Heat shock protein 47

Last updated
SERPINH1
Identifiers
Aliases SERPINH1 , AsTP3, CBP1, CBP2, HSP47, OI10, PIG14, PPROM, RA-A47, SERPINH2, gp46, serpin family H member 1
External IDs OMIM: 600943 MGI: 88283 HomoloGene: 20331 GeneCards: SERPINH1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001207014
NM_001235

NM_001111043
NM_001111044
NM_009825
NM_001285776

RefSeq (protein)

NP_001193943
NP_001226

NP_001104513
NP_001104514
NP_001272705
NP_033955

Location (UCSC) Chr 11: 75.56 – 75.57 Mb Chr 7: 98.99 – 99 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Heat shock protein 47, also known as SERPINH1 is a serpin which serves as a human chaperone protein for collagen. [5] [6]

Contents

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. [7] 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. [5]

Structure

HSP47 contains 3 beta sheets and 9 alpha helices. After binding with collagen no conformation change is observed. [8]

Interactions

Heat shock protein 47 has been shown to interact with collagens I, II, III, IV and V. [9] 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. [8]

Research on role in preventing deep vein thrombosis

Research published in 2023 indicates a potential role of HSP47 regarding deep vein thrombosis. [10] [11] 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. [12] 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. [13] HSP47 could be a potential therapeutic agent for fibrotic disease, a down-regulation of HSP47 leads to decreased fibrotic progression. [14]

Related Research Articles

<span class="mw-page-title-main">Serpin</span> Superfamily of proteins with similar structures and diverse functions

Serpins are a superfamily of proteins with similar structures that were first identified for their protease inhibition activity and are found in all kingdoms of life. The acronym serpin was originally coined because the first serpins to be identified act on chymotrypsin-like serine proteases. They are notable for their unusual mechanism of action, in which they irreversibly inhibit their target protease by undergoing a large conformational change to disrupt the target's active site. This contrasts with the more common competitive mechanism for protease inhibitors that bind to and block access to the protease active site.

<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">Calnexin</span> Mammalian protein found in Homo sapiens

Calnexin (CNX) is a 67kDa integral protein of the endoplasmic reticulum (ER). It consists of a large N-terminal calcium-binding lumenal domain, a single transmembrane helix and a short, acidic cytoplasmic tail. In humans, calnexin is encoded by the gene CANX.

<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">Hsp27</span> Protein-coding gene in the species Homo sapiens

Heat shock protein 27 (Hsp27) also known as heat shock protein beta-1 (HSPB1) is a protein that in humans is encoded by the HSPB1 gene.

<span class="mw-page-title-main">Collagen, type III, alpha 1</span>

Type III Collagen is a homotrimer, or a protein composed of three identical peptide chains (monomers), each called an alpha 1 chain of type III collagen. Formally, the monomers are called collagen type III, alpha-1 chain and in humans are encoded by the COL3A1 gene. Type III collagen is one of the fibrillar collagens whose proteins have a long, inflexible, triple-helical domain.

<span class="mw-page-title-main">HSPA1B</span> Human gene

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. 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. 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. A third, more modified paralog to these genes exists in the same region, HSPA1L, which shares a 90% homology with the other two.

<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">SPI1</span> Protein-coding gene in the species Homo sapiens

Transcription factor PU.1 is a protein that in humans is encoded by the SPI1 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">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">HSF2</span> Protein-coding gene in the species Homo sapiens

Heat shock factor protein 2 is a protein that in humans is encoded by the HSF2 gene.

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

Peptidylprolyl isomerase D (cyclophilin D), also known as PPID, is an enzyme which in humans is encoded by the PPID gene on chromosome 4. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to facilitate folding or repair of proteins. In addition, PPID participates in many biological processes, including mitochondrial metabolism, apoptosis, redox, and inflammation, as well as in related diseases and conditions, such as ischemic reperfusion injury, AIDS, and cancer.

<span class="mw-page-title-main">PFDN5</span> Protein-coding gene in the species Homo sapiens

Prefoldin subunit 5 is a protein that in humans is encoded by the PFDN5 gene.

<span class="mw-page-title-main">Integrin alpha 11</span> Protein-coding gene in the species Homo sapiens

Integrin alpha-11 is a protein that, in humans, is encoded by the ITGA11 gene.

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

Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. It breaks up the DNA during apoptosis and promotes cell differentiation. It is usually an inactive monomer inhibited by ICAD. This is cleaved before dimerization.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000149257 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000070436 - 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. 1 2 "Entrez Gene: SERPINH1 serpin peptidase inhibitor, clade H (heat shock protein 47), member 1, (collagen binding protein 1)".
  6. Dafforn TR, Della M, Miller AD (December 2001). "The molecular interactions of heat shock protein 47 (Hsp47) and their implications for collagen biosynthesis". The Journal of Biological Chemistry. 276 (52): 49310–9. doi: 10.1074/jbc.M108896200 . PMID   11592970.
  7. Williams RS (21 March 2000). "Heat Shock Protein 47: A Chaperone for the Fibrous Cap?". Circulation. 101 (11): 1227–1228. doi: 10.1161/01.CIR.101.11.1227 . PMID   10725278 . Retrieved 11 December 2017.
  8. 1 2 Widmer C, Gebauer J, 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. doi:10.2210/pdb3zha/pdb. PMC   3421173 . PMID   22847422 . Retrieved 2023-11-26.
  9. Mala JG, Rose C (November 2010). "Interactions of heat shock protein 47 with collagen and the stress response: an unconventional chaperone model?". Life Sciences. 87 (19–22): 579–86. doi:10.1016/j.lfs.2010.09.024. PMID   20888348.
  10. Schattner, Mirta, Sleep like a bear , Science, April 13, 2023
  11. Garcia de Jesús, Erin, Hibernating bears don’t get blood clots. Now scientists know why , Science News, April 13, 2023
  12. Balasubramaniam B, Balamurugan K (2020), "Role of Heat Shock Factors in Diseases and Immunity", Heat Shock Proteins in Human Diseases, Cham: Springer International Publishing, pp. 197–210, doi:10.1007/7515_2020_21, ISBN   978-3-030-62288-6, S2CID   226465376 , retrieved 2023-11-26
  13. Kim H, Park J, Shin J, Yang H, Lee H, Park I (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. doi: 10.1038/s41598-020-66547-z . ISSN   2045-2322. PMC   7280506 . PMID   32514115.
  14. Sakamoto N, Okuno D, Tokito T, Yura H, Kido T, Ishimoto H, Tanaka Y, Mukae H (2023-08-25). "HSP47: A Therapeutic Target in Pulmonary Fibrosis". Biomedicines. 11 (9): 2387. doi: 10.3390/biomedicines11092387 . ISSN   2227-9059. PMC   10525413 . PMID   37760828.

Further reading