Pathway Human Homo sapiens

MAPK targets/ Nuclear events mediated by MAP kinases

R-HSA-450282 in Reactome release 97: under MAP kinase activation, with 31 genes placed in it by the mapping files and 3 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-450282 (mouse), R-RNO-450282 (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-450282.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2010-03-16
Last updated: 2023-03-29
Events inside: 3, counted from the record

MAPKs are protein kinases that, once activated, phosphorylate their specific cytosolic or nuclear substrates at serine and/or threonine residues. Such phosphorylation events can either positively or negatively regulate substrate, and thus entire signaling cascade activity.

The major cytosolic target of activated ERKs are RSKs (90 kDa Ribosomal protein S6 Kinase). Active RSKs translocates to the nucleus and phosphorylates such factors as c-Fos(on Ser362), SRF (Serum Response Factor) at Ser103, and CREB (Cyclic AMP Response Element-Binding protein) at Ser133. In the nucleus activated ERKs phosphorylate many other targets such as MSKs (Mitogen- and Stress-activated protein kinases), MNK (MAP interacting kinase) and Elk1 (on Serine383 and Serine389). ERK can directly phosphorylate CREB and also AP-1 components c-Jun and c-Fos. Another important target of ERK is NF-KappaB. Recent studies reveals that nuclear pore proteins are direct substrates for ERK (Kosako H et al, 2009). Other ERK nuclear targets include c-Myc, HSF1 (Heat-Shock Factor-1), STAT1/3 (Signal Transducer and Activator of Transcription-1/3), and many more transcription factors.

Activated p38 MAPK is able to phosphorylate a variety of substrates, including transcription factors STAT1, p53, ATF2 (Activating transcription factor 2), MEF2 (Myocyte enhancer factor-2), protein kinases MSK1, MNK, MAPKAPK2/3, death/survival molecules (Bcl2, caspases), and cell cycle control factors (cyclin D1).

JNK, once activated, phosphorylates a range of nuclear substrates, including transcription factors Jun, ATF, Elk1, p53, STAT1/3 and many other factors. JNK has also been shown to directly phosphorylate many nuclear hormone receptors. For example, peroxisome proliferator-activated receptor 1 (PPAR-1) and retinoic acid receptors RXR and RAR are substrates for JNK. Other JNK targets are heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Other adaptor and scaffold proteins have also been characterized as nonnuclear substrates of JNK.

Literature Reactome attaches

Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinasesScience, 2002, vol. 298, p. 1911-2PubMed 12471242
Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinasesMicrobiol Mol Biol Rev, 2006, vol. 70, p. 1061-95PubMed 17158707
The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functionsGrowth Factors, 2006, vol. 24, p. 21-44PubMed 16393692

Reactome's record lists 13 orthologous events, R-RNO-450282 (Rattus norvegicus), R-MMU-450282 (Mus musculus) among the species this site serves, and 11 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"MAPK targets/ Nuclear events mediated by MAP kinases". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-450282 with StableID: R-HSA-450282.3 (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 31 genes in this human pathway; showing 1 to 31, 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
GeneATF1	AuthorityHGNC:783	Mapping file id466 NCBI file	EvidenceTAS
GeneATF2	AuthorityHGNC:784	Mapping file id1386 NCBI file	EvidenceTAS
GeneCREB1	AuthorityHGNC:2345	Mapping file id1385 NCBI file	EvidenceTAS
GeneDUSP3	AuthorityHGNC:3069	Mapping file id1845 NCBI file	EvidenceTAS
GeneDUSP4	AuthorityHGNC:3070	Mapping file id1846 NCBI file	EvidenceTAS
GeneDUSP6	AuthorityHGNC:3072	Mapping file id1848 NCBI file	EvidenceTAS
GeneDUSP7	AuthorityHGNC:3073	Mapping file id1849 NCBI file	EvidenceTAS
GeneELK1	AuthorityHGNC:3321	Mapping file id2002 NCBI file	EvidenceIEA
GeneFOS	AuthorityHGNC:3796	Mapping file id2353 NCBI file	EvidenceTAS
GeneJUN	AuthorityHGNC:6204	Mapping file id3725 NCBI file	EvidenceTAS
GeneMAPK1	AuthorityHGNC:6871	Mapping file id5594 NCBI file	EvidenceIEA, TAS
GeneMAPK10	AuthorityHGNC:6872	Mapping file id5602 NCBI file	EvidenceTAS
GeneMAPK11	AuthorityHGNC:6873	Mapping file id5600 NCBI file	EvidenceTAS
GeneMAPK14	AuthorityHGNC:6876	Mapping file id1432 NCBI file	EvidenceTAS
GeneMAPK3	AuthorityHGNC:6877	Mapping file id5595 NCBI file	EvidenceIEA, TAS
GeneMAPK7	AuthorityHGNC:6880	Mapping file id5598 NCBI file	EvidenceIEA, TAS
GeneMAPK8	AuthorityHGNC:6881	Mapping file id5599 NCBI file	EvidenceTAS
GeneMAPK9	AuthorityHGNC:6886	Mapping file id5601 NCBI file	EvidenceTAS
GeneMAPKAPK2	AuthorityHGNC:6887	Mapping file id9261 NCBI file	EvidenceTAS
GeneMEF2A	AuthorityHGNC:6993	Mapping file id4205 NCBI file	EvidenceIEA
GeneMEF2C	AuthorityHGNC:6996	Mapping file id4208 NCBI file	EvidenceIEA
GenePPP2CA	AuthorityHGNC:9299	Mapping file id5515 NCBI file	EvidenceTAS
GenePPP2CB	AuthorityHGNC:9300	Mapping file id5516 NCBI file	EvidenceTAS
GenePPP2R1A	AuthorityHGNC:9302	Mapping file id5518 NCBI file	EvidenceTAS
GenePPP2R1B	AuthorityHGNC:9303	Mapping file id5519 NCBI file	EvidenceTAS
GenePPP2R5D	AuthorityHGNC:9312	Mapping file id5528 NCBI file	EvidenceTAS
GeneRPS6KA1	AuthorityHGNC:10430	Mapping file id6195 NCBI file	EvidenceTAS
GeneRPS6KA2	AuthorityHGNC:10431	Mapping file id6196 NCBI file	EvidenceTAS
GeneRPS6KA3	AuthorityHGNC:10432	Mapping file id6197 NCBI file	EvidenceTAS
GeneRPS6KA5	AuthorityHGNC:10434	Mapping file id9252 NCBI file	EvidenceTAS
GeneVRK3	AuthorityHGNC:18996	Mapping file id51231 NCBI file	EvidenceTAS

Evidence codes on this page: IEA, 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

MAP kinase activationR-HSA-45029463 genes

Children

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.