Pathway Human Homo sapiens

Neddylation

R-HSA-8951664 in Reactome release 97: under Post-translational protein modification, with 234 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-8951664 (mouse), R-RNO-8951664 (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-8951664.7
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2017-03-27
Last updated: 2022-12-07
Events inside: 44, counted from the record

NEDD8 is a small ubiquitin-like molecule that is conjugated to substrate proteins through an E1 to E3 enzyme cascade similar to that for ubiquitin. The best characterized target of neddylation is the cullin scaffold subunit of cullin-RING E3 ubiquitin ligases (CRLs), which themselves target numerous cellular proteins for degradation by the proteasome (Hori et al, 1999; reviewed in Soucy et al, 2010; Lyedeard et al, 2013). The multisubunit CRL complexes are compositionally diverse, but each contains a scaffolding cullin protein (CUL1, 2, 3, 4A, 4B, 5, 7 or 9) and a RING box-containing E3 ligase subunit RBX, along with other adaptor and substrate-interacting subunits. RBX2 (also known as RNF7) interacts preferentially with CUL5, while RBX1 is the primary E3 for most other cullin family members (reviewed in Mahon et al, 2014). Neddylation of the cullin subunit increases the ubiquitination activity of the CRL complex (Podust et al, 2000; Read et al, 2000; Wu et al, 2000; Kawakami et al, 2001; Ohh et al, 2002; Yu et al, 2015). In addition to CRL complexes, a number of other less-well characterized NEDD8 targets have been identified. These include other E3 ubiquitin ligases such as SMURF1 and MDM2, receptor tyrosine kinases such as EGFR and TGF beta RII, and proteins that contribute to transcriptional regulation, among others (Xie et al, 2014; Watson et al, 2010; Oved et al, 2006; Zuo et al, 2013; Xirodimas et al, 2004; Singh et al, 2007; Abida et al, 2007; Liu et al 2010; Watson et al, 2006; Loftus et al, 2012; Aoki et al, 2013; reviewed in Enchev et al, 2015).

Like ubiquitin, NEDD8 undergoes post-translational processing to generate the mature form. UCHL3- or SENP8-mediated proteolysis removes the C-terminal 5 amino acids of NEDD8, generating a novel C-terminal glycine residue for conjugation to the cysteine residues in the E1, E2 enzymes or lysine residues in the substrate protein, usually the E3 NEDD8 ligase itself (Wada et al, 1998; reviewed in Enchev et al, 2015). Most substrates in vivo appear to be singly neddylated on one or more lysine residues, but NEDD8 chains have been formed on cullin substrates in vitro and on histone H4 in cultured human cells after DNA damage (Jones et al, 2008; Ohki et al, 2009; Xirodimas et al, 2008; Jeram et al, 2010; Ma et al, 2013; reviewed in Enchev et al, 2015). The significance of NEDD8 chains is still not clear.

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 234 genes in this human pathway; showing 201 to 234, in pages of 100, sorted by symbol for reading. The order carries no ranking. 1 of the rows shown carries an id the identity file does not name, kept as the source wrote it.

Genes Reactome places in this human pathway, page 3 of 3
Gene	Authority id	Mapping file id	Evidence codes
GeneSENP8	AuthorityHGNC:22992	Mapping file id123228 NCBI file	EvidenceTAS
GeneSKP1	AuthorityHGNC:10899	Mapping file id6500 NCBI file	EvidenceTAS
GeneSKP2	AuthorityHGNC:10901	Mapping file id6502 NCBI file	EvidenceTAS
GeneSOCS2	AuthorityHGNC:19382	Mapping file id8835 NCBI file	EvidenceTAS
GeneSOCS3	AuthorityHGNC:19391	Mapping file id9021 NCBI file	EvidenceTAS
GeneSOCS5	AuthorityHGNC:16852	Mapping file id9655 NCBI file	EvidenceTAS
GeneSOCS6	AuthorityHGNC:16833	Mapping file id9306 NCBI file	EvidenceTAS
GeneSPSB1	AuthorityHGNC:30628	Mapping file id80176 NCBI file	EvidenceTAS
GeneSPSB2	AuthorityHGNC:29522	Mapping file id84727 NCBI file	EvidenceTAS
GeneSPSB3	AuthorityHGNC:30629	Mapping file id90864 NCBI file	EvidenceTAS
GeneSPSB4	AuthorityHGNC:30630	Mapping file id92369 NCBI file	EvidenceTAS
GeneSQSTM1	AuthorityHGNC:11280	Mapping file id8878 NCBI file	EvidenceTAS
GeneTULP4	AuthorityHGNC:15530	Mapping file id56995 NCBI file	EvidenceTAS
GeneUBA3	AuthorityHGNC:12470	Mapping file id9039 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceTAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceTAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceTAS
GeneUBD	AuthorityHGNC:18795	Mapping file id10537 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
GeneUBE2F	AuthorityHGNC:12480	Mapping file id140739 NCBI file	EvidenceTAS
GeneUBE2M	AuthorityHGNC:12491	Mapping file id9040 NCBI file	EvidenceTAS
GeneUBXN7	AuthorityHGNC:29119	Mapping file id26043 NCBI file	EvidenceTAS
GeneUCHL3	AuthorityHGNC:12515	Mapping file id7347 NCBI file	EvidenceTAS
GeneUFD1	AuthorityHGNC:12520	Mapping file id7353 NCBI file	EvidenceTAS
GeneVCP	AuthorityHGNC:12666	Mapping file id7415 NCBI file	EvidenceTAS
GeneVHL	AuthorityHGNC:12687	Mapping file id7428 NCBI file	EvidenceTAS
GeneWDR5	AuthorityHGNC:12757	Mapping file id11091 NCBI file	EvidenceTAS
GeneWDTC1	AuthorityHGNC:29175	Mapping file id23038 NCBI file	EvidenceTAS
GeneWSB1	AuthorityHGNC:19221	Mapping file id26118 NCBI file	EvidenceTAS
GeneWSB2	AuthorityHGNC:19222	Mapping file id55884 NCBI file	EvidenceTAS
GeneZBTB16	AuthorityHGNC:12930	Mapping file id7704 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id944566 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

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