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

223-260 (Nucleolar targeting region)

Relief mechanism

Others

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

2 structures for P22202

Entry ID Method Resolution Chain Position Source
3UPV X-ray 160 A B 636-642 PDB
AF-P22202-F1 Predicted AlphaFoldDB

3 variants for P22202

Variant ID(s) Position Change Description Diseaes Association Provenance
s05-365974 464 P>S No SGRP
s05-366281 566 R>K No SGRP
s05-366430 616 P>S No SGRP

No associated diseases with P22202

3 regional properties for P22202

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 195 - 208 IPR018181-2
conserved_site Heat shock protein 70, conserved site 332 - 346 IPR018181-3

Functions

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

4 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.
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.

6 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.
unfolded protein binding Binding to an unfolded protein.

4 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.
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.
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.

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
P09435 SSA3 Heat shock protein SSA3 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
P10591 SSA1 Heat shock protein SSA1 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 NDRVEIIAND QGNRTTPSYV AFTDTERLIG DAAKNQAAMN
70 80 90 100 110 120
PHNTVFDAKR LIGRKFDDPE VTNDAKHYPF KVIDKGGKPV VQVEYKGETK TFTPEEISSM
130 140 150 160 170 180
ILTKMKETAE NFLGTEVKDA VVTVPAYFND SQRQATKDAG TIAGLNVLRI INEPTAAAIA
190 200 210 220 230 240
YGLDKKSQKE HNVLIFDLGG GTFDVSLLSI DEGVFEVKAT AGDTHLGGED FDSRLVNFLA
250 260 270 280 290 300
EEFKRKNKKD LTTNQRSLRR LRTAAERAKR TLSSSAQTSI EIDSLFEGID FYTSITRARF
310 320 330 340 350 360
EELCADLFRS TLEPVEKVLA DSKLDKSQID EIVLVGGSTR IPKVQKLVSD FFNGKEPNRS
370 380 390 400 410 420
INPDEAVAYG AAVQAAILTG DQSSTTQDLL LLDVAPLSLG IETAGGIMTK LIPRNSTIPT
430 440 450 460 470 480
KKSEVFSTYA DNQPGVLIQV FEGERTRTKD NNLLGKFELS GIPPAPRGVP QIEVTFDIDA
490 500 510 520 530 540
NGILNVSAVE KGTGKSNKIT ITNDKGRLSK EDIDKMVAEA EKFKAEDEQE AQRVQAKNQL
550 560 570 580 590 600
ESYAFTLKNS VSENNFKEKV GEEDARKLEA AAQDAINWLD ASQAASTEEY KERQKELEGV
610 620 630 640
ANPIMSKFYG AAGGAPGAGP VPGAGAGPTG APDNGPTVEE VD