Descriptions

HSPA8 (or hsc70) is a heat shock cognate protein involved in many cellular processes. During recovery from stress, HSPA8, initially accumulating in the nucleoplasm for folding/refolding of proteins, transiently concentrates in nucleoli for nucleolar morphology and function restoration. The inhibitory region is positioned at one of the three domains of HSPA8 protein, which is the N-terminal ATPase domain, specifically in residues 263-287 of domain IIB. Under normal growth conditions, the constitutive nucleolar targeting function that is provided by residues 225-262 is diminished by the autoinhibitory element located in residues 263-287. When cells recover from stress, the autoinhibitory element is inactivated, and the constitutive nucleolar targeting function restores.

Autoinhibitory domains (AIDs)

Target domain

222-259 (Nucleolar targeting region)

Relief mechanism

Others

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

5 structures for P10591

Entry ID Method Resolution Chain Position Source
3LCA X-ray 219 A Q 631-642 PDB
5LYN X-ray 200 A C/D 636-642 PDB
5Z8I NMR - A 382-554 PDB
5Z8Q NMR - A 523-622 PDB
AF-P10591-F1 Predicted AlphaFoldDB

2 variants for P10591

Variant ID(s) Position Change Description Diseaes Association Provenance
s01-141186 83 A>G No SGRP
s01-140164 424 I>V No SGRP

No associated diseases with P10591

3 regional properties for P10591

Type Name Position InterPro Accession
conserved_site Heat shock protein 70, conserved site 7 - 14 IPR018181-1
conserved_site Heat shock protein 70, conserved site 194 - 207 IPR018181-2
conserved_site Heat shock protein 70, conserved site 331 - 345 IPR018181-3

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Secreted, cell wall
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extracellular region The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
fungal-type cell wall A rigid yet dynamic structure surrounding the plasma membrane that affords protection from stresses and contributes to cell morphogenesis, consisting of extensively cross-linked glycoproteins and carbohydrates. The glycoproteins may be modified with N- or O-linked carbohydrates, or glycosylphosphatidylinositol (GPI) anchors; the polysaccharides are primarily branched glucans, including beta-linked and alpha-linked glucans, and may also include chitin and other carbohydrate polymers, but not cellulose or pectin. Enzymes involved in cell wall biosynthesis are also found in the cell wall. Note that some forms of fungi develop a capsule outside of the cell wall under certain circumstances; this is considered a separate structure.
fungal-type vacuole membrane The lipid bilayer surrounding a vacuole, the shape of which correlates with cell cycle phase. The membrane separates its contents from the cytoplasm of the cell. An example of this structure is found in Saccharomyces cerevisiae.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
transcription repressor complex A protein complex that possesses activity that prevents or downregulates transcription.

7 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
ATP hydrolysis activity Catalysis of the reaction
ATP-dependent protein folding chaperone Binding to a protein or a protein-containing complex to assist the protein folding process, driven by ATP hydrolysis.
heat shock protein binding Binding to a heat shock protein, a protein synthesized or activated in response to heat shock.
protein folding chaperone Binding to a protein or a protein-containing complex to assist the protein folding process.
tRNA binding Binding to a transfer RNA.
unfolded protein binding Binding to an unfolded protein.

14 GO annotations of biological process

Name Definition
chaperone cofactor-dependent protein refolding The process of assisting in the correct posttranslational noncovalent assembly of proteins, which is dependent on additional protein cofactors. This process occurs over one or several cycles of nucleotide hydrolysis-dependent binding and release.
clathrin coat disassembly The disaggregation of a clathrin coat into its constituent components; results in stripping or removing the clathrin coat from clathrin-coated vesicles (CCV) before fusing with their targets. CVVs transport cargo from plasma membrane and trans-Golgi to the endosomal system.
cytoplasmic translation The chemical reactions and pathways resulting in the formation of a protein in the cytoplasm. This is a ribosome-mediated process in which the information in messenger RNA (mRNA) is used to specify the sequence of amino acids in the protein.
mitochondria-associated ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of proteins transported from mitochondria and targeted to cytoplasmic proteasomes for degradation as a response to oxidative stress conditions.
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
proteasome-mediated ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
protein folding The process of assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure.
protein import into nucleus The directed movement of a protein from the cytoplasm to the nucleus.
protein polyubiquitination Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain.
protein refolding The process carried out by a cell that restores the biological activity of an unfolded or misfolded protein, using helper proteins such as chaperones.
protein targeting to mitochondrion The process of directing proteins towards and into the mitochondrion, usually mediated by mitochondrial proteins that recognize signals contained within the imported protein.
response to oxygen levels Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus reflecting the presence, absence, or concentration of oxygen.
SRP-dependent cotranslational protein targeting to membrane, translocation The process during cotranslational membrane targeting wherein proteins move across a membrane. SRP and its receptor initiate the transfer of the nascent chain across the endoplasmic reticulum (ER) membrane; they then dissociate from the chain, which is transferred to a set of transmembrane proteins, collectively called the translocon. Once the nascent chain translocon complex is assembled, the elongating chain passes directly from the large ribosomal subunit into the centers of the translocon, a protein-lined channel within the membrane. The growing chain is never exposed to the cytosol and does not fold until it reaches the ER lumen.
stress granule disassembly The disaggregation of a stress granule into its constituent protein and RNA parts.

27 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P11484 SSB1 Ribosome-associated molecular chaperone SSB1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P40150 SSB2 Ribosome-associated molecular chaperone SSB2 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P22202 SSA4 Heat shock protein SSA4 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P09435 SSA3 Heat shock protein SSA3 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P10592 SSA2 Heat shock protein SSA2 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P19120 HSPA8 Heat shock cognate 71 kDa protein Bos taurus (Bovine) SS
O73885 HSPA8 Heat shock cognate 71 kDa protein Gallus gallus (Chicken) SS
P77319 hscC Chaperone protein HscC Escherichia coli (strain K12) PR
P0A6Y8 dnaK Chaperone protein DnaK Escherichia coli (strain K12) SS
P29843 Hsc70-1 Heat shock 70 kDa protein cognate 1 Drosophila melanogaster (Fruit fly) SS
P11147 Hsc70-4 Heat shock 70 kDa protein cognate 4 Drosophila melanogaster (Fruit fly) SS
A2Q0Z1 HSPA8 Heat shock cognate 71 kDa protein Equus caballus (Horse) SS
P11142 HSPA8 Heat shock cognate 71 kDa protein Homo sapiens (Human) EV
P11143 HSP70 Heat shock 70 kDa protein Zea mays (Maize) SS
P63017 Hspa8 Heat shock cognate 71 kDa protein Mus musculus (Mouse) SS
P63018 Hspa8 Heat shock cognate 71 kDa protein Rattus norvegicus (Rat) SS
P09446 hsp-1 Heat shock protein hsp-1 Caenorhabditis elegans SS
P26413 HSP70 Heat shock 70 kDa protein Glycine max (Soybean) (Glycine hispida) SS
Q9S9N1 HSP70-5 Heat shock 70 kDa protein 5 Arabidopsis thaliana (Mouse-ear cress) SS
P22954 HSP70-2 Heat shock 70 kDa protein 2 Arabidopsis thaliana (Mouse-ear cress) SS
Q9C7X7 HSP70-18 Heat shock 70 kDa protein 18 Arabidopsis thaliana (Mouse-ear cress) SS
P22953 HSP70-1 Heat shock 70 kDa protein 1 Arabidopsis thaliana (Mouse-ear cress) SS
O65719 HSP70-3 Heat shock 70 kDa protein 3 Arabidopsis thaliana (Mouse-ear cress) SS
Q9LHA8 HSP70-4 Heat shock 70 kDa protein 4 Arabidopsis thaliana (Mouse-ear cress) SS
P27322 HSC-2 Heat shock cognate 70 kDa protein 2 Solanum lycopersicum (Tomato) (Lycopersicon esculentum) SS
P24629 HSC-I Heat shock cognate 70 kDa protein 1 Solanum lycopersicum (Tomato) (Lycopersicon esculentum) SS
Q90473 hspa8 Heat shock cognate 71 kDa protein Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MSKAVGIDLG TTYSCVAHFA NDRVDIIAND QGNRTTPSFV AFTDTERLIG DAAKNQAAMN
70 80 90 100 110 120
PSNTVFDAKR LIGRNFNDPE VQADMKHFPF KLIDVDGKPQ IQVEFKGETK NFTPEQISSM
130 140 150 160 170 180
VLGKMKETAE SYLGAKVNDA VVTVPAYFND SQRQATKDAG TIAGLNVLRI INEPTAAAIA
190 200 210 220 230 240
YGLDKKGKEE HVLIFDLGGG TFDVSLLSIE DGIFEVKATA GDTHLGGEDF DNRLVNHFIQ
250 260 270 280 290 300
EFKRKNKKDL STNQRALRRL RTACERAKRT LSSSAQTSVE IDSLFEGIDF YTSITRARFE
310 320 330 340 350 360
ELCADLFRST LDPVEKVLRD AKLDKSQVDE IVLVGGSTRI PKVQKLVTDY FNGKEPNRSI
370 380 390 400 410 420
NPDEAVAYGA AVQAAILTGD ESSKTQDLLL LDVAPLSLGI ETAGGVMTKL IPRNSTIPTK
430 440 450 460 470 480
KSEIFSTYAD NQPGVLIQVF EGERAKTKDN NLLGKFELSG IPPAPRGVPQ IEVTFDVDSN
490 500 510 520 530 540
GILNVSAVEK GTGKSNKITI TNDKGRLSKE DIEKMVAEAE KFKEEDEKES QRIASKNQLE
550 560 570 580 590 600
SIAYSLKNTI SEAGDKLEQA DKDTVTKKAE ETISWLDSNT TASKEEFDDK LKELQDIANP
610 620 630 640
IMSKLYQAGG APGGAAGGAP GGFPGGAPPA PEAEGPTVEE VD