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 2026-10-01 ET · Reactome pathway browser"Extracellular matrix organization". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-1474244 with StableID: R-HSA-1474244.5 (accessed 2026-10-01 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 321 genes in this human pathway; showing 101 to 200, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 4
Gene	Authority id	Mapping file id	Evidence codes
GeneCOL6A5	AuthorityHGNC:26674	Mapping file id256076 NCBI file	EvidenceIEA, TAS
GeneCOL6A6	AuthorityHGNC:27023	Mapping file id131873 NCBI file	EvidenceIEA, TAS
GeneCOL7A1	AuthorityHGNC:2214	Mapping file id1294 NCBI file	EvidenceIEA, TAS
GeneCOL8A1	AuthorityHGNC:2215	Mapping file id1295 NCBI file	EvidenceIEA, TAS
GeneCOL8A2	AuthorityHGNC:2216	Mapping file id1296 NCBI file	EvidenceIEA, TAS
GeneCOL9A1	AuthorityHGNC:2217	Mapping file id1297 NCBI file	EvidenceIEA, TAS
GeneCOL9A2	AuthorityHGNC:2218	Mapping file id1298 NCBI file	EvidenceIEA, TAS
GeneCOL9A3	AuthorityHGNC:2219	Mapping file id1299 NCBI file	EvidenceIEA, TAS
GeneCOLGALT1	AuthorityHGNC:26182	Mapping file id79709 NCBI file	EvidenceTAS
GeneCOLGALT2	AuthorityHGNC:16790	Mapping file id23127 NCBI file	EvidenceTAS
GeneCOMP	AuthorityHGNC:2227	Mapping file id1311 NCBI file	EvidenceTAS
GeneCRTAP	AuthorityHGNC:2379	Mapping file id10491 NCBI file	EvidenceTAS
GeneCTRB1	AuthorityHGNC:2521	Mapping file id1504 NCBI file	EvidenceTAS
GeneCTRB2	AuthorityHGNC:2522	Mapping file id440387 NCBI file	EvidenceTAS
GeneCTSB	AuthorityHGNC:2527	Mapping file id1508 NCBI file	EvidenceTAS
GeneCTSD	AuthorityHGNC:2529	Mapping file id1509 NCBI file	EvidenceTAS
GeneCTSG	AuthorityHGNC:2532	Mapping file id1511 NCBI file	EvidenceTAS
GeneCTSK	AuthorityHGNC:2536	Mapping file id1513 NCBI file	EvidenceTAS
GeneCTSL	AuthorityHGNC:2537	Mapping file id1514 NCBI file	EvidenceTAS
GeneCTSS	AuthorityHGNC:2545	Mapping file id1520 NCBI file	EvidenceIEA, TAS
GeneCTSV	AuthorityHGNC:2538	Mapping file id1515 NCBI file	EvidenceTAS
GeneDAG1	AuthorityHGNC:2666	Mapping file id1605 NCBI file	EvidenceIEA, TAS
GeneDCN	AuthorityHGNC:2705	Mapping file id1634 NCBI file	EvidenceIEA, TAS
GeneDDR1	AuthorityHGNC:2730	Mapping file id780 NCBI file	EvidenceTAS
GeneDDR2	AuthorityHGNC:2731	Mapping file id4921 NCBI file	EvidenceTAS
GeneDMD	AuthorityHGNC:2928	Mapping file id1756 NCBI file	EvidenceIEA, TAS
GeneDMP1	AuthorityHGNC:2932	Mapping file id1758 NCBI file	EvidenceTAS
GeneDRP2	AuthorityHGNC:3032	Mapping file id1821 NCBI file	EvidenceIEA, TAS
GeneDSPP	AuthorityHGNC:3054	Mapping file id1834 NCBI file	EvidenceTAS
GeneDST	AuthorityHGNC:1090	Mapping file id667 NCBI file	EvidenceTAS
GeneDTNA	AuthorityHGNC:3057	Mapping file id1837 NCBI file	EvidenceIEA, TAS
GeneDTNB	AuthorityHGNC:3058	Mapping file id1838 NCBI file	EvidenceIEA, TAS
GeneEFEMP1	AuthorityHGNC:3218	Mapping file id2202 NCBI file	EvidenceIEA, TAS
GeneEFEMP2	AuthorityHGNC:3219	Mapping file id30008 NCBI file	EvidenceIEA, TAS
GeneELANE	AuthorityHGNC:3309	Mapping file id1991 NCBI file	EvidenceIEA, TAS
GeneELN	AuthorityHGNC:3327	Mapping file id2006 NCBI file	EvidenceIEA, TAS
GeneEMILIN1	AuthorityHGNC:19880	Mapping file id11117 NCBI file	EvidenceIEA, TAS
GeneEMILIN2	AuthorityHGNC:19881	Mapping file id84034 NCBI file	EvidenceIEA, TAS
GeneEMILIN3	AuthorityHGNC:16123	Mapping file id90187 NCBI file	EvidenceIEA, TAS
GeneF11R	AuthorityHGNC:14685	Mapping file id50848 NCBI file	EvidenceTAS
GeneFBLN1	AuthorityHGNC:3600	Mapping file id2192 NCBI file	EvidenceIEA, TAS
GeneFBLN2	AuthorityHGNC:3601	Mapping file id2199 NCBI file	EvidenceIEA, TAS
GeneFBLN5	AuthorityHGNC:3602	Mapping file id10516 NCBI file	EvidenceIEA, TAS
GeneFBN1	AuthorityHGNC:3603	Mapping file id2200 NCBI file	EvidenceIEA, TAS
GeneFBN2	AuthorityHGNC:3604	Mapping file id2201 NCBI file	EvidenceIEA, TAS
GeneFBN3	AuthorityHGNC:18794	Mapping file id84467 NCBI file	EvidenceIEA, TAS
GeneFGA	AuthorityHGNC:3661	Mapping file id2243 NCBI file	EvidenceTAS
GeneFGB	AuthorityHGNC:3662	Mapping file id2244 NCBI file	EvidenceTAS
GeneFGF2	AuthorityHGNC:3676	Mapping file id2247 NCBI file	EvidenceTAS
GeneFGG	AuthorityHGNC:3694	Mapping file id2266 NCBI file	EvidenceTAS
GeneFMOD	AuthorityHGNC:3774	Mapping file id2331 NCBI file	EvidenceIEA
GeneFN1	AuthorityHGNC:3778	Mapping file id2335 NCBI file	EvidenceIEA, TAS
GeneFURIN	AuthorityHGNC:8568	Mapping file id5045 NCBI file	EvidenceIEA, TAS
GeneGDF5	AuthorityHGNC:4220	Mapping file id8200 NCBI file	EvidenceTAS
GeneHAPLN1	AuthorityHGNC:2380	Mapping file id1404 NCBI file	EvidenceTAS
GeneHSPG2	AuthorityHGNC:5273	Mapping file id3339 NCBI file	EvidenceIEA, TAS
GeneHTRA1	AuthorityHGNC:9476	Mapping file id5654 NCBI file	EvidenceTAS
GeneIBSP	AuthorityHGNC:5341	Mapping file id3381 NCBI file	EvidenceIEA, TAS
GeneICAM1	AuthorityHGNC:5344	Mapping file id3383 NCBI file	EvidenceTAS
GeneICAM2	AuthorityHGNC:5345	Mapping file id3384 NCBI file	EvidenceTAS
GeneICAM3	AuthorityHGNC:5346	Mapping file id3385 NCBI file	EvidenceTAS
GeneICAM4	AuthorityHGNC:5347	Mapping file id3386 NCBI file	EvidenceTAS
GeneICAM5	AuthorityHGNC:5348	Mapping file id7087 NCBI file	EvidenceTAS
GeneITGA1	AuthorityHGNC:6134	Mapping file id3672 NCBI file	EvidenceIEA, TAS
GeneITGA10	AuthorityHGNC:6135	Mapping file id8515 NCBI file	EvidenceIEA, TAS
GeneITGA11	AuthorityHGNC:6136	Mapping file id22801 NCBI file	EvidenceIEA, TAS
GeneITGA2	AuthorityHGNC:6137	Mapping file id3673 NCBI file	EvidenceIEA, TAS
GeneITGA2B	AuthorityHGNC:6138	Mapping file id3674 NCBI file	EvidenceTAS
GeneITGA3	AuthorityHGNC:6139	Mapping file id3675 NCBI file	EvidenceIEA, TAS
GeneITGA4	AuthorityHGNC:6140	Mapping file id3676 NCBI file	EvidenceIEA, TAS
GeneITGA5	AuthorityHGNC:6141	Mapping file id3678 NCBI file	EvidenceIEA, TAS
GeneITGA6	AuthorityHGNC:6142	Mapping file id3655 NCBI file	EvidenceIEA, TAS
GeneITGA7	AuthorityHGNC:6143	Mapping file id3679 NCBI file	EvidenceIEA, TAS
GeneITGA8	AuthorityHGNC:6144	Mapping file id8516 NCBI file	EvidenceIEA, TAS
GeneITGA9	AuthorityHGNC:6145	Mapping file id3680 NCBI file	EvidenceIEA, TAS
GeneITGAD	AuthorityHGNC:6146	Mapping file id3681 NCBI file	EvidenceTAS
GeneITGAE	AuthorityHGNC:6147	Mapping file id3682 NCBI file	EvidenceTAS
GeneITGAL	AuthorityHGNC:6148	Mapping file id3683 NCBI file	EvidenceTAS
GeneITGAM	AuthorityHGNC:6149	Mapping file id3684 NCBI file	EvidenceTAS
GeneITGAV	AuthorityHGNC:6150	Mapping file id3685 NCBI file	EvidenceIEA, TAS
GeneITGAX	AuthorityHGNC:6152	Mapping file id3687 NCBI file	EvidenceTAS
GeneITGB1	AuthorityHGNC:6153	Mapping file id3688 NCBI file	EvidenceIEA, TAS
GeneITGB2	AuthorityHGNC:6155	Mapping file id3689 NCBI file	EvidenceTAS
GeneITGB3	AuthorityHGNC:6156	Mapping file id3690 NCBI file	EvidenceIEA, TAS
GeneITGB4	AuthorityHGNC:6158	Mapping file id3691 NCBI file	EvidenceTAS
GeneITGB5	AuthorityHGNC:6160	Mapping file id3693 NCBI file	EvidenceIEA, TAS
GeneITGB6	AuthorityHGNC:6161	Mapping file id3694 NCBI file	EvidenceTAS
GeneITGB7	AuthorityHGNC:6162	Mapping file id3695 NCBI file	EvidenceTAS
GeneITGB8	AuthorityHGNC:6163	Mapping file id3696 NCBI file	EvidenceTAS
GeneJAM2	AuthorityHGNC:14686	Mapping file id58494 NCBI file	EvidenceTAS
GeneJAM3	AuthorityHGNC:15532	Mapping file id83700 NCBI file	EvidenceTAS
GeneKDR	AuthorityHGNC:6307	Mapping file id3791 NCBI file	EvidenceTAS
GeneKLK2	AuthorityHGNC:6363	Mapping file id3817 NCBI file	EvidenceTAS
GeneKLK7	AuthorityHGNC:6368	Mapping file id5650 NCBI file	EvidenceTAS
GeneKLKB1	AuthorityHGNC:6371	Mapping file id3818 NCBI file	EvidenceTAS
GeneLAMA1	AuthorityHGNC:6481	Mapping file id284217 NCBI file	EvidenceIEA, TAS
GeneLAMA2	AuthorityHGNC:6482	Mapping file id3908 NCBI file	EvidenceIEA, TAS
GeneLAMA3	AuthorityHGNC:6483	Mapping file id3909 NCBI file	EvidenceIEA, TAS
GeneLAMA4	AuthorityHGNC:6484	Mapping file id3910 NCBI file	EvidenceIEA, TAS
GeneLAMA5	AuthorityHGNC:6485	Mapping file id3911 NCBI file	EvidenceIEA, TAS

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.