Pathway Human Homo sapiens

Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide

R-HSA-9954709 in Reactome release 97: under Ribosome-associated quality control, with 103 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-9954709 (mouse), R-RNO-9954709 (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-9954709.2
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2025-09-18
Events inside: 13, counted from the record

After the 80S ribosome is split into a 40S subunit and a 60S subunit that contains the peptidyl-tRNA at the P site, NEMF (the human homolog of yeast RQC2) binds the exposed peptidyl-tRNA of the isolated 60S ribosomal subunit produced by either the RQT complex or ABCE1 and transfers alanine residues from aminoacyl tRNAs to the C-terminus of the nascent peptide, a process termed Carboxy-terminal Alanine and Threonine tailing (CAT-tailing) after the alanine and threonine tails observed in yeast (Udagawa et al. 2021, Thrun et al. 2021, inferred from the yeast homolog RQC2 in Shen et al. 2015, Kostova et al. 2017, Osuna et al. 2017). Structures of CAT-tailing intermediates in yeast indicate that RQC2 positions an aminoacyl-tRNA in the A site of the 60S subunit and eIF5A enables peptidyl transfer (Shen et al. 2015, Tesina et al. 2023).

The alanine C-terminal tails are believed to push the nascent peptide through the exit tunnel of the 60S ribosomal subunit to expose lysine residues for K48 ubiquitination by Listerin (LTN1), however alanine tails can cause aggregation of nascent peptides (Udagawa et al. 2021, and inferred from yeast homologs in Yonashiro et al. 2016). The alanine tails can also act as degrons by binding the CRL2-KHDC10 ubiquitin E3 ligase complex (Thrun et al. 2021, Patil et al. 2023) or the RCHY1 (PIRH2) ubiquitin E3 ligase (Thrun et al. 2021, Patil et al. 2023, Wang et al. 2023) CRL2-KHDC10 and RCHY1 ubiquitinate the nascent peptide using K48 polyubiquitin linkages, targeting the nascent peptide for destruction by the 26S proteasome.

Listerin (LTN1, also called RKR1 in yeast), a ubiquitin E3 ligase, is also capable of K48 ubiquitinating the nascent peptide after NEMF recruits LTN1 to the 60S ribosomal subunit (Shao et al. 2015). The N-terminal region of LTN1 contacts the 60S ribosomal subunit and NEMF while the C-terminal region of LTN1 binds the 60S ribosomal subunit near the exit tunnel (Shao et al. 2015, inferred from yeast homologs in Lyumkis et al. 2014). TCF25 (the homolog of RQC1 in yeast) interacts with LTN1 (inferred from yeast homologs in Defenouillère et al. 2013).

LTN1 ubiquitinates exposed lysine residues on the nascent peptide after the residues have emerged from the exit tunnel of the 60S ribosomal subunit (Osuna et al. 2017, Kuroha et al. 2018, Abaeva et al. 2025, inferred from yeast homologs in Bengtson and Joazeiro 2010, Shao et al. 2013, Shao and Hegde 2014, reviewed in Mishra et al. 2021). TCF25, the human homolog of RQC1 in yeast, interacts with the RING domain of LTN1 to orient the ubiquitin substrate molecules to produce lysine-48 (K48) linkages in the polyubiquitin product (Kuroha et al. 2018, Abaeva et al. 2025).

A hexamer of VCP subunits plus a heterodimer of UFDL1 (UFD1) and NPLOC4 bind polyubiquitin that contains lysine-48 linkages (K48polyUb) and is conjugated to the nascent peptide emerging from the exit tunnel of the 60S ribosomal subunit (Tsuchiya et al. 2017, Sato et al. 2019, Williams et al. 2023, and inferred from CDC48, the yeast orthologue of VCP, in Brandman et al. 2012, Defenouillère et al. 2013, Verma et al. 2013). In yeast, the Npl4:Ufd1 heterodimer (homolog of NPLOC4:UFD1L) acts as an adapter that binds K48-linked polyubiquitin and inserts it into the pore of the VCP hexamer (inferred from rat p97 and Ufd1:Npl4 in Meyer et al. 2000, reviewed in Meyer and van den Boom 2023).

ANKZF1, which interacts with VCP, cleaves the C-terminal 3 nucleotides, CCA, of the tRNA in the peptidyl-tRNA bound to the 60S ribosomal subunit, yielding a free tRNA and the nascent peptide covalently bound to the CCA sequence (Verma et al. 2018, Yip et al. 2019, and inferred from the yeast homolog, VMS1, in Verma et al. 2018, Yip et al. 2019). In yeast, Arb1 (mammalian ABCF2) occupies the E-site of the collided ribosome, extending a domain towards the peptidyl-tRNA that may help position it for release by Vms1/ANKZF1 (Su et al. 2019).

The VCP hexamer then extracts the ubiquitinated nascent peptide from the 60S ribosomal subunit. Six subunits of VCP surround the substrate protein, which is located in the central pore of the hexamer. Hydrolysis of ATP by a subunit causes it to disengage from the hexamer. Release of ADP and binding of ATP causes the subunit to rebind the hexamer more proximally to the 60S ribosomal subunit (reviewed in Meyer and van den Boom 2023). The result is a ratcheting effect that withdraws the nascent peptide from the 60S subunit. The extracted nascent peptide remains bound to the ribosome-associated quality control complex (RQC complex, LTN1:NEMF:TCF25:VCP hexamer) which dissociates from the 60S ribosomal subunit and escorts the nascent peptide to the proteasome (inferred from yeast homologs in Defenouillère et al. 2017). The region of the nascent peptide that is unfolded by the VCP hexamer is able to enter the proteasome, resulting in degradation of the nascent peptide (inferred from the yeast homolog CDC48 in Olszewski et al. 2019). After removal of the ubiquitinated nascent peptide and tRNA, and mRNA, the 60S subunit is able to be re-used in translation.

Literature Reactome attaches

Failure to Degrade CAT-Tailed Proteins Disrupts Neuronal Morphogenesis and Cell SurvivalCell Rep, 2021, vol. 34, p. 108599PubMed 33406423
Convergence of mammalian RQC and C-end rule proteolytic pathways via alanine tailingMol Cell, 2021, vol. 81, p. 2112-2122.e7PubMed 33909987
Protein synthesis. Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chainsScience, 2015, vol. 347, p. 75-8PubMed 25554787
CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptidesScience, 2017, vol. 357, p. 414-417PubMed 28751611
In vitro analysis of RQC activities provides insights into the mechanism and function of CAT tailingElife, 2017, vol. 6PubMed 28718767
Molecular basis of eIF5A-dependent CAT tailing in eukaryotic ribosome-associated quality controlMol Cell, 2023, vol. 83, p. 607-621.e4PubMed 36804914
The Rqc2/Tae2 subunit of the ribosome-associated quality control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation

Reactome's record lists 14 orthologous events, R-MMU-9954709 (Mus musculus), R-RNO-9954709 (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 2026-10-01 ET · Reactome pathway browser"Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9954709 with StableID: R-HSA-9954709.2 (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 103 genes in this human pathway; showing 1 to 100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneADRM1	AuthorityHGNC:15759	Mapping file id11047 NCBI file	EvidenceIEA, TAS
GeneANKZF1	AuthorityHGNC:25527	Mapping file id55139 NCBI file	EvidenceTAS
GeneCUL2	AuthorityHGNC:2552	Mapping file id8453 NCBI file	EvidenceTAS
GeneELOB	AuthorityHGNC:11619	Mapping file id6923 NCBI file	EvidenceTAS
GeneELOC	AuthorityHGNC:11617	Mapping file id6921 NCBI file	EvidenceTAS
GeneKLHDC10	AuthorityHGNC:22194	Mapping file id23008 NCBI file	EvidenceTAS
GeneLTN1	AuthorityHGNC:13082	Mapping file id26046 NCBI file	EvidenceIEA, TAS
GeneNEMF	AuthorityHGNC:10663	Mapping file id9147 NCBI file	EvidenceIEA, TAS
GeneNPLOC4	AuthorityHGNC:18261	Mapping file id55666 NCBI file	EvidenceIEA, TAS
GenePSMA1	AuthorityHGNC:9530	Mapping file id5682 NCBI file	EvidenceIEA, TAS
GenePSMA2	AuthorityHGNC:9531	Mapping file id5683 NCBI file	EvidenceIEA, TAS
GenePSMA3	AuthorityHGNC:9532	Mapping file id5684 NCBI file	EvidenceIEA, TAS
GenePSMA4	AuthorityHGNC:9533	Mapping file id5685 NCBI file	EvidenceIEA, TAS
GenePSMA5	AuthorityHGNC:9534	Mapping file id5686 NCBI file	EvidenceIEA, TAS
GenePSMA6	AuthorityHGNC:9535	Mapping file id5687 NCBI file	EvidenceIEA, TAS
GenePSMA7	AuthorityHGNC:9536	Mapping file id5688 NCBI file	EvidenceIEA, TAS
GenePSMB1	AuthorityHGNC:9537	Mapping file id5689 NCBI file	EvidenceIEA, TAS
GenePSMB2	AuthorityHGNC:9539	Mapping file id5690 NCBI file	EvidenceIEA, TAS
GenePSMB3	AuthorityHGNC:9540	Mapping file id5691 NCBI file	EvidenceIEA, TAS
GenePSMB4	AuthorityHGNC:9541	Mapping file id5692 NCBI file	EvidenceIEA, TAS
GenePSMB5	AuthorityHGNC:9542	Mapping file id5693 NCBI file	EvidenceIEA, TAS
GenePSMB6	AuthorityHGNC:9543	Mapping file id5694 NCBI file	EvidenceIEA, TAS
GenePSMB7	AuthorityHGNC:9544	Mapping file id5695 NCBI file	EvidenceIEA, TAS
GenePSMC1	AuthorityHGNC:9547	Mapping file id5700 NCBI file	EvidenceIEA, TAS
GenePSMC2	AuthorityHGNC:9548	Mapping file id5701 NCBI file	EvidenceIEA, TAS
GenePSMC3	AuthorityHGNC:9549	Mapping file id5702 NCBI file	EvidenceIEA, TAS
GenePSMC4	AuthorityHGNC:9551	Mapping file id5704 NCBI file	EvidenceIEA, TAS
GenePSMC5	AuthorityHGNC:9552	Mapping file id5705 NCBI file	EvidenceIEA, TAS
GenePSMC6	AuthorityHGNC:9553	Mapping file id5706 NCBI file	EvidenceIEA, TAS
GenePSMD1	AuthorityHGNC:9554	Mapping file id5707 NCBI file	EvidenceIEA, TAS
GenePSMD11	AuthorityHGNC:9556	Mapping file id5717 NCBI file	EvidenceIEA, TAS
GenePSMD12	AuthorityHGNC:9557	Mapping file id5718 NCBI file	EvidenceIEA, TAS
GenePSMD13	AuthorityHGNC:9558	Mapping file id5719 NCBI file	EvidenceIEA, TAS
GenePSMD14	AuthorityHGNC:16889	Mapping file id10213 NCBI file	EvidenceIEA, TAS
GenePSMD2	AuthorityHGNC:9559	Mapping file id5708 NCBI file	EvidenceIEA, TAS
GenePSMD3	AuthorityHGNC:9560	Mapping file id5709 NCBI file	EvidenceIEA, TAS
GenePSMD6	AuthorityHGNC:9564	Mapping file id9861 NCBI file	EvidenceIEA, TAS
GenePSMD7	AuthorityHGNC:9565	Mapping file id5713 NCBI file	EvidenceIEA, TAS
GenePSMD8	AuthorityHGNC:9566	Mapping file id5714 NCBI file	EvidenceIEA, TAS
GeneRBX1	AuthorityHGNC:9928	Mapping file id9978 NCBI file	EvidenceTAS
GeneRCHY1	AuthorityHGNC:17479	Mapping file id25898 NCBI file	EvidenceTAS
GeneRPL10	AuthorityHGNC:10298	Mapping file id6134 NCBI file	EvidenceIEA, TAS
GeneRPL10A	AuthorityHGNC:10299	Mapping file id4736 NCBI file	EvidenceIEA, TAS
GeneRPL10L	AuthorityHGNC:17976	Mapping file id140801 NCBI file	EvidenceIEA, TAS
GeneRPL11	AuthorityHGNC:10301	Mapping file id6135 NCBI file	EvidenceIEA, TAS
GeneRPL12	AuthorityHGNC:10302	Mapping file id6136 NCBI file	EvidenceIEA, TAS
GeneRPL13	AuthorityHGNC:10303	Mapping file id6137 NCBI file	EvidenceIEA, TAS
GeneRPL13A	AuthorityHGNC:10304	Mapping file id23521 NCBI file	EvidenceIEA, TAS
GeneRPL14	AuthorityHGNC:10305	Mapping file id9045 NCBI file	EvidenceIEA, TAS
GeneRPL15	AuthorityHGNC:10306	Mapping file id6138 NCBI file	EvidenceIEA, TAS
GeneRPL17	AuthorityHGNC:10307	Mapping file id6139 NCBI file	EvidenceIEA, TAS
GeneRPL18	AuthorityHGNC:10310	Mapping file id6141 NCBI file	EvidenceIEA, TAS
GeneRPL18A	AuthorityHGNC:10311	Mapping file id6142 NCBI file	EvidenceIEA, TAS
GeneRPL19	AuthorityHGNC:10312	Mapping file id6143 NCBI file	EvidenceIEA, TAS
GeneRPL21	AuthorityHGNC:10313	Mapping file id6144 NCBI file	EvidenceIEA, TAS
GeneRPL22	AuthorityHGNC:10315	Mapping file id6146 NCBI file	EvidenceIEA, TAS
GeneRPL22L1	AuthorityHGNC:27610	Mapping file id200916 NCBI file	EvidenceIEA, TAS
GeneRPL23	AuthorityHGNC:10316	Mapping file id9349 NCBI file	EvidenceIEA, TAS
GeneRPL23A	AuthorityHGNC:10317	Mapping file id6147 NCBI file	EvidenceIEA, TAS
GeneRPL24	AuthorityHGNC:10325	Mapping file id6152 NCBI file	EvidenceIEA, TAS
GeneRPL26	AuthorityHGNC:10327	Mapping file id6154 NCBI file	EvidenceIEA, TAS
GeneRPL26L1	AuthorityHGNC:17050	Mapping file id51121 NCBI file	EvidenceIEA, TAS
GeneRPL27	AuthorityHGNC:10328	Mapping file id6155 NCBI file	EvidenceIEA, TAS
GeneRPL27A	AuthorityHGNC:10329	Mapping file id6157 NCBI file	EvidenceIEA, TAS
GeneRPL28	AuthorityHGNC:10330	Mapping file id6158 NCBI file	EvidenceIEA, TAS
GeneRPL29	AuthorityHGNC:10331	Mapping file id6159 NCBI file	EvidenceIEA, TAS
GeneRPL3	AuthorityHGNC:10332	Mapping file id6122 NCBI file	EvidenceIEA, TAS
GeneRPL30	AuthorityHGNC:10333	Mapping file id6156 NCBI file	EvidenceIEA, TAS
GeneRPL31	AuthorityHGNC:10334	Mapping file id6160 NCBI file	EvidenceIEA, TAS
GeneRPL32	AuthorityHGNC:10336	Mapping file id6161 NCBI file	EvidenceIEA, TAS
GeneRPL34	AuthorityHGNC:10340	Mapping file id6164 NCBI file	EvidenceIEA, TAS
GeneRPL35	AuthorityHGNC:10344	Mapping file id11224 NCBI file	EvidenceIEA, TAS
GeneRPL35A	AuthorityHGNC:10345	Mapping file id6165 NCBI file	EvidenceIEA, TAS
GeneRPL36	AuthorityHGNC:13631	Mapping file id25873 NCBI file	EvidenceIEA, TAS
GeneRPL36A	AuthorityHGNC:10359	Mapping file id6173 NCBI file	EvidenceIEA, TAS
GeneRPL36AL	AuthorityHGNC:10346	Mapping file id6166 NCBI file	EvidenceIEA, TAS
GeneRPL37	AuthorityHGNC:10347	Mapping file id6167 NCBI file	EvidenceIEA, TAS
GeneRPL37A	AuthorityHGNC:10348	Mapping file id6168 NCBI file	EvidenceIEA, TAS
GeneRPL38	AuthorityHGNC:10349	Mapping file id6169 NCBI file	EvidenceIEA, TAS
GeneRPL39	AuthorityHGNC:10350	Mapping file id6170 NCBI file	EvidenceIEA, TAS
GeneRPL39L	AuthorityHGNC:17094	Mapping file id116832 NCBI file	EvidenceIEA, TAS
GeneRPL3L	AuthorityHGNC:10351	Mapping file id6123 NCBI file	EvidenceIEA, TAS
GeneRPL4	AuthorityHGNC:10353	Mapping file id6124 NCBI file	EvidenceIEA, TAS
GeneRPL41	AuthorityHGNC:10354	Mapping file id6171 NCBI file	EvidenceIEA, TAS
GeneRPL5	AuthorityHGNC:10360	Mapping file id6125 NCBI file	EvidenceIEA, TAS
GeneRPL6	AuthorityHGNC:10362	Mapping file id6128 NCBI file	EvidenceIEA, TAS
GeneRPL7	AuthorityHGNC:10363	Mapping file id6129 NCBI file	EvidenceIEA, TAS
GeneRPL7A	AuthorityHGNC:10364	Mapping file id6130 NCBI file	EvidenceIEA, TAS
GeneRPL8	AuthorityHGNC:10368	Mapping file id6132 NCBI file	EvidenceIEA, TAS
GeneRPL9	AuthorityHGNC:10369	Mapping file id6133 NCBI file	EvidenceIEA, TAS
GeneRPLP0	AuthorityHGNC:10371	Mapping file id6175 NCBI file	EvidenceIEA, TAS
GeneRPLP1	AuthorityHGNC:10372	Mapping file id6176 NCBI file	EvidenceIEA, TAS
GeneRPLP2	AuthorityHGNC:10377	Mapping file id6181 NCBI file	EvidenceIEA, TAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA, TAS
GeneSEM1	AuthorityHGNC:10845	Mapping file id7979 NCBI file	EvidenceIEA, TAS
GeneTCF25	AuthorityHGNC:29181	Mapping file id22980 NCBI file	EvidenceIEA, TAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceIEA, TAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceIEA, TAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceIEA, TAS
GeneUBE2D1	AuthorityHGNC:12474	Mapping file id7321 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

Ribosome-associated quality controlR-HSA-9948299145 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.