Pathway Human Homo sapiens

Extracellular matrix organization

R-HSA-1474244 in Reactome release 97: a top-level pathway, with 321 genes placed in it by the mapping files and 9 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-1474244 (mouse), R-RNO-1474244 (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-1474244.5
Class: TopLevelPathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2012-03-13
Last updated: 2020-09-24
Events inside: 9, counted from the record

The extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded in a viscoelastic gel of anionic proteoglycan polymers. It performs many functions in addition to its structural role; as a major component of the cellular microenvironment it influences cell behaviours such as proliferation, adhesion and migration, and regulates cell differentiation and death (Hynes 2009).

ECM composition is highly heterogeneous and dynamic, being constantly remodeled (Frantz et al. 2010) and modulated, largely by matrix metalloproteinases (MMPs) and growth factors that bind to the ECM influencing the synthesis, crosslinking and degradation of ECM components (Hynes 2009). ECM remodeling is involved in the regulation of cell differentiation processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. Redundant mechanisms modulate the expression and function of ECM modifying enzymes. Abnormal ECM dynamics can lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer.

Collagen is the most abundant fibrous protein within the ECM constituting up to 30% of total protein in multicellular animals. Collagen provides tensile strength. It associates with elastic fibres, composed of elastin and fibrillin microfibrils, which give tissues the ability to recover after stretching. Other ECM proteins such as fibronectin, laminins, and matricellular proteins participate as connectors or linking proteins (Daley et al. 2008).

Chondroitin sulfate, dermatan sulfate and keratan sulfate proteoglycans are structural components associated with collagen fibrils (Scott & Haigh 1985; Scott & Orford 1981), serving to tether the fibril to the surrounding matrix. Decorin belongs to the small leucine-rich repeat proteoglycan family (SLRPs) which also includes biglycan, fibromodulin, lumican and asporin. All appear to be involved in collagen fibril formation and matrix assembly (Ameye & Young 2002).

ECM proteins such as osteonectin (SPARC), osteopontin and thrombospondins -1 and -2, collectively referred to as matricellular proteins (reviewed in Mosher & Adams 2012) appear to modulate cell-matrix interactions. In general they induce de-adhesion, characterized by disruption of focal adhesions and a reorganization of actin stress fibers (Bornstein 2009). Thrombospondin (TS)-1 and -2 bind MMP2. The resulting complex is endocytosed by the low-density lipoprotein receptor-related protein (LRP), clearing MMP2 from the ECM (Yang et al. 2001).

Osteopontin (SPP1, bone sialoprotein-1) interacts with collagen and fibronectin (Mukherjee et al. 1995). It also contains several cell adhesive domains that interact with integrins and CD44.

Aggrecan is the predominant ECM proteoglycan in cartilage (Hardingham & Fosang 1992). Its relatives include versican, neurocan and brevican (Iozzo 1998). In articular cartilage the major non-fibrous macromolecules are aggrecan, hyaluronan and hyaluronan and proteoglycan link protein 1 (HAPLN1). The high negative charge density of these molecules leads to the binding of large amounts of water (Bruckner 2006). Hyaluronan is bound by several large proteoglycans proteoglycans belonging to the hyalectan family that form high-molecular weight aggregates (Roughley 2006), accounting for the turgid nature of cartilage.

The most significant enzymes in ECM remodeling are the Matrix Metalloproteinase (MMP) and A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) families (Cawston & Young 2010). Other notable ECM degrading enzymes include plasmin and cathepsin G. Many ECM proteinases are initially present as precursors, activated by proteolytic processing. MMP precursors include an amino prodomain which masks the catalytic Zn-binding motif (Page-McCawet al. 2007). This can be removed by other proteinases, often other MMPs. ECM proteinases can be inactivated by degradation, or blocked by inhibitors. Some of these inhibitors, including alpha2-macroglobulin, alpha1-proteinase inhibitor, and alpha1-chymotrypsin can inhibit a large variety of proteinases (Woessner & Nagase 2000). The tissue inhibitors of metalloproteinases (TIMPs) are potent MMP inhibitors (Brew & Nagase 2010).

Literature Reactome attaches

The extracellular matrix at a glanceJ Cell Sci, 2010, vol. 123, p. 4195-200PubMed 21123617
Extracellular matrix degradation and remodeling in development and diseaseCold Spring Harb Perspect Biol, 2011, vol. 3PubMed 21917992
Functional structure and composition of the extracellular matrixJ Pathol, 2003, vol. 200, p. 423-8PubMed 12845610

Reactome's record lists 13 orthologous events, R-MMU-1474244 (Mus musculus), R-RNO-1474244 (Rattus norvegicus) among the species this site serves, and 11 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-02 ET · Reactome pathway browser"Extracellular matrix organization". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-1474244 with StableID: R-HSA-1474244.5 (accessed 2026-10-02 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 321 genes in this human pathway; showing 301 to 321, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 4 of 4
Gene	Authority id	Mapping file id	Evidence codes
GeneTGFB1	AuthorityHGNC:11766	Mapping file id7040 NCBI file	EvidenceIEA, TAS
GeneTGFB2	AuthorityHGNC:11768	Mapping file id7042 NCBI file	EvidenceIEA, TAS
GeneTGFB3	AuthorityHGNC:11769	Mapping file id7043 NCBI file	EvidenceIEA, TAS
GeneTHBS1	AuthorityHGNC:11785	Mapping file id7057 NCBI file	EvidenceIEA, TAS
GeneTIMP1	AuthorityHGNC:11820	Mapping file id7076 NCBI file	EvidenceTAS
GeneTIMP2	AuthorityHGNC:11821	Mapping file id7077 NCBI file	EvidenceTAS
GeneTLL1	AuthorityHGNC:11843	Mapping file id7092 NCBI file	EvidenceTAS
GeneTLL2	AuthorityHGNC:11844	Mapping file id7093 NCBI file	EvidenceTAS
GeneTMPRSS6	AuthorityHGNC:16517	Mapping file id164656 NCBI file	EvidenceIEA, TAS
GeneTNC	AuthorityHGNC:5318	Mapping file id3371 NCBI file	EvidenceIEA, TAS
GeneTNN	AuthorityHGNC:22942	Mapping file id63923 NCBI file	EvidenceTAS
GeneTNR	AuthorityHGNC:11953	Mapping file id7143 NCBI file	EvidenceTAS
GeneTNXB	AuthorityHGNC:11976	Mapping file id7148 NCBI file	EvidenceTAS
GeneTPSAB1	AuthorityHGNC:12019	Mapping file id7177 NCBI file	EvidenceTAS
GeneTRAPPC4	AuthorityHGNC:19943	Mapping file id51399 NCBI file	EvidenceIEA
GeneTTR	AuthorityHGNC:12405	Mapping file id7276 NCBI file	EvidenceTAS
GeneUTRN	AuthorityHGNC:12635	Mapping file id7402 NCBI file	EvidenceIEA, TAS
GeneVCAM1	AuthorityHGNC:12663	Mapping file id7412 NCBI file	EvidenceTAS
GeneVCAN	AuthorityHGNC:2464	Mapping file id1462 NCBI file	EvidenceTAS
GeneVTN	AuthorityHGNC:12724	Mapping file id7448 NCBI file	EvidenceIEA, TAS
GeneVWF	AuthorityHGNC:12726	Mapping file id7450 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

None: this is a top-level pathway of the release.

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.