Pathway Human Homo sapiens

Deubiquitination

R-HSA-5688426 in Reactome release 97: under Post-translational protein modification, with 285 genes placed in it by the mapping files and 5 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-5688426 (mouse), R-RNO-5688426 (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-5688426.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-06-15
Last updated: 2022-09-14
Events inside: 5, counted from the record

Ubiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S proteasome. Ub conjugates linked via lysine 48 (K48) target substrates to the proteasome, whereas those linked via any of the six other Ub lysines can alter the function of the modified protein without leading to degradation. Deubiquitination, the reversal of this modification, regulates the function of ubiquitin-conjugated proteins. Deubiquitinating enzymes (DUBs) catalyze the removal of Ub and regulate Ub-mediated pathways.

Given that Ub is covalently-linked to proteins destined to be degraded, it is a surprisingly long-lived protein in vivo (Haas & Bright 1987). This is due to the removal of Ub from its conjugates by DUBs prior to proteolysis. This may represent a quality control mechanism that prevents the degradation of proteins that were inappropriately tagged for degradation (Lam et al. 1997). DUBs are responsible for processing inactive Ub precursors and for keeping the 26S proteasome free of unanchored Ub chains that compete for Ub-binding sites.

DUBs can be grouped into five families based on their conserved catalytic domains (Amerik & Hochstrasser 2004). Four of these families are thiol proteases and comprise the bulk of DUBs, while the fifth family is a small group of Ub specific metalloproteases.

Thiol protease DUBs contain a Cys-His-Asp/Asn catalytic triad in which the Asp/Asn functions to polarize and orient the His, while the His serves as a general acid/base by both priming the catalytic Cys for nucleophilic attack on the (iso)peptide carbonyl carbon and by donating a proton to the lysine epsilon-amino leaving group. The nucleophilic attack of the catalytic Cys on the carbonyl carbon produces a negatively charged transition state that is stabilized by an oxyanion hole composed of hydrogen bond donors. A Cys-carbonyl acyl intermediate ensues and is then hydrolyzed by nucleophilic attack of a water molecule to liberate a protein C-terminal carboxylate and regenerate the enzyme. Ub binding often causes structural rearrangements necessary for catalysis. Many DUBs are inactivated by oxidation of the catalytic cysteine to sulphenic acid (single bond SOH) (Cotto-Rios et al. 2012, Lee et al. 2013). This can be reversed by reduction with DTT or glutathione. The sulphenic acid can be irreversibly oxidized to sulphinic acid (single bond SO2H) or sulphonic acid (single bond SO3H).

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 285 genes in this human pathway; showing 101 to 200, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 3
Gene	Authority id	Mapping file id	Evidence codes
GeneMAVS	AuthorityHGNC:29233	Mapping file id57506 NCBI file	EvidenceTAS
GeneMBD5	AuthorityHGNC:20444	Mapping file id55777 NCBI file	EvidenceTAS
GeneMBD6	AuthorityHGNC:20445	Mapping file id114785 NCBI file	EvidenceTAS
GeneMCRS1	AuthorityHGNC:6960	Mapping file id10445 NCBI file	EvidenceTAS
GeneMDM2	AuthorityHGNC:6973	Mapping file id4193 NCBI file	EvidenceTAS
GeneMDM4	AuthorityHGNC:6974	Mapping file id4194 NCBI file	EvidenceTAS
GeneMUL1	AuthorityHGNC:25762	Mapping file id79594 NCBI file	EvidenceTAS
GeneMYC	AuthorityHGNC:7553	Mapping file id4609 NCBI file	EvidenceTAS
GeneMYSM1	AuthorityHGNC:29401	Mapping file id114803 NCBI file	EvidenceTAS
GeneNEDD8	AuthorityHGNC:7732	Mapping file id4738 NCBI file	EvidenceTAS
GeneNFKBIA	AuthorityHGNC:7797	Mapping file id4792 NCBI file	EvidenceTAS
GeneNFRKB	AuthorityHGNC:7802	Mapping file id4798 NCBI file	EvidenceTAS
GeneNLRP3	AuthorityHGNC:16400	Mapping file id114548 NCBI file	EvidenceTAS
GeneNOD1	AuthorityHGNC:16390	Mapping file id10392 NCBI file	EvidenceTAS
GeneNOD2	AuthorityHGNC:5331	Mapping file id64127 NCBI file	EvidenceTAS
GeneOGT	AuthorityHGNC:8127	Mapping file id8473 NCBI file	EvidenceTAS
GeneOTUB1	AuthorityHGNC:23077	Mapping file id55611 NCBI file	EvidenceTAS
GeneOTUB2	AuthorityHGNC:20351	Mapping file id78990 NCBI file	EvidenceTAS
GeneOTUD3	AuthorityHGNC:29038	Mapping file id23252 NCBI file	EvidenceTAS
GeneOTUD5	AuthorityHGNC:25402	Mapping file id55593 NCBI file	EvidenceTAS
GeneOTUD7A	AuthorityHGNC:20718	Mapping file id161725 NCBI file	EvidenceTAS
GeneOTUD7B	AuthorityHGNC:16683	Mapping file id56957 NCBI file	EvidenceTAS
GenePOLB	AuthorityHGNC:9174	Mapping file id5423 NCBI file	EvidenceTAS
GenePRKN	AuthorityHGNC:8607	Mapping file id5071 NCBI file	EvidenceTAS
GenePSMA1	AuthorityHGNC:9530	Mapping file id5682 NCBI file	EvidenceTAS
GenePSMA2	AuthorityHGNC:9531	Mapping file id5683 NCBI file	EvidenceTAS
GenePSMA3	AuthorityHGNC:9532	Mapping file id5684 NCBI file	EvidenceTAS
GenePSMA4	AuthorityHGNC:9533	Mapping file id5685 NCBI file	EvidenceTAS
GenePSMA5	AuthorityHGNC:9534	Mapping file id5686 NCBI file	EvidenceTAS
GenePSMA6	AuthorityHGNC:9535	Mapping file id5687 NCBI file	EvidenceTAS
GenePSMA7	AuthorityHGNC:9536	Mapping file id5688 NCBI file	EvidenceTAS
GenePSMB1	AuthorityHGNC:9537	Mapping file id5689 NCBI file	EvidenceTAS
GenePSMB2	AuthorityHGNC:9539	Mapping file id5690 NCBI file	EvidenceTAS
GenePSMB3	AuthorityHGNC:9540	Mapping file id5691 NCBI file	EvidenceTAS
GenePSMB4	AuthorityHGNC:9541	Mapping file id5692 NCBI file	EvidenceTAS
GenePSMB5	AuthorityHGNC:9542	Mapping file id5693 NCBI file	EvidenceTAS
GenePSMB6	AuthorityHGNC:9543	Mapping file id5694 NCBI file	EvidenceTAS
GenePSMB7	AuthorityHGNC:9544	Mapping file id5695 NCBI file	EvidenceTAS
GenePSMC1	AuthorityHGNC:9547	Mapping file id5700 NCBI file	EvidenceTAS
GenePSMC2	AuthorityHGNC:9548	Mapping file id5701 NCBI file	EvidenceTAS
GenePSMC3	AuthorityHGNC:9549	Mapping file id5702 NCBI file	EvidenceTAS
GenePSMC4	AuthorityHGNC:9551	Mapping file id5704 NCBI file	EvidenceTAS
GenePSMC5	AuthorityHGNC:9552	Mapping file id5705 NCBI file	EvidenceTAS
GenePSMC6	AuthorityHGNC:9553	Mapping file id5706 NCBI file	EvidenceTAS
GenePSMD1	AuthorityHGNC:9554	Mapping file id5707 NCBI file	EvidenceTAS
GenePSMD11	AuthorityHGNC:9556	Mapping file id5717 NCBI file	EvidenceTAS
GenePSMD12	AuthorityHGNC:9557	Mapping file id5718 NCBI file	EvidenceTAS
GenePSMD13	AuthorityHGNC:9558	Mapping file id5719 NCBI file	EvidenceTAS
GenePSMD14	AuthorityHGNC:16889	Mapping file id10213 NCBI file	EvidenceTAS
GenePSMD2	AuthorityHGNC:9559	Mapping file id5708 NCBI file	EvidenceTAS
GenePSMD3	AuthorityHGNC:9560	Mapping file id5709 NCBI file	EvidenceTAS
GenePSMD6	AuthorityHGNC:9564	Mapping file id9861 NCBI file	EvidenceTAS
GenePSMD7	AuthorityHGNC:9565	Mapping file id5713 NCBI file	EvidenceTAS
GenePSMD8	AuthorityHGNC:9566	Mapping file id5714 NCBI file	EvidenceTAS
GenePTEN	AuthorityHGNC:9588	Mapping file id5728 NCBI file	EvidenceTAS
GenePTRH2	AuthorityHGNC:24265	Mapping file id51651 NCBI file	EvidenceTAS
GeneRAD23A	AuthorityHGNC:9812	Mapping file id5886 NCBI file	EvidenceTAS
GeneRAD23B	AuthorityHGNC:9813	Mapping file id5887 NCBI file	EvidenceTAS
GeneRCE1	AuthorityHGNC:13721	Mapping file id9986 NCBI file	EvidenceTAS
GeneRHOA	AuthorityHGNC:667	Mapping file id387 NCBI file	EvidenceTAS
GeneRHOT1	AuthorityHGNC:21168	Mapping file id55288 NCBI file	EvidenceTAS
GeneRIGI	AuthorityHGNC:19102	Mapping file id23586 NCBI file	EvidenceTAS
GeneRIPK1	AuthorityHGNC:10019	Mapping file id8737 NCBI file	EvidenceTAS
GeneRIPK2	AuthorityHGNC:10020	Mapping file id8767 NCBI file	EvidenceTAS
GeneRNF123	AuthorityHGNC:21148	Mapping file id63891 NCBI file	EvidenceTAS
GeneRNF128	AuthorityHGNC:21153	Mapping file id79589 NCBI file	EvidenceTAS
GeneRNF135	AuthorityHGNC:21158	Mapping file id84282 NCBI file	EvidenceTAS
GeneRNF146	AuthorityHGNC:21336	Mapping file id81847 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA, TAS
GeneRUVBL1	AuthorityHGNC:10474	Mapping file id8607 NCBI file	EvidenceTAS
GeneSEM1	AuthorityHGNC:10845	Mapping file id7979 NCBI file	EvidenceTAS
GeneSENP8	AuthorityHGNC:22992	Mapping file id123228 NCBI file	EvidenceTAS
GeneSIAH2	AuthorityHGNC:10858	Mapping file id6478 NCBI file	EvidenceTAS
GeneSKP2	AuthorityHGNC:10901	Mapping file id6502 NCBI file	EvidenceTAS
GeneSMAD1	AuthorityHGNC:6767	Mapping file id4086 NCBI file	EvidenceTAS
GeneSMAD2	AuthorityHGNC:6768	Mapping file id4087 NCBI file	EvidenceTAS
GeneSMAD3	AuthorityHGNC:6769	Mapping file id4088 NCBI file	EvidenceTAS
GeneSMAD4	AuthorityHGNC:6770	Mapping file id4089 NCBI file	EvidenceTAS
GeneSMAD7	AuthorityHGNC:6773	Mapping file id4092 NCBI file	EvidenceIEA, TAS
GeneSMURF2	AuthorityHGNC:16809	Mapping file id64750 NCBI file	EvidenceTAS
GeneSNX3	AuthorityHGNC:11174	Mapping file id8724 NCBI file	EvidenceTAS
GeneSTAM	AuthorityHGNC:11357	Mapping file id8027 NCBI file	EvidenceTAS
GeneSTAM2	AuthorityHGNC:11358	Mapping file id10254 NCBI file	EvidenceTAS
GeneSTAMBP	AuthorityHGNC:16950	Mapping file id10617 NCBI file	EvidenceTAS
GeneSTAMBPL1	AuthorityHGNC:24105	Mapping file id57559 NCBI file	EvidenceTAS
GeneSUDS3	AuthorityHGNC:29545	Mapping file id64426 NCBI file	EvidenceTAS
GeneTAB1	AuthorityHGNC:18157	Mapping file id10454 NCBI file	EvidenceTAS
GeneTADA2B	AuthorityHGNC:30781	Mapping file id93624 NCBI file	EvidenceTAS
GeneTADA3	AuthorityHGNC:19422	Mapping file id10474 NCBI file	EvidenceTAS
GeneTAF10	AuthorityHGNC:11543	Mapping file id6881 NCBI file	EvidenceTAS
GeneTAF9B	AuthorityHGNC:17306	Mapping file id51616 NCBI file	EvidenceTAS
GeneTFPT	AuthorityHGNC:13630	Mapping file id29844 NCBI file	EvidenceTAS
GeneTGFB1	AuthorityHGNC:11766	Mapping file id7040 NCBI file	EvidenceIEA
GeneTGFBR1	AuthorityHGNC:11772	Mapping file id7046 NCBI file	EvidenceIEA, TAS
GeneTGFBR2	AuthorityHGNC:11773	Mapping file id7048 NCBI file	EvidenceIEA
GeneTNFAIP3	AuthorityHGNC:11896	Mapping file id7128 NCBI file	EvidenceTAS
GeneTNIP1	AuthorityHGNC:16903	Mapping file id10318 NCBI file	EvidenceTAS
GeneTNIP2	AuthorityHGNC:19118	Mapping file id79155 NCBI file	EvidenceTAS
GeneTNIP3	AuthorityHGNC:19315	Mapping file id79931 NCBI file	EvidenceTAS
GeneTNKS	AuthorityHGNC:11941	Mapping file id8658 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

Post-translational protein modificationR-HSA-5975921,507 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.