Heat shock protein 47 explained

Heat shock protein 47, also known as SERPINH1 is a serpin which serves as a human chaperone protein for collagen.^{[1] [2]}

Function

This protein is a member of the serpin superfamily of serine proteinase inhibitors. Its expression is induced by heat shock. HSP47 is expressed in the endoplasmic reticulum. These cells synthesize and secrete type I and type II collagen. ^[3] The protein localizes to the endoplasmic reticulum lumen and binds collagen; thus it is thought to be a molecular chaperone involved in the maturation of collagen molecules. HSP47 is essential for the correct folding of procollagen. Antibodies directed to this protein have been found in patients with rheumatoid arthritis.^[1]

Structure

HSP47 contains 3 beta sheets and 9 alpha helices. After binding with collagen no conformation change is observed.^[4]

Interactions

Heat shock protein 47 has been shown to interact with collagens I, II, III, IV and V.^[5] It is involved in the secretion of collagen as well as the processing, assembly, and folding of collagen proteins. Hsp 47 binds specifically to procollagen and collagen only. The protein recognizes the triple helix of procollagen, two HSP47 proteins will bind to the leading and trailing strands of procollagen.

Research on role in preventing deep vein thrombosis

Research published in 2023 indicates a potential role of HSP47 regarding deep vein thrombosis.^{[6] [7]} This initial research will be followed by additional studies.

Role in Fibrosis

Fibrosis is the scarring of connective tissue, one attribute is the excess deposition of collagen in the extracellular matrix of tissue. Research has shown that HSPs have a role in fibrotic diseases. HSP47 has been shown to be pro-fibrosis in various fibrotic diseases. During the process of fibrosis, HSP47 is expressed and is involved in the production of collagen.^[8] HSP47 could be a potential therapeutic agent for fibrotic disease, a down-regulation of HSP47 leads to decreased fibrotic progression.^[9]

Further reading

• Razzaque MS, Taguchi T . The possible role of colligin/HSP47, a collagen-binding protein, in the pathogenesis of human and experimental fibrotic diseases . Histology and Histopathology . 14 . 4 . 1199–212 . October 1999 . 10506936 .
• Gettins PG . Serpin structure, mechanism, and function . Chemical Reviews . 102 . 12 . 4751–804 . December 2002 . 12475206 . 10.1021/cr010170 .
• Clarke EP, Sanwal BD . Cloning of a human collagen-binding protein, and its homology with rat gp46, chick hsp47 and mouse J6 proteins . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1129 . 2 . 246–8 . January 1992 . 1309665 . 10.1016/0167-4781(92)90498-o .
• Ikegawa S, Sudo K, Okui K, Nakamura Y . Isolation, characterization and chromosomal assignment of human colligin-2 gene (CBP2) . Cytogenetics and Cell Genetics . 71 . 2 . 182–6 . 1995 . 7656593 . 10.1159/000134103 .
• Ikegawa S, Nakamura Y . Structure of the gene encoding human colligin-2 (CBP2) . Gene . 194 . 2 . 301–3 . July 1997 . 9272875 . 10.1016/S0378-1119(97)00209-6 .
• Bekri S, Adélaïde J, Merscher S, Grosgeorge J, Caroli-Bosc F, Perucca-Lostanlen D, Kelley PM, Pébusque MJ, Theillet C, Birnbaum D, Gaudray P . Detailed map of a region commonly amplified at 11q13-->q14 in human breast carcinoma . Cytogenetics and Cell Genetics . 79 . 1–2 . 125–31 . 1998 . 9533029 . 10.1159/000134699 .
• Hattori T, Fujisawa T, Sasaki K, Yutani Y, Nakanishi T, Takahashi K, Takigawa M . Isolation and characterization of a rheumatoid arthritis-specific antigen (RA-A47) from a human chondrocytic cell line (HCS-2/8) . Biochemical and Biophysical Research Communications . 245 . 3 . 679–83 . April 1998 . 9588174 . 10.1006/bbrc.1998.8505 .
• Nagai N, Yorihuzi T, Hosokawa N, Nagata K . The human genome has only one functional hsp47 gene (CBP2) and a pseudogene (pshsp47) . Gene . 227 . 2 . 241–8 . February 1999 . 10023073 . 10.1016/S0378-1119(98)00592-7 .
• Hebert C, Norris K, Della Coletta R, Reynolds M, Ordóñez J, Sauk JJ . Cell surface colligin/Hsp47 associates with tetraspanin protein CD9 in epidermoid carcinoma cell lines . Journal of Cellular Biochemistry . 73 . 2 . 248–58 . May 1999 . 10227388 . 10.1002/(SICI)1097-4644(19990501)73:2<248::AID-JCB11>3.0.CO;2-A . 41309881 .
• Koide T, Aso A, Yorihuzi T, Nagata K . Conformational requirements of collagenous peptides for recognition by the chaperone protein HSP47 . The Journal of Biological Chemistry . 275 . 36 . 27957–63 . September 2000 . 10862616 . 10.1074/jbc.M003026200 . free .
• Hattori T, Takahash K, Yutani Y, Fujisawa T, Nakanishi T, Takigawa M . Rheumatoid arthritis-related antigen 47kDa (RA-A47) is a product of colligin-2 and acts as a human HSP47 . Journal of Bone and Mineral Metabolism . 18 . 6 . 328–34 . 2001 . 11052465 . 10.1007/s007740070004 . 35696096 .
• Pelletier G, Stefanovsky VY, Faubladier M, Hirschler-Laszkiewicz I, Savard J, Rothblum LI, Côté J, Moss T . Competitive recruitment of CBP and Rb-HDAC regulates UBF acetylation and ribosomal transcription . Molecular Cell . 6 . 5 . 1059–66 . November 2000 . 11106745 . 10.1016/S1097-2765(00)00104-0 . free .
• Matsuda M, Koide T, Yorihuzi T, Hosokawa N, Nagata K . Molecular cloning of a novel ubiquitin-like protein, UBIN, that binds to ER targeting signal sequences . Biochemical and Biophysical Research Communications . 280 . 2 . 535–40 . January 2001 . 11162551 . 10.1006/bbrc.2000.4149 .
• Zhou M, Nekhai S, Bharucha DC, Kumar A, Ge H, Price DH, Egly JM, Brady JN . TFIIH inhibits CDK9 phosphorylation during human immunodeficiency virus type 1 transcription . The Journal of Biological Chemistry . 276 . 48 . 44633–40 . November 2001 . 11572868 . 10.1074/jbc.M107466200 . free .
• Song CZ, Keller K, Murata K, Asano H, Stamatoyannopoulos G. George Stamatoyannopoulos . Functional interaction between coactivators CBP/p300, PCAF, and transcription factor FKLF2 . The Journal of Biological Chemistry . 277 . 9 . 7029–36 . March 2002 . 11748222 . 2808425 . 10.1074/jbc.M108826200 . free .
• Sasaki H, Sato T, Yamauchi N, Okamoto T, Kobayashi D, Iyama S, Kato J, Matsunaga T, Takimoto R, Takayama T, Kogawa K, Watanabe N, Niitsu Y . Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1 . Journal of Immunology . 168 . 10 . 5178–83 . May 2002 . 11994473 . 10.4049/jimmunol.168.10.5178 . free .
• Razzaque MS, Ahmed AR . Collagens, collagen-binding heat shock protein 47 and transforming growth factor-beta 1 are induced in cicatricial pemphigoid: possible role(s) in dermal fibrosis . Cytokine . 17 . 6 . 311–6 . March 2002 . 12061838 . 10.1006/cyto.2002.1020 .
• Sato K, Yomogida K, Wada T, Yorihuzi T, Nishimune Y, Hosokawa N, Nagata K . Type XXVI collagen, a new member of the collagen family, is specifically expressed in the testis and ovary . The Journal of Biological Chemistry . 277 . 40 . 37678–84 . October 2002 . 12145293 . 10.1074/jbc.M205347200 . free.
• Rocnik EF, van der Veer E, Cao H, Hegele RA, Pickering JG . Functional linkage between the endoplasmic reticulum protein Hsp47 and procollagen expression in human vascular smooth muscle cells . The Journal of Biological Chemistry . 277 . 41 . 38571–8 . October 2002 . 12163502 . 10.1074/jbc.M206689200 . free .

External links

• The MEROPS online database for peptidases and their inhibitors: I04.035

Notes and References

1. Web site: Entrez Gene: SERPINH1 serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding protein 1).
2. Dafforn TR, Della M, Miller AD . The molecular interactions of heat shock protein 47 (Hsp47) and their implications for collagen biosynthesis . The Journal of Biological Chemistry . 276 . 52 . 49310–9 . December 2001 . 11592970 . 10.1074/jbc.M108896200 . free .
3. Williams. R. Sanders. Heat Shock Protein 47: A Chaperone for the Fibrous Cap?. Circulation. 101. 11. 11 December 2017. 1227–1228. en. 10.1161/01.CIR.101.11.1227. 21 March 2000. 10725278. free.
4. Widmer . C. . Gebauer . J.M. . Baumann . U. . 2013-01-09 . Molecular basis for the action of the collagen-specific chaperone Hsp47 SERPINH1 and its structure-specific client recognition. . Proceedings of the National Academy of Sciences of the United States of America . 109 . 33 . 13243–13247 . 2023-11-26 . 10.2210/pdb3zha/pdb . 22847422 . 3421173 .
5. Mala JG, Rose C . Interactions of heat shock protein 47 with collagen and the stress response: an unconventional chaperone model? . Life Sciences . 87 . 19–22 . 579–86 . November 2010 . 20888348 . 10.1016/j.lfs.2010.09.024 .
6. Schattner, Mirta, Sleep like a bear, Science, April 13, 2023
7. Garcia de Jesús, Erin, Hibernating bears don’t get blood clots. Now scientists know why, Science News, April 13, 2023
8. Kim . Hae-Ji . Park . Joo-Hoo . Shin . Jae-Min . Yang . Hyun-Woo . Lee . Heung-Man . Park . Il-Ho . 2020-06-09 . Author Correction: TGF-β1-induced HSP47 regulates extracellular matrix accumulation via Smad2/3 signaling pathways in nasal fibroblasts . Scientific Reports . 10 . 1 . 9585 . 10.1038/s41598-020-66547-z . 32514115 . 7280506 . 2045-2322. free . 2020NatSR..10.9585K .
9. Sakamoto . Noriho . Okuno . Daisuke . Tokito . Takatomo . Yura . Hirokazu . Kido . Takashi . Ishimoto . Hiroshi . Tanaka . Yoshimasa . Mukae . Hiroshi . 2023-08-25 . HSP47: A Therapeutic Target in Pulmonary Fibrosis . Biomedicines . 11 . 9 . 2387 . 10.3390/biomedicines11092387 . 37760828 . 10525413 . 2227-9059 . free .