Pathway Human Homo sapiens

Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

R-HSA-381426 in Reactome release 97: under Metabolism of proteins, with 126 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-381426 (mouse), R-RNO-381426 (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-381426.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2008-12-17
Last updated: 2018-03-26
Events inside: 14, counted from the record
Also named: Regulation of IGF Activity by IGFBP

The family of Insulin like Growth Factor Binding Proteins (IGFBPs) share 50% amino acid identity with conserved N terminal and C terminal regions responsible for binding Insulin like Growth Factors I and II (IGF I and IGF II). Most circulating IGFs are in complexes with IGFBPs, which are believed to increase the residence of IGFs in the body, modulate availability of IGFs to target receptors for IGFs, reduce insulin like effects of IGFs, and act as signaling molecules independently of IGFs. About 75% of circulating IGFs are in 1500 220 KDa complexes with IGFBP3 and ALS. Such complexes are too large to pass the endothelial barrier. The remaining 20 25% of IGFs are bound to other IGFBPs in 40 50 KDa complexes. IGFs are released from IGF:IGFBP complexes by proteolysis of the IGFBP. IGFs become active after release, however IGFs may also have activity when still bound to some IGFBPs. IGFBP1 is enriched in amniotic fluid and is produced in the liver under control of insulin (insulin suppresses production). IGFBP1 binding stimulates IGF function. It is unknown which if any protease degrades IGFBP1. IGFBP2 is enriched in cerebrospinal fluid; its binding inhibits IGF function. IGFBP2 is not significantly degraded in circulation. IGFB3, which binds most IGF in the body is enriched in follicular fluid and found in many other tissues. IGFBP 3 may be cleaved by plasmin, thrombin, Prostate specific Antigen (PSA, KLK3), Matrix Metalloprotease-1 (MMP1), and Matrix Metalloprotease-2 (MMP2). IGFBP3 also binds extracellular matrix and binding lowers its affinity for IGFs. IGFBP3 binding stimulates the effects of IGFs. IGFBP4 acts to inhibit IGF function and is cleaved by Pregnancy associated Plasma Protein A (PAPPA) to release IGF. IGFBP5 is enriched in bone matrix; its binding stimulates IGF function. IGFBP5 is cleaved by Pregnancy Associated Plasma Protein A2 (PAPPA2), ADAM9, complement C1s from smooth muscle, and thrombin. Only the cleavage site for PAPPA2 is known. IGFBP6 is enriched in cerebrospinal fluid. It is unknown which if any protease degrades IGFBP6.

Literature Reactome attaches

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 126 genes in this human pathway; showing 101 to 126, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 2
Gene	Authority id	Mapping file id	Evidence codes
GenePRKCSH	AuthorityHGNC:9411	Mapping file id5589 NCBI file	EvidenceTAS
GenePROC	AuthorityHGNC:9451	Mapping file id5624 NCBI file	EvidenceTAS
GenePRSS23	AuthorityHGNC:14370	Mapping file id11098 NCBI file	EvidenceTAS
GeneQSOX1	AuthorityHGNC:9756	Mapping file id5768 NCBI file	EvidenceTAS
GeneRCN1	AuthorityHGNC:9934	Mapping file id5954 NCBI file	EvidenceTAS
GeneSCG2	AuthorityHGNC:10575	Mapping file id7857 NCBI file	EvidenceTAS
GeneSCG3	AuthorityHGNC:13707	Mapping file id29106 NCBI file	EvidenceTAS
GeneSDC2	AuthorityHGNC:10659	Mapping file id6383 NCBI file	EvidenceTAS
GeneSERPINA1	AuthorityHGNC:8941	Mapping file id5265 NCBI file	EvidenceTAS
GeneSERPINA10	AuthorityHGNC:15996	Mapping file id51156 NCBI file	EvidenceTAS
GeneSERPINC1	AuthorityHGNC:775	Mapping file id462 NCBI file	EvidenceTAS
GeneSERPIND1	AuthorityHGNC:4838	Mapping file id3053 NCBI file	EvidenceTAS
GeneSHISA5	AuthorityHGNC:30376	Mapping file id51246 NCBI file	EvidenceTAS
GeneSPARCL1	AuthorityHGNC:11220	Mapping file id8404 NCBI file	EvidenceTAS
GeneSPP1	AuthorityHGNC:11255	Mapping file id6696 NCBI file	EvidenceTAS
GeneSPP2	AuthorityHGNC:11256	Mapping file id6694 NCBI file	EvidenceTAS
GeneSTC2	AuthorityHGNC:11374	Mapping file id8614 NCBI file	EvidenceTAS
GeneTF	AuthorityHGNC:11740	Mapping file id7018 NCBI file	EvidenceTAS
GeneTGOLN2	AuthorityHGNC:15450	Mapping file id10618 NCBI file	EvidenceTAS
GeneTIMP1	AuthorityHGNC:11820	Mapping file id7076 NCBI file	EvidenceTAS
GeneTMEM132A	AuthorityHGNC:31092	Mapping file id54972 NCBI file	EvidenceTAS
GeneTNC	AuthorityHGNC:5318	Mapping file id3371 NCBI file	EvidenceTAS
GeneVCAN	AuthorityHGNC:2464	Mapping file id1462 NCBI file	EvidenceTAS
GeneVGF	AuthorityHGNC:12684	Mapping file id7425 NCBI file	EvidenceTAS
GeneVWA1	AuthorityHGNC:30910	Mapping file id64856 NCBI file	EvidenceTAS
GeneWFS1	AuthorityHGNC:12762	Mapping file id7466 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

Metabolism of proteinsR-HSA-3924992,148 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.