HSPA4 explained

Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the HSPA4 gene.^{[1] [2]}

The protein encoded by this gene was originally suggested to be a member of the heat shock protein 70 family. However it is now known that human HSPA4 is an equivalent to mouse the Apg-2 protein and is a member of the Hsp110 family.^[3]

Interactions

HSPA4 has been shown to interact with:

• APAF1^[4]
• DNAJB1,
• HDAC1,^[5]
• HSF1,^{[6] [7]}
• HSPBP1,
• Histone deacetylase 2,^[5]
• NAD(P)H dehydrogenase (quinone 1),^[8]
• STUB1,^[9] and
• TTC1.^[10]

Further reading

• Abravaya K, Myers MP, Murphy SP, Morimoto RI . The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression . Genes & Development . 6 . 7 . 1153–64 . Jul 1992 . 1628823 . 10.1101/gad.6.7.1153 . free .
• Liao J, Lowthert LA, Ghori N, Omary MB . The 70-kDa heat shock proteins associate with glandular intermediate filaments in an ATP-dependent manner . The Journal of Biological Chemistry . 270 . 2 . 915–22 . Jan 1995 . 7529764 . 10.1074/jbc.270.2.915 . free .
• Furlini G, Vignoli M, Re MC, Gibellini D, Ramazzotti E, Zauli G, La Placa M . Human immunodeficiency virus type 1 interaction with the membrane of CD4+ cells induces the synthesis and nuclear translocation of 70K heat shock protein . The Journal of General Virology . 75 . 1 . 193–9 . Jan 1994 . 7906708 . 10.1099/0022-1317-75-1-193 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Schulte AM, Fischer S, Sachse GE, Häfner S, Stelck S, Gassen HG . Identification and characterization of a novel hsc70-like gene in the human lung tumor cell line HS24 . DNA and Cell Biology . 16 . 3 . 257–68 . Mar 1997 . 9115634 . 10.1089/dna.1997.16.257 .
• Kaneko Y, Kimura T, Kishishita M, Noda Y, Fujita J . Cloning of apg-2 encoding a novel member of heat shock protein 110 family . Gene . 189 . 1 . 19–24 . Apr 1997 . 9161406 . 10.1016/S0378-1119(96)00807-4 .
• Bruner KL, Derfoul A, Robertson NM, Guerriero G, Fernandes-Alnemri T, Alnemri ES, Litwack G . The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52 . Receptors & Signal Transduction . 7 . 2 . 85–98 . 1998 . 9392437 .
• Satyal SH, Chen D, Fox SG, Kramer JM, Morimoto RI . Negative regulation of the heat shock transcriptional response by HSBP1 . Genes & Development . 12 . 13 . 1962–74 . Jul 1998 . 9649501 . 316975 . 10.1101/gad.12.13.1962 .
• Naylor DJ, Stines AP, Hoogenraad NJ, Høj PB . Evidence for the existence of distinct mammalian cytosolic, microsomal, and two mitochondrial GrpE-like proteins, the Co-chaperones of specific Hsp70 members . The Journal of Biological Chemistry . 273 . 33 . 21169–77 . Aug 1998 . 9694873 . 10.1074/jbc.273.33.21169 . free .
• Melville MW, Tan SL, Wambach M, Song J, Morimoto RI, Katze MG . The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity . The Journal of Biological Chemistry . 274 . 6 . 3797–803 . Feb 1999 . 9920933 . 10.1074/jbc.274.6.3797 . free .
• Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C . Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions . Molecular and Cellular Biology . 19 . 6 . 4535–45 . Jun 1999 . 10330192 . 104411 . 10.1128/mcb.19.6.4535.
• Liu H, Vuyyuru VB, Pham CD, Yang Y, Singh B . Evidence of an interaction between Mos and Hsp70: a role of the Mos residue serine 3 in mediating Hsp70 association . Oncogene . 18 . 23 . 3461–70 . Jun 1999 . 10376524 . 10.1038/sj.onc.1202699 . free .
• Nonoguchi K, Itoh K, Xue JH, Tokuchi H, Nishiyama H, Kaneko Y, Tatsumi K, Okuno H, Tomiwa K, Fujita J . Cloning of human cDNAs for Apg-1 and Apg-2, members of the Hsp110 family, and chromosomal assignment of their genes . Gene . 237 . 1 . 21–8 . Sep 1999 . 10524232 . 10.1016/S0378-1119(99)00325-X .
• O'Keeffe B, Fong Y, Chen D, Zhou S, Zhou Q . Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription . The Journal of Biological Chemistry . 275 . 1 . 279–87 . Jan 2000 . 10617616 . 10.1074/jbc.275.1.279 . free .
• Agostini I, Popov S, Li J, Dubrovsky L, Hao T, Bukrinsky M . Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral preintegration complex . Experimental Cell Research . 259 . 2 . 398–403 . Sep 2000 . 10964507 . 10.1006/excr.2000.4992 .
• Kim M, Jiang LH, Wilson HL, North RA, Surprenant A . Proteomic and functional evidence for a P2X7 receptor signalling complex . The EMBO Journal . 20 . 22 . 6347–58 . Nov 2001 . 11707406 . 125721 . 10.1093/emboj/20.22.6347 .
• Johnson CA, White DA, Lavender JS, O'Neill LP, Turner BM . Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70 . The Journal of Biological Chemistry . 277 . 11 . 9590–7 . Mar 2002 . 11777905 . 10.1074/jbc.M107942200 . free .
• Gurer C, Cimarelli A, Luban J . Specific incorporation of heat shock protein 70 family members into primate lentiviral virions . Journal of Virology . 76 . 9 . 4666–70 . May 2002 . 11932435 . 155079 . 10.1128/JVI.76.9.4666-4670.2002 .
• Freeman BC, Yamamoto KR . Disassembly of transcriptional regulatory complexes by molecular chaperones . Science . 296 . 5576 . 2232–5 . Jun 2002 . 12077419 . 10.1126/science.1073051 . 8844179 .

Notes and References

1. Fathallah DM, Cherif D, Dellagi K, Arnaout MA . Molecular cloning of a novel human hsp70 from a B cell line and its assignment to chromosome 5 . Journal of Immunology . 151 . 2 . 810–3 . Jul 1993 . 10.4049/jimmunol.151.2.810 . 8335910 . free .
2. Web site: Entrez Gene: HSPA4 heat shock 70kDa protein 4.
3. Kaneko Y, Kimura T, Kishishita M, Noda Y, Fujita J . Cloning of apg-2 encoding a novel member of heat shock protein 110 family . Gene . 189 . 1 . 19–24 . Apr 1997 . 9161406 . 10.1016/S0378-1119(96)00807-4 .
4. Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES . Negative regulation of the Apaf-1 apoptosome by Hsp70 . Nature Cell Biology . 2 . 8 . 476–83 . Aug 2000 . 10934467 . 10.1038/35019510 . 20374981 .
5. Johnson CA, White DA, Lavender JS, O'Neill LP, Turner BM . Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70 . The Journal of Biological Chemistry . 277 . 11 . 9590–7 . Mar 2002 . 11777905 . 10.1074/jbc.M107942200 . free .
6. Nair SC, Toran EJ, Rimerman RA, Hjermstad S, Smithgall TE, Smith DF . A pathway of multi-chaperone interactions common to diverse regulatory proteins: estrogen receptor, Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor . Cell Stress & Chaperones . 1 . 4 . 237–50 . Dec 1996 . 10.1379/1466-1268(1996)001<0237:apomci>2.3.co;2 . 2024-04-02 . 9222609 . 376461 .
7. Abravaya K, Myers MP, Murphy SP, Morimoto RI . The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression . Genes & Development . 6 . 7 . 1153–64 . Jul 1992 . 1628823 . 10.1101/gad.6.7.1153. free .
8. Anwar A, Siegel D, Kepa JK, Ross D . Interaction of the molecular chaperone Hsp70 with human NAD(P)H:quinone oxidoreductase 1 . The Journal of Biological Chemistry . 277 . 16 . 14060–7 . Apr 2002 . 11821413 . 10.1074/jbc.M111576200 . free .
9. Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C . Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions . Molecular and Cellular Biology . 19 . 6 . 4535–45 . Jun 1999 . 10330192 . 104411 . 10.1128/mcb.19.6.4535.
10. Oh WK, Song J . Cooperative interaction of Hsp40 and TPR1 with Hsp70 reverses Hsp70-HspBp1 complex formation . Molecules and Cells . 16 . 1 . 84–91 . Aug 2003 . 10.1016/S1016-8478(23)13770-8 . 14503850 . free .