively regulates heat
CC shock-induced HSF1 transcriptional activity during the attenuation and
CC recovery phase period of the heat shock response.
CC {ECO:0000250|UniProtKB:P0DMV8, ECO:0000250|UniProtKB:P0DMW0}.
CC -!- SUBUNIT: Component of the CatSper complex. Identified in a IGF2BP1-
CC dependent mRNP granule complex containing untranslated mRNAs.
CC Identified in a IGF2BP1-dependent mRNP granule complex containing
CC untranslated mRNAs. Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and
CC TSC2. Interacts with TERT; the interaction occurs in the absence of the
CC RNA component, TERC, and dissociates once the TERT complex has formed.
CC Interacts with TRIM5 (via B30.2/SPRY domain). Interacts with METTL21A.
CC Interacts with DNAAF2. Interacts with PRKN. Interacts with FOXP3.
CC Interacts with NOD2; the interaction enhances NOD2 stability. Interacts
CC with DNAJC9 (via J domain). Interacts with ATF5; the interaction
CC protects ATF5 from degradation via proteasome-dependent and caspase-
CC dependent processes. Interacts with RNF207 (via the C-terminus); this
CC interaction additively increases KCNH2 expression. Interacts with HSF1
CC (via transactivation domain); this interaction results in the
CC inhibition of heat shock- and HSF1-induced transcriptional activity
CC during the attenuation and recovery phase period of the heat shock
CC response. Interacts with NAA10, HSP40, HSP90 and HDAC4. Interacts (via
CC C-terminus) with STUB1 (via TPR repeats) (By similarity). The
CC acetylated form and the non-acetylated form interact with HOPX and
CC STUB1 respectively. Interacts with NEDD1 and SMAD3. Interacts (via NBD)
CC with BAG1, BAG2, BAG3 and HSPH1/HSP105. Interacts with DNAJC8.
CC Interacts with NLRP12. Interacts with PGLYRP.
CC {ECO:0000250|UniProtKB:P0DMV8, ECO:0000250|UniProtKB:P0DMW0,
CC ECO:0000250|UniProtKB:Q61696}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P0DMV8}. Nucleus
CC {ECO:0000250|UniProtKB:P0DMV8}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:P0DMV8}. Secreted
CC {ECO:0000250|UniProtKB:Q61696}. Note=Localized in cytoplasmic mRNP
CC granules containing untranslated mRNAs. {ECO:0000250|UniProtKB:P0DMV8}.
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:P0DMV8}.
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:P0DMV8}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR EMBL; M69100; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; S35718; S35718.
DR AlphaFoldDB; P34930; -.
DR BMRB; P34930; -.
DR SMR; P34930; -.
DR CORUM; P34930; -.
DR IntAct; P34930; 2.
DR MINT; P34930; -.
DR PeptideAtlas; P34930; -.
DR InParanoid; P34930; -.
DR PRO; PR:P34930; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR Proteomes; UP000694570; Unplaced.
DR Proteomes; UP000694571; Unplaced.
DR Proteomes; UP000694720; Unplaced.
DR Proteomes; UP000694722; Unplaced.
DR Proteomes; UP000694723; Unplaced.
DR Proteomes; UP000694724; Unplaced.
DR Proteomes; UP000694725; Unplaced.
DR Proteomes; UP000694726; Unplaced.
DR Proteomes; UP000694727; Unplaced.
DR Proteomes; UP000694728; Unplaced.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central.
DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central.
DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0042026; P:protein refolding; ISS:UniProtKB.
DR GO; GO:1901673; P:regulation of mitotic spindle assembly; ISS:UniProtKB.
DR CDD; cd10233; HSPA1-2_6-8-like_NBD; 1.
DR Gene3D; 1.20.1270.10; -; 1.
DR Gene3D; 3.30.30.30; -; 1.
DR Gene3D; 3.30.420.40; -; 2.
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:SF223; HEAT SHOCK 70 KDA PROTEIN 1A-RELATED; 1.
DR PANTHER; PTHR19375; HEAT SHOCK PROTEIN 70KDA; 1.
DR Pfam; PF00012; HSP70; 1.
DR PRINTS; PR00301; HEATSHOCK70.
DR SUPFAM; SSF53067; Actin-like ATPase domain; 2.
DR SUPFAM; SSF100934; Heat shock protein 70kD (HSP70), C-terminal subdomain; 1.
DR SUPFAM; SSF100920; Heat shock protein 70kD (HSP70), peptide-binding domain; 1.
DR PROSITE; PS00297; HSP70_1; 1.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 3: Inferred from homology;
KW Acetylation; ATP-binding; Chaperone; Cytoplasm; Cytoskeleton; Methylation;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Secreted;
KW Stress response.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT CHAIN 2..641
FT /note="Heat shock 70 kDa protein 1A"
FT /id="PRO_0000078252"
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 614..641
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:P0DMV8"
FT MOD_RES 77
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 108
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 246
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 348
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 469
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 561
FT /note="N6,N6,N6-trimethyllysine; by METTL21A; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 561
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 636
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
SQ SEQUENCE 641 AA; 70083 MW; FE77BB20A03E0A33 CRC64;
MAKSVAIGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS SVAFTDTERL IGDAAKNQVA
LNPQNTVFDA KRLIGRKFGD PVVQGDMKHW PFRVINDGDK PKVQVSYKGE TKGFYPEEIS
SMVLTKMKEI AEGYLGHPVS NAVITVPAYF NDSQRQATKD AGVIAGLNVL RIINEPTAAA
IAYGLDRTGK GERNVLIFDL GGGTFDVSIL TIDDGIFEVK ATAGDTHLGG EDFDNRLVNH
FVEEFKRKHK KDYSQNKRAV RRLRTACERA KRTLSSSTQA SLEIDSLFEG IDFYTSITRA
RFEELCSDLF RSTLEPVEKA LRDAKLDKAQ IHDLVLVGGS TRIPKVQKLL QDFFNGRDLN
KSINPDEAVA YGAAVQAAIL MGDKSENVQD LLLLDVAPLS LGLETAGGVM TALIKRNSTI
PTKQTQIFTT YSDNQPGVLI QVYEGERAMT RDNNLLGRFE LSGIPPAPRG VPQIEVTFDI
DANGILNVTA TDKSTGKANK ITITNDKGRL SKEEIERMVQ EAEKYKAEDE IQRERVGAKN
ALESYAFNMK SVVEDEGLKG KISEADKKKV LDKCQEVISW LDANTLAEKD EFEHKRKELE
QVCNPIISGL YQGAGGPGPG GFGAPDLKGG SGSGPTIEEV D
//
