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

228-265 (Nucleolar targeting region)

Relief mechanism

Others

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for P14659

Entry ID Method Resolution Chain Position Source
AF-P14659-F1 Predicted AlphaFoldDB

No variants for P14659

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P14659

No associated diseases with P14659

5 regional properties for P14659

Type Name Position InterPro Accession
domain Protein kinase domain 18 - 294 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 22 - 287 IPR001245
domain CARD domain 432 - 524 IPR001315
active_site Serine/threonine-protein kinase, active site 142 - 154 IPR008271
domain RIP2, CARD domain 438 - 524 IPR042149

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm, cytoskeleton, spindle
  • Colocalizes with SHCBP1L at spindle during the meiosis process
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
CatSper complex A sperm-specific voltage-gated calcium channel that controls the intracellular calcium ion concentration and, thereby, the swimming behavior of sperm. Consists of a heteromeric tetramer surrounding a calcium ion- selective pore. May also contain additional auxiliary subunits.
cell surface The external part of the cell wall and/or plasma membrane.
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.
male germ cell nucleus The nucleus of a male germ cell, a reproductive cell in males.
meiotic spindle A spindle that forms as part of meiosis. Several proteins, such as budding yeast Spo21p, fission yeast Spo2 and Spo13, and C. elegans mei-1, localize specifically to the meiotic spindle and are absent from the mitotic spindle.
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.
synaptonemal complex A proteinaceous scaffold found between homologous chromosomes during meiosis. It consists of 2 lateral elements and a central element, all running parallel to each other. Transverse filaments connect the lateral elements to the central element.

11 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.
disordered domain specific binding Binding to a disordered domain of a protein.
enzyme binding Binding to an enzyme, a protein with catalytic activity.
glycolipid binding Binding to a glycolipid, any compound containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic group such as an acylglycerol, a sphingoid, a ceramide (N-acylsphingoid) or a prenyl phosphate.
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-folding chaperone binding Binding to a chaperone protein, a class of proteins that bind to nascent or unfolded polypeptides and ensure correct folding or transport.
tau protein binding Binding to tau protein. tau is a microtubule-associated protein, implicated in Alzheimer's disease, Down Syndrome and ALS.
unfolded protein binding Binding to an unfolded protein.

12 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.
male meiosis I A cell cycle process comprising the steps by which a cell progresses through male meiosis I, the first meiotic division in the male germline.
male meiotic nuclear division A cell cycle process by which the cell nucleus divides as part of a meiotic cell cycle in the male germline.
negative regulation of inclusion body assembly Any process that decreases the rate, frequency, or extent of inclusion body assembly. Inclusion body assembly is the aggregation, arrangement and bonding together of a set of components to form an inclusion body.
positive regulation of G2/M transition of mitotic cell cycle Any signalling pathway that activates or increases the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G2 phase to M phase of the mitotic cell cycle.
positive regulation of protein phosphorylation Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
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.
response to cold 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 cold stimulus, a temperature stimulus below the optimal temperature for that organism.
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.
spermatid development The process whose specific outcome is the progression of a spermatid over time, from its formation to the mature structure.
spermatogenesis The developmental process by which male germ line stem cells self renew or give rise to successive cell types resulting in the development of a spermatozoa.
synaptonemal complex disassembly The controlled breakdown of a synaptonemal complex.

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
Q27975 HSPA1A Heat shock 70 kDa protein 1A 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
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
P11147 Hsc70-4 Heat shock 70 kDa protein cognate 4 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
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
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
P11142 HSPA8 Heat shock cognate 71 kDa protein Homo sapiens (Human) EV
P54652 HSPA2 Heat shock-related 70 kDa protein 2 Homo sapiens (Human) SS
P11143 HSP70 Heat shock 70 kDa protein Zea mays (Maize) SS
P16627 Hspa1l Heat shock 70 kDa protein 1-like 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
Q8K0U4 Hspa12a Heat shock 70 kDa protein 12A Mus musculus (Mouse) PR
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
P17156 Hspa2 Heat shock-related 70 kDa protein 2 Mus musculus (Mouse) SS
Q6S4N2 HSPA1B Heat shock 70 kDa protein 1B Sus scrofa (Pig) 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
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
MSARGPAIGI DLGTTYSCVG VFQHGKVEII ANDQGNRTTP SYVAFTDTER LIGDAAKNQV
70 80 90 100 110 120
AMNPTNTIFD AKRLIGRKFE DATVQSDMKH WPFRVVSEGG KPKVQVEYKG EMKTFFPEEI
130 140 150 160 170 180
SSMVLTKMKE IAEAYLGGKV QSAVITVPAY FNDSQRQATK DAGTITGLNV LRIINEPTAA
190 200 210 220 230 240
AIAYGLDKKG CAGGEKNVLI FDLGGGTFDV SILTIEDGIF EVKSTAGDTH LGGEDFDNRM
250 260 270 280 290 300
VSHLAEEFKR KHKKDIGPNK RAVRRLRTAC ERAKRTLSSS TQASIEIDSL YEGVDFYTSI
310 320 330 340 350 360
TRARFEELNA DLFRGTLEPV EKALRDAKLD KGQIQEIVLV GGSTRIPKIQ KLLQDFFNGK
370 380 390 400 410 420
ELNKSINPDE AVAYGAAVQA AILIGDKSEN VQDLLLLDVT PLSLGIETAG GVMTPLIKRN
430 440 450 460 470 480
TTIPTKQTQT FTTYSDNQSS VLVQVYEGER AMTKDNNLLG KFDLTGIPPA PRGVPQIEVT
490 500 510 520 530 540
FDIDANGILN VTAADKSTGK ENKITITNDK GRLSKDDIDR MVQEAERYKS EDEANRDRVA
550 560 570 580 590 600
AKNAVESYTY NIKQTVEDEK LRGKISEQDK NKILDKCQEV INWLDRNQMA EKDEYEHKQK
610 620 630
ELERVCNPII SKLYQGGPGG GGSSGGPTIE EVD