Insulin-like growth factor 2 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 blood tibialis anterior muscle monocyte spleen upper lobe of left lung right lung left adrenal gland islet of Langerhans Top expressed in atrium belly cord atrioventricular valve internal carotid artery endocardial cushion lacrimal gland left lung lobe abdominal wall calvaria right ventricle 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
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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

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

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

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

Evolution

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

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

References

Further reading

External links

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