Pathway Human Homo sapiens

Protein ubiquitination

R-HSA-8852135 in Reactome release 97: under Post-translational protein modification, with 79 genes placed in it by the mapping files and 2 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-8852135 (mouse), R-RNO-8852135 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

Scripts are off

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-8852135.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-09-19
Last updated: 2023-09-13
Events inside: 2, counted from the record

Ubiquitin is a small, 76 amino acid residue protein that is conjugated by E3 ubiquitin ligases to other proteins in order to regulate their function or degradation (enzymatic cascade reviewed in Neutzner and Neutzner 2012, Kleiger and Mayor 2014, structures and mechanisms of conjugating enzymes reviewed in Lorenz et al. 2013). Ubiquitination of target proteins usually occurs between the C-terminal glycine residue of ubiquitin and a lysine residue of the target, although linkages with cysteine, serine, and threonine residues are also observed (reviewed in Wang et al. 2012, McDowell and Philpott 2013).

Ubiquitin must first be processed from larger precursors and then activated by formation of a thiol ester bond between ubiquitin and an E1 activating enzyme (UBA1 or UBA6) and transfer to an E2 conjugating enzyme before being transferred by an E3 ligase to a target protein. Precursor proteins containing multiple ubiquitin monomers (polyubiquitins) are produced from the UBB and UBC genes; precursors containing a single ubiquitin monomer and a ribosomal protein are produced from the UBA52 and RPS27A genes. Many proteases (deubiquitinases) may potentially process these precursors yielding monomeric ubiquitin. The proteases OTULIN and USP5 are particularly active in cleaving the polyubiquitin precursors, whereas the proteases UCHL3, USP7, and USP9X cleave the ubiquitin-ribosomal protein precursors yielding ubiquitin monomers (Grou et al. 2015). A resultant ubiquitin monomer is activated by adenylation of the C-terminal glycine followed by conjugation of the C-terminus to a cysteine residue of the E1 enzymes UBA1 or UBA6 via a thiol ester bond. The ubiquitin is then transferred from the E1 enzyme to a cysteine residue of one of several E2 enzymes (reviewed in van Wijk and Timmers 2010, Stewart et al. 2016). Through a less well characterized mechanism, E3 ubiquitin ligases then bring a target protein and the E2-ubiquitin conjugate into proximity so that the ubiquitin is transferred via formation of an amide bond to a particular lysine residue (or, in rarer cases, a thiol ester bond to a cysteine residue or an ester bond to a serine or threonine residue) of the target protein (reviewed in Berndsen and Wolberger 2014). Based on protein homologies, families of E3 ubiquitin ligases have been identified that include RING-type ligases (reviewed in Deshaies et al. 2009, Metzger et al. 2012, Metzger et al. 2014), HECT-type ligases (reviewed in Rotin et al. 2009, Metzger et al. 2012), and RBR-type ligases (reviewed in Dove et al. 2016). A subset of the RING-type ligases participate in CULLIN-RING ligase complexes (CRLs which include SCF complexes, reviewed in Lee and Zhou 2007, Genschik et al. 2013, Skaar et al. 2013, Lee et al. 2014).

Some E3-E2 combinations catalyze mono-ubiquitination of the target protein (reviewed in Nakagawa and Nakayama 2015). Other E3-E2 combinations catalyze conjugation of further ubiquitin monomers to the initial ubiquitin, forming polyubiquitin chains. (It may also be possible for some E3-E2 combinations to preassemble polyubiquitin and transfer it as a unit to the target protein.) Ubiquitin contains several lysine (K) residues and a free alpha amino group to which further ubiquitin can be conjugated. Thus different types of polyubiquitin are possible: K11 linked polyubiquitin is observed in endoplasmic reticulum-associated degradation (ERAD), K29 linked polyubiquitin is observed in lysosomal degradation, K48 linked polyubiquitin directs target proteins to the proteasome for degradation, whereas K63 linked polyubiquitin generally acts as a scaffold to recruit other proteins in several cellular processes, notably DNA repair (reviewed in Komander et al. 2009). Ubiquitination is highly regulated (reviewed in Vittal et al. 2015) and affects all cellular processes including DNA damage response (reviewed in Brown and Jackson 2015), immune signaling (reviewed in Park et al. 2014, Lutz-Nicoladoni et al. 2015), and regulation of normal and cancerous cell growth (reviewed in Skaar and Pagano 2009, Yerlikaya and Yontem 2013, Strikoudis et al. 2014).

Literature Reactome attaches

Enzymes of ubiquitination and deubiquitinationEssays Biochem., 2012, vol. 52, p. 37-50PubMed 22708562
Regulating the Regulators: Recent Revelations in the Control of E3 Ubiquitin LigasesJ. Biol. Chem., 2015, vol. 290, p. 21244-51PubMed 26187467
Protein monoubiquitylation: targets and diverse functionsGenes Cells, 2015, vol. 20, p. 543-62PubMed 26085183
Ubiquitylation, neddylation and the DNA damage responseOpen Biol, 2015, vol. 5, p. 150018PubMed 25833379
Modulation of Immune Cell Functions by the E3 Ligase Cbl-bFront Oncol, 2015, vol. 5, p. 58PubMed 25815272
The ubiquitin system in immune regulationAdv. Immunol., 2014, vol. 124, p. 17-66PubMed 25175772
New insights into ubiquitin E3 ligase mechanismNat. Struct. Mol. Biol., 2014, vol. 21, p. 301-7PubMed 24699078

Reactome's record lists 12 orthologous events, R-MMU-8852135 (Mus musculus), R-RNO-8852135 (Rattus norvegicus) among the species this site serves, and 10 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Protein ubiquitination". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-8852135 with StableID: R-HSA-8852135.4 (accessed 2026-10-01 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 79 genes in this human pathway; showing 1 to 79, 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
GeneBCL10	AuthorityHGNC:989	Mapping file id8915 NCBI file	EvidenceTAS
GeneCDC34	AuthorityHGNC:1734	Mapping file id997 NCBI file	EvidenceTAS
GeneCDC73	AuthorityHGNC:16783	Mapping file id79577 NCBI file	EvidenceTAS
GeneCTR9	AuthorityHGNC:16850	Mapping file id9646 NCBI file	EvidenceTAS
GeneDERL1	AuthorityHGNC:28454	Mapping file id79139 NCBI file	EvidenceTAS
GeneH2BC1	AuthorityHGNC:18730	Mapping file id255626 NCBI file	EvidenceTAS
GeneH2BC10	AuthorityHGNC:4756	Mapping file id8346 NCBI file	EvidenceTAS
GeneH2BC11	AuthorityHGNC:4761	Mapping file id8970 NCBI file	EvidenceTAS
GeneH2BC12	AuthorityHGNC:13954	Mapping file id85236 NCBI file	EvidenceTAS
GeneH2BC13	AuthorityHGNC:4748	Mapping file id8340 NCBI file	EvidenceTAS
GeneH2BC14	AuthorityHGNC:4750	Mapping file id8342 NCBI file	EvidenceTAS
GeneH2BC15	AuthorityHGNC:4749	Mapping file id8341 NCBI file	EvidenceTAS
GeneH2BC17	AuthorityHGNC:4758	Mapping file id8348 NCBI file	EvidenceTAS
GeneH2BC3	AuthorityHGNC:4751	Mapping file id3018 NCBI file	EvidenceTAS
GeneH2BC4	AuthorityHGNC:4757	Mapping file id8347 NCBI file	EvidenceTAS
GeneH2BC5	AuthorityHGNC:4747	Mapping file id3017 NCBI file	EvidenceTAS
GeneH2BC6	AuthorityHGNC:4753	Mapping file id8344 NCBI file	EvidenceTAS
GeneH2BC7	AuthorityHGNC:4752	Mapping file id8343 NCBI file	EvidenceTAS
GeneH2BC8	AuthorityHGNC:4746	Mapping file id8339 NCBI file	EvidenceTAS
GeneH2BC9	AuthorityHGNC:4755	Mapping file id8345 NCBI file	EvidenceTAS
GeneHLA-A	AuthorityHGNC:4931	Mapping file id3105 NCBI file	EvidenceTAS
GeneHLTF	AuthorityHGNC:11099	Mapping file id6596 NCBI file	EvidenceTAS
GeneLEO1	AuthorityHGNC:30401	Mapping file id123169 NCBI file	EvidenceTAS
GeneOTULIN	AuthorityHGNC:25118	Mapping file id90268 NCBI file	EvidenceTAS
GenePAF1	AuthorityHGNC:25459	Mapping file id54623 NCBI file	EvidenceTAS
GenePCNA	AuthorityHGNC:8729	Mapping file id5111 NCBI file	EvidenceTAS
GenePEX10	AuthorityHGNC:8851	Mapping file id5192 NCBI file	EvidenceTAS
GenePEX12	AuthorityHGNC:8854	Mapping file id5193 NCBI file	EvidenceTAS
GenePEX13	AuthorityHGNC:8855	Mapping file id5194 NCBI file	EvidenceTAS
GenePEX14	AuthorityHGNC:8856	Mapping file id5195 NCBI file	EvidenceTAS
GenePEX2	AuthorityHGNC:9717	Mapping file id5828 NCBI file	EvidenceTAS
GenePEX5	AuthorityHGNC:9719	Mapping file id5830 NCBI file	EvidenceTAS
GenePRKDC	AuthorityHGNC:9413	Mapping file id5591 NCBI file	EvidenceTAS
GeneRAD18	AuthorityHGNC:18278	Mapping file id56852 NCBI file	EvidenceTAS
GeneRNF144A	AuthorityHGNC:20457	Mapping file id9781 NCBI file	EvidenceTAS
GeneRNF152	AuthorityHGNC:26811	Mapping file id220441 NCBI file	EvidenceTAS
GeneRNF181	AuthorityHGNC:28037	Mapping file id51255 NCBI file	EvidenceTAS
GeneRNF20	AuthorityHGNC:10062	Mapping file id56254 NCBI file	EvidenceTAS
GeneRNF40	AuthorityHGNC:16867	Mapping file id9810 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA, TAS
GeneRRAGA	AuthorityHGNC:16963	Mapping file id10670 NCBI file	EvidenceTAS
GeneRTF1	AuthorityHGNC:28996	Mapping file id23168 NCBI file	EvidenceTAS
GeneSELENOS	AuthorityHGNC:30396	Mapping file id55829 NCBI file	EvidenceTAS
GeneSHPRH	AuthorityHGNC:19336	Mapping file id257218 NCBI file	EvidenceTAS
GeneSKIC8	AuthorityHGNC:30300	Mapping file id80349 NCBI file	EvidenceTAS
GeneTMEM129	AuthorityHGNC:25137	Mapping file id92305 NCBI file	EvidenceTAS
GeneUBA1	AuthorityHGNC:12469	Mapping file id7317 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceIEA, TAS
GeneUBA6	AuthorityHGNC:25581	Mapping file id55236 NCBI file	EvidenceIEA, TAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceIEA, TAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceIEA, TAS
GeneUBE2A	AuthorityHGNC:12472	Mapping file id7319 NCBI file	EvidenceTAS
GeneUBE2B	AuthorityHGNC:12473	Mapping file id7320 NCBI file	EvidenceTAS
GeneUBE2C	AuthorityHGNC:15937	Mapping file id11065 NCBI file	EvidenceTAS
GeneUBE2D1	AuthorityHGNC:12474	Mapping file id7321 NCBI file	EvidenceTAS
GeneUBE2D2	AuthorityHGNC:12475	Mapping file id7322 NCBI file	EvidenceTAS
GeneUBE2D3	AuthorityHGNC:12476	Mapping file id7323 NCBI file	EvidenceTAS
GeneUBE2E1	AuthorityHGNC:12477	Mapping file id7324 NCBI file	EvidenceTAS
GeneUBE2E3	AuthorityHGNC:12479	Mapping file id10477 NCBI file	EvidenceTAS
GeneUBE2G1	AuthorityHGNC:12482	Mapping file id7326 NCBI file	EvidenceTAS
GeneUBE2G2	AuthorityHGNC:12483	Mapping file id7327 NCBI file	EvidenceTAS
GeneUBE2H	AuthorityHGNC:12484	Mapping file id7328 NCBI file	EvidenceTAS
GeneUBE2J2	AuthorityHGNC:19268	Mapping file id118424 NCBI file	EvidenceTAS
GeneUBE2K	AuthorityHGNC:4914	Mapping file id3093 NCBI file	EvidenceTAS
GeneUBE2L3	AuthorityHGNC:12488	Mapping file id7332 NCBI file	EvidenceTAS
GeneUBE2N	AuthorityHGNC:12492	Mapping file id7334 NCBI file	EvidenceTAS
GeneUBE2Q2	AuthorityHGNC:19248	Mapping file id92912 NCBI file	EvidenceTAS
GeneUBE2R2	AuthorityHGNC:19907	Mapping file id54926 NCBI file	EvidenceTAS
GeneUBE2S	AuthorityHGNC:17895	Mapping file id27338 NCBI file	EvidenceTAS
GeneUBE2T	AuthorityHGNC:25009	Mapping file id29089 NCBI file	EvidenceTAS
GeneUBE2V2	AuthorityHGNC:12495	Mapping file id7336 NCBI file	EvidenceTAS
GeneUBE2W	AuthorityHGNC:25616	Mapping file id55284 NCBI file	EvidenceTAS
GeneUBE2Z	AuthorityHGNC:25847	Mapping file id65264 NCBI file	EvidenceTAS
GeneUCHL3	AuthorityHGNC:12515	Mapping file id7347 NCBI file	EvidenceTAS
GeneUSP5	AuthorityHGNC:12628	Mapping file id8078 NCBI file	EvidenceTAS
GeneUSP7	AuthorityHGNC:12630	Mapping file id7874 NCBI file	EvidenceTAS
GeneUSP9X	AuthorityHGNC:12632	Mapping file id8239 NCBI file	EvidenceTAS
GeneVCP	AuthorityHGNC:12666	Mapping file id7415 NCBI file	EvidenceTAS
GeneWAC	AuthorityHGNC:17327	Mapping file id51322 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.