HSPA1B

Last updated
HSPA1B
Heat shock protein 70.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HSPA1B , HSP70-1B, HSP70-2, HSP70.2, heat shock protein family A (Hsp70) member 1B, HSX70, HSPA1, HSP70-1, HSP72, HSP70.1
External IDs OMIM: 603012 MGI: 96244 HomoloGene: 74294 GeneCards: HSPA1B
Orthologs
SpeciesHumanMouse
Entrez

3304

193740

Ensembl

ENSMUSG00000091971

UniProt

P0DMV8
P0DMV9

Q61696

RefSeq (mRNA)

NM_005346

NM_010479

RefSeq (protein)

NP_005337
NP_005336
NP_005336
NP_005336.3
NP_005337.2

NP_034609

Location (UCSC) Chr 6: 31.83 – 31.83 Mb Chr 17: 35.19 – 35.19 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Human gene HSPA1B is an intron-less gene which encodes for the heat shock protein HSP70-2, a member of the Hsp70 family of proteins. [5] The gene is located in the major histocompatibility complex, on the short arm of chromosome 6, in a cluster with two paralogous genes, HSPA1A and HSPA1L. [6] [7] [8] HSPA1A and HSPA1B produce nearly identical proteins because the few differences in their DNA sequences are almost exclusively synonymous substitutions or in the three prime untranslated region, heat shock 70kDa protein 1A, from HSPA1A, and heat shock 70kDa protein 1B, from HSPA1B. [6] A third, more modified paralog to these genes exists in the same region, HSPA1L, which shares a 90% homology with the other two. [8]

Function

Heat shock 70kDa protein 1B is a chaperone protein, cooperating with other heat shock proteins and chaperone systems to maintain proteostasis by stabilizing the structural conformation of other proteins in the cell and protecting against stress-induced aggregation. [9] Hsp70s have also been shown to bind and stabilize mRNA rich in adenine and uracil bases, independent of the occupational states of its other binding sites. [10] This protein is deactivated by binding ATP, and activated by its dephosphorylation to ADP, which requires a potassium ion to facilitate the hydrolysis, or ATP-ADP exchange. [11]

Hsp70-2 specifically is developmentally expressed in male germ line cells during meiosis, where it is necessary for the formation of the complex between CDC2 and cyclin B1. [12] It later becomes incorporated into the CatSper complex, a specialized calcium ion channel that enables spermatozoa motility. [13]

Clinical significance

Infertility has been observed in mice when HSA1B expression is disrupted, as CDC2 in unable to form the required heterodimer with cyclin B1 for the meiotic cell cycle to progress beyond S phase. [12]

Expression of heat shock protein 70kDa protein 2 in transformed tumor cells has been implicated in the rapid proliferation, metastasis, and inhibition of apoptosis in ovarian, bladder urothelial, and breast cancers. [14] [15] [16] Patients with chronic hepatitis B or hepatitis C virus infection who harbor a HSPA1B-1267 single nucleotide polymorphism have a higher risk for developing hepatocellular carcinoma. [17]

Interactions

Interactions have been characterized between Hsp70-2 and the following proteins:

See also

Related Research Articles

<span class="mw-page-title-main">Chaperone (protein)</span> Proteins assisting in protein folding

In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis.

Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including exposure to cold, UV light and during wound healing or tissue remodeling. Many members of this group perform chaperone functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress. This increase in expression is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). HSPs are found in virtually all living organisms, from bacteria to humans.

<span class="mw-page-title-main">Hsp70</span> Family of heat shock proteins

The 70 kilodalton heat shock proteins are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an important part of the cell's machinery for protein folding, performing chaperoning functions, and helping to protect cells from the adverse effects of physiological stresses. Additionally, membrane-bound Hsp70s have been identified as a potential target for cancer therapies and their extracellularly localized counterparts have been identified as having both membrane-bound and membrane-free structures.

<span class="mw-page-title-main">Hop (protein)</span> Protein-coding gene in the species Homo sapiens

Hop, occasionally written HOP, is an abbreviation for Hsp70-Hsp90 Organizing Protein. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90.

<span class="mw-page-title-main">HSPA8</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene on chromosome 11. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, autophagy, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence, and aging.

<span class="mw-page-title-main">Aryl hydrocarbon receptor</span> Vertebrate transcription factor

The aryl hydrocarbon receptor is a protein that in humans is encoded by the AHR gene. The aryl hydrocarbon receptor is a transcription factor that regulates gene expression. It was originally thought to function primarily as a sensor of xenobiotic chemicals and also as the regulator of enzymes such as cytochrome P450s that metabolize these chemicals. The most notable of these xenobiotic chemicals are aromatic (aryl) hydrocarbons from which the receptor derives its name.

<span class="mw-page-title-main">HSPA1A</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 1, also termed Hsp72, is a protein that in humans is encoded by the HSPA1A gene. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. In addition, Hsp72 also facilitates DNA repair. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and inflammatory diseases such as Diabetes mellitus type 2 and rheumatoid arthritis.

<span class="mw-page-title-main">Heat shock protein 90kDa alpha (cytosolic), member A1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein HSP 90-alpha is a protein that in humans is encoded by the HSP90AA1 gene.

<span class="mw-page-title-main">HSF1</span> Protein-coding gene in the species Homo sapiens

Heat shock factor 1 (HSF1) is a protein that in humans is encoded by the HSF1 gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regulation such as development and metabolism.

<span class="mw-page-title-main">HSP90B1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein 90kDa beta member 1 (HSP90B1), known also as endoplasmin, gp96, grp94, or ERp99, is a chaperone protein that in humans is encoded by the HSP90B1 gene.

<span class="mw-page-title-main">CDC37</span> Protein-coding gene in the species Homo sapiens

Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the CDC37 gene. This protein is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a HSP90 Co-chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF1, MOK, as well as eIF-2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases.

<span class="mw-page-title-main">HSP90AB1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein HSP 90-beta also called HSP90beta is a protein that in humans is encoded by the HSP90AB1 gene.

<span class="mw-page-title-main">PTGES3</span> Protein-coding gene in the species Homo sapiens

Prostaglandin E synthase 3 (cytosolic) is an enzyme that in humans is encoded by the PTGES3 gene.

<span class="mw-page-title-main">HSPA4</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the HSPA4 gene.

<span class="mw-page-title-main">HSPA9</span> Protein-coding gene in the species Homo sapiens

Mitochondrial 70kDa heat shock protein (mtHsp70), also known as mortalin, is a protein that in humans is encoded by the HSPA9 gene.

<span class="mw-page-title-main">STUB1</span> Protein-coding gene in the species Homo sapiens

STUB1 is a human gene that codes for the protein CHIP.

<span class="mw-page-title-main">DNAJB1</span> Protein-coding gene in the species Homo sapiens

DnaJ homolog subfamily B member 1 is a protein that in humans is encoded by the DNAJB1 gene.

<span class="mw-page-title-main">ST13</span>

Hsc70-interacting protein also known as suppression of tumorigenicity 13 (ST13) is a protein that in humans is encoded by the ST13 gene.

<span class="mw-page-title-main">HSPA1L</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 1L is a protein that in humans is encoded by the HSPA1L gene on chromosome 6. As a member of the heat shock protein 70 (Hsp70) family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease.

<span class="mw-page-title-main">HSPA2</span> Protein-coding gene in the species Homo sapiens

Heat shock-related 70 kDa protein 2 is a protein that in humans is encoded by the HSPA2 gene.

References

  1. 1 2 3 ENSG00000224501, ENSG00000212866, ENSG00000204388, ENSG00000231555 GRCh38: Ensembl release 89: ENSG00000232804, ENSG00000224501, ENSG00000212866, ENSG00000204388, ENSG00000231555 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000091971 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Milner CM, Campbell RD (1990). "Structure and expression of the three MHC-linked HSP70 genes". Immunogenetics. 32 (4): 242–251. doi:10.1007/BF00187095. PMID   1700760. S2CID   9531492.
  6. 1 2 "Entrez Gene: HSPA1A heat shock 70kDa protein 1B".
  7. ↑ Ito Y, Ando A, Ando H, Ando J, Saijoh Y, Inoko H, Fujimoto H (August 1998). "Genomic structure of the spermatid-specific hsp70 homolog gene located in the class III region of the major histocompatibility complex of mouse and man". Journal of Biochemistry. 124 (2): 347–353. doi:10.1093/oxfordjournals.jbchem.a022118. PMID   9685725.
  8. 1 2 Sargent CA, Dunham I, Trowsdale J, Campbell RD (March 1989). "Human major histocompatibility complex contains genes for the major heat shock protein HSP70". Proceedings of the National Academy of Sciences of the United States of America. 86 (6): 1968–1972. Bibcode:1989PNAS...86.1968S. doi: 10.1073/pnas.86.6.1968 . PMC   286826 . PMID   2538825.
  9. ↑ Rosenzweig R, Nillegoda NB, Mayer MP, Bukau B (November 2019). "The Hsp70 chaperone network". Nature Reviews. Molecular Cell Biology. 20 (11): 665–680. doi:10.1038/s41580-019-0133-3. PMID   31253954. S2CID   195739183.
  10. ↑ Kishor A, White EJ, Matsangos AE, Yan Z, Tandukar B, Wilson GM (August 2017). "Hsp70's RNA-binding and mRNA-stabilizing activities are independent of its protein chaperone functions". The Journal of Biological Chemistry. 292 (34): 14122–14133. doi: 10.1074/jbc.M117.785394 . PMC   5572911 . PMID   28679534.
  11. ↑ Arakawa A, Handa N, Shirouzu M, Yokoyama S (August 2011). "Biochemical and structural studies on the high affinity of Hsp70 for ADP". Protein Science. 20 (8): 1367–1379. doi:10.1002/pro.663. PMC   3189522 . PMID   21608060.
  12. 1 2 Eddy EM (January 1999). "Role of heat shock protein HSP70-2 in spermatogenesis". Reviews of Reproduction. 4 (1): 23–30. doi: 10.1530/ror.0.0040023 . PMID   10051099. S2CID   13035273.
  13. 1 2 Liu J, Xia J, Cho KH, Clapham DE, Ren D (June 2007). "CatSperbeta, a novel transmembrane protein in the CatSper channel complex". The Journal of Biological Chemistry. 282 (26): 18945–18952. doi: 10.1074/jbc.M701083200 . PMID   17478420.
  14. ↑ Gupta N, Jagadish N, Surolia A, Suri A (2017). "Heat shock protein 70-2 (HSP70-2) a novel cancer testis antigen that promotes growth of ovarian cancer". American Journal of Cancer Research. 7 (6): 1252–1269. PMC   5489776 . PMID   28670489.
  15. ↑ Garg M, Kanojia D, Seth A, Kumar R, Gupta A, Surolia A, Suri A (January 2010). "Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associated with tumour progression and promotes migration and invasion". European Journal of Cancer. 46 (1): 207–215. doi:10.1016/j.ejca.2009.10.020. PMID   19914824.
  16. ↑ Rohde M, Daugaard M, Jensen MH, Helin K, Nylandsted J, Jäättelä M (March 2005). "Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms". Genes & Development. 19 (5): 570–582. doi:10.1101/gad.305405. PMC   551577 . PMID   15741319.
  17. ↑ Jeng JE, Tsai JF, Chuang LY, Ho MS, Lin ZY, Hsieh MY, et al. (March 2008). "Heat shock protein A1B 1267 polymorphism is highly associated with risk and prognosis of hepatocellular carcinoma: a case-control study". Medicine. 87 (2): 87–98. doi: 10.1097/MD.0b013e31816be95c . PMID   18344806. S2CID   26906991.
  18. ↑ Liu X, Liu D, Qian D, Dai J, An Y, Jiang S, et al. (June 2012). "Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5 (ATF5) protein and promotes proteasome- and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells". The Journal of Biological Chemistry. 287 (23): 19599–19609. doi: 10.1074/jbc.M112.363622 . PMC   3365995 . PMID   22528486.
  19. 1 2 3 4 Rauch JN, Gestwicki JE (January 2014). "Binding of human nucleotide exchange factors to heat shock protein 70 (Hsp70) generates functionally distinct complexes in vitro". The Journal of Biological Chemistry. 289 (3): 1402–1414. doi: 10.1074/jbc.M113.521997 . PMC   3894324 . PMID   24318877.
  20. ↑ Zhu D, Dix DJ, Eddy EM (August 1997). "HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes". Development. 124 (15): 3007–3014. doi:10.1242/dev.124.15.3007. PMID   9247342.
  21. ↑ Darshi M, Mendiola VL, Mackey MR, Murphy AN, Koller A, Perkins GA, et al. (January 2011). "ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function". The Journal of Biological Chemistry. 286 (4): 2918–2932. doi: 10.1074/jbc.M110.171975 . PMC   3024787 . PMID   21081504.
  22. ↑ Brychzy A, Rein T, Winklhofer KF, Hartl FU, Young JC, Obermann WM (July 2003). "Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system". The EMBO Journal. 22 (14): 3613–3623. doi:10.1093/emboj/cdg362. PMC   165632 . PMID   12853476.
  23. ↑ Moffatt NS, Bruinsma E, Uhl C, Obermann WM, Toft D (August 2008). "Role of the cochaperone Tpr2 in Hsp90 chaperoning". Biochemistry. 47 (31): 8203–8213. doi:10.1021/bi800770g. PMID   18620420.
  24. ↑ Ito N, Kamiguchi K, Nakanishi K, Sokolovskya A, Hirohashi Y, Tamura Y, et al. (June 2016). "A novel nuclear DnaJ protein, DNAJC8, can suppress the formation of spinocerebellar ataxia 3 polyglutamine aggregation in a J-domain independent manner". Biochemical and Biophysical Research Communications. 474 (4): 626–633. doi:10.1016/j.bbrc.2016.03.152. PMID   27133716.
  25. ↑ Han C, Chen T, Li N, Yang M, Wan T, Cao X (February 2007). "HDJC9, a novel human type C DnaJ/HSP40 member interacts with and cochaperones HSP70 through the J domain". Biochemical and Biophysical Research Communications. 353 (2): 280–285. doi:10.1016/j.bbrc.2006.12.013. PMID   17182002.
  26. ↑ Hammond CM, Bao H, Hendriks IA, Carraro M, García-Nieto A, Liu Y, et al. (June 2021). "DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network". Molecular Cell. 81 (12): 2533–2548.e9. doi:10.1016/j.molcel.2021.03.041. PMC   8221569 . PMID   33857403.
  27. ↑ Chen Z, Barbi J, Bu S, Yang HY, Li Z, Gao Y, et al. (August 2013). "The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3". Immunity. 39 (2): 272–285. doi:10.1016/j.immuni.2013.08.006. PMC   3817295 . PMID   23973223.
  28. 1 2 3 4 5 6 Seo JH, Park JH, Lee EJ, Vo TT, Choi H, Kim JY, et al. (October 2016). "ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation". Nature Communications. 7: 12882. Bibcode:2016NatCo...712882S. doi:10.1038/ncomms12882. PMC   5059642 . PMID   27708256.
  29. ↑ Haag Breese E, Uversky VN, Georgiadis MM, Harrington MA (December 2006). "The disordered amino-terminus of SIMPL interacts with members of the 70-kDa heat-shock protein family". DNA and Cell Biology. 25 (12): 704–714. doi:10.1089/dna.2006.25.704. PMID   17233114.
  30. ↑ Jakobsson ME, Moen A, Bousset L, Egge-Jacobsen W, Kernstock S, Melki R, Falnes PØ (September 2013). "Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation". The Journal of Biological Chemistry. 288 (39): 27752–27763. doi: 10.1074/jbc.M113.483248 . PMC   3784692 . PMID   23921388.
  31. ↑ Fang CT, Kuo HH, Pan TS, Yu FC, Yih LH (October 2016). "HSP70 regulates the function of mitotic centrosomes". Cellular and Molecular Life Sciences. 73 (20): 3949–3960. doi:10.1007/s00018-016-2236-8. PMID   27137183. S2CID   14824854.
  32. ↑ Mohanan V, Grimes CL (July 2014). "The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease". The Journal of Biological Chemistry. 289 (27): 18987–18998. doi: 10.1074/jbc.M114.557686 . PMC   4081938 . PMID   24790089.
  33. ↑ Zeke T, Morrice N, Vázquez-Martin C, Cohen PT (January 2005). "Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole". The Biochemical Journal. 385 (Pt 1): 45–56. doi:10.1042/BJ20040690. PMC   1134672 . PMID   15383005.
  34. ↑ Hasson SA, Kane LA, Yamano K, Huang CH, Sliter DA, Buehler E, et al. (December 2013). "High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy". Nature. 504 (7479): 291–295. Bibcode:2013Natur.504..291H. doi:10.1038/nature12748. PMC   5841086 . PMID   24270810.
  35. ↑ Shang Y, Xu X, Duan X, Guo J, Wang Y, Ren F, et al. (March 2014). "Hsp70 and Hsp90 oppositely regulate TGF-β signaling through CHIP/Stub1". Biochemical and Biophysical Research Communications. 446 (1): 387–392. doi:10.1016/j.bbrc.2014.02.124. PMID   24613385.
  36. ↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE (May 2001). "Stable association of hsp90 and p23, but Not hsp70, with active human telomerase". The Journal of Biological Chemistry. 276 (19): 15571–15574. doi: 10.1074/jbc.C100055200 . PMID   11274138.
  37. ↑ Hwang CY, Holl J, Rajan D, Lee Y, Kim S, Um M, et al. (March 2010). "Hsp70 interacts with the retroviral restriction factor TRIM5alpha and assists the folding of TRIM5alpha". The Journal of Biological Chemistry. 285 (10): 7827–7837. doi: 10.1074/jbc.M109.040618 . PMC   2844226 . PMID   20053985.
  38. ↑ Nellist M, Burgers PC, van den Ouweland AM, Halley DJ, Luider TM (August 2005). "Phosphorylation and binding partner analysis of the TSC1-TSC2 complex". Biochemical and Biophysical Research Communications. 333 (3): 818–826. doi:10.1016/j.bbrc.2005.05.175. PMID   15963462.

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