Stress-induced-phosphoprotein 1

Last updated
STIP1
Protein STIP1 PDB 1elr.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases STIP1 , HEL-S-94n, HOP, IEF-SSP-3521, P60, STI1, STI1L, stress induced phosphoprotein 1
External IDs OMIM: 605063; MGI: 109130; HomoloGene: 4965; GeneCards: STIP1; OMA:STIP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10963

20867

Ensembl

ENSG00000168439

ENSMUSG00000024966

UniProt

P31948

Q60864

RefSeq (mRNA)

NM_006819
NM_001282652
NM_001282653

NM_016737

RefSeq (protein)

NP_001269581
NP_001269582
NP_006810

NP_058017

Location (UCSC) Chr 11: 64.19 – 64.2 Mb Chr 19: 7 – 7.02 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Stress-induced-phosphoprotein 1 also Hsp70-Hsp90 organising protein (Hop) is encoded in the human by the STIP1 gene. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90. [5]

Contents

STI1 belongs to the large group of co-chaperones, which regulate and assist the major chaperones (mainly heat shock proteins). It is one of the best studied co-chaperones of the Hsp70-Hsp90 complex. It was first discovered in yeast and homologues were identified in humans, mice, rats, insects, plants, parasites, and viruses. The family of these proteins is referred to as STI1 (stress inducible protein) and can be divided into yeast, plant, and animal STI1 (Hop).

Synonyms

  • Hop
  • Hsc70/Hsp90-organizing protein
  • NY-REN-11 antigen
  • P60
  • STI1
  • STI1L
  • STIP1
  • Transformation-sensitive protein IEF-SSP-3521

Gene

STIP1 is located on chromosome 11q13.1 and consists of 14 exons.

Structure

STI proteins are characterized by some structural features: All homologues have nine tetratricopeptide repeat (TPR) motifs, that are clustered into domains of three TPRs. The TPR motif is a very common structural feature used by many proteins and provides the ability of directing protein-protein interactions. Crystallographic structural information is available for the N-terminal TPR1 and the central TPR2A domains in complex with Hsp90 resp. Hsp70 ligand peptides. [6]

The Hsp70-Hsp90 Organizing Protein (Hop, STIP1 in humans) is the co-chaperone responsible for the transfer of client proteins between Hsp70 and Hsp90. Hop is evolutionarily conserved in Eukaryotes and is found in both the nucleus and cytoplasm. [7] Drosophila Hop is a monomeric protein that consists of three tetratricopeptide repeat domain regions (TPR1, TPR2A, TPR2B), one aspartic acid-proline repeat domain (DP). The TPR domains interact with the c-terminals of Hsp90 and Hsp70, with TPR1 and TPR2B binding to Hsp70 and TPR2A binding preferentially to Hsp90. The intermediate structures of heat shock machinery are difficult to characterize completely because of the transient and fast paced nature of chaperone function. [8]

Function

The main function of Hop is to link Hsp70 and Hsp90 together. But recent investigations indicate that it also modulates the chaperone activities of the linked proteins and possibly interacts with other chaperones and proteins. Apart from its role in the Hsp70/Hsp90 "chaperone machine" it seems to participate in other protein complexes too (for example in the signal transduction complex EcR/USP and in the Hepatitis B virus reverse transcriptase complex, which enables the viral replication). It acts as a receptor for prion proteins too. [9] [10] Hop is located in diverse cellular regions and also moves between the cytoplasm and the nucleus.

In Drosophila RNA interference pathways, Hop has been shown to be an integral part of the pre-RISC complex for siRNAs. [11] In the Drosophila Piwi-interacting RNA pathway, the RNA interference pathway responsible for the repression of transposable elements (transposons), Hop has been shown to interact with Piwi, [12] and in the absence of Hop, transposons are derepressed, leading to severe genomic instability and infertility. [13]

Interactions

STI1 has been shown to interact with PRNP [14] and Heat shock protein 90kDa alpha (cytosolic), member A1. [15] [16]

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 (HSPs) 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">Hsp90</span> Heat shock proteins with a molecular mass around 90kDa

Hsp90 is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs.

<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 receptor protein and 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">FKBP4</span> Protein-coding gene in humans

FK506-binding protein 4 is a protein that in humans is encoded by the FKBP4 gene.

Co-chaperones are proteins that assist chaperones in protein folding and other functions. Co-chaperones are the non-client binding molecules that assist in protein folding mediated by Hsp70 and Hsp90. They are particularly essential in stimulation of the ATPase activity of these chaperone proteins. There are a great number of different co-chaperones however based on their domain structure most of them fall into two groups: J-domain proteins and tetratricopeptide repeats (TPR).

<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">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 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">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">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.

The chaperone code refers to post-translational modifications of molecular chaperones that control protein folding. Whilst the genetic code specifies how DNA makes proteins, and the histone code regulates histone-DNA interactions, the chaperone code controls how proteins are folded to produce a functional proteome.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000168439 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024966 – 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. ↑ Odunuga OO, Longshaw VM, Blatch GL (October 2004). "Hop: more than an Hsp70/Hsp90 adaptor protein". BioEssays. 26 (10): 1058–68. doi:10.1002/bies.20107. PMID   15382137. S2CID   45168091.
  6. ↑ Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I (April 2000). "Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine". Cell. 101 (2): 199–210. doi: 10.1016/S0092-8674(00)80830-2 . PMID   10786835. S2CID   18200460.
  7. ↑ Schmid AB, et al. (2012). "The architecture of functional modules in the Hsp90 co-chaperone Sti1/Hop". EMBO J. 31 (6): 1506–17. doi:10.1038/emboj.2011.472. PMC   3321170 . PMID   22227520.
  8. ↑ Yamamoto S, et al. (2014). "ATPase activity and ATP-dependent conformational change in the co-chaperone HSP70/HSP90-organizing protein (HOP)". J. Biol. Chem. 289 (14): 9880–6. doi: 10.1074/jbc.m114.553255 . PMC   3975032 . PMID   24535459.
  9. ↑ Martins VR, Graner E, Garcia-Abreu J, de Souza SJ, Mercadante AF, Veiga SS, Zanata SM, Neto VM, Brentani RR (December 1997). "Complementary hydropathy identifies a cellular prion protein receptor". Nature Medicine. 3 (12): 1376–82. doi:10.1038/nm1297-1376. PMID   9396608. S2CID   20605773.
  10. ↑ Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR (July 2002). "Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection". The EMBO Journal. 21 (13): 3307–16. doi:10.1093/emboj/cdf325. PMC   125391 . PMID   12093732.
  11. ↑ Iwasaki S, Sasaki HM, Sakaguchi Y, Suzuki T, Tadakuma H, Tomari Y (May 2015). "Defining fundamental steps in the assembly of the Drosophila RNAi enzyme complex". Nature. 521 (7553): 533–6. Bibcode:2015Natur.521..533I. doi:10.1038/nature14254. PMID   25822791. S2CID   4450303.
  12. ↑ Gangaraju VK, Yin H, Weiner MM, Wang J, Huang XA, Lin H (February 2011). "Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation". Nature Genetics. 43 (2): 153–8. doi:10.1038/ng.743. PMC   3443399 . PMID   21186352.
  13. ↑ Karam JA, Parikh RY, Nayak D, Rosenkranz D, Gangaraju VK (April 2017). "Co-chaperone Hsp70/Hsp90-organizing protein (Hop) is required for transposon silencing and Piwi-interacting RNA (piRNA) biogenesis". The Journal of Biological Chemistry. 292 (15): 6039–6046. doi: 10.1074/jbc.C117.777730 . PMC   5391737 . PMID   28193840.
  14. ↑ Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR (July 2002). "Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection". The EMBO Journal. 21 (13): 3307–16. doi:10.1093/emboj/cdf325. PMC   125391 . PMID   12093732.
  15. ↑ Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I (April 2000). "Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine". Cell. 101 (2): 199–210. doi: 10.1016/S0092-8674(00)80830-2 . PMID   10786835. S2CID   18200460.
  16. ↑ Johnson BD, Schumacher RJ, Ross ED, Toft DO (February 1998). "Hop modulates Hsp70/Hsp90 interactions in protein folding". The Journal of Biological Chemistry. 273 (6): 3679–86. doi: 10.1074/jbc.273.6.3679 . PMID   9452498.

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