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

43 structures for P19120

Entry ID Method Resolution Chain Position Source
1ATR X-ray 234 A A 1-386 PDB
1ATS X-ray 243 A A 1-386 PDB
1BA0 X-ray 190 A A 1-386 PDB
1BA1 X-ray 170 A A 1-386 PDB
1BUP X-ray 170 A A 1-386 PDB
1HPM X-ray 170 A A 1-386 PDB
1HX1 X-ray 190 A A 4-381 PDB
1KAX X-ray 170 A A 1-381 PDB
1KAY X-ray 170 A A 1-381 PDB
1KAZ X-ray 170 A A 1-381 PDB
1NGA X-ray 218 A A 1-386 PDB
1NGB X-ray 218 A A 1-386 PDB
1NGC X-ray 220 A A 1-386 PDB
1NGD X-ray 218 A A 1-386 PDB
1NGE X-ray 205 A A 1-386 PDB
1NGF X-ray 217 A A 1-386 PDB
1NGG X-ray 219 A A 1-386 PDB
1NGH X-ray 223 A A 1-386 PDB
1NGI X-ray 215 A A 1-386 PDB
1NGJ X-ray 210 A A 1-386 PDB
1QQM X-ray 190 A A 4-381 PDB
1QQN X-ray 190 A A 4-381 PDB
1QQO X-ray 190 A A 4-381 PDB
1YUW X-ray 260 A A 1-554 PDB
2BUP X-ray 170 A A 1-381 PDB
2QW9 X-ray 185 A A/B 1-394 PDB
2QWL X-ray 175 A A/B 1-394 PDB
2QWM X-ray 186 A A/B 1-394 PDB
2QWN X-ray 240 A A 1-394 PDB
2QWO X-ray 170 A A 1-394 PDB
2QWP X-ray 175 A A 1-394 PDB
2QWQ X-ray 221 A A 1-394 PDB
2QWR X-ray 221 A A 1-394 PDB
3C7N X-ray 312 A B 1-554 PDB
3HSC X-ray 193 A A 1-386 PDB
4FL9 X-ray 190 A A 1-554 PDB
6H54 X-ray 202 A A 1-554 PDB
7O6R X-ray 200 A A 1-554 PDB
7ODB X-ray 166 A A 1-554 PDB
7ODD X-ray 198 A A 1-554 PDB
7ODI X-ray 183 A A 1-554 PDB
7PLK X-ray 249 A A 1-554 PDB
AF-P19120-F1 Predicted AlphaFoldDB

No variants for P19120

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P19120

No associated diseases with P19120

3 regional properties for P19120

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 3.6.4.10 Acting on ATP; involved in cellular and subcellular movement
Subcellular Localization
  • Cytoplasm
  • Melanosome
  • Nucleus, nucleolus
  • Cell membrane
  • Lysosome membrane ; Peripheral membrane protein ; Cytoplasmic side
  • Localized in cytoplasmic mRNP granules containing untranslated mRNAs
  • Translocates rapidly from the cytoplasm to the nuclei, and especially to the nucleoli, upon heat shock
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

15 GO annotations of cellular component

Name Definition
autophagosome A double-membrane-bounded compartment that engulfs endogenous cellular material as well as invading microorganisms to target them to the lytic vacuole/lysosome for degradation as part of macroautophagy.
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.
dendrite A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
lysosomal membrane The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm.
melanosome A tissue-specific, membrane-bounded cytoplasmic organelle within which melanin pigments are synthesized and stored. Melanosomes are synthesized in melanocyte cells.
nucleolus A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
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.
postsynaptic cytosol The region of the cytosol consisting of all cytosol that is part of the postsynapse.
presynaptic cytosol The region of the cytosol consisting of all cytosol that is part of the presynapse.
Prp19 complex A protein complex consisting of Prp19 and associated proteins that is involved in the transition from the precatalytic spliceosome to the activated form that catalyzes step 1 of splicing, and which remains associated with the spliceosome through the second catalytic step. It is widely conserved, found in both yeast and mammals, though the exact composition varies. In S. cerevisiae, it contains Prp19p, Ntc20p, Snt309p, Isy1p, Syf2p, Cwc2p, Prp46p, Clf1p, Cef1p, and Syf1p.
ribonucleoprotein complex A macromolecular complex that contains both RNA and protein molecules.
spliceosomal complex Any of a series of ribonucleoprotein complexes that contain snRNA(s) and small nuclear ribonucleoproteins (snRNPs), and are formed sequentially during the spliceosomal splicing of one or more substrate RNAs, and which also contain the RNA substrate(s) from the initial target RNAs of splicing, the splicing intermediate RNA(s), to the final RNA products. During cis-splicing, the initial target RNA is a single, contiguous RNA transcript, whether mRNA, snoRNA, etc., and the released products are a spliced RNA and an excised intron, generally as a lariat structure. During trans-splicing, there are two initial substrate RNAs, the spliced leader RNA and a pre-mRNA.
terminal bouton Terminal inflated portion of the axon, containing the specialized apparatus necessary to release neurotransmitters. The axon terminus is considered to be the whole region of thickening and the terminal bouton is a specialized region of it.

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.
clathrin-uncoating ATPase activity Catalysis of the reaction
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.
protein-macromolecule adaptor activity The binding activity of a protein that brings together two or more macromolecules in contact, permitting those molecules to function in a coordinated way. The adaptor can bring together two proteins, or a protein and another macromolecule such as a lipid or a nucleic acid.

11 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.
chaperone-mediated autophagy translocation complex disassembly The disaggregation of a chaperone-mediated autophagy translocation complex into its constituent components.
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.
late endosomal microautophagy The autophagy process by which cytosolic proteins targeted for degradation are tagged with a chaperone and are directly transferred into and degraded in a late endosomal compartment.
mRNA processing Any process involved in the conversion of a primary mRNA transcript into one or more mature mRNA(s) prior to translation into polypeptide.
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
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 lysosome involved in chaperone-mediated autophagy The targeting of a protein to the lysosome process in which an input protein binds to a chaperone and subsequently to a lysosomal receptor.
RNA splicing The process of removing sections of the primary RNA transcript to remove sequences not present in the mature form of the RNA and joining the remaining sections to form the mature form of the RNA.
slow axonal transport The directed slow movement of non-membranous molecules in nerve cell axons. It is comprised of a Slow Component a (SCa) and a Slow Component b (SCb) which differ in transport rates and protein composition.
synaptic vesicle uncoating The removal of the protein coat on a synaptic vesicle following the pinching step at the end of budding from the presynaptic membrane.

61 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
P10591 SSA1 Heat shock protein SSA1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) 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
Q2YDD0 HSPA14 Heat shock 70 kDa protein 14 Bos taurus (Bovine) SS
E1C2P3 HSPA14 Heat shock 70 kDa protein 14 Gallus gallus (Chicken) SS
P08106 Heat shock 70 kDa protein Gallus gallus (Chicken) 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
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
Q9VG58 Hsp70Bbb Major heat shock 70 kDa protein Bbb Drosophila melanogaster (Fruit fly) SS
Q9BIR7 Hsp70Bc Major heat shock 70 kDa protein Bc Drosophila melanogaster (Fruit fly) SS
Q8INI8 Hsp70Ba Major heat shock 70 kDa protein Ba Drosophila melanogaster (Fruit fly) SS
Q9BIS2 Hsp70Bb Major heat shock 70 kDa protein Bb Drosophila melanogaster (Fruit fly) SS
P11146 Hsc70-2 Heat shock 70 kDa protein cognate 2 Drosophila melanogaster (Fruit fly) SS
O97125 Hsp68 Heat shock protein 68 Drosophila melanogaster (Fruit fly) SS
P11147 Hsc70-4 Heat shock 70 kDa protein cognate 4 Drosophila melanogaster (Fruit fly) SS
P29843 Hsc70-1 Heat shock 70 kDa protein cognate 1 Drosophila melanogaster (Fruit fly) SS
A2Q0Z1 HSPA8 Heat shock cognate 71 kDa protein Equus caballus (Horse) 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
P0DMV9 HSPA1B Heat shock 70 kDa protein 1B Homo sapiens (Human) SS
P0DMV8 HSPA1A Heat shock 70 kDa protein 1A Homo sapiens (Human) SS
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
P11143 HSP70 Heat shock 70 kDa protein Zea mays (Maize) SS
P16627 Hspa1l Heat shock 70 kDa protein 1-like Mus musculus (Mouse) SS
Q99M31 Hspa14 Heat shock 70 kDa protein 14 Mus musculus (Mouse) SS
Q8K0U4 Hspa12a Heat shock 70 kDa protein 12A Mus musculus (Mouse) PR
P17156 Hspa2 Heat shock-related 70 kDa protein 2 Mus musculus (Mouse) SS
Q61696 Hspa1a Heat shock 70 kDa protein 1A Mus musculus (Mouse) SS
Q9CZJ2 Hspa12b Heat shock 70 kDa protein 12B Mus musculus (Mouse) PR
P17879 Hspa1b Heat shock 70 kDa protein 1B Mus musculus (Mouse) SS
P63017 Hspa8 Heat shock cognate 71 kDa protein 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
P0DMW1 Hspa1b Heat shock 70 kDa protein 1B Rattus norvegicus (Rat) SS
P0DMW0 Hspa1a Heat shock 70 kDa protein 1A Rattus norvegicus (Rat) SS
P55063 Hspa1l Heat shock 70 kDa protein 1-like Rattus norvegicus (Rat) 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
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
MSKGPAVGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL IGDAAKNQVA
70 80 90 100 110 120
MNPTNTVFDA KRLIGRRFDD AVVQSDMKHW PFMVVNDAGR PKVQVEYKGE TKSFYPEEVS
130 140 150 160 170 180
SMVLTKMKEI AEAYLGKTVT NAVVTVPAYF NDSQRQATKD AGTIAGLNVL RIINEPTAAA
190 200 210 220 230 240
IAYGLDKKVG AERNVLIFDL GGGTFDVSIL TIEDGIFEVK STAGDTHLGG EDFDNRMVNH
250 260 270 280 290 300
FIAEFKRKHK KDISENKRAV RRLRTACERA KRTLSSSTQA SIEIDSLYEG IDFYTSITRA
310 320 330 340 350 360
RFEELNADLF RGTLDPVEKA LRDAKLDKSQ IHDIVLVGGS TRIPKIQKLL QDFFNGKELN
370 380 390 400 410 420
KSINPDEAVA YGAAVQAAIL SGDKSENVQD LLLLDVTPLS LGIETAGGVM TVLIKRNTTI
430 440 450 460 470 480
PTKQTQTFTT YSDNQPGVLI QVYEGERAMT KDNNLLGKFE LTGIPPAPRG VPQIEVTFDI
490 500 510 520 530 540
DANGILNVSA VDKSTGKENK ITITNDKGRL SKEDIERMVQ EAEKYKAEDE KQRDKVSSKN
550 560 570 580 590 600
SLESYAFNMK ATVEDEKLQG KINDEDKQKI LDKCNEIINW LDKNQTAEKE EFEHQQKELE
610 620 630 640
KVCNPIITKL YQSAGGMPGG MPGGMPGGFP GGGAPPSGGA SSGPTIEEVD