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

225-262 (Nucleolar targeting region)

Relief mechanism

Others

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q61696

Entry ID Method Resolution Chain Position Source
AF-Q61696-F1 Predicted AlphaFoldDB

4 variants for Q61696

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389452616 447 R>M No EVA
rs3389451368 517 R>S No EVA
rs3389465612 548 N>T No EVA
rs3553381762 624 A>T No EVA

No associated diseases with Q61696

3 regional properties for Q61696

Type Name Position InterPro Accession
conserved_site Heat shock protein 70, conserved site 9 - 16 IPR018181-1
conserved_site Heat shock protein 70, conserved site 197 - 210 IPR018181-2
conserved_site Heat shock protein 70, conserved site 334 - 348 IPR018181-3

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
  • Secreted
  • Localized in cytoplasmic mRNP granules containing untranslated mRNAs
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

13 GO annotations of cellular component

Name Definition
apical plasma membrane The region of the plasma membrane located at the apical end of the cell.
basolateral plasma membrane The region of the plasma membrane that includes the basal end and sides of the cell. Often used in reference to animal polarized epithelial membranes, where the basal membrane is the part attached to the extracellular matrix, or in plant cells, where the basal membrane is defined with respect to the zygotic axis.
blood microparticle A phospholipid microvesicle that is derived from any of several cell types, such as platelets, blood cells, endothelial cells, or others, and contains membrane receptors as well as other proteins characteristic of the parental cell. Microparticles are heterogeneous in size, and are characterized as microvesicles free of nucleic acids.
centrosome A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
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.
membrane raft Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
mitochondrion A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
nuclear speck A discrete extra-nucleolar subnuclear domain, 20-50 in number, in which splicing factors are seen to be localized by immunofluorescence microscopy.
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.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
vesicle Any small, fluid-filled, spherical organelle enclosed by membrane.

9 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.
NF-kappaB binding Binding to NF-kappaB, a transcription factor for eukaryotic RNA polymerase II promoters.
protease binding Binding to a protease or a peptidase.
protein folding chaperone Binding to a protein or a protein-containing complex to assist the protein folding process.
transcription corepressor activity A transcription coregulator activity that represses or decreases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Corepressors often act by altering chromatin structure and modifications. For example, one class of transcription corepressors modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.

15 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.
DNA repair The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway.
lysosomal transport The directed movement of substances into, out of or within a lysosome.
mRNA catabolic process The chemical reactions and pathways resulting in the breakdown of mRNA, messenger RNA, which is responsible for carrying the coded genetic 'message', transcribed from DNA, to sites of protein assembly at the ribosomes.
negative regulation of cell growth Any process that stops, prevents, or reduces the frequency, rate, extent or direction of cell growth.
negative regulation of cell population proliferation Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of transcription by RNA polymerase II Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
positive regulation of microtubule nucleation Any process that increases the rate, frequency or extent of microtubule nucleation. Microtubule nucleation is the 'de novo' formation of a microtubule, in which tubulin heterodimers form metastable oligomeric aggregates, some of which go on to support formation of a complete microtubule. Microtubule nucleation usually occurs from a specific site within a cell.
positive regulation of proteasomal ubiquitin-dependent protein catabolic process Any process that activates or increases the frequency, rate or extent of 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 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.
regulation of mitotic spindle assembly Any process that modulates the frequency, rate or extent of mitotic spindle assembly.
response to heat 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 heat stimulus, a temperature stimulus above the optimal temperature for that organism.
response to unfolded protein 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 an unfolded protein stimulus.
telomere maintenance Any process that contributes to the maintenance of proper telomeric length and structure by affecting and monitoring the activity of telomeric proteins, the length of telomeric DNA and the replication and repair of the DNA. These processes includes those that shorten, lengthen, replicate and repair the telomeric DNA sequences.

54 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P19120 HSPA8 Heat shock cognate 71 kDa protein Bos taurus (Bovine) SS
Q2YDD0 HSPA14 Heat shock 70 kDa protein 14 Bos taurus (Bovine) SS
P0CB32 HSPA1L Heat shock 70 kDa protein 1-like Bos taurus (Bovine) SS
Q27975 HSPA1A Heat shock 70 kDa protein 1A Bos taurus (Bovine) SS
O73885 HSPA8 Heat shock cognate 71 kDa protein Gallus gallus (Chicken) SS
E1C2P3 HSPA14 Heat shock 70 kDa protein 14 Gallus gallus (Chicken) SS
P08106 Heat shock 70 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
P02825 Hsp70Ab Major heat shock 70 kDa protein Ab Drosophila melanogaster (Fruit fly) SS
P82910 Hsp70Aa Major heat shock 70 kDa protein Aa Drosophila melanogaster (Fruit fly) SS
Q8INI8 Hsp70Ba Major heat shock 70 kDa protein Ba Drosophila melanogaster (Fruit fly) SS
Q9BIR7 Hsp70Bc Major heat shock 70 kDa protein Bc Drosophila melanogaster (Fruit fly) SS
Q9BIS2 Hsp70Bb Major heat shock 70 kDa protein Bb Drosophila melanogaster (Fruit fly) SS
O97125 Hsp68 Heat shock protein 68 Drosophila melanogaster (Fruit fly) SS
P11146 Hsc70-2 Heat shock 70 kDa protein cognate 2 Drosophila melanogaster (Fruit fly) SS
P11147 Hsc70-4 Heat shock 70 kDa protein cognate 4 Drosophila melanogaster (Fruit fly) SS
Q9VG58 Hsp70Bbb Major heat shock 70 kDa protein Bbb Drosophila melanogaster (Fruit fly) SS
Q96MM6 HSPA12B Heat shock 70 kDa protein 12B Homo sapiens (Human) PR
P17066 HSPA6 Heat shock 70 kDa protein 6 Homo sapiens (Human) SS
O43301 HSPA12A Heat shock 70 kDa protein 12A Homo sapiens (Human) PR
P34931 HSPA1L Heat shock 70 kDa protein 1-like Homo sapiens (Human) SS
Q0VDF9 HSPA14 Heat shock 70 kDa protein 14 Homo sapiens (Human) SS
P54652 HSPA2 Heat shock-related 70 kDa protein 2 Homo sapiens (Human) SS
P11142 HSPA8 Heat shock cognate 71 kDa protein Homo sapiens (Human) EV
P0DMV9 HSPA1B Heat shock 70 kDa protein 1B Homo sapiens (Human) SS
P0DMV8 HSPA1A Heat shock 70 kDa protein 1A Homo sapiens (Human) SS
P11143 HSP70 Heat shock 70 kDa protein Zea mays (Maize) SS
Q8K0U4 Hspa12a Heat shock 70 kDa protein 12A Mus musculus (Mouse) PR
Q9CZJ2 Hspa12b Heat shock 70 kDa protein 12B Mus musculus (Mouse) PR
P16627 Hspa1l Heat shock 70 kDa protein 1-like Mus musculus (Mouse) SS
P17156 Hspa2 Heat shock-related 70 kDa protein 2 Mus musculus (Mouse) SS
P17879 Hspa1b Heat shock 70 kDa protein 1B Mus musculus (Mouse) SS
P63017 Hspa8 Heat shock cognate 71 kDa protein Mus musculus (Mouse) SS
Q99M31 Hspa14 Heat shock 70 kDa protein 14 Mus musculus (Mouse) SS
Q6S4N2 HSPA1B Heat shock 70 kDa protein 1B Sus scrofa (Pig) SS
P14659 Hspa2 Heat shock-related 70 kDa protein 2 Rattus norvegicus (Rat) SS
P63018 Hspa8 Heat shock cognate 71 kDa protein Rattus norvegicus (Rat) SS
P55063 Hspa1l Heat shock 70 kDa protein 1-like Rattus norvegicus (Rat) SS
P0DMW0 Hspa1a Heat shock 70 kDa protein 1A Rattus norvegicus (Rat) SS
P0DMW1 Hspa1b Heat shock 70 kDa protein 1B 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
O65719 HSP70-3 Heat shock 70 kDa protein 3 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
Q9LHA8 HSP70-4 Heat shock 70 kDa protein 4 Arabidopsis thaliana (Mouse-ear cress) SS
Q9S9N1 HSP70-5 Heat shock 70 kDa protein 5 Arabidopsis thaliana (Mouse-ear cress) SS
P22953 HSP70-1 Heat shock 70 kDa protein 1 Arabidopsis thaliana (Mouse-ear cress) SS
P24629 HSC-I Heat shock cognate 70 kDa protein 1 Solanum lycopersicum (Tomato) (Lycopersicon esculentum) SS
P27322 HSC-2 Heat shock cognate 70 kDa protein 2 Solanum lycopersicum (Tomato) (Lycopersicon esculentum) SS
Q5RGE6 hspa14 Heat shock 70 kDa protein 14 Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q90473 hspa8 Heat shock cognate 71 kDa protein Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MAKNTAIGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
70 80 90 100 110 120
LNPQNTVFDA KRLIGRKFGD AVVQSDMKHW PFQVVNDGDK PKVQVNYKGE SRSFFPEEIS
130 140 150 160 170 180
SMVLTKMKEI AEAYLGHPVT NAVITVPAYF NDSQRQATKD AGVIAGLNVL RIINEPTAAA
190 200 210 220 230 240
IAYGLDRTGK GERNVLIFDL GGGTFDVSIL TIDDGIFEVK ATAGDTHLGG EDFDNRLVSH
250 260 270 280 290 300
FVEEFKRKHK KDISQNKRAV RRLRTACERA KRTLSSSTQA SLEIDSLFEG IDFYTSITRA
310 320 330 340 350 360
RFEELCSDLF RGTLEPVEKA LRDAKMDKAQ IHDLVLVGGS TRIPKVQKLL QDFFNGRDLN
370 380 390 400 410 420
KSINPDEAVA YGAAVQAAIL MGDKSENVQD LLLLDVAPLS LGLETAGGVM TALIKRNSTI
430 440 450 460 470 480
PTKQTQTFTT YSDNQPGVLI QVYEGERAMT RDNNLLGRFE LSGIPPAPRG VPQIEVTFDI
490 500 510 520 530 540
DANGILNVTA TDKSTGKANK ITITNDKGRL SKEEIERMVQ EAERYKAEDE VQRDRVAAKN
550 560 570 580 590 600
ALESYAFNMK SAVEDEGLKG KLSEADKKKV LDKCQEVISW LDSNTLADKE EFVHKREELE
610 620 630 640
RVCSPIISGL YQGAGAPGAG GFGAQAPKGA SGSGPTIEEV D