Insulin-like growth factor 2 receptor

Protein found in humans

This article is about the cation-independent mannose 6-phosphate receptor. For the cation-dependent receptor, see cation-dependent mannose-6-phosphate receptor.

IGF2R

| Available structures

PDB| Ortholog search: PDBe RCSB
| List of PDB id codes

1E6F, 1GP0, 1GP3, 1GQB, 1JPL, 1JWG, 1LF8, 2CNJ, 2V5N, 2V5O, 2V5P, 2L29, 2L2A, 2M68, 5IEI, 2M6T

Identifiers
Aliases| IGF2R, CD222, CIMPR, M6P-R, MPR1, MPRI, M6P/MPR 300, CI-M6PR, MPR300, insulin like growth factor 2 receptor
External IDs| OMIM: 147280; MGI: 96435; HomoloGene: 676; GeneCards: IGF2R; OMA:IGF2R - orthologs
| Gene location (Human)

Chr.| Chromosome 6 (human)[1]

Band| 6q25.3| Start| 159,969,082 bp[1]
End| 160,113,507 bp[1]
| Gene location (Mouse)

Chr.| Chromosome 17 (mouse)[2]

Band| 17 A1|17 8.64 cM| Start| 12,901,293 bp[2]
End| 12,988,551 bp[2]
| RNA expression pattern

Bgee| | Human| Mouse (ortholog)

|

| Top expressed in

* stromal cell of endometrium

* gastrocnemius muscle

* granulocyte

* blood

* muscle of thigh

* tibialis anterior muscle

* monocyte

* spleen

* upper lobe of left lung

* right adrenal cortex

| Top expressed in

* atrium

* umbilical cord

* atrioventricular valve

* internal carotid artery

* endocardial cushion

* lacrimal gland

* epithelium of small intestine

* human fetus

* left lung lobe

* Ileal epithelium

More reference expression data
BioGPS| |

More reference expression data
| Gene ontology

Molecular function|

* retinoic acid binding
* insulin-like growth factor binding
* G protein-coupled receptor activity
* transporter activity
* phosphoprotein binding
* insulin-like growth factor-activated receptor activity
* insulin-like growth factor II binding
* mannose binding
* identical protein binding
* enzyme binding
* G-protein alpha-subunit binding
* protein binding
* kringle domain binding
* signaling receptor activity

Cellular component|

* cytoplasm
* integral component of membrane
* endosome
* late endosome
* membrane
* focal adhesion
* clathrin coat
* endocytic vesicle
* integral component of plasma membrane
* cell surface
* lysosomal membrane
* trans-Golgi network
* early endosome
* nuclear envelope lumen
* perinuclear region of cytoplasm
* trans-Golgi network transport vesicle
* lysosome
* extracellular exosome
* nucleus
* trans-Golgi network membrane
* transport vesicle
* extracellular space
* Golgi apparatus
* plasma membrane
* clathrin-coated vesicle membrane
* secretory granule membrane
* clathrin-coated vesicle

Biological process|

* regulation of apoptotic process
* G protein-coupled receptor signaling pathway
* response to retinoic acid
* post-embryonic development
* receptor-mediated endocytosis
* animal organ regeneration
* spermatogenesis
* positive regulation of apoptotic process
* liver development
* signal transduction
* insulin-like growth factor receptor signaling pathway
* neutrophil degranulation
* membrane organization
* transport
* post-Golgi vesicle-mediated transport
* lysosomal transport

Sources:Amigo / QuickGO
| Orthologs

Species| Human| Mouse
Entrez| |

3482

16004

Ensembl| |

ENSG00000197081

ENSMUSG00000023830

UniProt| |

P11717

Q07113

RefSeq (mRNA)| |

NM_000876

NM_010515

RefSeq (protein)| |

NP_000867

NP_034645

Location (UCSC)| Chr 6: 159.97 – 160.11 Mb| Chr 17: 12.9 – 12.99 Mb
PubMed search| [3]| [4]
Wikidata
| View/Edit Human| View/Edit Mouse

|

Insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR) is a protein that in humans is encoded by the IGF2R gene.[5][6] IGF2R is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the trans-Golgi network.[6]

## Structure

[edit]

The structure of the IGF2R is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-terminus on the cytoplasmic side of lipid membranes) with a large extracellular/lumenal domain and a relatively short cytoplasmic tail.[7] The extracellular domain consists of a small region homologous to the collagen-binding domain of fibronectin and of fifteen repeats of approximately 147 amino acid residues. Each of these repeats is homologous to the 157-residue extracytoplasmic domain of the mannose 6-phosphate receptor. Binding to IGF2 is mediated through one of the repeats, while two different repeats are responsible for binding to mannose-6-phosphate. The IGF2R is approximately 300 kDa in size; it appears to exist and function as a dimer.

## Function

[edit]

IGF2R functions to clear IGF2 from the cell surface to attenuate signalling, and to transport lysosomal acid hydrolase precursors from the Golgi apparatus to the lysosome. After binding IGF2 at the cell surface, IGF2Rs accumulate in forming clathrin-coated vesicles and are internalized. In the lumen of the trans-Golgi network, the IGF2R binds M6P-tagged cargo.[7] The IGF2Rs (bound to their cargo) are recognized by the GGA family of clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles.[8] IGF2Rs from both the cell surface and the Golgi are trafficked to the early endosome where, in the relatively low pH environment of the endosome, the IGF2Rs release their cargo. The IGF2Rs are recycled back to the Golgi by the retromer complex, again by way of interaction with GGAs and vesicles. The cargo proteins are then trafficked to the lysosome via the late endosome independently of the IGF2Rs.

## Interactions

[edit]

Insulin-like growth factor 2 receptor has been shown to interact with M6PRBP1.[9][10]

## Evolution

[edit]

The insulin-like growth factor 2 receptor function evolved from the cation-independent mannose 6-phosphate receptor and is first seen in Monotremes. The IGF-2 binding site was likely acquired fortuitously with the generation of an exonic splice site enhancer cluster in exon 34, presumably necessitated by several kilobases of repeat element insertions in the preceding intron. A six-fold affinity maturation then followed during therian evolution, coincident with the onset of imprinting and consistent with the theory of parental conflict.[11]

## See also

[edit]

* Cluster of differentiation
* IGF-1 Receptor
* Mannose 6-phosphate receptor

## References

[edit]

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000197081 – Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023830 – Ensembl, May 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Oshima A, Nolan CM, Kyle JW, Grubb JH, Sly WS (February 1988). "The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells". J. Biol. Chem. 263 (5): 2553–62\. doi:10.1016/S0021-9258(18)69243-9. PMID 2963003.
6. ^ a b Laureys G, Barton DE, Ullrich A, Francke U (October 1988). "Chromosomal mapping of the gene for the type II insulin-like growth factor receptor/cation-independent mannose 6-phosphate receptor in man and mouse". Genomics. 3 (3): 224–9\. doi:10.1016/0888-7543(88)90083-3. PMID 2852162.
7. ^ a b Ghosh P, Dahms NM, Kornfeld S (March 2003). "Mannose 6-phosphate receptors: new twists in the tale". Nat. Rev. Mol. Cell Biol. 4 (3): 202–12\. doi:10.1038/nrm1050. PMID 12612639. S2CID 16991464.
8. ^ Ghosh P, Kornfeld S (July 2004). "The GGA proteins: key players in protein sorting at the trans-Golgi network". Eur. J. Cell Biol. 83 (6): 257–62\. doi:10.1078/0171-9335-00374. PMID 15511083.
9. ^ Díaz E, Pfeffer SR (May 1998). "TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking". Cell. 93 (3): 433–43\. doi:10.1016/S0092-8674(00)81171-X. PMID 9590177. S2CID 17161071.
10. ^ Orsel JG, Sincock PM, Krise JP, Pfeffer SR (August 2000). "Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein". Proc. Natl. Acad. Sci. U.S.A. 97 (16): 9047–51\. Bibcode:2000PNAS...97.9047O. doi:10.1073/pnas.160251397. PMC 16819. PMID 10908666.
11. ^ Williams C, Hoppe HJ, Rezgui D, Strickland M, Forbes BE, Grutzner F, Frago S, Ellis RZ, Wattana-Amorn P, Prince SN, Zaccheo OJ, Nolan CM, Mungall AJ, Jones EY, Crump MP, Hassan AB (November 2012). "Exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution". Science. 338 (6111): 1209–1213\. Bibcode:2012Sci...338.1209W. doi:10.1126/science.1228633. PMC 4658703. PMID 23197533.

## Further reading

[edit]

* O'Dell SD, Day IN (1998). "Insulin-like growth factor II (IGF-II)". Int. J. Biochem. Cell Biol. 30 (7): 767–71\. doi:10.1016/S1357-2725(98)00048-X. PMID 9722981.
* Hawkes C, Kar S (2004). "The insulin-like growth factor-II/mannose-6-phosphate receptor: structure, distribution and function in the central nervous system". Brain Res. Brain Res. Rev. 44 (2–3): 117–40\. doi:10.1016/j.brainresrev.2003.11.002. PMID 15003389. S2CID 20434586.2–3&rft.pages=117-40&rft.date=2004&rft_id=https://api.semanticscholar.org/CorpusID:20434586#id-name=S2CID&rft_id=info:pmid/15003389&rft_id=info:doi/10.1016/j.brainresrev.2003.11.002&rft.aulast=Hawkes&rft.aufirst=C&rft.au=Kar,+S&rfr_id=info:sid/en.wikipedia.org:Insulin-like+growth+factor+2+receptor" class="Z3988">
* Scott CD, Firth SM (2005). "The role of the M6P/IGF-II receptor in cancer: tumor suppression or garbage disposal?". Horm. Metab. Res. 36 (5): 261–71\. doi:10.1055/s-2004-814477. PMID 15156403. S2CID 260166901.
* Antoniades HN, Galanopoulos T, Neville-Golden J, Maxwell M (1992). "Expression of insulin-like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry". Int. J. Cancer. 50 (2): 215–22\. doi:10.1002/ijc.2910500210. PMID 1370435. S2CID 22632952.
* Zhou J, Bondy C (1992). "Insulin-like growth factor-II and its binding proteins in placental development". Endocrinology. 131 (3): 1230–40\. doi:10.1210/en.131.3.1230. PMID 1380437.
* Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA, Rutter WJ (1987). "Insulin-like growth factor II receptor as a multifunctional binding protein". Nature. 329 (6137): 301–7\. Bibcode:1987Natur.329..301M. doi:10.1038/329301a0. PMID 2957598. S2CID 4308631.
* Oshima A, Nolan CM, Kyle JW, Grubb JH, Sly WS (1988). "The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells". J. Biol. Chem. 263 (5): 2553–62\. doi:10.1016/S0021-9258(18)69243-9. PMID 2963003.
* De Souza AT, Hankins GR, Washington MK, Orton TC, Jirtle RL (1996). "M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity". Nat. Genet. 11 (4): 447–9\. doi:10.1038/ng1295-447. PMID 7493029. S2CID 21787312.
* Ilvesmäki V, Blum WF, Voutilainen R (1994). "Insulin-like growth factor binding proteins in the human adrenal gland". Mol. Cell. Endocrinol. 97 (1–2): 71–9\. doi:10.1016/0303-7207(93)90212-3. PMID 7511544. S2CID 22503525.1–2&rft.pages=71-9&rft.date=1994&rft_id=https://api.semanticscholar.org/CorpusID:22503525#id-name=S2CID&rft_id=info:pmid/7511544&rft_id=info:doi/10.1016/0303-7207(93)90212-3&rft.aulast=Ilvesmäki&rft.aufirst=V&rft.au=Blum,+WF&rft.au=Voutilainen,+R&rfr_id=info:sid/en.wikipedia.org:Insulin-like+growth+factor+2+receptor" class="Z3988">
* De Souza AT, Hankins GR, Washington MK, Fine RL, Orton TC, Jirtle RL (1995). "Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors". Oncogene. 10 (9): 1725–9\. PMID 7753549.
* Schmidt B, Kiecke-Siemsen C, Waheed A, Braulke T, von Figura K (1995). "Localization of the insulin-like growth factor II binding site to amino acids 1508-1566 in repeat 11 of the mannose 6-phosphate/insulin-like growth factor II receptor". J. Biol. Chem. 270 (25): 14975–82\. doi:10.1074/jbc.270.25.14975. PMID 7797478.
* Rao PH, Murty VV, Gaidano G, Hauptschein R, Dalla-Favera R, Chaganti RS (1994). "Subregional mapping of 8 single copy loci to chromosome 6 by fluorescence in situ hybridization". Cytogenet. Cell Genet. 66 (4): 272–3\. doi:10.1159/000133710. PMID 8162705.
* Ishiwata T, Bergmann U, Kornmann M, Lopez M, Beger HG, Korc M (1997). "Altered expression of insulin-like growth factor II receptor in human pancreatic cancer". Pancreas. 15 (4): 367–73\. doi:10.1097/00006676-199711000-00006. PMID 9361090. S2CID 42073680.
* Tikkanen R, Peltola M, Oinonen C, Rouvinen J, Peltonen L (1998). "Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase". EMBO J. 16 (22): 6684–93\. doi:10.1093/emboj/16.22.6684. PMC 1170273. PMID 9362483.
* Nykjaer A, Christensen EI, Vorum H, Hager H, Petersen CM, Røigaard H, Min HY, Vilhardt F, Møller LB, Kornfeld S, Gliemann J (1998). "Mannose 6-Phosphate/Insulin-like Growth Factor–II Receptor Targets the Urokinase Receptor to Lysosomes via a Novel Binding Interaction". J. Cell Biol. 141 (3): 815–28\. doi:10.1083/jcb.141.3.815. PMC 2132758. PMID 9566979.
* Díaz E, Pfeffer SR (1998). "TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking". Cell. 93 (3): 433–43\. doi:10.1016/S0092-8674(00)81171-X. PMID 9590177. S2CID 17161071.
* Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G (1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization". Cell. 94 (2): 205–16\. doi:10.1016/S0092-8674(00)81420-8. PMID 9695949. S2CID 15027198.
* Killian JK, Jirtle RL (1999). "Genomic structure of the human M6P/IGF2 receptor". Mamm. Genome. 10 (1): 74–7\. CiteSeerX 10.1.1.564.5806. doi:10.1007/s003359900947. PMID 9892739. S2CID 20181915.
* Kumar S, Hand AT, Connor JR, Dodds RA, Ryan PJ, Trill JJ, Fisher SM, Nuttall ME, Lipshutz DB, Zou C, Hwang SM, Votta BJ, James IE, Rieman DJ, Gowen M, Lee JC (1999). "Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions". J. Biol. Chem. 274 (24): 17123–31\. doi:10.1074/jbc.274.24.17123. PMID 10358067.

## External links

[edit]

* Insulin-Like-Growth-Factor+II+Receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

* v
* t
* e

PDB gallery

* 1e6f: HUMAN MIR-RECEPTOR, REPEAT 11

* 1gp0: HUMAN IGF2R DOMAIN 11

* 1gp3: HUMAN IGF2R DOMAIN 11

* 1gqb: HUMAN MIR-RECEPTOR, REPEAT 11

* 2cnj: NMR STUDIES ON THE INTERACTION OF INSULIN-GROWTH FACTOR II (IGF-II) WITH IGF2R DOMAIN 11

* v
* t
* e

Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1–50|

* CD1
* a-c
* 1A
* 1B
* 1D
* 1E
* CD2
* CD3
* γ
* δ
* ε
* CD4
* CD5
* CD6
* CD7
* CD8
* a
* CD9
* CD10
* CD11
* a
* b
* c
* d
* CD13
* CD14
* CD15
* CD16
* A
* B
* CD18
* CD19
* CD20
* CD21
* CD22
* CD23
* CD24
* CD25
* CD26
* CD27
* CD28
* CD29
* CD30
* CD31
* CD32
* A
* B
* CD33
* CD34
* CD35
* CD36
* CD37
* CD38
* CD39
* CD40
* CD41
* CD42
* a
* b
* c
* d
* CD43
* CD44
* CD45
* CD46
* CD47
* CD48
* CD49
* a
* b
* c
* d
* e
* f
* CD50

51–100|

* CD51
* CD52
* CD53
* CD54
* CD55
* CD56
* CD57
* CD58
* CD59
* CD61
* CD62
* E
* L
* P
* CD63
* CD64
* A
* B
* C
* CD66
* a
* b
* c
* d
* e
* f
* CD68
* CD69
* CD70
* CD71
* CD72
* CD73
* CD74
* CD78
* CD79
* a
* b
* CD80
* CD81
* CD82
* CD83
* CD84
* CD85
* a
* d
* e
* h
* j
* k
* CD86
* CD87
* CD88
* CD89
* CD90
* CD91 \- CD92
* CD93
* CD94
* CD95
* CD96
* CD97
* CD98
* CD99
* CD100

101–150|

* CD101
* CD102
* CD103
* CD104
* CD105
* CD106
* CD107
* a
* b
* CD108
* CD109
* CD110
* CD111
* CD112
* CD113
* CD114
* CD115
* CD116
* CD117
* CD118
* CD119
* CD120
* a
* b
* CD121
* a
* b
* CD122
* CD123
* CD124
* CD125
* CD126
* CD127
* CD129
* CD130
* CD131
* CD132
* CD133
* CD134
* CD135
* CD136
* CD137
* CD138
* CD140b
* CD141
* CD142
* CD143
* CD144
* CD146
* CD147
* CD148
* CD150

151–200|

* CD151
* CD152
* CD153
* CD154
* CD155
* CD156
* a
* b
* c
* CD157
* CD158 (a
* d
* e
* i
* k)
* CD159
* a
* c
* CD160
* CD161
* CD162
* CD163
* CD164
* CD166
* CD167
* a
* b
* CD168
* CD169
* CD170
* CD171
* CD172
* a
* b
* g
* CD174
* CD177
* CD178
* CD179
* a
* b
* CD180
* CD181
* CD182
* CD183
* CD184
* CD185
* CD186
* CD191
* CD192
* CD193
* CD194
* CD195
* CD196
* CD197
* CDw198
* CDw199
* CD200

201–250|

* CD201
* CD202b
* CD204
* CD205
* CD206
* CD207
* CD208
* CD209
* CDw210
* a
* b
* CD212
* CD213a
* 1
* 2
* CD217
* CD218 (a
* b)
* CD220
* CD221
* CD222
* CD223
* CD224
* CD225
* CD226
* CD227
* CD228
* CD229
* CD230
* CD233
* CD234
* CD235
* a
* b
* CD236
* CD238
* CD239
* CD240CE
* CD240D
* CD241
* CD243
* CD244
* CD246
* CD247 \- CD248
* CD249

251–300|

* CD252
* CD253
* CD254
* CD256
* CD257
* CD258
* CD261
* CD262
* CD263
* CD264
* CD265
* CD266
* CD267
* CD268
* CD269
* CD271
* CD272
* CD273
* CD274
* CD275
* CD276
* CD278
* CD279
* CD280
* CD281
* CD282
* CD283
* CD284
* CD286
* CD288
* CD289
* CD290
* CD292
* CDw293
* CD294
* CD295
* CD297
* CD298
* CD299

301–350|

* CD300A
* CD301
* CD302
* CD303
* CD304
* CD305
* CD306
* CD307
* CD309
* CD312
* CD314
* CD315
* CD316
* CD317
* CD318
* CD320
* CD321
* CD322
* CD324
* CD325
* CD326
* CD327
* CD328
* CD329
* CD331
* CD332
* CD333
* CD334
* CD335
* CD336
* CD337
* CD338
* CD339
* CD340
* CD344
* CD349
* CD350

* v
* t
* e

Receptors: growth factor receptors

Type I cytokine receptor|

* Nerve growth factors: Ciliary neurotrophic factor
* Erythropoietin

Receptor protein serine/threonine kinase|

* TGF pathway: TGF-beta
* 1
* 2
* Activin
* 1
* 2
* Bone morphogenetic protein
* 1
* 2

Receptor tyrosine kinase|

* Fibroblast growth factor
* 1
* 2
* 3
* 4

* Nerve growth factors: high affinity Trk
* TrkA
* TrkB
* TrkC

* Hepatocyte growth factor

* Somatomedin
* Insulin-like growth factor 1

* ErbB/Epidermal growth factor

* VEGF
* 1
* 2
* 3

Tumor necrosis factor receptor|

* Nerve growth factors: Low affinity/p75

Ig superfamily|

* Platelet-derived growth factor
* A
* B
* Stem cell factor

Other/ungrouped|

* Somatomedin
* Insulin-like growth factor 2

* v
* t
* e

Growth factor receptor modulators

Angiopoietin|

* Agonists: Angiopoietin 1
* Angiopoietin 4

* Antagonists: Angiopoietin 2
* Angiopoietin 3

* Kinase inhibitors: Altiratinib
* CE-245677
* Rebastinib

* Antibodies: Evinacumab (against angiopoietin 3)
* Nesvacumab (against angiopoietin 2)

CNTF|

* Agonists: Axokine
* CNTF
* Dapiclermin

EGF (ErbB)|

| EGF
(ErbB1/HER1)|

* Agonists: Amphiregulin
* Betacellulin
* EGF (urogastrone)
* Epigen
* Epiregulin
* Heparin-binding EGF-like growth factor (HB-EGF)
* Murodermin
* Nepidermin
* Transforming growth factor alpha (TGFα)

* Kinase inhibitors: Afatinib
* Agerafenib
* Brigatinib
* Canertinib
* Dacomitinib
* Erlotinib
* Gefitinib
* Grandinin
* Icotinib
* Lapatinib
* Neratinib
* Osimertinib
* Vandetanib
* WHI-P 154

* Antibodies: Cetuximab
* Depatuxizumab
* Depatuxizumab mafodotin
* Futuximab
* Imgatuzumab
* Matuzumab
* Necitumumab
* Nimotuzumab
* Panitumumab
* Zalutumumab

|

ErbB2/HER2|

* Agonists: Unknown/none

* Antibodies: Ertumaxomab
* Pertuzumab
* Trastuzumab
* Trastuzumab deruxtecan
* Trastuzumab duocarmazine
* Trastuzumab emtansine

* Kinase inhibitors: Afatinib
* Lapatinib
* Mubritinib
* Neratinib
* Tucatinib

ErbB3/HER3|

* Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C))

* Antibodies: Duligotumab
* Patritumab
* Seribantumab

ErbB4/HER4|

* Agonists: Betacellulin
* Epigen
* Heparin-binding EGF-like growth factor (HB-EGF)
* Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))

FGF|

| FGFR1|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20)
* Repifermin
* Selpercatinib
* Trafermin
* Velafermin

|

FGFR2|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22)
* Palifermin
* Repifermin
* Selpercatinib
* Sprifermin
* Trafermin

* Antibodies: Aprutumab
* Aprutumab ixadotin

* Kinase inhibitors: Infigratinib

FGFR3|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 4, 8, 9, 18, 23)
* Selpercatinib
* Sprifermin
* Trafermin

* Antibodies: Burosumab (against FGF23)

FGFR4|

* Agonists: Ersofermin
* FGF (1, 2 (bFGF), 4, 6, 8, 9, 19)
* Trafermin

Unsorted|

* Agonists: FGF15/19

HGF (c-Met)|

* Agonists: Fosgonimeton
* Hepatocyte growth factor

* Potentiators: Dihexa (PNB-0408)

* Kinase inhibitors: Altiratinib
* AM7
* AMG-458
* Amuvatinib
* BMS-777607
* Cabozantinib
* Capmatinib
* Crizotinib
* Foretinib
* Golvatinib
* INCB28060
* JNJ-38877605
* K252a
* MK-2461
* PF-04217903
* PF-2341066
* PHA-665752
* SU-11274
* Tivantinib
* Volitinib

* Antibodies: Emibetuzumab
* Ficlatuzumab
* Flanvotumab
* Onartuzumab
* Rilotumumab
* Telisotuzumab
* Telisotuzumab vedotin

IGF|

| IGF-1|

* Agonists: des(1-3)IGF-1
* Insulin-like growth factor-1 (somatomedin C)
* IGF-1 LR3
* Insulin-like growth factor-2 (somatomedin A)
* Insulin
* Mecasermin
* Mecasermin rinfabate

* Kinase inhibitors: BMS-754807
* Linsitinib
* NVP-ADW742
* NVP-AEW541
* OSl-906

* Antibodies: AVE-1642
* Cixutumumab
* Dalotuzumab
* Figitumumab
* Ganitumab
* Robatumumab
* R1507
* Teprotumumab
* Xentuzumab (against IGF-1 and IGF-2)

|

IGF-2|

* Agonists: Insulin-like growth factor-2 (somatomedin A)

* Antibodies: Dusigitumab
* Xentuzumab (against IGF-1 and IGF-2)

Others|

* Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7)

* Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1)
* Trofinetide

LNGF (p75NTR)|

* Agonists: BDNF
* BNN-20
* BNN-27
* Cenegermin
* DHEA
* DHEA-S
* NGF
* NT-3
* NT-4

* Antagonists: ALE-0540
* Dexamethasone
* EVT-901 (SAR-127963)
* Testosterone

* Antibodies: Against NGF: ABT-110 (PG110)
* ASP-6294
* Fasinumab
* Frunevetmab
* Fulranumab
* MEDI-578
* Ranevetmab
* Tanezumab

* Aptamers: Against NGF: RBM-004

* Decoy receptors: LEVI-04 (p75NTR-Fc)

PDGF|

* Agonists: Becaplermin
* Platelet-derived growth factor (A, B, C, D)

* Kinase inhibitors: Agerafenib
* Avapritinib
* Axitinib
* Crenolanib
* Imatinib
* Lenvatinib
* Masitinib
* Motesanib
* Nintedanib
* Pazopanib
* Radotinib
* Quizartinib
* Ripretinib
* Sunitinib
* Sorafenib
* Toceranib

* Antibodies: Olaratumab
* Ramucirumab
* Tovetumab

RET (GFL)|

| GFRα1|

* Agonists: Glial cell line-derived neurotrophic factor (GDNF)
* Liatermin

* Kinase inhibitors: Vandetanib

|

GFRα2|

* Agonists: Neurturin (NRTN)

* Kinase inhibitors: Vandetanib

GFRα3|

* Agonists: Artemin (ARTN)

* Kinase inhibitors: Vandetanib

GFRα4|

* Agonists: Persephin (PSPN)

* Kinase inhibitors: Vandetanib

Unsorted|

* Kinase inhibitors: Agerafenib

SCF (c-Kit)|

* Agonists: Ancestim
* Stem cell factor

* Kinase inhibitors: Agerafenib
* Axitinib
* Dasatinib
* Imatinib
* Masitinib
* Nilotinib
* Pazopanib
* Quizartinib
* Sorafenib
* Sunitinib
* Toceranib

TGFβ|

* See here instead.

Trk|

| TrkA|

* Agonists: Amitriptyline
* BNN-20
* BNN-27
* Cenegermin
* DHEA
* DHEA-S
* Gambogic amide
* NGF
* Tavilermide

* Antagonists: ALE-0540
* Dexamethasone
* FX007
* Testosterone

* Negative allosteric modulators: VM-902A

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* Milciclib
* ONO-4474
* ONO-5390556
* PLX-7486
* Rebastinib
* SNA-120 (pegylated K252a))

* Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110)
* ASP-6294
* Fasinumab
* Frunevetmab
* Fulranumab
* MEDI-578
* Ranevetmab
* Tanezumab

* Aptamers: Against NGF: RBM-004

* Decoy receptors: ReN-1820 (TrkAd5)

|

TrkB|

* Agonists: 3,7-DHF
* 3,7,8,2'-THF
* 4'-DMA-7,8-DHF
* 7,3'-DHF
* 7,8-DHF
* 7,8,2'-THF
* 7,8,3'-THF
* Amitriptyline
* BDNF
* BNN-20
* Deoxygedunin
* Deprenyl
* Diosmetin
* DMAQ-B1
* HIOC
* LM22A-4
* N-Acetylserotonin
* NT-3
* NT-4
* Norwogonin (5,7,8-THF)
* R7
* R13
* TDP6

* Antagonists: ANA-12
* Cyclotraxin B
* Gossypetin (3,5,7,8,3',4'-HHF)

* Ligands: DHEA

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* ONO-4474
* ONO-5390556
* PLX-7486

TrkC|

* Agonists: BNN-20
* DHEA
* NT-3

* Kinase inhibitors: Altiratinib
* AZD-6918
* CE-245677
* CH-7057288
* DS-6051
* Entrectinib
* GZ-389988
* K252a
* Larotrectinib
* Lestaurtinib
* ONO-4474
* ONO-5390556
* PLX-7486

VEGF|

* Agonists: Placental growth factor (PGF)
* Ripretinib
* Telbermin
* VEGF (A, B, C, D (FIGF))

* Allosteric modulators: Cyclotraxin B

* Kinase inhibitors: Agerafenib
* Altiratinib
* Axitinib
* Cabozantinib
* Cediranib
* Fruquintinib
* Lapatinib
* Lenvatinib
* Motesanib
* Nintedanib
* Pazopanib
* Pegaptanib
* Rebastinib
* Regorafenib
* Semaxanib
* Sorafenib
* Sunitinib
* Toceranib
* Tivozanib
* Vandetanib
* WHI-P 154

* Antibodies: Alacizumab pegol
* Bevacizumab
* Icrucumab
* Ramucirumab
* Ranibizumab

* Decoy receptors: Aflibercept

Others|

* Additional growth factors: Adrenomedullin
* Colony-stimulating factors (see here instead)
* Connective tissue growth factor (CTGF)
* Ephrins (A1, A2, A3, A4, A5, B1, B2, B3)
* Erythropoietin (see here instead)
* Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
* Glia maturation factor (GMF)
* Hepatoma-derived growth factor (HDGF)
* Interleukins/T-cell growth factors (see here instead)
* Leukemia inhibitory factor (LIF)
* Macrophage-stimulating protein (MSP; HLP, HGFLP)
* Midkine (NEGF2)
* Migration-stimulating factor (MSF; PRG4)
* Oncomodulin
* Pituitary adenylate cyclase-activating peptide (PACAP)
* Pleiotrophin
* Renalase
* Thrombopoietin (see here instead)
* Wnt signaling proteins

* Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)

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