Wikipedia

Stress-induced-phosphoprotein 1

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]

STIP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSTIP1, HEL-S-94n, HOP, IEF-SSP-3521, P60, STI1, STI1L, stress induced phosphoprotein 1
External IDsOMIM: 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 MbChr 19: 7 – 7.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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

Gene

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

Structure

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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

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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

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

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000168439 – Ensembl, May 2017
  2. ^ a b c 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.

Further reading

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