Regulation of IGF transport and uptake by IGF binding proteins (Homo sapiens)

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11, 22, 29, 33, 47...5, 19, 21, 22, 26...2, 6, 12, 22, 26...4, 14, 21, 22, 25...1, 3, 4, 13, 14, 19...22, 33, 42, 47, 50...11, 21, 22, 26, 30...9, 18, 22, 33, 504617, 18, 22, 33, 34, 5018, 22, 29, 32, 33, 50...15, 19, 21, 22, 26...438, 10, 11, 22-24, 33...9, 18, 22, 27, 31...endoplasmic reticulum lumencytosolp-IGFBP7 p-SERPINC1 p-KTN1 IGF:IGFBP5:ALSp-IGFBP1 SERPINA10 p-GAS6 Prostate SpecificAntigenIGF1 FAM20A APOE LTBP1 ENAM IGFBP2 AMELX PNPLA2 p-MBTPS1 MFGE8 p-AMTN CHRDL1 LAMB2 MEN1 FAM20C:FAM20CsubstratesCST3 FAM20C ATPIGF:IGFBP4p-HRC STC2 p-MGAT4A p-FGF23 IGF:IGFBP1CSF1 p-LAMB1 TNC IGF1 p-GPC3 p-ENAM CTSG C3 p-DMP1 IGFBP4 p-TNC MIA3 MMP1(100-469) BMP15 IGFBP7 IGFBP3 TF p-SPP2 EVA1A IGFBP1 MMP2(110-660) p-TGOLN2 p-LAMB2 p-FUCA2 IGF1,2IGFBP3p-AHSG CALU IGFBP5 p-VGF p-APOL1 p-P4HB p-IGFBP4 ITIH2 KTN1 p-IL6 p-PROC MSLN p-GOLM1 p-CST3 p-MSLN FBN1 p-APOA5 IGF:IGFBP6p-FBN1 p-MEPE MBTPS1 IGF1 SERPINA1 p-APOA2 p-APOB(28-4563) AMBN PCSK9 SPP1 IGF:IGFBP2C4A PAPPA2 IGFBP3(234-291)APOA2 IGF1 IGFBP3(127-291)p-ADAM10 APOL1 p-CYR61 GOLM1 KLK13 CDH2 p-LGALS1 FSTL3 APOB(28-4563) KLK3 TIMP1 IGF2(25-91) IGF1,2p-AMBN SERPIND1 IGF1 IGFBP3(28-126)IGFBP4IGF2(25-91) FGA IGFBP3(28-186)IGF2(25-91) IGFBP5p-C4A IGFALSAPLP2 thrombin heavy chain IGFBP3 SERPINC1 p-SHISA5 IGFBP3(169-226)CP LAMB1 IGF:IGFBP3:ALSp-MXRA8 p-BMP4 CYR61 p-AMELX IGFBP3(227-291)WFS1 IGFBP3(125-187)p-QSOX1 IGF1 p-C3 PAPPA IGFBP4 IGF2(25-91) APOA5 HSP90B1 IGFBP6MELTF p-APOA1 AMTN p-MATN3 p-CHRDL1 Cathepsin Gp-MEN1 CHGB SCG2 p-VWA1 SDC2 IGFBP1p-WFS1 ADAM10 p-SCG3 FGF23 SHISA5 thrombin light chain p-CALU IGF2(25-91) MATN3 VCAN p-PRKCSH FAM20C p-CKAP4 p-Factor V precursor activated thrombin(factor IIa)IGF2(25-91) p-PRSS23 IGFBP5(21-163)GPC3 p-LTBP1 p-PCSK9 QSOX1 IGFBP3(188-291)p-SDC2 PRSS23 IGFBP6 p-LAMC1 FSTL1 p-TF IGF1 IGFBP3(28-168)p-SPARCL1 DNAJC3 IGFBP3(28-124)PRKCSH IGFALSSCG3 BMP4 p-TMEM132A FAM20C:Phosphorylated FAM20C substratesGAS6 IGFBP4(22-156)Ca2+ p-FSTL1 FGG p-SERPINA1 p-MELTF FN1 p-CDH2 APP p-IGFBP3 RCN1 p-SPP1 MEPE PAPPA,PAPPA2p-APP p-FGG p-CHGB PENK p-SERPIND1 AHSG p-BMP15 MGAT4A ANO8 IGFALS p-CSF1 ALB PLG(20-580) IGF2(25-91) p-BPIFB2 p-KNG1 MXRA8 LAMC1 NOTUM IGF1 CKAP4 PDIA6 BPIFB2 PLG(581-810) p-DNAJC3 PROC P4HB p-FSTL3 TGOLN2 p-TIMP1 p-SCG2 p-AFP p-PDIA6 KLK1 IGF2(25-91) AFP APOA1 DMP1 SPP2 p-PENK NUCB1 p-IGFBP5 VWA1 p-STC2 SPARCL1 Factor V precursor IGFBP3(125-233)PlasminIGFBP5(164-272)p-FGA IGFBP5 ADPp-VCAN p-FN1 p-RCN1 p-APOE VGF FUCA2 p-CP p-NOTUM FAM20C:FAM20Ap-ITIH2 IGFBP3(291-187)p-PNPLA2 p-APLP2 IGFBP4(157-237)TMEM132A IGFBP2KLK2 HRC p-ALB p-SERPINA10 p-MIA3 IL6 FAM20C p-NUCB1 IGFALS LGALS1 p-HSP90B1 p-EVA1A GZMH p-ANO8 IGFBP1 p-MFGE8 KNG1 MMP1,27, 1648567, 16


Description

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.

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Reactome version: 75

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Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
116730view10:28, 11 May 2021EweitzModified title
114814view16:31, 25 January 2021ReactomeTeamReactome version 75
113259view11:32, 2 November 2020ReactomeTeamReactome version 74
112474view15:42, 9 October 2020ReactomeTeamReactome version 73
101385view11:27, 1 November 2018ReactomeTeamreactome version 66
100923view21:03, 31 October 2018ReactomeTeamreactome version 65
100463view19:37, 31 October 2018ReactomeTeamreactome version 64
100009view16:21, 31 October 2018ReactomeTeamreactome version 63
99562view14:54, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
94031view13:52, 16 August 2017ReactomeTeamreactome version 61
93653view11:29, 9 August 2017ReactomeTeamreactome version 61
88140view12:55, 26 July 2016RyanmillerOntology Term : 'peptide and protein metabolic process' added !
88139view12:55, 26 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
86771view09:25, 11 July 2016ReactomeTeamreactome version 56
83284view10:37, 18 November 2015ReactomeTeamVersion54
81777view10:36, 26 August 2015ReactomeTeamVersion53
77094view08:39, 17 July 2014ReactomeTeamFixed remaining interactions
76800view12:18, 16 July 2014ReactomeTeamFixed remaining interactions
76123view10:19, 11 June 2014ReactomeTeamRe-fixing comment source
75835view11:40, 10 June 2014ReactomeTeamReactome 48 Update
75195view09:42, 9 May 2014AnweshaFixing comment source for displaying WikiPathways description
74841view10:06, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADAM10 ProteinO14672 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:456216 (ChEBI)
AFP ProteinP02771 (Uniprot-TrEMBL)
AHSG ProteinP02765 (Uniprot-TrEMBL)
ALB ProteinP02768 (Uniprot-TrEMBL)
AMBN ProteinQ9NP70 (Uniprot-TrEMBL)
AMELX ProteinQ99217 (Uniprot-TrEMBL)
AMTN ProteinQ6UX39 (Uniprot-TrEMBL)
ANO8 ProteinQ9HCE9 (Uniprot-TrEMBL)
APLP2 ProteinQ06481 (Uniprot-TrEMBL)
APOA1 ProteinP02647 (Uniprot-TrEMBL)
APOA2 ProteinP02652 (Uniprot-TrEMBL)
APOA5 ProteinQ6Q788 (Uniprot-TrEMBL)
APOB(28-4563) ProteinP04114 (Uniprot-TrEMBL)
APOE ProteinP02649 (Uniprot-TrEMBL)
APOL1 ProteinO14791 (Uniprot-TrEMBL)
APP ProteinP05067 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:30616 (ChEBI)
BMP15 ProteinO95972 (Uniprot-TrEMBL)
BMP4 ProteinP12644 (Uniprot-TrEMBL)
BPIFB2 ProteinQ8N4F0 (Uniprot-TrEMBL)
C3 ProteinP01024 (Uniprot-TrEMBL)
C4A ProteinP0C0L4 (Uniprot-TrEMBL)
CALU ProteinO43852 (Uniprot-TrEMBL)
CDH2 ProteinP19022 (Uniprot-TrEMBL)
CHGB ProteinP05060 (Uniprot-TrEMBL)
CHRDL1 ProteinQ9BU40 (Uniprot-TrEMBL)
CKAP4 ProteinQ07065 (Uniprot-TrEMBL)
CP ProteinP00450 (Uniprot-TrEMBL)
CSF1 ProteinP09603 (Uniprot-TrEMBL)
CST3 ProteinP01034 (Uniprot-TrEMBL)
CTSG ProteinP08311 (Uniprot-TrEMBL) After secretion Cathepsin G is extracellular and associated with the plasma membrane.
CYR61 ProteinO00622 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Cathepsin GComplexR-HSA-2990877 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
DMP1 ProteinQ13316 (Uniprot-TrEMBL)
DNAJC3 ProteinQ13217 (Uniprot-TrEMBL)
ENAM ProteinQ9NRM1 (Uniprot-TrEMBL)
EVA1A ProteinQ9H8M9 (Uniprot-TrEMBL)
FAM20A ProteinQ96MK3 (Uniprot-TrEMBL)
FAM20C ProteinQ8IXL6 (Uniprot-TrEMBL)
FAM20C:FAM20AComplexR-HSA-8957338 (Reactome)
FAM20C:FAM20C substratesComplexR-HSA-8952321 (Reactome)
FAM20C:Phosphorylated FAM20C substratesComplexR-HSA-8952335 (Reactome)
FBN1 ProteinP35555 (Uniprot-TrEMBL)
FGA ProteinP02671 (Uniprot-TrEMBL)
FGF23 ProteinQ9GZV9 (Uniprot-TrEMBL)
FGG ProteinP02679 (Uniprot-TrEMBL)
FN1 ProteinP02751 (Uniprot-TrEMBL)
FSTL1 ProteinQ12841 (Uniprot-TrEMBL)
FSTL3 ProteinO95633 (Uniprot-TrEMBL)
FUCA2 ProteinQ9BTY2 (Uniprot-TrEMBL)
Factor V precursor ProteinP12259 (Uniprot-TrEMBL)
GAS6 ProteinQ14393 (Uniprot-TrEMBL)
GOLM1 ProteinQ8NBJ4 (Uniprot-TrEMBL)
GPC3 ProteinP51654 (Uniprot-TrEMBL)
GZMH ProteinP20718 (Uniprot-TrEMBL)
HRC ProteinP23327 (Uniprot-TrEMBL)
HSP90B1 ProteinP14625 (Uniprot-TrEMBL)
IGF1 ProteinP05019 (Uniprot-TrEMBL)
IGF1,2ComplexR-HSA-381451 (Reactome)
IGF2(25-91) ProteinP01344 (Uniprot-TrEMBL)
IGF:IGFBP1ComplexR-HSA-381539 (Reactome)
IGF:IGFBP2ComplexR-HSA-381473 (Reactome)
IGF:IGFBP3:ALSComplexR-HSA-381536 (Reactome)
IGF:IGFBP4ComplexR-HSA-381509 (Reactome)
IGF:IGFBP5:ALSComplexR-HSA-381423 (Reactome)
IGF:IGFBP6ComplexR-HSA-381482 (Reactome)
IGFALS ProteinP35858 (Uniprot-TrEMBL)
IGFALSProteinP35858 (Uniprot-TrEMBL)
IGFBP1 ProteinP08833 (Uniprot-TrEMBL)
IGFBP1ProteinP08833 (Uniprot-TrEMBL)
IGFBP2 ProteinP18065 (Uniprot-TrEMBL)
IGFBP2ProteinP18065 (Uniprot-TrEMBL)
IGFBP3 ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(125-187)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(125-233)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(127-291)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(169-226)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(188-291)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(227-291)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(234-291)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(28-124)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(28-126)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(28-168)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(28-186)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3(291-187)ProteinP17936 (Uniprot-TrEMBL)
IGFBP3ProteinP17936 (Uniprot-TrEMBL)
IGFBP4 ProteinP22692 (Uniprot-TrEMBL)
IGFBP4(157-237)ProteinP22692 (Uniprot-TrEMBL)
IGFBP4(22-156)ProteinP22692 (Uniprot-TrEMBL)
IGFBP4ProteinP22692 (Uniprot-TrEMBL)
IGFBP5 ProteinP24593 (Uniprot-TrEMBL)
IGFBP5(164-272)ProteinP24593 (Uniprot-TrEMBL)
IGFBP5(21-163)ProteinP24593 (Uniprot-TrEMBL)
IGFBP5ProteinP24593 (Uniprot-TrEMBL)
IGFBP6 ProteinP24592 (Uniprot-TrEMBL)
IGFBP6ProteinP24592 (Uniprot-TrEMBL)
IGFBP7 ProteinQ16270 (Uniprot-TrEMBL)
IL6 ProteinP05231 (Uniprot-TrEMBL)
ITIH2 ProteinP19823 (Uniprot-TrEMBL)
KLK1 ProteinP06870 (Uniprot-TrEMBL)
KLK13 ProteinQ9UKR3 (Uniprot-TrEMBL)
KLK2 ProteinP20151 (Uniprot-TrEMBL)
KLK3 ProteinP07288 (Uniprot-TrEMBL)
KNG1 ProteinP01042 (Uniprot-TrEMBL)
KTN1 ProteinQ86UP2 (Uniprot-TrEMBL)
LAMB1 ProteinP07942 (Uniprot-TrEMBL)
LAMB2 ProteinP55268 (Uniprot-TrEMBL)
LAMC1 ProteinP11047 (Uniprot-TrEMBL)
LGALS1 ProteinP09382 (Uniprot-TrEMBL)
LTBP1 ProteinQ14766 (Uniprot-TrEMBL)
MATN3 ProteinO15232 (Uniprot-TrEMBL)
MBTPS1 ProteinQ14703 (Uniprot-TrEMBL)
MELTF ProteinP08582 (Uniprot-TrEMBL)
MEN1 ProteinO00255 (Uniprot-TrEMBL)
MEPE ProteinQ9NQ76 (Uniprot-TrEMBL)
MFGE8 ProteinQ08431 (Uniprot-TrEMBL)
MGAT4A ProteinQ9UM21 (Uniprot-TrEMBL)
MIA3 ProteinQ5JRA6 (Uniprot-TrEMBL)
MMP1(100-469) ProteinP03956 (Uniprot-TrEMBL)
MMP1,2ComplexR-HSA-381470 (Reactome)
MMP2(110-660) ProteinP08253 (Uniprot-TrEMBL)
MSLN ProteinQ13421 (Uniprot-TrEMBL)
MXRA8 ProteinQ9BRK3 (Uniprot-TrEMBL)
NOTUM ProteinQ6P988 (Uniprot-TrEMBL)
NUCB1 ProteinQ02818 (Uniprot-TrEMBL)
P4HB ProteinP07237 (Uniprot-TrEMBL)
PAPPA ProteinQ13219 (Uniprot-TrEMBL)
PAPPA,PAPPA2ComplexR-HSA-381483 (Reactome)
PAPPA2 ProteinQ9BXP8 (Uniprot-TrEMBL)
PCSK9 ProteinQ8NBP7 (Uniprot-TrEMBL)
PDIA6 ProteinQ15084 (Uniprot-TrEMBL)
PENK ProteinP01210 (Uniprot-TrEMBL)
PLG(20-580) ProteinP00747 (Uniprot-TrEMBL)
PLG(581-810) ProteinP00747 (Uniprot-TrEMBL)
PNPLA2 ProteinQ96AD5 (Uniprot-TrEMBL)
PRKCSH ProteinP14314 (Uniprot-TrEMBL)
PROC ProteinP04070 (Uniprot-TrEMBL)
PRSS23 ProteinO95084 (Uniprot-TrEMBL)
PlasminComplexR-HSA-158770 (Reactome)
Prostate Specific AntigenComplexR-HSA-2990872 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
QSOX1 ProteinO00391 (Uniprot-TrEMBL)
RCN1 ProteinQ15293 (Uniprot-TrEMBL)
SCG2 ProteinP13521 (Uniprot-TrEMBL)
SCG3 ProteinQ8WXD2 (Uniprot-TrEMBL)
SDC2 ProteinP34741 (Uniprot-TrEMBL)
SERPINA1 ProteinP01009 (Uniprot-TrEMBL)
SERPINA10 ProteinQ9UK55 (Uniprot-TrEMBL)
SERPINC1 ProteinP01008 (Uniprot-TrEMBL)
SERPIND1 ProteinP05546 (Uniprot-TrEMBL)
SHISA5 ProteinQ8N114 (Uniprot-TrEMBL)
SPARCL1 ProteinQ14515 (Uniprot-TrEMBL)
SPP1 ProteinP10451 (Uniprot-TrEMBL)
SPP2 ProteinQ13103 (Uniprot-TrEMBL)
STC2 ProteinO76061 (Uniprot-TrEMBL)
TF ProteinP02787 (Uniprot-TrEMBL)
TGOLN2 ProteinO43493 (Uniprot-TrEMBL)
TIMP1 ProteinP01033 (Uniprot-TrEMBL)
TMEM132A ProteinQ24JP5 (Uniprot-TrEMBL)
TNC ProteinP24821 (Uniprot-TrEMBL)
VCAN ProteinP13611 (Uniprot-TrEMBL)
VGF ProteinO15240 (Uniprot-TrEMBL)
VWA1 ProteinQ6PCB0 (Uniprot-TrEMBL)
WFS1 ProteinO76024 (Uniprot-TrEMBL)
activated thrombin (factor IIa)ComplexR-HSA-156786 (Reactome)
p-ADAM10 ProteinO14672 (Uniprot-TrEMBL)
p-AFP ProteinP02771 (Uniprot-TrEMBL)
p-AHSG ProteinP02765 (Uniprot-TrEMBL)
p-ALB ProteinP02768 (Uniprot-TrEMBL)
p-AMBN ProteinQ9NP70 (Uniprot-TrEMBL)
p-AMELX ProteinQ99217 (Uniprot-TrEMBL)
p-AMTN ProteinQ6UX39 (Uniprot-TrEMBL)
p-ANO8 ProteinQ9HCE9 (Uniprot-TrEMBL)
p-APLP2 ProteinQ06481 (Uniprot-TrEMBL)
p-APOA1 ProteinP02647 (Uniprot-TrEMBL)
p-APOA2 ProteinP02652 (Uniprot-TrEMBL)
p-APOA5 ProteinQ6Q788 (Uniprot-TrEMBL)
p-APOB(28-4563) ProteinP04114 (Uniprot-TrEMBL)
p-APOE ProteinP02649 (Uniprot-TrEMBL)
p-APOL1 ProteinO14791 (Uniprot-TrEMBL)
p-APP ProteinP05067 (Uniprot-TrEMBL)
p-BMP15 ProteinO95972 (Uniprot-TrEMBL)
p-BMP4 ProteinP12644 (Uniprot-TrEMBL)
p-BPIFB2 ProteinQ8N4F0 (Uniprot-TrEMBL)
p-C3 ProteinP01024 (Uniprot-TrEMBL)
p-C4A ProteinP0C0L4 (Uniprot-TrEMBL)
p-CALU ProteinO43852 (Uniprot-TrEMBL)
p-CDH2 ProteinP19022 (Uniprot-TrEMBL)
p-CHGB ProteinP05060 (Uniprot-TrEMBL)
p-CHRDL1 ProteinQ9BU40 (Uniprot-TrEMBL)
p-CKAP4 ProteinQ07065 (Uniprot-TrEMBL)
p-CP ProteinP00450 (Uniprot-TrEMBL)
p-CSF1 ProteinP09603 (Uniprot-TrEMBL)
p-CST3 ProteinP01034 (Uniprot-TrEMBL)
p-CYR61 ProteinO00622 (Uniprot-TrEMBL)
p-DMP1 ProteinQ13316 (Uniprot-TrEMBL)
p-DNAJC3 ProteinQ13217 (Uniprot-TrEMBL)
p-ENAM ProteinQ9NRM1 (Uniprot-TrEMBL)
p-EVA1A ProteinQ9H8M9 (Uniprot-TrEMBL)
p-FBN1 ProteinP35555 (Uniprot-TrEMBL)
p-FGA ProteinP02671 (Uniprot-TrEMBL)
p-FGF23 ProteinQ9GZV9 (Uniprot-TrEMBL)
p-FGG ProteinP02679 (Uniprot-TrEMBL)
p-FN1 ProteinP02751 (Uniprot-TrEMBL)
p-FSTL1 ProteinQ12841 (Uniprot-TrEMBL)
p-FSTL3 ProteinO95633 (Uniprot-TrEMBL)
p-FUCA2 ProteinQ9BTY2 (Uniprot-TrEMBL)
p-Factor V precursor ProteinP12259 (Uniprot-TrEMBL)
p-GAS6 ProteinQ14393 (Uniprot-TrEMBL)
p-GOLM1 ProteinQ8NBJ4 (Uniprot-TrEMBL)
p-GPC3 ProteinP51654 (Uniprot-TrEMBL)
p-HRC ProteinP23327 (Uniprot-TrEMBL)
p-HSP90B1 ProteinP14625 (Uniprot-TrEMBL)
p-IGFBP1 ProteinP08833 (Uniprot-TrEMBL)
p-IGFBP3 ProteinP17936 (Uniprot-TrEMBL)
p-IGFBP4 ProteinP22692 (Uniprot-TrEMBL)
p-IGFBP5 ProteinP24593 (Uniprot-TrEMBL)
p-IGFBP7 ProteinQ16270 (Uniprot-TrEMBL)
p-IL6 ProteinP05231 (Uniprot-TrEMBL)
p-ITIH2 ProteinP19823 (Uniprot-TrEMBL)
p-KNG1 ProteinP01042 (Uniprot-TrEMBL)
p-KTN1 ProteinQ86UP2 (Uniprot-TrEMBL)
p-LAMB1 ProteinP07942 (Uniprot-TrEMBL)
p-LAMB2 ProteinP55268 (Uniprot-TrEMBL)
p-LAMC1 ProteinP11047 (Uniprot-TrEMBL)
p-LGALS1 ProteinP09382 (Uniprot-TrEMBL)
p-LTBP1 ProteinQ14766 (Uniprot-TrEMBL)
p-MATN3 ProteinO15232 (Uniprot-TrEMBL)
p-MBTPS1 ProteinQ14703 (Uniprot-TrEMBL)
p-MELTF ProteinP08582 (Uniprot-TrEMBL)
p-MEN1 ProteinO00255 (Uniprot-TrEMBL)
p-MEPE ProteinQ9NQ76 (Uniprot-TrEMBL)
p-MFGE8 ProteinQ08431 (Uniprot-TrEMBL)
p-MGAT4A ProteinQ9UM21 (Uniprot-TrEMBL)
p-MIA3 ProteinQ5JRA6 (Uniprot-TrEMBL)
p-MSLN ProteinQ13421 (Uniprot-TrEMBL)
p-MXRA8 ProteinQ9BRK3 (Uniprot-TrEMBL)
p-NOTUM ProteinQ6P988 (Uniprot-TrEMBL)
p-NUCB1 ProteinQ02818 (Uniprot-TrEMBL)
p-P4HB ProteinP07237 (Uniprot-TrEMBL)
p-PCSK9 ProteinQ8NBP7 (Uniprot-TrEMBL)
p-PDIA6 ProteinQ15084 (Uniprot-TrEMBL)
p-PENK ProteinP01210 (Uniprot-TrEMBL)
p-PNPLA2 ProteinQ96AD5 (Uniprot-TrEMBL)
p-PRKCSH ProteinP14314 (Uniprot-TrEMBL)
p-PROC ProteinP04070 (Uniprot-TrEMBL)
p-PRSS23 ProteinO95084 (Uniprot-TrEMBL)
p-QSOX1 ProteinO00391 (Uniprot-TrEMBL)
p-RCN1 ProteinQ15293 (Uniprot-TrEMBL)
p-SCG2 ProteinP13521 (Uniprot-TrEMBL)
p-SCG3 ProteinQ8WXD2 (Uniprot-TrEMBL)
p-SDC2 ProteinP34741 (Uniprot-TrEMBL)
p-SERPINA1 ProteinP01009 (Uniprot-TrEMBL)
p-SERPINA10 ProteinQ9UK55 (Uniprot-TrEMBL)
p-SERPINC1 ProteinP01008 (Uniprot-TrEMBL)
p-SERPIND1 ProteinP05546 (Uniprot-TrEMBL)
p-SHISA5 ProteinQ8N114 (Uniprot-TrEMBL)
p-SPARCL1 ProteinQ14515 (Uniprot-TrEMBL)
p-SPP1 ProteinP10451 (Uniprot-TrEMBL)
p-SPP2 ProteinQ13103 (Uniprot-TrEMBL)
p-STC2 ProteinO76061 (Uniprot-TrEMBL)
p-TF ProteinP02787 (Uniprot-TrEMBL)
p-TGOLN2 ProteinO43493 (Uniprot-TrEMBL)
p-TIMP1 ProteinP01033 (Uniprot-TrEMBL)
p-TMEM132A ProteinQ24JP5 (Uniprot-TrEMBL)
p-TNC ProteinP24821 (Uniprot-TrEMBL)
p-VCAN ProteinP13611 (Uniprot-TrEMBL)
p-VGF ProteinO15240 (Uniprot-TrEMBL)
p-VWA1 ProteinQ6PCB0 (Uniprot-TrEMBL)
p-WFS1 ProteinO76024 (Uniprot-TrEMBL)
thrombin heavy chain ProteinP00734 (Uniprot-TrEMBL)
thrombin light chain ProteinP00734 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-8952289 (Reactome)
ATPR-HSA-8952289 (Reactome)
Cathepsin Gmim-catalysisR-HSA-381500 (Reactome)
FAM20C:FAM20AArrowR-HSA-8952289 (Reactome)
FAM20C:FAM20C substratesR-HSA-8952289 (Reactome)
FAM20C:FAM20C substratesmim-catalysisR-HSA-8952289 (Reactome)
FAM20C:Phosphorylated FAM20C substratesArrowR-HSA-8952289 (Reactome)
IGF1,2ArrowR-HSA-381435 (Reactome)
IGF1,2ArrowR-HSA-381446 (Reactome)
IGF1,2ArrowR-HSA-381461 (Reactome)
IGF1,2ArrowR-HSA-381466 (Reactome)
IGF1,2ArrowR-HSA-381500 (Reactome)
IGF1,2ArrowR-HSA-381518 (Reactome)
IGF1,2ArrowR-HSA-381537 (Reactome)
IGF1,2R-HSA-381412 (Reactome)
IGF1,2R-HSA-381487 (Reactome)
IGF1,2R-HSA-381496 (Reactome)
IGF1,2R-HSA-381503 (Reactome)
IGF1,2R-HSA-381543 (Reactome)
IGF1,2R-HSA-381545 (Reactome)
IGF:IGFBP1ArrowR-HSA-381487 (Reactome)
IGF:IGFBP2ArrowR-HSA-381412 (Reactome)
IGF:IGFBP3:ALSArrowR-HSA-381496 (Reactome)
IGF:IGFBP3:ALSR-HSA-381435 (Reactome)
IGF:IGFBP3:ALSR-HSA-381446 (Reactome)
IGF:IGFBP3:ALSR-HSA-381461 (Reactome)
IGF:IGFBP3:ALSR-HSA-381466 (Reactome)
IGF:IGFBP3:ALSR-HSA-381500 (Reactome)
IGF:IGFBP4ArrowR-HSA-381543 (Reactome)
IGF:IGFBP4R-HSA-381518 (Reactome)
IGF:IGFBP5:ALSArrowR-HSA-381545 (Reactome)
IGF:IGFBP5:ALSR-HSA-381537 (Reactome)
IGF:IGFBP6ArrowR-HSA-381503 (Reactome)
IGFALSArrowR-HSA-381435 (Reactome)
IGFALSArrowR-HSA-381446 (Reactome)
IGFALSArrowR-HSA-381461 (Reactome)
IGFALSArrowR-HSA-381466 (Reactome)
IGFALSArrowR-HSA-381500 (Reactome)
IGFALSArrowR-HSA-381537 (Reactome)
IGFALSR-HSA-381496 (Reactome)
IGFALSR-HSA-381545 (Reactome)
IGFBP1R-HSA-381487 (Reactome)
IGFBP2R-HSA-381412 (Reactome)
IGFBP3(125-187)ArrowR-HSA-381461 (Reactome)
IGFBP3(125-233)ArrowR-HSA-381446 (Reactome)
IGFBP3(127-291)ArrowR-HSA-381435 (Reactome)
IGFBP3(169-226)ArrowR-HSA-381500 (Reactome)
IGFBP3(188-291)ArrowR-HSA-381461 (Reactome)
IGFBP3(227-291)ArrowR-HSA-381500 (Reactome)
IGFBP3(234-291)ArrowR-HSA-381446 (Reactome)
IGFBP3(28-124)ArrowR-HSA-381446 (Reactome)
IGFBP3(28-124)ArrowR-HSA-381461 (Reactome)
IGFBP3(28-126)ArrowR-HSA-381435 (Reactome)
IGFBP3(28-168)ArrowR-HSA-381500 (Reactome)
IGFBP3(28-186)ArrowR-HSA-381466 (Reactome)
IGFBP3(291-187)ArrowR-HSA-381466 (Reactome)
IGFBP3R-HSA-381496 (Reactome)
IGFBP4(157-237)ArrowR-HSA-381518 (Reactome)
IGFBP4(22-156)ArrowR-HSA-381518 (Reactome)
IGFBP4R-HSA-381543 (Reactome)
IGFBP5(164-272)ArrowR-HSA-381537 (Reactome)
IGFBP5(21-163)ArrowR-HSA-381537 (Reactome)
IGFBP5R-HSA-381545 (Reactome)
IGFBP6R-HSA-381503 (Reactome)
MMP1,2mim-catalysisR-HSA-381435 (Reactome)
PAPPA,PAPPA2mim-catalysisR-HSA-381518 (Reactome)
PAPPA,PAPPA2mim-catalysisR-HSA-381537 (Reactome)
Plasminmim-catalysisR-HSA-381461 (Reactome)
Prostate Specific Antigenmim-catalysisR-HSA-381466 (Reactome)
R-HSA-381412 (Reactome) IGFBP 2 binds IGF I or IGF II via the conserved N terminus and C terminus of IGFBP 2.

IGFBP 2 is enriched in cerebrospinal fluid and inhibits IGF function. IGFBP 2 is not significantly degraded in circulation.


R-HSA-381435 (Reactome) Matrix Metalloprotease-1 and -2 cleave IGFBP-3 in the IGF:IGFBP-3:ALS Complex between amino acids 126 and 127, releasing IGF. The reaction has been demonstrated in vivo.
R-HSA-381446 (Reactome) Thrombin cleaves IGFBP-3 in the IGF:IGFBP-3:ALS Complex between amino acids 124 and 125 and between amino acids 233 and 234, releasing IGF.
R-HSA-381461 (Reactome) Plasmin cleaves IGFBP-3 in the IGF:IGFBP-3:ALS Complex between amino acids 124 and 125 and between amino acids 187 and 188, releasing IGF.
R-HSA-381466 (Reactome) Prostate specific Antigen (PSA, KLK3) cleaves IGFBP-3 in the IGF:IGFBP-3:ALS Complex between amino acids 186 and 187. Other cleavage sites were observed but not reproducibly. These may have been caused by impurities in the PSA preparation.
R-HSA-381487 (Reactome) IGFBP 1 binds IGF I or IGF II via the conserved N terminus and C terminus of IGFBP 1.

IGFBP 1 is enriched in amniotic fluid and is produced in the liver under control of insulin (insulin suppresses production). IGFBP 1 acts to stimulate IGF function. It is unknown which if any protease degrades IGFBP 1.


R-HSA-381496 (Reactome) IGFBP3 binds IGF I or IGF II via the conserved N terminus and C terminus of IGFBP 3. IGFBP3 also binds ALS via the C terminal portion of IGFBP3. The interaction is dependent on the glycosylation of ALS.
IGFBP3, which binds most IGF in the body, is enriched in follicular fluid and found in many other tissues. IGFBP3 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 stimulates the effects of IGFs.

R-HSA-381500 (Reactome) Cathepsin G cleaves IGFBP-3 between amino acids 168 and 169 and between amino acids 226 and 227, releasing IGF from the IGF:IGFBP-3:ALS Complex.
R-HSA-381503 (Reactome) IGFBP-6 binds IGF I or IGF II via the conserved N terminus and C terminus of IGFBP-6. IGFBP-6 binds IGF II with greater affinity than IGF I.
R-HSA-381518 (Reactome) Pregnancy associated Plasma Protein A (PPAP-A) cleaves IGFBP-4 in the IGF:IGFBP-4 Complex between amino acids 156 and 157, releasing IGF.
R-HSA-381537 (Reactome) Both Pregnancy Associated Plasma Protein A (PAPP-A) and A2 (PAPP-A2) cleave IGFBP-5 in the IGF:IGFBP-5:ALS Complex between amino acids 163 and 164, releasing IGF. PPAP-A has also been shown to cleave IGFBP-5 that is not complexed with IGF.
R-HSA-381543 (Reactome) IGFBP 4 binds IGF I or IGF II via the conserved N terminus and C terminus of IGFBP 4.
R-HSA-381545 (Reactome) IGFBP 5 binds IGF I or IGF II via the conserved N terminus and C terminus of IGFBP 5. IGFBP 5 also binds ALS via the central portion of IGFBP 5. About 55% of IGF:IGFBP 5 complexes contain ALS.

IGFBP 5 is enriched in bone matrix and acts to stimulate IGF function. IGFBP 5 is cleaved by Pregnancy associated Plasma Protein A2 (PAPP A2), ADAM 9, complement C1s from smooth muscle, and thrombin. Only the cleavage site for PAPP A2 is known. About 55% of IGF:IGFBP 5 complexes contain ALS; 45% contain only IGF and IGFBP 5.


R-HSA-8952289 (Reactome) Extracellular serine/threonine protein kinase FAM20C is an extracellular kinase that can phosphorylate a broad range of secreted protein. FAM20C is bound and allosterically activated by the pseudokinase FAM20A (Tagliabracchi et al. 2012, 2015, Cui et al. 2015).
Loss of function mutations in Fam20C cause Raine Syndrome, an osteosclerotic bone dysplasia (Faundes et al. 2014).
activated thrombin (factor IIa)mim-catalysisR-HSA-381446 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2799"
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