Pathway Human Homo sapiens

RAB GEFs exchange GTP for GDP on RABs

R-HSA-8876198 in Reactome release 97: under Rab regulation of trafficking, with 90 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-8876198 (mouse), R-RNO-8876198 (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-8876198.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-09-19
Events inside: 21, counted from the record

Human cells have more than 60 RAB proteins that are key regulators of intracellular membrane trafficking. These small GTPases contribute to trafficking specificity by localizing to the membranes of different organelles and interacting with effectors such as sorting adaptors, tethering factors, kinases, phosphatases and tubular-vesicular cargo (reviewed in Stenmark et al, 2009; Wandinger-Ness and Zerial, 2014; Zhen and Stenmark, 2015).

RAB localization depends on a number of factors including C-terminal prenylation, the sequence of upstream hypervariable regions and what nucleotide is bound, as well as interaction with RAB-interacting proteins (Chavrier et al, 1991; Ullrich et al, 1993; Soldati et al, 1994; Farnsworth et al, 1994; Seabra, 1996; Wu et al, 2010; reviewed in Stenmark, 2009; Wandinger-Ness and Zerial, 2014). More recently, the activity of RAB GEFs has also been implicated in regulating the localization of RAB proteins (Blumer et al, 2103; Schoebel et al, 2009; Cabrera and Ungermann, 2013; reviewed in Barr, 2013; Zhen and Stenmark, 2015)

In the active, GTP-bound form, RAB proteins are membrane-associated, while in the inactive GDP-bound form, RABs are extracted from the target membrane and exist in a soluble form in complex with GDP dissociation inhibitors (GDIs) (Ullrich et al, 1993; Soldati et al, 1994; Gavriljuk et al, 2013). Conversion between the inactive and active form relies on the activities of RAB guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) (Yoshimura et al, 2010; Wu et al, 2011; Pan et al, 2006; Frasa et al, 2012; reviewed in Stenmark, 2009; Wandinger-Ness and Zerial, 2014; Ishida et al, 2016).

Newly synthesized RABs are bound to a RAB escort protein, CHM (also known as REP1) or CHML (REP2) (Alexandrov et al, 1994; Shen and Seabra, 1996). CHM/REP proteins are the substrate-binding component of the trimeric RAB geranylgeranyltransferase enzyme (GGTaseII) along with the two catalytic subunits RABGGTA and RABGGTB (reviewed in Gutkowska and Swiezewska, 2012; Palsuledesai and Distefano, 2015). REP proteins recruit the unmodified RAB in its GDP-bound state to the GGTase for sequential geranylgeranylation at one or two C-terminal cysteine residues (Alexandrov et al, 1994; Seabra et al 1996; Shen and Seabra, 1996; Baron and Seabra, 2008). After geranylation, CHM/REP proteins remain in complex with the geranylated RAB and escort it to its target membrane, where RAB activity is regulated by GAPs, GEFs, GDIs and membrane-bound GDI displacement factors (GDFs) (Sivars et al, 2003; reviewed in Stenmark, 2009; Wandinger-Ness and Zerial, 2014).

Unlike the RAB GAPS, which (to date) all contain a shared TBC domain, RAB GEFs are structurally diverse and range from monomeric to multisubunit complexes (reviewed in Fukuda et al, 2011; Frasa et al, 2012; Cherfils and Zeghouf, 2013; Ishida et al, 2016). While many GEFs contain one of three conserved GEF domains identified to date - the DENN (differentially expressed in normal and neoplastic cell) domain, the VPS9 domain and the SEC2 domain- other GEFs lack a conserved domain (reviewed in Ishida et al, 2016). Based on sequence conservation and subunit organization, GEFs can be grouped into 6 general classes: the DENND-containing GEFs, the VPS9-containing GEFs (both monomeric), the SEC2-containing GEFs (homodimeric), heterodimeric GEF complexes such as RIC1:RGP1, the multisubunit TRAPPC GEF, and others (reviewed in Barr and Lambright, 2010; Marat et al, 2011; Ishida et al, 2016). GEFs for many RABs have still not been identified, however.

Literature Reactome attaches

Rab GTPases as coordinators of vesicle trafficNat. Rev. Mol. Cell Biol., 2009, vol. 10, p. 513-25PubMed 19603039
Rab proteins and the compartmentalization of the endosomal systemCold Spring Harb Perspect Biol, 2014, vol. 6, p. a022616PubMed 25341920
Hypervariable C-terminal domain of rab proteins acts as a targeting signalNature, 1991, vol. 353, p. 769-72PubMed 1944536
Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteinsJ. Biol. Chem., 1993, vol. 268, p. 18143-50PubMed 8349690
Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchangeNature, 1994, vol. 369, p. 76-8PubMed 8164745
Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5AProc. Natl. Acad. Sci. U.S.A., 1994, vol. 91, p. 11963-7PubMed 7991565
Nucleotide dependence of Rab geranylgeranylation. Rab escort protein interacts preferentially with GDP-bound RabJ. Biol. Chem., 1996, vol. 271, p. 14398-404

Reactome's record lists 14 orthologous events, R-MMU-8876198 (Mus musculus), R-RNO-8876198 (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 2026-10-03 ET · Reactome pathway browser"RAB GEFs exchange GTP for GDP on RABs". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-8876198 with StableID: R-HSA-8876198.4 (accessed 2026-10-03 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 90 genes in this human pathway; showing 1 to 90, 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
GeneAKT1	AuthorityHGNC:391	Mapping file id207 NCBI file	EvidenceTAS
GeneAKT2	AuthorityHGNC:392	Mapping file id208 NCBI file	EvidenceTAS
GeneAKT3	AuthorityHGNC:393	Mapping file id10000 NCBI file	EvidenceTAS
GeneALS2	AuthorityHGNC:443	Mapping file id57679 NCBI file	EvidenceTAS
GeneALS2CL	AuthorityHGNC:20605	Mapping file id259173 NCBI file	EvidenceTAS
GeneANKRD27	AuthorityHGNC:25310	Mapping file id84079 NCBI file	EvidenceTAS
GeneCCZ1	AuthorityHGNC:21691	Mapping file id51622 NCBI file	EvidenceTAS
GeneCCZ1B	AuthorityHGNC:21717	Mapping file id221960 NCBI file	EvidenceTAS
GeneCHM	AuthorityHGNC:1940	Mapping file id1121 NCBI file	EvidenceTAS
GeneCHML	AuthorityHGNC:1941	Mapping file id1122 NCBI file	EvidenceTAS
GeneDENND1A	AuthorityHGNC:29324	Mapping file id57706 NCBI file	EvidenceTAS
GeneDENND1B	AuthorityHGNC:28404	Mapping file id163486 NCBI file	EvidenceTAS
GeneDENND1C	AuthorityHGNC:26225	Mapping file id79958 NCBI file	EvidenceTAS
GeneDENND2A	AuthorityHGNC:22212	Mapping file id27147 NCBI file	EvidenceTAS
GeneDENND2B	AuthorityHGNC:11350	Mapping file id6764 NCBI file	EvidenceTAS
GeneDENND2C	AuthorityHGNC:24748	Mapping file id163259 NCBI file	EvidenceTAS
GeneDENND2D	AuthorityHGNC:26192	Mapping file id79961 NCBI file	EvidenceTAS
GeneDENND3	AuthorityHGNC:29134	Mapping file id22898 NCBI file	EvidenceTAS
GeneDENND4A	AuthorityHGNC:24321	Mapping file id10260 NCBI file	EvidenceTAS
GeneDENND4B	AuthorityHGNC:29044	Mapping file id9909 NCBI file	EvidenceTAS
GeneDENND4C	AuthorityHGNC:26079	Mapping file id55667 NCBI file	EvidenceTAS
GeneDENND5A	AuthorityHGNC:19344	Mapping file id23258 NCBI file	EvidenceTAS
GeneDENND5B	AuthorityHGNC:28338	Mapping file id160518 NCBI file	EvidenceTAS
GeneDENND6A	AuthorityHGNC:26635	Mapping file id201627 NCBI file	EvidenceTAS
GeneDENND6B	AuthorityHGNC:32690	Mapping file id414918 NCBI file	EvidenceTAS
GeneGAPVD1	AuthorityHGNC:23375	Mapping file id26130 NCBI file	EvidenceTAS
GeneGDI1	AuthorityHGNC:4226	Mapping file id2664 NCBI file	EvidenceTAS
GeneGDI2	AuthorityHGNC:4227	Mapping file id2665 NCBI file	EvidenceTAS
GeneHPS1	AuthorityHGNC:5163	Mapping file id3257 NCBI file	EvidenceTAS
GeneHPS4	AuthorityHGNC:15844	Mapping file id89781 NCBI file	EvidenceTAS
GeneMADD	AuthorityHGNC:6766	Mapping file id8567 NCBI file	EvidenceTAS
GeneMON1A	AuthorityHGNC:28207	Mapping file id84315 NCBI file	EvidenceTAS
GeneMON1B	AuthorityHGNC:25020	Mapping file id22879 NCBI file	EvidenceTAS
GeneRAB10	AuthorityHGNC:9759	Mapping file id10890 NCBI file	EvidenceTAS
GeneRAB12	AuthorityHGNC:31332	Mapping file id201475 NCBI file	EvidenceTAS
GeneRAB13	AuthorityHGNC:9762	Mapping file id5872 NCBI file	EvidenceTAS
GeneRAB14	AuthorityHGNC:16524	Mapping file id51552 NCBI file	EvidenceTAS
GeneRAB18	AuthorityHGNC:14244	Mapping file id22931 NCBI file	EvidenceTAS
GeneRAB1A	AuthorityHGNC:9758	Mapping file id5861 NCBI file	EvidenceTAS
GeneRAB1B	AuthorityHGNC:18370	Mapping file id81876 NCBI file	EvidenceTAS
GeneRAB21	AuthorityHGNC:18263	Mapping file id23011 NCBI file	EvidenceTAS
GeneRAB27A	AuthorityHGNC:9766	Mapping file id5873 NCBI file	EvidenceTAS
GeneRAB27B	AuthorityHGNC:9767	Mapping file id5874 NCBI file	EvidenceTAS
GeneRAB31	AuthorityHGNC:9771	Mapping file id11031 NCBI file	EvidenceTAS
GeneRAB32	AuthorityHGNC:9772	Mapping file id10981 NCBI file	EvidenceTAS
GeneRAB35	AuthorityHGNC:9774	Mapping file id11021 NCBI file	EvidenceTAS
GeneRAB38	AuthorityHGNC:9776	Mapping file id23682 NCBI file	EvidenceTAS
GeneRAB39A	AuthorityHGNC:16521	Mapping file id54734 NCBI file	EvidenceTAS
GeneRAB39B	AuthorityHGNC:16499	Mapping file id116442 NCBI file	EvidenceTAS
GeneRAB3A	AuthorityHGNC:9777	Mapping file id5864 NCBI file	EvidenceTAS
GeneRAB3GAP1	AuthorityHGNC:17063	Mapping file id22930 NCBI file	EvidenceTAS
GeneRAB3GAP2	AuthorityHGNC:17168	Mapping file id25782 NCBI file	EvidenceTAS
GeneRAB3IL1	AuthorityHGNC:9780	Mapping file id5866 NCBI file	EvidenceTAS
GeneRAB3IP	AuthorityHGNC:16508	Mapping file id117177 NCBI file	EvidenceTAS
GeneRAB5A	AuthorityHGNC:9783	Mapping file id5868 NCBI file	EvidenceTAS
GeneRAB5B	AuthorityHGNC:9784	Mapping file id5869 NCBI file	EvidenceTAS
GeneRAB5C	AuthorityHGNC:9785	Mapping file id5878 NCBI file	EvidenceTAS
GeneRAB6A	AuthorityHGNC:9786	Mapping file id5870 NCBI file	EvidenceTAS
GeneRAB6B	AuthorityHGNC:14902	Mapping file id51560 NCBI file	EvidenceTAS
GeneRAB7A	AuthorityHGNC:9788	Mapping file id7879 NCBI file	EvidenceTAS
GeneRAB7B	AuthorityHGNC:30513	Mapping file id338382 NCBI file	EvidenceTAS
GeneRAB8A	AuthorityHGNC:7007	Mapping file id4218 NCBI file	EvidenceTAS
GeneRAB8B	AuthorityHGNC:30273	Mapping file id51762 NCBI file	EvidenceTAS
GeneRAB9A	AuthorityHGNC:9792	Mapping file id9367 NCBI file	EvidenceTAS
GeneRAB9B	AuthorityHGNC:14090	Mapping file id51209 NCBI file	EvidenceTAS
GeneRABGEF1	AuthorityHGNC:17676	Mapping file id27342 NCBI file	EvidenceTAS
GeneRGP1	AuthorityHGNC:21965	Mapping file id9827 NCBI file	EvidenceTAS
GeneRIC1	AuthorityHGNC:17686	Mapping file id57589 NCBI file	EvidenceTAS
GeneRIN1	AuthorityHGNC:18749	Mapping file id9610 NCBI file	EvidenceTAS
GeneRIN2	AuthorityHGNC:18750	Mapping file id54453 NCBI file	EvidenceTAS
GeneRIN3	AuthorityHGNC:18751	Mapping file id79890 NCBI file	EvidenceTAS
GeneRINL	AuthorityHGNC:24795	Mapping file id126432 NCBI file	EvidenceTAS
GeneSBF1	AuthorityHGNC:10542	Mapping file id6305 NCBI file	EvidenceTAS
GeneSBF2	AuthorityHGNC:2135	Mapping file id81846 NCBI file	EvidenceTAS
GeneTRAPPC1	AuthorityHGNC:19894	Mapping file id58485 NCBI file	EvidenceTAS
GeneTRAPPC10	AuthorityHGNC:11868	Mapping file id7109 NCBI file	EvidenceTAS
GeneTRAPPC11	AuthorityHGNC:25751	Mapping file id60684 NCBI file	EvidenceTAS
GeneTRAPPC12	AuthorityHGNC:24284	Mapping file id51112 NCBI file	EvidenceTAS
GeneTRAPPC13	AuthorityHGNC:25828	Mapping file id80006 NCBI file	EvidenceTAS
GeneTRAPPC2	AuthorityHGNC:23068	Mapping file id6399 NCBI file	EvidenceTAS
GeneTRAPPC2L	AuthorityHGNC:30887	Mapping file id51693 NCBI file	EvidenceTAS
GeneTRAPPC3	AuthorityHGNC:19942	Mapping file id27095 NCBI file	EvidenceTAS
GeneTRAPPC4	AuthorityHGNC:19943	Mapping file id51399 NCBI file	EvidenceTAS
GeneTRAPPC5	AuthorityHGNC:23067	Mapping file id126003 NCBI file	EvidenceTAS
GeneTRAPPC6A	AuthorityHGNC:23069	Mapping file id79090 NCBI file	EvidenceTAS
GeneTRAPPC6B	AuthorityHGNC:23066	Mapping file id122553 NCBI file	EvidenceTAS
GeneTRAPPC8	AuthorityHGNC:29169	Mapping file id22878 NCBI file	EvidenceTAS
GeneTRAPPC9	AuthorityHGNC:30832	Mapping file id83696 NCBI file	EvidenceTAS
GeneULK1	AuthorityHGNC:12558	Mapping file id8408 NCBI file	EvidenceTAS
GeneYWHAE	AuthorityHGNC:12851	Mapping file id7531 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

Rab regulation of traffickingR-HSA-9007101123 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.