HSP71_CHLAE
ID HSP71_CHLAE Reviewed; 638 AA.
AC Q28222;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Heat shock 70 kDa protein 1;
GN Name=HSPA1;
OS Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=7988690; DOI=10.1016/0014-5793(94)01210-5;
RA Sainis I., Angelidis C., Pagoulatos G., Lazaridis I.;
RT "The hsc70 gene which is slightly induced by heat is the main virus
RT inducible member of the hsp70 gene family.";
RL FEBS Lett. 355:282-286(1994).
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:P0DMV8}.
CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex
CC containing untranslated mRNAs, IRAK1BP1, KTU and TSC2. Interacts with
CC TERT; the interaction occurs in the absence of the RNA component, TERC,
CC and dissociates once the TERT complex has formed. Interacts with
CC CHCHD3. Interacts with TRIM5 (via B30.2/SPRY domain). Interacts with
CC PRKN. Interacts with FOXP3. Interacts with DNAJC9 (via J domain).
CC Interacts with NAA10, HSP40, HSP90 and HDAC4. The acetylated form and
CC the non-acetylated form interact with HOPX and STUB1 respectively.
CC Interacts with NEDD1 and SMAD3. Interacts (via NBD) with BAG1, BAG2,
CC BAG3 and HSPH1/HSP105. Interacts with DNAJC8.
CC {ECO:0000250|UniProtKB:P0DMV8}.
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}.
CC Note=Localized in cytoplasmic mRNP granules containing untranslated
CC mRNAs. {ECO:0000250|UniProtKB:P0DMV8}.
CC -!- INDUCTION: By heat shock.
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; X70684; CAA50019.1; -; mRNA.
DR PIR; S31766; S31766.
DR AlphaFoldDB; Q28222; -.
DR SMR; Q28222; -.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; ISS:UniProtKB.
DR GO; GO:0042026; P:protein refolding; ISS:UniProtKB.
DR GO; GO:1901673; P:regulation of mitotic spindle assembly; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Chaperone; Cytoplasm; Cytoskeleton; Methylation;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Stress response.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT CHAIN 2..638
FT /note="Heat shock 70 kDa protein 1"
FT /id="PRO_0000078248"
FT REGION 2..384
FT /note="Nucleotide-binding domain (NBD)"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT REGION 392..506
FT /note="Substrate-binding domain (SBD)"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT REGION 606..638
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 201..203
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 266..273
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 337..340
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 244
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 346
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 558
FT /note="N6,N6,N6-trimethyllysine; by METTL21A; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 558
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 628
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 630
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
FT MOD_RES 633
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P0DMV8"
SQ SEQUENCE 638 AA; 69920 MW; D55076A0FFAB6AB3 CRC64;
MAKAAAIGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
LNPQNTVFDA KRLIGRKFGD PVVQSDMKHW PFQVINDGDK PKVQVSYKGE TKAFYPEEIS
SMVLTKMKEI AEADLGYPVT NAVITVPAYF NDSQRQATKD AGVIAGLNVL RIINEPTRTI
AYALDRTGKG ERNVLIFDLG GGTFDVSILT IDDGIFEVKA TAGDTTWVED FDNRLVNHFV
EEFKRKHKKD ISQNKRAVRR LRTACERAKR TLSSSTQASL EIDSLFEGID FYTSITRARF
EELCSDLFRS TLEPVEKALR DAKLDKAQIH DLVLVGGSTR IPKVQKLLQD FFNGRDLNKS
INPDEAVAYG AAVQAAILMG DKSENVQDLL LLDVAPLSLG LETPGGVMTA LIKRNSTIPT
KQTQIFTTYS DNQPGVLIQV YEGERAMTKD NNLLGRFELS GIPPAPGVPQ IEVTFEIDAN
GILNVTATDK STGKANKITI TNDKGRLSKE EIERMVQEAE KYKAEDEVQR ERVSAKNALE
SYALNMKSAV EDEGLKGKIS EADKKKVLDK CQEVISWLDA NTLAEKDEFE HKRKELEQVC
NPIISGLYQG GGGPGPGGFG AQGPKGGSGS GPTIEEVD
