Pathway Human Homo sapiens

HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand

R-HSA-3371497 in Reactome release 97: under Cellular responses to stress, with 57 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-3371497 (mouse), R-RNO-3371497 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-3371497.7
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2017-03-27
Last updated: 2022-06-09
Events inside: 22, counted from the record
Also named: HSP90 chaperone cycle for SHRs

Steroid hormone receptors (SHR) are transcription factors that become activated upon sensing steroid hormones such as glucocorticoids, mineralocorticoids, progesterone, androgens, or estrogen (Escriva et al 2000; Griekspoor A et al. 2007; Eick GN & Thornton JW. 2011). Depending on SHR type and the presence of ligand, they show different subcellular localizations. Whereas both unliganded and liganded estrogen receptors (ERalpha and ERbeta) are predominantly nuclear, unliganded glucocorticoid (GR) and androgen receptors (AR) are mostly located in the cytoplasm and completely translocate to the nucleus only after binding hormone (Htun H et al. 1999; Stenoien D et al. 2000; Tyagi RK et al. 2000; Cadepond F et al. 1992; Jewell CM et al. 1995; Kumar S et al. 2006). The unliganded mineralocorticoid receptor (MR) is partially cytoplasmic but can be found in nucleus in the ligand-bound or ligand-free form (Nishi M & Kawata M 2007). The progesterone receptor (PR) exists in two forms (PRA and PRB) with different ratios of nuclear versus cytoplasmic localization of the unliganded receptor. In most cell contexts, the PRA isoform is a repressor of the shorter PRB isoform, and without hormone induction it is mostly located in the nucleus, whereas PRB distributes both in the nucleus and in the cytoplasm (Lim CS et al. 1999; Griekspoor A et al. 2007). In the absence of ligand, members of the steroid receptor family remain sequestered in the cytoplasm and/or nucleus in the complex with proteins of HSP70/HSP90 chaperone machinery (Pratt WB & Dittmar KD1998). The highly dynamic ATP-dependent interactions of SHRs with HSP90 complexes regulate SHR cellular location, protein stability, competency to bind steroid hormones and transcriptional activity (Echeverria PC & Picard D 2010). Understanding the mechanism of ATPase activity of HSP90 is mostly based on structural and functional studies of the Saccharomyces cerevisiae Hsp90 complexes (Meyer P et al. 2003, 2004; Ali MM et al. 2006; Prodromou C et al. 2000; Prodromou C 2012). The ATPase cycle of human HSP90 is less well understood, however several studies suggest that the underlying enzymatic mechanisms and a set of conformational changes that accompany the ATPase cycle are highly similar in both species (Richter K et al. 2008; Vaughan CK et al. 2009). Nascent SHR proteins are chaperoned by HSP70 and HSP40 to HSP90 cycle via STIP1 (HOP) (and its TPR domains) (Hernández MP et al. 2002a,b; EcheverriaPC & Picard D 2010; Li J et al. 2011). The ATP-bound form of HSP90 leads to the displacement of STIP1 by immunophilins FKBP5 or FKBP4 resulting in conformational changes that allow efficient hormone binding (Li J et al. 2011). PTGES3 (p23) binds to HSP90 complex finally stabilizing it in the conformation with a high hormone binding affinity. After hydrolysis of ATP the hormone bound SHR is released from HSP90 complex. The cytosolic hormone-bound SHR can be transported to the nucleus by several import pathways such as the dynein-based nuclear transport along microtubules involving the transport of the entire HSP90 complex or nuclear localization signals (NLS)-mediated nuclear targeting by importins (Tyagi RK et al. 2000; Cadepond F et al. 1992; Jewell CM et al. 1995; Kumar S et al. 2006). It is worth noting that GR-importin interactions can be ligand-dependent or independent (Freedman & Yamamoto 2004; Picard & Yamamoto 1987). In the nucleus ligand-activated SHR dimerizes, binds specific sequences in the DNA, called Hormone Responsive Elements (HRE), and recruits a number of coregulators that facilitate gene transcription. Nuclear localization is essential for SHRs to transactivate their target genes, but the same receptors also possess non-genomic functions in the cytoplasm.

The Reactome module describes the ATPase-driven conformational cycle of HSP90 that regulates ligand-dependent activation of SHRs.

Literature Reactome attaches

Hsp90: structure and functionTop Curr Chem, 2013, vol. 328, p. 155-240PubMed 22955504
Structure, function and regulation of the hsp90 machineryBiomed J, 2013, vol. 36, p. 106-17PubMed 23806880
Molecular chaperones, essential partners of steroid hormone receptors for activity and mobilityBiochim. Biophys. Acta, 2010, vol. 1803, p. 641-9PubMed 20006655

Reactome's record lists 14 orthologous events, R-MMU-3371497 (Mus musculus), R-RNO-3371497 (Rattus norvegicus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-3371497 with StableID: R-HSA-3371497.7 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 57 genes in this human pathway; showing 1 to 57, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneACTR10	AuthorityHGNC:17372	Mapping file id55860 NCBI file	EvidenceTAS
GeneACTR1A	AuthorityHGNC:167	Mapping file id10121 NCBI file	EvidenceTAS
GeneAR	AuthorityHGNC:644	Mapping file id367 NCBI file	EvidenceTAS
GeneCAPZA1	AuthorityHGNC:1488	Mapping file id829 NCBI file	EvidenceTAS
GeneCAPZA2	AuthorityHGNC:1490	Mapping file id830 NCBI file	EvidenceTAS
GeneCAPZA3	AuthorityHGNC:24205	Mapping file id93661 NCBI file	EvidenceTAS
GeneCAPZB	AuthorityHGNC:1491	Mapping file id832 NCBI file	EvidenceTAS
GeneDCTN1	AuthorityHGNC:2711	Mapping file id1639 NCBI file	EvidenceTAS
GeneDCTN2	AuthorityHGNC:2712	Mapping file id10540 NCBI file	EvidenceTAS
GeneDCTN3	AuthorityHGNC:2713	Mapping file id11258 NCBI file	EvidenceTAS
GeneDCTN4	AuthorityHGNC:15518	Mapping file id51164 NCBI file	EvidenceTAS
GeneDCTN5	AuthorityHGNC:24594	Mapping file id84516 NCBI file	EvidenceTAS
GeneDCTN6	AuthorityHGNC:16964	Mapping file id10671 NCBI file	EvidenceTAS
GeneDNAJA1	AuthorityHGNC:5229	Mapping file id3301 NCBI file	EvidenceTAS
GeneDNAJA2	AuthorityHGNC:14884	Mapping file id10294 NCBI file	EvidenceTAS
GeneDNAJA4	AuthorityHGNC:14885	Mapping file id55466 NCBI file	EvidenceTAS
GeneDNAJB1	AuthorityHGNC:5270	Mapping file id3337 NCBI file	EvidenceTAS
GeneDYNC1H1	AuthorityHGNC:2961	Mapping file id1778 NCBI file	EvidenceTAS
GeneDYNC1I1	AuthorityHGNC:2963	Mapping file id1780 NCBI file	EvidenceTAS
GeneDYNC1I2	AuthorityHGNC:2964	Mapping file id1781 NCBI file	EvidenceTAS
GeneDYNC1LI1	AuthorityHGNC:18745	Mapping file id51143 NCBI file	EvidenceTAS
GeneDYNC1LI2	AuthorityHGNC:2966	Mapping file id1783 NCBI file	EvidenceTAS
GeneDYNLL1	AuthorityHGNC:15476	Mapping file id8655 NCBI file	EvidenceTAS
GeneDYNLL2	AuthorityHGNC:24596	Mapping file id140735 NCBI file	EvidenceTAS
GeneFKBP4	AuthorityHGNC:3720	Mapping file id2288 NCBI file	EvidenceTAS
GeneFKBP5	AuthorityHGNC:3721	Mapping file id2289 NCBI file	EvidenceTAS
GeneHSP90AA1	AuthorityHGNC:5253	Mapping file id3320 NCBI file	EvidenceTAS
GeneHSP90AB1	AuthorityHGNC:5258	Mapping file id3326 NCBI file	EvidenceTAS
GeneHSPA1A	AuthorityHGNC:5232	Mapping file id3303 NCBI file	EvidenceTAS
GeneHSPA1B	AuthorityHGNC:5233	Mapping file id3304 NCBI file	EvidenceTAS
GeneHSPA1L	AuthorityHGNC:5234	Mapping file id3305 NCBI file	EvidenceTAS
GeneHSPA2	AuthorityHGNC:5235	Mapping file id3306 NCBI file	EvidenceTAS
GeneHSPA8	AuthorityHGNC:5241	Mapping file id3312 NCBI file	EvidenceTAS
GeneNR3C1	AuthorityHGNC:7978	Mapping file id2908 NCBI file	EvidenceTAS
GeneNR3C2	AuthorityHGNC:7979	Mapping file id4306 NCBI file	EvidenceTAS
GenePGR	AuthorityHGNC:8910	Mapping file id5241 NCBI file	EvidenceTAS
GenePTGES3	AuthorityHGNC:16049	Mapping file id10728 NCBI file	EvidenceTAS
GeneSTIP1	AuthorityHGNC:11387	Mapping file id10963 NCBI file	EvidenceTAS
GeneTUBA1A	AuthorityHGNC:20766	Mapping file id7846 NCBI file	EvidenceTAS
GeneTUBA1B	AuthorityHGNC:18809	Mapping file id10376 NCBI file	EvidenceTAS
GeneTUBA1C	AuthorityHGNC:20768	Mapping file id84790 NCBI file	EvidenceTAS
GeneTUBA3C	AuthorityHGNC:12408	Mapping file id7278 NCBI file	EvidenceTAS
GeneTUBA3D	AuthorityHGNC:24071	Mapping file id113457 NCBI file	EvidenceTAS
GeneTUBA3E	AuthorityHGNC:20765	Mapping file id112714 NCBI file	EvidenceTAS
GeneTUBA4A	AuthorityHGNC:12407	Mapping file id7277 NCBI file	EvidenceTAS
GeneTUBA4B	AuthorityHGNC:18637	Mapping file id80086 NCBI file	EvidenceTAS
GeneTUBA8	AuthorityHGNC:12410	Mapping file id51807 NCBI file	EvidenceTAS
GeneTUBAL3	AuthorityHGNC:23534	Mapping file id79861 NCBI file	EvidenceTAS
GeneTUBB1	AuthorityHGNC:16257	Mapping file id81027 NCBI file	EvidenceTAS
GeneTUBB2A	AuthorityHGNC:12412	Mapping file id7280 NCBI file	EvidenceTAS
GeneTUBB2B	AuthorityHGNC:30829	Mapping file id347733 NCBI file	EvidenceTAS
GeneTUBB3	AuthorityHGNC:20772	Mapping file id10381 NCBI file	EvidenceTAS
GeneTUBB4A	AuthorityHGNC:20774	Mapping file id10382 NCBI file	EvidenceTAS
GeneTUBB4B	AuthorityHGNC:20771	Mapping file id10383 NCBI file	EvidenceTAS
GeneTUBB6	AuthorityHGNC:20776	Mapping file id84617 NCBI file	EvidenceTAS
GeneTUBB8	AuthorityHGNC:20773	Mapping file id347688 NCBI file	EvidenceTAS
GeneTUBB8B	AuthorityHGNC:24983	Mapping file id260334 NCBI file	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Cellular responses to stressR-HSA-2262752815 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.