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HSPA8 (heat shock 70kDa protein 8)

Written2013-08Tuoen Liu, Shousong Cao
Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St Louis, Missouri, United States (TL); Department of Medicine, Roswell Park Cancer Institute, Elm, Carlton Streets, Buffalo, New York 14263, United States (SC)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesHSPA10
heat shock 70kD protein 8
heat shock 70kDa protein 8
Alias_symbol (synonym)HSC71
HSC70
HSP73
Other aliasHSC54
HSP71
LAP1
NIP71
HGNC (Hugo) HSPA8
LocusID (NCBI) 3312
Atlas_Id 40878
Location 11q24.1  [Link to chromosome band 11q24]
Location_base_pair Starts at 123057492 and ends at 123062335 bp from pter ( according to hg19-Feb_2009)  [Mapping HSPA8.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
C16orf72 (16p13.2) / HSPA8 (11q24.1)CCDC47 (17q23.3) / HSPA8 (11q24.1)CLMP (11q24.1) / HSPA8 (11q24.1)
GOLGA4 (3p22.2) / HSPA8 (11q24.1)GSN (9q33.2) / HSPA8 (11q24.1)HIST1H1D (6p22.2) / HSPA8 (11q24.1)
HSPA8 (11q24.1) / ALDH1A1 (9q21.13)HSPA8 (11q24.1) / HSPA8 (11q24.1)HSPA8 (11q24.1) / HSPD1 (2q33.1)
HSPA8 (11q24.1) / PATJ (1p31.3)HSPA8 (11q24.1) / SLC7A6 (16q22.1)HSPA8 (11q24.1) / STX3 (11q12.1)
MAP4 (3p21.31) / HSPA8 (11q24.1)NCL (2q37.1) / HSPA8 (11q24.1)RND3 (2q23.3) / HSPA8 (11q24.1)
RNU12 (22q13.2) / HSPA8 (11q24.1)UTP18 (17q21.33) / HSPA8 (11q24.1)

DNA/RNA

Note The human HSPA8 gene includes nine exons and eight introns. It is mapped into chromosome 11, 11q23.3-q25 (Sonna et al., 2002). Introns 5, 6 and 8 contain highly conserved repeats about 90 bp which code for U14 snoRNA (Chen et al., 1996). Exons 2, 3, 6, 7, and 9 code for the peptides of extremely uniform length, between 61 and 69 amino acids while exons 4, 8 and 5 code for peptides of 51, 78 and 185 amino acids, respectively. Two 150 bp direct repeats (nt 674 to nt 829 and nt 1783 to nt 1937) are 85% homologous to each other (Dworniczak and Mirault, 1987).
Description The gene coding for HSC70, HSPA8 affects the posttranscriptional silencing mediated by RNAi and is a component of the RNAi pathway in Drosophila cultured cells (Dorner et al., 2006). The promoter region of the HSPa8 gene includes a TATA box, two CCAAT boxes, two SP1 elements and two sets of heat shock response elements (HSE) where the heat shock transcriptional factors bind (Chen et al., 2002).

Protein

Note The HSPA8 gene coding for the protein HSC70, also known as HSP73, is a 73 kDa heat shock cognate protein. HSC70 is an ATP binding chaperone and has intrinsic ATPase activity which hydrolyzes ATP into ADP (Jakob et al., 1996). HSC70 hydrolyzing ATP initiates the conformational change of HSC70 and further causes substrate binding by HSC70 (Sullivan and Pipas, 2002).
 
  The model for HSC70 and substrates binding and releasing cycle. In the ATP-bound state, HSC70 has low affinity with the substrates. After hydrolysis of ATP with the ATPase activity, HSC70 in the ADP bound state binds with the substrates with high affinity. Some co-chaperones such as Dna J homologues enhance the ATPase activity of HSC70. Nucleotide exchange factors such as GrpE enhance the dissociation of bound ADP from HSC70 to allow the binding of ATP, resetting the cycle.
Description HSC70, also called HSP73, is a 73 kDa heat shock cognate protein. The basic structure of human HSC70 includes three parts: a 44 kDa amino-terminal adenosine triphosphatase (ATPase) domain (residues 1-384), also known as the ATP-binding domain, an 18 kDa peptide (substrate) binding domain (residues 385-543), and a 10 kDa carboxyl-terminal domain (residues 544-646) which is also designated as the variable or "lid" domain (Smith et al., 1998; Tsukahara et al., 2000; Sullivan and Pipas, 2002). The carboxyl-terminal amino acid sequence Glu-Glu-Val-Asp (EEVD motif), which is absolutely conserved in all eukaryotic HSC70 and HSP70 family members, is essential for association with some co-chaperones (Mosser et al., 2000). Two amino acid sequences have the characteristics of nuclear localization signals in human HSC70 which are involved in nuclear import of HSC70: DAKRL69-73 in the amino-terminal and KRKHKKDISENKRAVRR246-262 in the ATPase domain (Lamian et al., 1996; Tsukahara and Maru, 2004).
 
  The structure of HSC70. The basic structure of human HSC70 includes three parts: a 44 kDa ATPase domain, an 18 kDa peptide (substrate) binding domain and a 10 kDa carboxyl-terminal domain, also known as "lid" domain.
Expression Various conditions and molecules can affect the expression of the HSPA8 gene. The table below summarizes the factors which affect the expression of the HSPA8 gene (Liu et al., 2012).
 
Localisation HSC70 is a major cytosolic molecular chaperone (Place and Hofmann, 2005). However, HSC70 is also located in various cellular locations such as nuclear and close to cellular membrane (Arispe et al., 2002). HSC70 can interact with the lipid bilayer in the cellular membrane directly and form ion-conductance channels allowing ion flow through the cellular membrane. HSC70 is also identified as a tyrosine-phosphorylated protein associated with the nuclear envelope. HSC70 supports the nuclear import of karyophilic proteins and may play a role in nucleocytoplasmic transport (Otto et al., 2001).
Function 1. As a molecular chaperone, HSC70 regulates protein folding, maintains protein normal structure and functions, and protects cells from physical and chemcial damage. HSC70 regulates protein maturation and interacts with nascent polypeptides in the process of new protein synthesis (Beckmann et al., 1990; Beckmann et al.,1992). HSC70 can also regulate the translocation of proteins into different cellular organelles such as endoplasmic reticulum and mitochondria (Chirico et al., 1998, Sheffield et al., 1990).
2. HSC70 was oginally characterized as an uncoating ATPase that dissociates clathrin triskelions from clathrin-coated vesicles. It catalyzes the ATP-dependent uncoating of clathrin-coated pits (chappell et al., 1986; Goldfarb et al., 2005).
3. HSC70 is involved in targeting protein to lysosomes for degradation (Terlecky et al., 1992) and to ubiquitin/proteasome machinery for degradation (Massyuki, 1994).
4. HSC70 regulates cellular signaling and functions such as steroid receptor maturation and Akt signaling pathway (Kimmins and MacRae, 2000; Shiota et al., 2010).
5. HSC70 is important in regulating apoptosis, embryonic development and aging (Beere, 2004; Sreedhar and Csermely, 2004; Kodiha et al., 2005).
Homology HSC70 belongs to the HSP70 family in which includes other three members: the HSP70, the glucose-regulated protein 78 (GRP78), and HSP75. Human HSC70 shares 85% amino acid similarity with HSP70 (Ali et al., 2003). They have similar functions and interact with each other in an ATP-dependent manner. HSC70 can form a stable complex with newly synthesized HSP70 upon heat shock (Brown et al., 1993).

Implicated in

Note
  
Entity Various cancers
Note The HSPA8 gene is higher expressed in some cancer cells such as human colon cancer (Kubota et al., 2000).
HSC70 regulates functions of various cancer-related genes and proteins. HSC70 functions as a molecular stabilizer of nonphosphorylated retinoblastoma protein (pRb) by directly binding to it (Inoue et al., 1995). HSC70 binds to a mutant form of p53 and p73 and links them for degradation. HSPA8 gene can suppress oncogene (such as mutant p53 and Ras) mediated transformation (Yehiely and Oren, 1992; Gaiddon et al., 2001).
Cytogenetics Intronic polymorphism (1541-1542delGT) of HSPA8 is associated with decrease of lung cancer risk (Rusin et al., 2004).
  
  
Entity Cadiovascular diseases
Note HSC70 plays a protective role in myocardial injuries. HSC70 is commknly doend in atherosclerotic plaques during the atherogenesis and therosclerotic plaque progression and it appears to be a protective factor against cellular stress (Dupont et al., 2008). HSC70 expression is significantly decreased in diabetic myocardium because of insulin deficiency. Insulin directly increases the abundance of HSC70 in cultured cardiomyocytes and overexpression of HSC70 leads to protect against stress via suppression of apoptosis signalling (Chen et al., 2006).
  
  
Entity Neurological diseases
Note HSC70 is directly involved in cell survival during neurulation and HSC70 acts as an intrinsic protector of neuroepithelial and neural precursor cells (Rubio et al., 2002). HSC70 mediates the chaperone mediated lysosomal degradation of α-synuclei which is accumulated in Parkingson's disease and other neurodegenerative diseases (Mak et al., 2010). HSC70 facilitates degradation of the amyotrophic lateral sclerosis (ALS) -linked mutant SOD1 protein in an ubiquitination-dependent manner (Urushitani et al., 2004; Casoni et al., 2005). HSC70 mediates the autophagy for the degradation of mutant huntingtin protein which can cause Huntington's disease (Bauer et al., 2010).
  
  
Entity Liver diseases
Note HSC70 has been implicated in the pathogenesis and the pathophysiology of hepatic diseases such as hepatitis B and C, non-alcoholic steatohepatitis autoimmune hepatitis, and primary biliary cirrhosis. HSC70 plays important role in the replication of hepatitis B virus and hepatitis C virus. HSC70 could be a novel molecular target for diagnosis and treatment of hepatitis B and C (Wang et al., 2010).
  

To be noted

HSC70 interacts with many molecules and plays an important role in regulating cellualr functions. As a molecular chaperone, HSC70 interacts with co-chaperones, also called co-factors. Those co-chaperones include auxilin, BAG family members, Hip, Hop, HSPBP1 and CHIP (Liu et al., 2012). In addition to co-chaperones, HSC70 interacts with many other cellular molecules. The cooperation of HSC70 with HSP90 regulates the glucocorticoid receptor activation and signaling pathway (Furay et al., 2006). HSC70 facilitates the heat-shock factor1 mediated cell survival in response to cellular stress (Ahn et al., 2005). HSC70 interacts and forms a complex with histone deacetylase 3 (HDAC3). HSC70 interacts with newly synthesized cyclin D1 and mature cyclin D1/CDK4 holoenzyme complex, thus involved in cell cycle regulation (Diehl et al., 2003). HSC70 interacts genetically with target of rapamycin (TOR) and acts as a regulator of endocytosis (Hennig et al., 2006). HSC70 can regulate the synthesis of GABA by interacting with the rate-limiting enzyme L-glutamic acid decarboxylase (GAD).
Research has been conducted to use HSC70 as a drug target for cancer therapy. A recombinant vaccine composed of CD4+ and CD8+ T cell epitopes fused to HSC70 may prevent tumor growth and metastasis (Mizukami et al., 2008). Fusion the ATPase domain of HSC70 with tyrosinase-related protein-2 acts as a tumor vaccine against B16 melanoma (Zhang et al., 2006).

Bibliography

Tissue- and stressor-specific differential expression of two hsc70 genes in carp.
Ali KS, Dorgai L, Abraham M, Hermesz E.
Biochem Biophys Res Commun. 2003 Aug 1;307(3):503-9.
PMID 12893250
 
ATP and ADP modulate a cation channel formed by Hsc70 in acidic phospholipid membranes.
Arispe N, De Maio A.
J Biol Chem. 2000 Oct 6;275(40):30839-43.
PMID 10899168
 
Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein.
Bauer PO, Goswami A, Wong HK, Okuno M, Kurosawa M, Yamada M, Miyazaki H, Matsumoto G, Kino Y, Nagai Y, Nukina N.
Nat Biotechnol. 2010 Mar;28(3):256-63. doi: 10.1038/nbt.1608. Epub 2010 Feb 28.
PMID 20190739
 
Examining the function and regulation of hsp 70 in cells subjected to metabolic stress.
Beckmann RP, Lovett M, Welch WJ.
J Cell Biol. 1992 Jun;117(6):1137-50.
PMID 1607378
 
"The stress of dying": the role of heat shock proteins in the regulation of apoptosis.
Beere HM.
J Cell Sci. 2004 Jun 1;117(Pt 13):2641-51. (REVIEW)
PMID 15169835
 
The constitutive and stress inducible forms of hsp 70 exhibit functional similarities and interact with one another in an ATP-dependent fashion.
Brown CR, Martin RL, Hansen WJ, Beckmann RP, Welch WJ.
J Cell Biol. 1993 Mar;120(5):1101-12.
PMID 8436586
 
Protein nitration in a mouse model of familial amyotrophic lateral sclerosis: possible multifunctional role in the pathogenesis.
Casoni F, Basso M, Massignan T, Gianazza E, Cheroni C, Salmona M, Bendotti C, Bonetto V.
J Biol Chem. 2005 Apr 22;280(16):16295-304. Epub 2005 Feb 7.
PMID 15699043
 
Uncoating ATPase is a member of the 70 kilodalton family of stress proteins.
Chappell TG, Welch WJ, Schlossman DM, Palter KB, Schlesinger MJ, Rothman JE.
Cell. 1986 Apr 11;45(1):3-13.
PMID 2937542
 
Downregulation of the constitutively expressed Hsc70 in diabetic myocardium is mediated by insulin deficiency.
Chen HS, Jia J, Su HF, Lin HD, Chen JW, Lin SJ, Yang JY, Lai HC, Mestril R, Wang PH.
J Endocrinol. 2006 Aug;190(2):433-40.
PMID 16899576
 
Amplification and altered expression of the hsc70/U14 snoRNA gene in a heat resistant Chinese hamster cell line.
Chen MS, Featherstone T, Laszlo A.
Cell Stress Chaperones. 1996 Apr;1(1):47-61.
PMID 9222589
 
Differential accumulation of U14 snoRNA and hsc70 mRNA in Chinese hamster cells after exposure to various stress conditions.
Chen MS, Goswami PC, Laszlo A.
Cell Stress Chaperones. 2002 Jan;7(1):65-72.
PMID 11892989
 
70K heat shock related proteins stimulate protein translocation into microsomes.
Chirico WJ, Waters MG, Blobel G.
Nature. 1988 Apr 28;332(6167):805-10.
PMID 3282179
 
Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase.
Diehl JA, Yang W, Rimerman RA, Xiao H, Emili A.
Mol Cell Biol. 2003 Mar;23(5):1764-74.
PMID 12588994
 
A genomewide screen for components of the RNAi pathway in Drosophila cultured cells.
Dorner S, Lum L, Kim M, Paro R, Beachy PA, Green R.
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11880-5. Epub 2006 Aug 1.
PMID 16882716
 
Application of saturation dye 2D-DIGE proteomics to characterize proteins modulated by oxidized low density lipoprotein treatment of human macrophages.
Dupont A, Chwastyniak M, Beseme O, Guihot AL, Drobecq H, Amouyel P, Pinet F.
J Proteome Res. 2008 Aug;7(8):3572-82. doi: 10.1021/pr700683s. Epub 2008 Jun 13.
PMID 18549265
 
Structure and expression of a human gene coding for a 71 kd heat shock 'cognate' protein.
Dworniczak B, Mirault ME.
Nucleic Acids Res. 1987 Jul 10;15(13):5181-97.
PMID 3037489
 
Region-specific regulation of glucocorticoid receptor/HSP90 expression and interaction in brain.
Furay AR, Murphy EK, Mattson MP, Guo Z, Herman JP.
J Neurochem. 2006 Aug;98(4):1176-84.
PMID 16895583
 
A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain.
Gaiddon C, Lokshin M, Ahn J, Zhang T, Prives C.
Mol Cell Biol. 2001 Mar;21(5):1874-87.
PMID 11238924
 
Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels.
Goldfarb SB, Kashlan OB, Watkins JN, Suaud L, Yan W, Kleyman TR, Rubenstein RC.
Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5817-22. Epub 2006 Apr 3.
PMID 16585520
 
TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth.
Hennig KM, Colombani J, Neufeld TP.
J Cell Biol. 2006 Jun 19;173(6):963-74.
PMID 16785324
 
70-kDa heat shock cognate protein interacts directly with the N-terminal region of the retinoblastoma gene product pRb. Identification of a novel region of pRb-mediating protein interaction.
Inoue A, Torigoe T, Sogahata K, Kamiguchi K, Takahashi S, Sawada Y, Saijo M, Taya Y, Ishii S, Sato N, Kikuchi K.
J Biol Chem. 1995 Sep 22;270(38):22571-6.
PMID 7673249
 
Assessment of the ATP binding properties of Hsp90.
Jakob U, Scheibel T, Bose S, Reinstein J, Buchner J.
J Biol Chem. 1996 Apr 26;271(17):10035-41.
PMID 8626558
 
Maturation of steroid receptors: an example of functional cooperation among molecular chaperones and their associated proteins.
Kimmins S, MacRae TH.
Cell Stress Chaperones. 2000 Apr;5(2):76-86. (REVIEW)
PMID 11147968
 
Stress inhibits nucleocytoplasmic shuttling of heat shock protein hsc70.
Kodiha M, Chu A, Lazrak O, Stochaj U.
Am J Physiol Cell Physiol. 2005 Oct;289(4):C1034-41. Epub 2005 Jun 1.
PMID 15930140
 
Increased expression of co-chaperone HOP with HSP90 and HSC70 and complex formation in human colonic carcinoma.
Kubota H, Yamamoto S, Itoh E, Abe Y, Nakamura A, Izumi Y, Okada H, Iida M, Nanjo H, Itoh H, Yamamoto Y.
Cell Stress Chaperones. 2010 Nov;15(6):1003-11. doi: 10.1007/s12192-010-0211-0. Epub 2010 Jul 9.
PMID 20617406
 
Evidence for the existence of a novel mechanism for the nuclear import of Hsc70.
Lamian V, Small GM, Feldherr CM.
Exp Cell Res. 1996 Oct 10;228(1):84-91.
PMID 8892974
 
Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential.
Liu T, Daniels CK, Cao S.
Pharmacol Ther. 2012 Dec;136(3):354-74. doi: 10.1016/j.pharmthera.2012.08.014. Epub 2012 Aug 29. (REVIEW)
PMID 22960394
 
Lysosomal degradation of alpha-synuclein in vivo.
Mak SK, McCormack AL, Manning-Bog AB, Cuervo AM, Di Monte DA.
J Biol Chem. 2010 Apr 30;285(18):13621-9. doi: 10.1074/jbc.M109.074617. Epub 2010 Mar 3.
PMID 20200163
 
The chaperone function of hsp70 is required for protection against stress-induced apoptosis.
Mosser DD, Caron AW, Bourget L, Meriin AB, Sherman MY, Morimoto RI, Massie B.
Mol Cell Biol. 2000 Oct;20(19):7146-59.
PMID 10982831
 
A 70-kDa heat shock cognate protein suppresses the defects caused by a proteasome mutation in Saccharomyces cerevisiae.
Ohba M.
FEBS Lett. 1994 Sep 5;351(2):263-6.
PMID 8082777
 
Identification of tyrosine-phosphorylated proteins associated with the nuclear envelope.
Otto H, Dreger M, Bengtsson L, Hucho F.
Eur J Biochem. 2001 Jan;268(2):420-8.
PMID 11168378
 
Comparison of Hsc70 orthologs from polar and temperate notothenioid fishes: differences in prevention of aggregation and refolding of denatured proteins.
Place SP, Hofmann GE.
Am J Physiol Regul Integr Comp Physiol. 2005 May;288(5):R1195-202. Epub 2005 Jan 6.
PMID 15637165
 
Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70.
Rubio E, Valenciano AI, Segundo C, Sanchez N, de Pablo F, de la Rosa EJ.
Eur J Neurosci. 2002 May;15(10):1646-54.
PMID 12059972
 
Intronic polymorphism (1541-1542delGT) of the constitutive heat shock protein 70 gene has functional significance and shows evidence of association with lung cancer risk.
Rusin M, Zientek H, Krzesniak M, Malusecka E, Zborek A, Krzyzowska-Gruca S, Butkiewicz D, Vaitiekunaite R, Lisowska K, Grzybowska E, Krawczyk Z.
Mol Carcinog. 2004 Mar;39(3):155-63.
PMID 14991745
 
Mitochondrial precursor protein. Effects of 70-kilodalton heat shock protein on polypeptide folding, aggregation, and import competence.
Sheffield WP, Shore GC, Randall SK.
J Biol Chem. 1990 Jul 5;265(19):11069-76.
PMID 2193031
 
Heat shock cognate protein 70 is essential for Akt signaling in endothelial function.
Shiota M, Kusakabe H, Izumi Y, Hikita Y, Nakao T, Funae Y, Miura K, Iwao H.
Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):491-7. doi: 10.1161/ATVBAHA.109.193631. Epub 2009 Dec 17.
PMID 20018937
 
Molecular chaperones: biology and prospects for pharmacological intervention.
Smith DF, Whitesell L, Katsanis E.
Pharmacol Rev. 1998 Dec;50(4):493-514. (REVIEW)
PMID 9860803
 
Invited review: Effects of heat and cold stress on mammalian gene expression.
Sonna LA, Fujita J, Gaffin SL, Lilly CM.
J Appl Physiol (1985). 2002 Apr;92(4):1725-42. (REVIEW)
PMID 11896043
 
Heat shock proteins in the regulation of apoptosis: new strategies in tumor therapy: a comprehensive review.
Sreedhar AS, Csermely P.
Pharmacol Ther. 2004 Mar;101(3):227-57. (REVIEW)
PMID 15031001
 
T antigens of simian virus 40: molecular chaperones for viral replication and tumorigenesis.
Sullivan CS, Pipas JM.
Microbiol Mol Biol Rev. 2002 Jun;66(2):179-202. (REVIEW)
PMID 12040123
 
Protein and peptide binding and stimulation of in vitro lysosomal proteolysis by the 73-kDa heat shock cognate protein.
Terlecky SR, Chiang HL, Olson TS, Dice JF.
J Biol Chem. 1992 May 5;267(13):9202-9.
PMID 1577755
 
Identification of novel nuclear export and nuclear localization-related signals in human heat shock cognate protein 70.
Tsukahara F, Maru Y.
J Biol Chem. 2004 Mar 5;279(10):8867-72. Epub 2003 Dec 18.
PMID 14684748
 
CHIP promotes proteasomal degradation of familial ALS-linked mutant SOD1 by ubiquitinating Hsp/Hsc70.
Urushitani M, Kurisu J, Tateno M, Hatakeyama S, Nakayama K, Kato S, Takahashi R.
J Neurochem. 2004 Jul;90(1):231-44.
PMID 15198682
 
Heat stress cognate 70 host protein as a potential drug target against drug resistance in hepatitis B virus.
Wang YP, Liu F, He HW, Han YX, Peng ZG, Li BW, You XF, Song DQ, Li ZR, Yu LY, Cen S, Hong B, Sun CH, Zhao LX, Kreiswirth B, Perlin D, Shao RG, Jiang JD.
Antimicrob Agents Chemother. 2010 May;54(5):2070-7. doi: 10.1128/AAC.01764-09. Epub 2010 Feb 22.
PMID 20176893
 
The gene for the rat heat-shock cognate, hsc70, can suppress oncogene-mediated transformation.
Yehiely F, Oren M.
ell Growth Differ. 1992 Nov;3(11):803-9.
PMID 1467307
 
Fusion protein of ATPase domain of Hsc70 with TRP2 acting as a tumor vaccine against B16 melanoma.
Zhang H, Wang W, Li Q, Huang W.
Immunol Lett. 2006 Jun 15;105(2):167-73. Epub 2006 Mar 10.
PMID 16580737
 

Citation

This paper should be referenced as such :
Liu, T ; Cao, S
HSPA8 (heat shock 70kDa protein 8)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(3):169-173.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/HSPA8ID40878ch11q24.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Soft Tissues: Extraskeletal myxoid chondrosarcoma


External links

Nomenclature
HGNC (Hugo)HSPA8   5241
Cards
AtlasHSPA8ID40878ch11q24
Entrez_Gene (NCBI)HSPA8  3312  heat shock protein family A (Hsp70) member 8
AliasesHEL-33; HEL-S-72p; HSC54; HSC70; 
HSC71; HSP71; HSP73; HSPA10; LAP-1; LAP1; NIP71
GeneCards (Weizmann)HSPA8
Ensembl hg19 (Hinxton)ENSG00000109971 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000109971 [Gene_View]  chr11:123057492-123062335 [Contig_View]  HSPA8 [Vega]
ICGC DataPortalENSG00000109971
TCGA cBioPortalHSPA8
AceView (NCBI)HSPA8
Genatlas (Paris)HSPA8
WikiGenes3312
SOURCE (Princeton)HSPA8
Genetics Home Reference (NIH)HSPA8
Genomic and cartography
GoldenPath hg38 (UCSC)HSPA8  -     chr11:123057492-123062335 -  11q24.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)HSPA8  -     11q24.1   [Description]    (hg19-Feb_2009)
EnsemblHSPA8 - 11q24.1 [CytoView hg19]  HSPA8 - 11q24.1 [CytoView hg38]
Mapping of homologs : NCBIHSPA8 [Mapview hg19]  HSPA8 [Mapview hg38]
OMIM600816   
Gene and transcription
Genbank (Entrez)AB034951 AB073886 AF217511 AF352832 AK000571
RefSeq transcript (Entrez)NM_006597 NM_153201
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)HSPA8
Cluster EST : UnigeneHs.180414 [ NCBI ]
CGAP (NCI)Hs.180414
Alternative Splicing GalleryENSG00000109971
Gene ExpressionHSPA8 [ NCBI-GEO ]   HSPA8 [ EBI - ARRAY_EXPRESS ]   HSPA8 [ SEEK ]   HSPA8 [ MEM ]
Gene Expression Viewer (FireBrowse)HSPA8 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3312
GTEX Portal (Tissue expression)HSPA8
Human Protein AtlasENSG00000109971-HSPA8 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP11142   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP11142  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP11142
Splice isoforms : SwissVarP11142
PhosPhoSitePlusP11142
Domaine pattern : Prosite (Expaxy)HSP70_1 (PS00297)    HSP70_2 (PS00329)    HSP70_3 (PS01036)   
Domains : Interpro (EBI)Heat_shock_70_CS    HSP70_C    HSP70_peptide-bd    Hsp_70_fam   
Domain families : Pfam (Sanger)HSP70 (PF00012)   
Domain families : Pfam (NCBI)pfam00012   
Conserved Domain (NCBI)HSPA8
DMDM Disease mutations3312
Blocks (Seattle)HSPA8
PDB (SRS)3AGY    3AGZ    3ESK    3FZF    3FZH    3FZK    3FZL    3FZM    3LDQ    3M3Z    4H5N    4H5R    4H5T    4H5V    4H5W    4HWI    4KBQ    5AQF    5AQG    5AQH    5AQI    5AQJ    5AQK    5AQL    5AQM    5AQN    5AQO    5AQP    5AQQ    5AQR    5AQS    5AQT    5AQU    5AQV   
PDB (PDBSum)3AGY    3AGZ    3ESK    3FZF    3FZH    3FZK    3FZL    3FZM    3LDQ    3M3Z    4H5N    4H5R    4H5T    4H5V    4H5W    4HWI    4KBQ    5AQF    5AQG    5AQH    5AQI    5AQJ    5AQK    5AQL    5AQM    5AQN    5AQO    5AQP    5AQQ    5AQR    5AQS    5AQT    5AQU    5AQV   
PDB (IMB)3AGY    3AGZ    3ESK    3FZF    3FZH    3FZK    3FZL    3FZM    3LDQ    3M3Z    4H5N    4H5R    4H5T    4H5V    4H5W    4HWI    4KBQ    5AQF    5AQG    5AQH    5AQI    5AQJ    5AQK    5AQL    5AQM    5AQN    5AQO    5AQP    5AQQ    5AQR    5AQS    5AQT    5AQU    5AQV   
PDB (RSDB)3AGY    3AGZ    3ESK    3FZF    3FZH    3FZK    3FZL    3FZM    3LDQ    3M3Z    4H5N    4H5R    4H5T    4H5V    4H5W    4HWI=/A>nbwp;   4KBQ    5AQF    5AQG    5AQH    5AQI    5AQJ    5AQK    5AQL    5AQM    5AQN    5AQO    5AQP    5AQQ    5AQR    5AQS    5AQT    5AQU    5AQV   
Structural Biology KnowledgeBase3AGY    3AGZ    3ESK    3FZF    3FZH    3FZK    3FZL    3FZM    3LDQ    3M3Z    4H5N    4H5R    4H5T    4H5V    4H5W    4HWI    4KBQ    5AQF    5AQG    5AQH    5AQI    5AQJ    5AQK    5AQL    5AQM    5AQN    5AQO    5AQP    5AQQ    5AQR    5AQS    5AQT    5AQU    5AQV   
SCOP (Structural Classification of Proteins)3AGY    3AGZ    3ESK    3FZF    3FZH    3FZK    3FZL    3FZM    3LDQ    3M3Z    4H5N    4H5R    4H5T    4H5V    4H5W    4HWI    4KBQ    5AQF    5AQG    5AQH    5AQI    5AQJ    5AQK    5AQL    5AQM    5AQN    5AQO    5AQP    5AQQ    5AQR    5AQS    5AQT    5AQU    5AQV   
CATH (Classification of proteins structures)3AGY    3AGZ    3ESK    3FZF    3FZH    3FZK    3FZL    3FZM    3LDQ    3M3Z    4H5N    4H5R    4H5T    4H5V    4H5W    4HWI    4KBQ    5AQF    5AQG    5AQH    5AQI    5AQJ    5AQK    5AQL    5AQM    5AQN    5AQO    5AQP    5AQQ    5AQR    5AQS    5AQT    5AQU    5AQV   
SuperfamilyP11142
Human Protein Atlas [tissue]ENSG00000109971-HSPA8 [tissue]
Peptide AtlasP11142
HPRD07205
IPIIPI00003865   IPI00910870   IPI00037070   IPI00980749   IPI00980343   IPI00981943   IPI00983398   IPI00984555   IPI00984226   IPI00978818   IPI00981926   IPI01008803   IPI00981429   IPI00981268   IPI00980651   IPI00983926   
Protein Interaction databases
DIP (DOE-UCLA)P11142
IntAct (EBI)P11142
FunCoupENSG00000109971
BioGRIDHSPA8
STRING (EMBL)HSPA8
ZODIACHSPA8
Ontologies - Pathways
QuickGOP11142
Ontology : AmiGOubiquitin ligase complex  mRNA splicing, via spliceosome  Prp19 complex  G-protein coupled receptor binding  phosphatidylserine binding  RNA binding  protein binding  ATP binding  extracellular region  extracellular space  intracellular  intracellular  nucleus  nucleoplasm  spliceosomal complex  nucleolus  lysosomal membrane  late endosome  cytosol  cytosol  plasma membrane  focal adhesion  transcription, DNA-templated  protein folding  protein methylation  response to unfolded protein  neurotransmitter secretion  cellular response to starvation  membrane  viral process  ATPase activity  ATPase activity  enzyme binding  MHC class II protein complex binding  intracellular ribonucleoprotein complex  extracellular matrix  heat shock protein binding  ubiquitin protein ligase binding  regulation of protein stability  secretory granule lumen  protein refolding  melanosome  ATPase activity, coupled  lysosomal lumen  myelin sheath  regulation of protein complex assembly  neutrophil degranulation  regulation of mRNA stability  positive regulation by host of viral genome replication  cadherin binding  negative regulation of transcription, DNA-templated  ATP metabolic process  positive regulation of mRNA splicing, via spliceosome  unfolded protein binding  chaperone mediated protein folding requiring cofactor  regulation of cell cycle  C3HC4-type RING finger domain binding  membrane organization  clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane  regulation of protein complex stability  chaperone-mediated autophagy  chaperone-mediated autophagy  late endosomal microautophagy  protein targeting to lysosome involved in chaperone-mediated autophagy  protein targeting to lysosome involved in chaperone-mediated autophagy  chaperone-mediated protein transport involved in chaperone-mediated autophagy  extracellular exosome  clathrin coat disassembly  blood microparticle  lumenal side of lysosomal membrane  presynapse  regulation of cellular response to heat  negative regulation of supramolecular fiber organization  regulation of protein import  chaperone-mediated autophagy translocation complex disassembly  ficolin-1-rich granule lumen  
Ontology : EGO-EBIubiquitin ligase complex  mRNA splicing, via spliceosome  Prp19 complex  G-protein coupled receptor binding  phosphatidylserine binding  RNA binding  protein binding  ATP binding  extracellular region  extracellular space  intracellular  intracellular  nucleus  nucleoplasm  spliceosomal complex  nucleolus  Lysnsomal membrane  late endosome  cytosol  cytosol  plasma membrane  focal adhesion  transcription, DNA-templated  protein folding  protein methylation  response to unfolded protein  neurotransmitter secretion  cellular response to starvation  membrane  viral process  ATPase activity  ATPase activity  enzyme binding  MHC class II protein complex binding  intracellular ribonucleoprotein complex  extracellular matrix  heat shock protein binding  ubiquitin protein ligase binding  regulation of protein stability  secretory granule lumen  protein refolding  melanosome  ATPase activity, coupled  lysosomal lumen  myelin sheath  regulation of protein complex assembly  neutrophil degranulation  regulation of mRNA stability  positive regulation by host of viral genome replication  cadherin binding  negative regulation of transcription, DNA-templated  ATP metabolic process  positive regulation of mRNA splicing, via spliceosome  unfolded protein binding  chaperone mediated protein folding requiring cofactor  regulation of cell cycle  C3HC4-type RING finger domain binding  membrane organization  clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane  regulation of protein complex stability  chaperone-mediated autophagy  chaperone-mediated autophagy  late endosomal microautophagy  protein targeting to lysosome involved in chaperone-mediated autophagy  protein targeting to lysosome involved in chaperone-mediated autophagy  chaperone-mediated protein transport involved in chaperone-mediated autophagy  extracellular exosome  clathrin coat disassembly  blood microparticle  lumenal side of lysosomal membrane  presynapse  regulation of cellular response to heat  negative regulation of supramolecular fiber organization  regulation of protein import  chaperone-mediated autophagy translocation complex disassembly  ficolin-1-rich granule lumen  
Pathways : KEGG   
REACTOMEP11142 [protein]
REACTOME PathwaysR-HSA-888590 [pathway]   
NDEx NetworkHSPA8
Atlas of Cancer Signalling NetworkHSPA8
Wikipedia pathwaysHSPA8
Orthology - Evolution
OrthoDB3312
GeneTree (enSembl)ENSG00000109971
Phylogenetic Trees/Animal Genes : TreeFamHSPA8
HOVERGENP11142
HOGENOMP11142
Homologs : HomoloGeneHSPA8
Homology/Alignments : Family Browser (UCSC)HSPA8
Gene fusions - Rearrangements
Fusion : MitelmanGOLGA4/HSPA8 [3p22.2/11q24.1]  [t(3;11)(p22;q24)]  
Fusion : MitelmanGSN/HSPA8 [9q33.2/11q24.1]  [t(9;11)(q33;q24)]  
Fusion: TCGAGOLGA4 3p22.2 HSPA8 11q24.1 BRCA
Fusion: TCGAGSN 9q33.2 HSPA8 11q24.1 BLCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHSPA8 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HSPA8
dbVarHSPA8
ClinVarHSPA8
1000_GenomesHSPA8 
Exome Variant ServerHSPA8
ExAC (Exome Aggregation Consortium)ENSG00000109971
GNOMAD BrowserENSG00000109971
Genetic variants : HAPMAP3312
Genomic Variants (DGV)HSPA8 [DGVbeta]
DECIPHERHSPA8 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisHSPA8 
Mutations
ICGC Data PortalHSPA8 
TCGA Data PortalHSPA8 
Broad Tumor PortalHSPA8
OASIS PortalHSPA8 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHSPA8  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDHSPA8
intOGen PortalHSPA8
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch HSPA8
DgiDB (Drug Gene Interaction Database)HSPA8
DoCM (Curated mutations)HSPA8 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HSPA8 (select a term)
intoGenHSPA8
NCG5 (London)HSPA8
Cancer3DHSPA8(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600816   
Orphanet
MedgenHSPA8
Genetic Testing Registry HSPA8
NextProtP11142 [Medical]
TSGene3312
GENETestsHSPA8
Target ValidationHSPA8
Huge Navigator HSPA8 [HugePedia]
snp3D : Map Gene to Disease3312
BioCentury BCIQHSPA8
ClinGenHSPA8
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3312
Chemical/Pharm GKB GenePA29507
Clinical trialHSPA8
Miscellaneous
canSAR (ICR)HSPA8 (select the gene name)
Probes
Litterature
PubMed494 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineHSPA8
EVEXHSPA8
GoPubMedHSPA8
iHOPHSPA8
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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