Pathway Human Homo sapiens

Clathrin-mediated endocytosis

R-HSA-8856828 in Reactome release 97: under Membrane Trafficking, with 146 genes placed in it by the mapping files and 1 child pathway 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-8856828 (mouse), R-RNO-8856828 (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-8856828.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-06-15
Last updated: 2020-09-24
Events inside: 21, counted from the record

Clathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1975; reviewed in Robinson, 2015; McMahon and Boucrot, 2011; Kirchhausen et al, 2014). CME contributes to signal transduction by regulating the cell surface expression and signaling of receptor tyrosine kinases (RTKs) and G-protein coupled receptors (GPCRs). Most RTKs exhibit a robust increase in internalization rate after binding specific ligands; however, some RTKs may also exhibit significant ligand-independent internalization (reviewed in Goh and Sorkin, 2013). CME controls RTK and GPCR signaling by organizing signaling both within the plasma membrane and on endosomes (reviewed in Eichel et al, 2016; Garay et al, 2015; Vieira et al, 1996; Sorkin and von Zastrow, 2014; Di Fiori and von Zastrow, 2014; Barbieri et al, 2016). CME also contributes to the uptake of material such as metabolites, hormones and other proteins from the extracellular space, and regulates membrane composition by recycling membrane components and/or targeting them for degradation.

Clathrin-mediated endocytosis involves initiation of clathrin-coated pit (CCP) formation, cargo selection, coat assembly and stabilization, membrane scission and vesicle uncoating. Although for simplicity in this pathway, the steps leading to a mature CCP are represented in a linear and temporally distinct fashion, the formation of a clathrin-coated vesicle is a highly heterogeneous process and clear temporal boundaries between these processes may not exist (see for instance Taylor et al, 2011; Antonescu et al, 2011; reviewed in Kirchhausen et al, 2014). Cargo selection in particular is a critical aspect of the formation of a mature and stable CCP, and many of the proteins involved in the initiation and maturation of a CCP contribute to cargo selection and are themselves stabilized upon incorporation of cargo into the nascent vesicle (reviewed in Kirchhausen et al, 2014; McMahon and Boucrot, 2011).

Although the clathrin triskelion was identified early as a major component of the coated vesicles, clathrin does not bind directly to membranes or to the endocytosed cargo. Vesicle formation instead relies on many proteins and adaptors that can bind the plasma membrane and interact with cargo molecules. Cargo selection depends on the recognition of endocytic signals in cytoplasmic tails of the cargo proteins by adaptors that interact with components of the vesicle's inner coat. The classic adaptor for clathrin-coated vesicles is the tetrameric AP-2 complex, which along with clathrin was identified early as a major component of the coat. Some cargo indeed bind directly to AP-2, but subsequent work has revealed a large family of proteins collectively known as CLASPs (clathrin- associated sorting proteins) that mediate the recruitment of diverse cargo into the emerging clathrin-coated vesicles (reviewed in Traub and Bonifacino, 2013). Many of these CLASP proteins themselves interact with AP-2 and clathrin, coordinating cargo recruitment with coat formation (Schmid et al, 2006; Edeling et al, 2006; reviewed in Traub and Bonifacino, 2013; Kirchhausen et al, 2014).

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 146 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
GeneAAK1	AuthorityHGNC:19679	Mapping file id22848 NCBI file	EvidenceTAS
GeneACTB	AuthorityHGNC:132	Mapping file id60 NCBI file	EvidenceTAS
GeneACTG1	AuthorityHGNC:144	Mapping file id71 NCBI file	EvidenceTAS
GeneACTR2	AuthorityHGNC:169	Mapping file id10097 NCBI file	EvidenceTAS
GeneACTR3	AuthorityHGNC:170	Mapping file id10096 NCBI file	EvidenceTAS
GeneADRB2	AuthorityHGNC:286	Mapping file id154 NCBI file	EvidenceTAS
GeneAGFG1	AuthorityHGNC:5175	Mapping file id3267 NCBI file	EvidenceTAS
GeneAGTR1	AuthorityHGNC:336	Mapping file id185 NCBI file	EvidenceTAS
GeneAMPH	AuthorityHGNC:471	Mapping file id273 NCBI file	EvidenceTAS
GeneAP2A1	AuthorityHGNC:561	Mapping file id160 NCBI file	EvidenceTAS
GeneAP2A2	AuthorityHGNC:562	Mapping file id161 NCBI file	EvidenceTAS
GeneAP2B1	AuthorityHGNC:563	Mapping file id163 NCBI file	EvidenceTAS
GeneAP2M1	AuthorityHGNC:564	Mapping file id1173 NCBI file	EvidenceTAS
GeneAP2S1	AuthorityHGNC:565	Mapping file id1175 NCBI file	EvidenceTAS
GeneAPOB	AuthorityHGNC:603	Mapping file id338 NCBI file	EvidenceTAS
GeneAREG	AuthorityHGNC:651	Mapping file id374 NCBI file	EvidenceTAS
GeneARF6	AuthorityHGNC:659	Mapping file id382 NCBI file	EvidenceTAS
GeneARFGAP1	AuthorityHGNC:15852	Mapping file id55738 NCBI file	EvidenceTAS
GeneARPC1A	AuthorityHGNC:703	Mapping file id10552 NCBI file	EvidenceTAS
GeneARPC2	AuthorityHGNC:705	Mapping file id10109 NCBI file	EvidenceTAS
GeneARPC3	AuthorityHGNC:706	Mapping file id10094 NCBI file	EvidenceTAS
GeneARPC4	AuthorityHGNC:707	Mapping file id10093 NCBI file	EvidenceTAS
GeneARPC5	AuthorityHGNC:708	Mapping file id10092 NCBI file	EvidenceTAS
GeneARRB1	AuthorityHGNC:711	Mapping file id408 NCBI file	EvidenceTAS
GeneARRB2	AuthorityHGNC:712	Mapping file id409 NCBI file	EvidenceTAS
GeneAVP	AuthorityHGNC:894	Mapping file id551 NCBI file	EvidenceTAS
GeneAVPR2	AuthorityHGNC:897	Mapping file id554 NCBI file	EvidenceTAS
GeneBIN1	AuthorityHGNC:1052	Mapping file id274 NCBI file	EvidenceTAS
GeneBTC	AuthorityHGNC:1121	Mapping file id685 NCBI file	EvidenceTAS
GeneCBL	AuthorityHGNC:1541	Mapping file id867 NCBI file	EvidenceTAS
GeneCD3D	AuthorityHGNC:1673	Mapping file id915 NCBI file	EvidenceTAS
GeneCD3G	AuthorityHGNC:1675	Mapping file id917 NCBI file	EvidenceTAS
GeneCD4	AuthorityHGNC:1678	Mapping file id920 NCBI file	EvidenceTAS
GeneCFTR	AuthorityHGNC:1884	Mapping file id1080 NCBI file	EvidenceTAS
GeneCHRM2	AuthorityHGNC:1951	Mapping file id1129 NCBI file	EvidenceTAS
GeneCLTA	AuthorityHGNC:2090	Mapping file id1211 NCBI file	EvidenceTAS
GeneCLTB	AuthorityHGNC:2091	Mapping file id1212 NCBI file	EvidenceTAS
GeneCLTC	AuthorityHGNC:2092	Mapping file id1213 NCBI file	EvidenceTAS
GeneCLTCL1	AuthorityHGNC:2093	Mapping file id8218 NCBI file	EvidenceTAS
GeneCOPS2	AuthorityHGNC:30747	Mapping file id9318 NCBI file	EvidenceTAS
GeneCOPS3	AuthorityHGNC:2239	Mapping file id8533 NCBI file	EvidenceTAS
GeneCOPS4	AuthorityHGNC:16702	Mapping file id51138 NCBI file	EvidenceTAS
GeneCOPS5	AuthorityHGNC:2240	Mapping file id10987 NCBI file	EvidenceTAS
GeneCOPS6	AuthorityHGNC:21749	Mapping file id10980 NCBI file	EvidenceTAS
GeneCOPS7A	AuthorityHGNC:16758	Mapping file id50813 NCBI file	EvidenceTAS
GeneCOPS7B	AuthorityHGNC:16760	Mapping file id64708 NCBI file	EvidenceTAS
GeneCOPS8	AuthorityHGNC:24335	Mapping file id10920 NCBI file	EvidenceTAS
GeneCTTN	AuthorityHGNC:3338	Mapping file id2017 NCBI file	EvidenceTAS
GeneDAB2	AuthorityHGNC:2662	Mapping file id1601 NCBI file	EvidenceTAS
GeneDNAJC6	AuthorityHGNC:15469	Mapping file id9829 NCBI file	EvidenceTAS
GeneDNM1	AuthorityHGNC:2972	Mapping file id1759 NCBI file	EvidenceTAS
GeneDNM2	AuthorityHGNC:2974	Mapping file id1785 NCBI file	EvidenceTAS
GeneDNM3	AuthorityHGNC:29125	Mapping file id26052 NCBI file	EvidenceTAS
GeneDVL2	AuthorityHGNC:3086	Mapping file id1856 NCBI file	EvidenceTAS
GeneEGF	AuthorityHGNC:3229	Mapping file id1950 NCBI file	EvidenceTAS
GeneEGFR	AuthorityHGNC:3236	Mapping file id1956 NCBI file	EvidenceTAS
GeneEPGN	AuthorityHGNC:17470	Mapping file id255324 NCBI file	EvidenceTAS
GeneEPN1	AuthorityHGNC:21604	Mapping file id29924 NCBI file	EvidenceTAS
GeneEPN2	AuthorityHGNC:18639	Mapping file id22905 NCBI file	EvidenceTAS
GeneEPS15	AuthorityHGNC:3419	Mapping file id2060 NCBI file	EvidenceTAS
GeneEPS15L1	AuthorityHGNC:24634	Mapping file id58513 NCBI file	EvidenceTAS
GeneEREG	AuthorityHGNC:3443	Mapping file id2069 NCBI file	EvidenceTAS
GeneFCHO1	AuthorityHGNC:29002	Mapping file id23149 NCBI file	EvidenceTAS
GeneFCHO2	AuthorityHGNC:25180	Mapping file id115548 NCBI file	EvidenceTAS
GeneFNBP1	AuthorityHGNC:17069	Mapping file id23048 NCBI file	EvidenceTAS
GeneFNBP1L	AuthorityHGNC:20851	Mapping file id54874 NCBI file	EvidenceTAS
GeneFZD4	AuthorityHGNC:4042	Mapping file id8322 NCBI file	EvidenceTAS
GeneGAK	AuthorityHGNC:4113	Mapping file id2580 NCBI file	EvidenceTAS
GeneGAPVD1	AuthorityHGNC:23375	Mapping file id26130 NCBI file	EvidenceTAS
GeneGPS1	AuthorityHGNC:4549	Mapping file id2873 NCBI file	EvidenceTAS
GeneGRB2	AuthorityHGNC:4566	Mapping file id2885 NCBI file	EvidenceTAS
GeneGRK2	AuthorityHGNC:289	Mapping file id156 NCBI file	EvidenceTAS
GeneGRK3	AuthorityHGNC:290	Mapping file id157 NCBI file	EvidenceTAS
GeneHBEGF	AuthorityHGNC:3059	Mapping file id1839 NCBI file	EvidenceTAS
GeneHGS	AuthorityHGNC:4897	Mapping file id9146 NCBI file	EvidenceTAS
GeneHIP1	AuthorityHGNC:4913	Mapping file id3092 NCBI file	EvidenceTAS
GeneHIP1R	AuthorityHGNC:18415	Mapping file id9026 NCBI file	EvidenceTAS
GeneHSPA8	AuthorityHGNC:5241	Mapping file id3312 NCBI file	EvidenceTAS
GeneIGF2R	AuthorityHGNC:5467	Mapping file id3482 NCBI file	EvidenceTAS
GeneIL7R	AuthorityHGNC:6024	Mapping file id3575 NCBI file	EvidenceTAS
GeneITSN1	AuthorityHGNC:6183	Mapping file id6453 NCBI file	EvidenceTAS
GeneITSN2	AuthorityHGNC:6184	Mapping file id50618 NCBI file	EvidenceTAS
GeneKIAA0319	AuthorityHGNC:21580	Mapping file id9856 NCBI file	EvidenceTAS
GeneLDLR	AuthorityHGNC:6547	Mapping file id3949 NCBI file	EvidenceTAS
GeneLDLRAP1	AuthorityHGNC:18640	Mapping file id26119 NCBI file	EvidenceTAS
GeneLRP2	AuthorityHGNC:6694	Mapping file id4036 NCBI file	EvidenceTAS
GeneM6PR	AuthorityHGNC:6752	Mapping file id4074 NCBI file	EvidenceTAS
GeneNECAP1	AuthorityHGNC:24539	Mapping file id25977 NCBI file	EvidenceTAS
GeneNECAP2	AuthorityHGNC:25528	Mapping file id55707 NCBI file	EvidenceTAS
GeneNEDD8	AuthorityHGNC:7732	Mapping file id4738 NCBI file	EvidenceTAS
GeneOCRL	AuthorityHGNC:8108	Mapping file id4952 NCBI file	EvidenceTAS
GenePACSIN1	AuthorityHGNC:8570	Mapping file id29993 NCBI file	EvidenceTAS
GenePACSIN2	AuthorityHGNC:8571	Mapping file id11252 NCBI file	EvidenceTAS
GenePACSIN3	AuthorityHGNC:8572	Mapping file id29763 NCBI file	EvidenceTAS
GenePICALM	AuthorityHGNC:15514	Mapping file id8301 NCBI file	EvidenceTAS
GenePIK3C2A	AuthorityHGNC:8971	Mapping file id5286 NCBI file	EvidenceTAS
GenePIP5K1C	AuthorityHGNC:8996	Mapping file id23396 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

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

Membrane TraffickingR-HSA-199991636 genes

Children

Cargo recognition for clathrin-mediated endocytosisR-HSA-8856825106 genes

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.