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

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10, 11, 14, 16, 31...4, 10, 11, 14, 15, 25...10, 11, 14, 22, 44...2, 9-11, 14...7, 10, 11, 14, 21...2, 10, 11, 14, 15, 21...6, 10, 11, 14, 16...3, 10, 11, 14, 15, 21...10, 11, 14, 19, 4410-12, 14, 26...458, 10, 11, 14, 31...185, 10, 11, 13, 14, 17...10, 11, 14, 15, 21...PDIA6 PRKCSH PLG(581-810) PCSK9 IGFBP4 NUCB1 p-MSLN APP APOA1 IGFBP1 IGF:IGFBP6KLK2 p-SERPINA1 CSF1 p-MBTPS1 SPP2 FUCA2 p-ALB p-CSF1 p-FGF23 MIA3 PNPLA2 p-FUCA2 p-SDC2 p-PRSS23 NOTUM MMP1(100-469) AFP p-LAMB2 IGF1 STC2 p-ANO8 p-Factor V precursor IGF1,2p-SPP1 IGFBP3(28-124)IGF1 p-SCG2 IGFBP3(28-168)p-SHISA5 IGF1 IGFBP2 IGFBP5 IGF2(25-91) p-VCAN AMTN p-IGFBP1 p-MEPE AHSG IGFBP3(291-187)IGFBP3(127-291)HSP90B1 p-TNC ADAM10 LAMC1 p-KNG1 PAPPA2 p-APOE p-MEN1 p-WFS1 p-FBN1 SDC2 p-BMP15 CP p-C3 VCAN LAMB2 MMP2(110-660) IGFBP3(188-291)p-FSTL3 p-IGFBP7 p-IGFBP4 p-LGALS1 KNG1 LAMB1 p-FSTL1 p-CALU p-RCN1 MMP1,2IGFBP5(21-163)PAPPA p-GPC3 SPARCL1 APLP2 p-PDIA6 IGF1 MXRA8 p-APOA2 IGFBP3(28-186)p-APLP2 p-PCSK9 IGFBP4p-MIA3 WFS1 p-VWA1 CDH2 IGF1 p-PROC p-EVA1A IGF2(25-91) IGF2(25-91) PENK MSLN CTSG IGFBP7 p-CYR61 p-APOL1 IGFBP2IGFALS p-FGG p-STC2 BPIFB2 p-GAS6 p-APP p-LAMB1 Ca2+ p-TMEM132A FBN1 FAM20C p-CST3 VGF LGALS1 SCG3 p-BPIFB2 TF IGFBP4(157-237)LTBP1 p-PENK IGFBP4 TGOLN2 KTN1 IGF1 PROC HRC SHISA5 p-QSOX1 p-MXRA8 PlasminIGF2(25-91) APOL1 APOA2 AMELX p-AMTN MELTF IGFBP5 APOB(28-4563) IGFBP5IGFBP3(234-291)CHGB KLK3 P4HB p-MFGE8 IGFBP1p-GOLM1 FGG FSTL1 QSOX1 AMBN IGF2(25-91) IGFBP3ENAM BMP4 GOLM1 DMP1 SCG2 KLK13 p-AHSG IGFBP3 GPC3 p-PRKCSH C4A p-AMELX p-ENAM KLK1 p-IGFBP5 p-IGFBP3 p-AFP IGFBP1 MEN1 GZMH CKAP4 VWA1 SERPINC1 p-CHGB RCN1 p-NUCB1 APOE p-CP thrombin light chain p-C4A SPP1 GAS6 IGF:IGFBP1IGFALS EVA1A IGF1,2TIMP1 SERPINA1 p-DNAJC3 ALB p-TIMP1 CYR61 IGF1 p-BMP4 p-CKAP4 IGFBP6MFGE8 TNC IGFALSIGF2(25-91) p-KTN1 IGFBP3(125-187)IGFBP5(164-272)p-TGOLN2 p-MGAT4A p-PNPLA2 IGF1 IGFBP3(28-126)FAM20C p-HRC PRSS23 p-SCG3 p-CDH2 p-DMP1 SERPINA10 DNAJC3 IGFBP4(22-156)APOA5 Cathepsin Gp-VGF p-TF Factor V precursor MEPE ANO8 MBTPS1 IGFBP3(227-291)CHRDL1 IGF:IGFBP5:ALSp-P4HB p-LAMC1 p-ADAM10 p-SPARCL1 CST3 p-LTBP1 CALU p-APOA5 IGFBP3(125-233)IGFBP3 PLG(20-580) IGFBP3(169-226)FGF23 FAM20C:FAM20CsubstratesIGF2(25-91) MATN3 p-MATN3 IGF2(25-91) p-APOB(28-4563) p-ITIH2 thrombin heavy chain p-FGA p-SERPINA10 BMP15 p-MELTF p-APOA1 Prostate SpecificAntigenp-FN1 FN1 FAM20C:Phosphorylated FAM20C substratesp-SERPIND1 p-NOTUM IL6 p-IL6 MGAT4A FGA IGF:IGFBP2IGFALSIGF:IGFBP3:ALSITIH2 activated thrombin(factor IIa)FSTL3 PAPPA,PAPPA2p-HSP90B1 TMEM132A SERPIND1 IGFBP6 p-SPP2 p-CHRDL1 p-AMBN p-SERPINC1 C3 IGF:IGFBP41, 201, 203329


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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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)
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)
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)
FAM20C ProteinQ8IXL6 (Uniprot-TrEMBL)
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
Cathepsin Gmim-catalysisR-HSA-381500 (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)
IGFBP1mim-catalysisR-HSA-381487 (Reactome)
IGFBP2R-HSA-381412 (Reactome)
IGFBP2mim-catalysisR-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)
IGFBP3mim-catalysisR-HSA-381496 (Reactome)
IGFBP4(157-237)ArrowR-HSA-381518 (Reactome)
IGFBP4(22-156)ArrowR-HSA-381518 (Reactome)
IGFBP4R-HSA-381543 (Reactome)
IGFBP4mim-catalysisR-HSA-381543 (Reactome)
IGFBP5(164-272)ArrowR-HSA-381537 (Reactome)
IGFBP5(21-163)ArrowR-HSA-381537 (Reactome)
IGFBP5R-HSA-381545 (Reactome)
IGFBP5mim-catalysisR-HSA-381545 (Reactome)
IGFBP6R-HSA-381503 (Reactome)
IGFBP6mim-catalysisR-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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