HSP7C_HORSE
ID HSP7C_HORSE Reviewed; 646 AA.
AC A2Q0Z1;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Heat shock cognate 71 kDa protein;
DE EC=3.6.4.10 {ECO:0000250|UniProtKB:P11142};
DE AltName: Full=Heat shock 70 kDa protein 8;
GN Name=HSPA8; Synonyms=HSC70;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Thoroughbred; TISSUE=Tendon;
RA Hasegawa T., Hayashi K., Kagawa Y., Akiyama Y., Suzuki Y., Sugano S.,
RA Ishida N.;
RT "Cloning of genes expressed in equine tendon.";
RL Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases.
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 of HSP70, but they also have an individual specificity
CC such that one co-chaperone may promote folding of a substrate while
CC another may promote degradation. The affinity of HSP70 for polypeptides
CC is regulated by its nucleotide bound state. In the ATP-bound form, it
CC has a low affinity for substrate proteins. However, upon hydrolysis of
CC the ATP to ADP, it undergoes a conformational change that increases its
CC affinity for substrate proteins. HSP70 goes through repeated cycles of
CC ATP hydrolysis and nucleotide exchange, which permits cycles of
CC substrate binding and release. The HSP70-associated co-chaperones are
CC of three types: J-domain co-chaperones HSP40s (stimulate ATPase
CC hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as
CC BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-
CC bound state thereby promoting substrate release), and the TPR domain
CC chaperones such as HOPX and STUB1. Plays a critical role in
CC mitochondrial import, delivers preproteins to the mitochondrial import
CC receptor TOMM70. Acts as a repressor of transcriptional activation.
CC Inhibits the transcriptional coactivator activity of CITED1 on Smad-
CC mediated transcription. Component of the PRP19-CDC5L complex that forms
CC an integral part of the spliceosome and is required for activating pre-
CC mRNA splicing. May have a scaffolding role in the spliceosome assembly
CC as it contacts all other components of the core complex. Binds
CC bacterial lipopolysaccharide (LPS) and mediates LPS-induced
CC inflammatory response, including TNF secretion by monocytes.
CC Participates in the ER-associated degradation (ERAD) quality control
CC pathway in conjunction with J domain-containing co-chaperones and the
CC E3 ligase STUB1. Interacts with VGF-derived peptide TLQP-21.
CC {ECO:0000250|UniProtKB:P11142}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.10;
CC Evidence={ECO:0000250|UniProtKB:P11142};
CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex
CC containing untranslated mRNAs (By similarity). Interacts with PACRG (By
CC similarity). Interacts with HSPH1/HSP105 (By similarity). Interacts
CC with IRAK1BP1 and BAG1 (By similarity). Interacts with DNAJC7 (By
CC similarity). Interacts with DNAJB12 (via J domain) (By similarity).
CC Interacts with DNAJB14 (via J domain) (By similarity). Interacts (via
CC C-terminus) with the E3 ligase STUB1 forming a 210 kDa complex of one
CC STUB1 and two HSPA8 molecules (By similarity). Interacts with CITED1
CC (via N-terminus); the interaction suppresses the association of CITED1
CC to p300/CBP and Smad-mediated transcription transactivation (By
CC similarity). Component of the PRP19-CDC5L splicing complex composed of
CC a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and
CC BCAS2, and at least three less stably associated proteins CTNNBL1,
CC CWC15 and HSPA8 (By similarity). Interacts with TRIM5 (By similarity).
CC Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8,
CC CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may
CC have a histone H3-specific methyltransferase activity (By similarity).
CC Interacts with METTL21A (By similarity). Following LPS binding, may
CC form a complex with CXCR4, GDF5 and HSP90AA1 (By similarity). Interacts
CC with PRKN (By similarity). Interacts with FOXP3 (By similarity).
CC Interacts with DNAJC9 (via J domain) (By similarity). Interacts with
CC MLLT11 (By similarity). Interacts with RNF207 (By similarity).
CC Interacts with DNAJC21 (By similarity). Interacts with DNAJB2 (By
CC similarity). Interacts with TTC1 (via TPR repeats) (By similarity).
CC Interacts with SGTA (via TPR repeats) (By similarity). Interacts with
CC HSF1 (via transactivation domain) (By similarity). Interacts with HOPX,
CC STUB1, HSP40, HSP901, BAG2 and BAG3 (By similarity). Interacts with
CC HSPC138 (By similarity). Interacts with ZMYND10 (By similarity).
CC Interacts with VGF-derived peptide TLQP-21 (By similarity). Interacts
CC with BCL2L1, GIMAP5 and MCL1; the interaction with BCL2L1 or MCL1 is
CC impaired in the absence of GIMAP5 (By similarity). Interacts with
CC NLPR12 (By similarity). Interacts with TTC4 (By similarity). Interacts
CC with TOMM70; the interaction is required for preprotein mitochondrial
CC import (By similarity). May interact with DNJC9; the interaction seems
CC to be histone-dependent (By similarity). {ECO:0000250|UniProtKB:P11142,
CC ECO:0000250|UniProtKB:P63017, ECO:0000250|UniProtKB:P63018}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Melanosome
CC {ECO:0000250}. Nucleus, nucleolus {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Localized in cytoplasmic mRNP granules containing
CC untranslated mRNAs. Translocates rapidly from the cytoplasm to the
CC nuclei, and especially to the nucleoli, upon heat shock (By
CC similarity). {ECO:0000250}.
CC -!- INDUCTION: Constitutively synthesized.
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:P11142}.
CC -!- PTM: Acetylated. {ECO:0000250|UniProtKB:P11142}.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P11142}.
CC -!- PTM: Trimethylation at Lys-561 reduces fibrillar SNCA binding.
CC {ECO:0000250|UniProtKB:P11142}.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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DR EMBL; AB292109; BAF46109.1; -; mRNA.
DR RefSeq; NP_001075247.1; NM_001081778.2.
DR AlphaFoldDB; A2Q0Z1; -.
DR BMRB; A2Q0Z1; -.
DR SMR; A2Q0Z1; -.
DR STRING; 9796.ENSECAP00000031747; -.
DR PaxDb; A2Q0Z1; -.
DR PeptideAtlas; A2Q0Z1; -.
DR PRIDE; A2Q0Z1; -.
DR Ensembl; ENSECAT00000014388; ENSECAP00000011500; ENSECAG00000037704.
DR GeneID; 100009679; -.
DR KEGG; ecb:100009679; -.
DR CTD; 3312; -.
DR GeneTree; ENSGT00950000183206; -.
DR HOGENOM; CLU_005965_3_0_1; -.
DR InParanoid; A2Q0Z1; -.
DR OMA; KANPIMM; -.
DR OrthoDB; 288077at2759; -.
DR Proteomes; UP000002281; Chromosome 7.
DR Bgee; ENSECAG00000037704; Expressed in retina and 23 other tissues.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0099524; C:postsynaptic cytosol; IBA:GO_Central.
DR GO; GO:0099523; C:presynaptic cytosol; IBA:GO_Central.
DR GO; GO:0000974; C:Prp19 complex; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0005681; C:spliceosomal complex; IEA:UniProtKB-KW.
DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
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:1990833; F:clathrin-uncoating ATPase activity; IBA:GO_Central.
DR GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
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:1904764; P:chaperone-mediated autophagy translocation complex disassembly; IBA:GO_Central.
DR GO; GO:0061738; P:late endosomal microautophagy; IBA:GO_Central.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0042026; P:protein refolding; IBA:GO_Central.
DR GO; GO:0061740; P:protein targeting to lysosome involved in chaperone-mediated autophagy; IBA:GO_Central.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:1990832; P:slow axonal transport; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Cell membrane; Chaperone; Cytoplasm; Hydrolase;
KW Isopeptide bond; Membrane; Methylation; mRNA processing; mRNA splicing;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Spliceosome; Stress response; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT CHAIN 2..646
FT /note="Heat shock cognate 71 kDa protein"
FT /id="PRO_0000286046"
FT REGION 2..386
FT /note="Nucleotide-binding domain (NBD)"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT REGION 186..377
FT /note="Interaction with BAG1"
FT /evidence="ECO:0000250"
FT REGION 394..509
FT /note="Substrate-binding domain (SBD)"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT REGION 614..646
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 108
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63017"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 246
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 319
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 319
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P63017"
FT MOD_RES 328
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63017"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 469
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 512
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P63017"
FT MOD_RES 512
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P63017"
FT MOD_RES 524
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63017"
FT MOD_RES 541
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 561
FT /note="N6,N6,N6-trimethyllysine; by METTL21A; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 561
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 589
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 597
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT MOD_RES 601
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT CROSSLNK 512
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:P11142"
FT CROSSLNK 512
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P11142"
SQ SEQUENCE 646 AA; 70898 MW; 9AA27B210730670C CRC64;
MSKGPAVGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
MNPTNTVFDA KRLIGRRFDD AVVQSDMKHW PFMVVNDAGR PKVQVEYKGE TKSFYPEEVS
SMVLTKMKEI AEAYLGKTVT NAVVTVPAYF NDSQRQATKD AGTIAGLNVL RIINEPTAAA
IAYGLDKKVG AERNVLIFDL GGGTFDVSIL TIEDGIFEVK STAGDTHLGG EDFDNRMVNH
FIAEFKRKHK KDISENKRAV RRLRTACERA KRTLSSSTQA SIEIDSLYEG IDFYTSITRA
RFEELNADLF RGTLDPVEKA LRDAKLDKSQ IHDIVLVGGS TRIPKIQKLL QDFFNGKELN
KSINPDEAVA YGAAVQAAIL SGDKSENVQD LLLLDVTPLS LGIETAGGVM TVLIKRNTTI
PTKQTQTFTT YSDNQPGVLI QVYEGERAMT KDNNLLGKFE LTGIPPAPRG VPQIEVTFDI
DANGILNVSA VDKSTGKENK ITITNDKGRL SKEDIERMVQ EAEKYKAEDE KQRDKVSSKN
SLESYAFNMK ATVEDEKLQG KINDEDKQKI LDKCNEIINW LDKNQTAEKE EFEHQQKELE
KVCNPIITKL YQSAGGMPGG MPGGFPGGGA PPSGGASSGP TIEEVD
