Insulin-like growth factor 2 receptor: Difference between revisions

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)
End	160,113,507 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	12,988,551 bp
RNA expression pattern
	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
	; ;
	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
	3482
	16004
	ENSG00000197081
	ENSMUSG00000023830
	P11717
	Q07113
	NM_000876
	NM_010515
	NP_000867
	NP_034645
	Wikidata
View/Edit Human	View/Edit Mouse

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Latest revision as of 16:27, 25 May 2024

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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000197081 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000023830 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^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.
^ ^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.
^ 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.
^ 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.
^ 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.
^ 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.

External links

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000197081 – Ensembl, May 2017

[refGRCm38Ensembl-2] 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.

[pmid2963003-5] 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.

[pmid2852162-6] 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.

[pmid12612639-7] 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.

[pmid15511083-8] 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.

[pmid9590177-9] 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.

[pmid10908666-10] 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.

[PMID_23197533-11] 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.

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@@ Line 1: / Line 1: @@
+{{cs1 config|name-list-style=vanc}}
-{{PBB|geneid=3482}}
+{{Short description|Protein found in humans}}
 {{about|the cation-independent mannose 6-phosphate receptor|the cation-dependent receptor|cation-dependent mannose-6-phosphate receptor}}
+{{Infobox_gene}}
-In the fields of [[biochemistry]] and [[cell biology]], the '''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]].<ref name="pmid2963003">{{cite journal | author = Oshima A, Nolan CM, Kyle JW, Grubb JH, Sly WS | title = The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells | journal = J. Biol. Chem. | volume = 263 | issue = 5 | pages = 2553–62 | year = 1988 | month = February | pmid = 2963003 | doi = | url =  }}</ref><ref name="pmid2852162">{{cite journal | author = Laureys G, Barton DE, Ullrich A, Francke U | title = Chromosomal mapping of the gene for the type II insulin-like growth factor receptor/cation-independent mannose 6-phosphate receptor in man and mouse | journal = Genomics | volume = 3 | issue = 3 | pages = 224–9 | year = 1988 | month = October | pmid = 2852162 | doi = 10.1016/0888-7543(88)90083-3| url =  }}</ref> IGF2R is a multifunctional protein [[receptor (biochemistry)|receptor]] that binds [[insulin-like growth factor 2]] (IGF2) at the [[plasma membrane|cell surface]] and [[mannose-6-phosphate]] (M6P)-tagged proteins in the ''trans''-[[Golgi apparatus|Golgi network]].<ref name="pmid2852162"/>
+'''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]].<ref name="pmid2963003">{{cite journal |vauthors=Oshima A, Nolan CM, Kyle JW, Grubb JH, Sly WS | title = The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells | journal = J. Biol. Chem. | volume = 263 | issue = 5 | pages = 2553–62 | date = February 1988 | doi = 10.1016/S0021-9258(18)69243-9 | pmid = 2963003 | doi-access = free }}</ref><ref name="pmid2852162">{{cite journal |vauthors=Laureys G, Barton DE, Ullrich A, Francke U | title = Chromosomal mapping of the gene for the type II insulin-like growth factor receptor/cation-independent mannose 6-phosphate receptor in man and mouse | journal = Genomics | volume = 3 | issue = 3 | pages = 224–9 | date = October 1988 | pmid = 2852162 | doi = 10.1016/0888-7543(88)90083-3 }}</ref> IGF2R is a multifunctional protein [[receptor (biochemistry)|receptor]] that binds [[insulin-like growth factor 2]] (IGF2) at the [[plasma membrane|cell surface]] and [[mannose-6-phosphate]] (M6P)-tagged proteins in the ''trans''-[[Golgi apparatus|Golgi network]].<ref name="pmid2852162"/>
 == 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 [[cytoplasm]]ic side of [[lipid bilayer|lipid membrane]]s) with a large extracellular/lumenal domain and a relatively short cytoplasmic tail.<ref name="pmid12612639"/> 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 [[kiloDalton|kDa]] in size; it appears to exist and function as a [[protein dimer|dimer]].
+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 [[cytoplasm]]ic side of [[lipid bilayer|lipid membrane]]s) with a large extracellular/lumenal domain and a relatively short cytoplasmic tail.<ref name="pmid12612639"/> 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 [[kiloDalton|kDa]] in size; it appears to exist and function as a [[protein dimer|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 [[vesicle (biology)|vesicles]] and are [[endocytosis|internalized]]. In the [[Lumen (anatomy)|lumen]] of the ''trans''-Golgi network, the IGF2R binds M6P-tagged cargo.<ref name="pmid12612639">{{cite journal | author = Ghosh P, Dahms NM, Kornfeld S | title = Mannose 6-phosphate receptors: new twists in the tale | journal = Nat. Rev. Mol. Cell Biol. | volume = 4 | issue = 3 | pages = 202–12 | year = 2003 | month = March | pmid = 12612639 | doi = 10.1038/nrm1050 | url =  }}</ref> The IGF2Rs (bound to their cargo) are recognized by the [[GGA1|GGA]] family of [[clathrin]] adaptor proteins and accumulate in forming clathrin-coated vesicles.<ref name="pmid15511083">{{cite journal | author = Ghosh P, Kornfeld S | title = The GGA proteins: key players in protein sorting at the trans-Golgi network | journal = Eur. J. Cell Biol. | volume = 83 | issue = 6 | pages = 257–62 | year = 2004 | month = July | pmid = 15511083 | doi = 10.1078/0171-9335-00374 | url =  }}</ref> 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.
+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 [[vesicle (biology)|vesicles]] and are [[endocytosis|internalized]]. In the [[Lumen (anatomy)|lumen]] of the ''trans''-Golgi network, the IGF2R binds M6P-tagged cargo.<ref name="pmid12612639">{{cite journal |vauthors=Ghosh P, Dahms NM, Kornfeld S | title = Mannose 6-phosphate receptors: new twists in the tale | journal = Nat. Rev. Mol. Cell Biol. | volume = 4 | issue = 3 | pages = 202–12 | date = March 2003 | pmid = 12612639 | doi = 10.1038/nrm1050 | s2cid = 16991464 }}</ref> The IGF2Rs (bound to their cargo) are recognized by the [[GGA1|GGA]] family of [[clathrin]] adaptor proteins and accumulate in forming clathrin-coated vesicles.<ref name="pmid15511083">{{cite journal |vauthors=Ghosh P, Kornfeld S | title = The GGA proteins: key players in protein sorting at the trans-Golgi network | journal = Eur. J. Cell Biol. | volume = 83 | issue = 6 | pages = 257–62 | date = July 2004 | pmid = 15511083 | doi = 10.1078/0171-9335-00374 }}</ref> 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 [[Protein-protein_interaction|interact]] with [[M6PRBP1]].<ref name="pmid9590177">{{cite journal | author = Díaz E, Pfeffer SR | title = TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking | journal = Cell | volume = 93 | issue = 3 | pages = 433–43 | year = 1998 | month = May | pmid = 9590177 | doi = 10.1016/S0092-8674(00)81171-X| url =  }}</ref><ref name="pmid10908666">{{cite journal | author = Orsel JG, Sincock PM, Krise JP, Pfeffer SR | title = Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 16 | pages = 9047–51 | year = 2000 | month = August | pmid = 10908666 | pmc = 16819 | doi = 10.1073/pnas.160251397 | url =  }}</ref>
+Insulin-like growth factor 2 receptor has been shown to [[Protein-protein interaction|interact]] with [[M6PRBP1]].<ref name="pmid9590177">{{cite journal |vauthors=Díaz E, Pfeffer SR | title = TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking | journal = Cell | volume = 93 | issue = 3 | pages = 433–43 | date = May 1998 | pmid = 9590177 | doi = 10.1016/S0092-8674(00)81171-X | s2cid = 17161071 | doi-access = free }}</ref><ref name="pmid10908666">{{cite journal |vauthors=Orsel JG, Sincock PM, Krise JP, Pfeffer SR | title = Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 16 | pages = 9047–51 | date = August 2000 | pmid = 10908666 | pmc = 16819 | doi = 10.1073/pnas.160251397 | bibcode = 2000PNAS...97.9047O | doi-access = free }}</ref>
 == 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.  <ref name="PMID: 23197533 ">{{cite journal | author = Williams C, Hoppe HJ et al. | title = Exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution | journal = Science | volume = 338 | issue = 6111 | pages = 1209-1213 | year = 2012| month = November| pmid = 23197533 | doi = 10.1126/science.1228633| url =  }}</ref>
+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.<ref name="PMID 23197533 ">{{cite journal |vauthors=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 | title = Exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution | journal = Science | volume = 338 | issue = 6111 | pages = 1209–1213 | date = November 2012 | pmid = 23197533 | doi = 10.1126/science.1228633 | pmc=4658703| bibcode = 2012Sci...338.1209W }}</ref>
 ==See also==
@@ Line 26: / Line 28: @@
 == References ==
-{{Reflist}}
+{{Reflist|35em}}
 == Further reading ==
-{{refbegin | 2}}
+{{refbegin|35em}}
+*{{cite journal |vauthors=O'Dell SD, Day IN | title = Insulin-like growth factor II (IGF-II) | journal = Int. J. Biochem. Cell Biol. | volume = 30 | issue = 7 | pages = 767–71 | year = 1998 | pmid = 9722981 | doi = 10.1016/S1357-2725(98)00048-X }}
-{{PBB_Further_reading
+*{{cite journal |vauthors=Hawkes C, Kar S | title = The insulin-like growth factor-II/mannose-6-phosphate receptor: structure, distribution and function in the central nervous system | journal = Brain Res. Brain Res. Rev. | volume = 44 | issue = 2–3 | pages = 117–40 | year = 2004 | pmid = 15003389 | doi = 10.1016/j.brainresrev.2003.11.002 | s2cid = 20434586 }}
-| citations =
-*{{cite journal  | author=O'Dell SD, Day IN |title=Insulin-like growth factor II (IGF-II) |journal=Int. J. Biochem. Cell Biol. |volume=30 |issue= 7 |pages= 767–71 |year= 1998 |pmid= 9722981 |doi=10.1016/S1357-2725(98)00048-X  }}
+*{{cite journal |vauthors=Scott CD, Firth SM | title = The role of the M6P/IGF-II receptor in cancer: tumor suppression or garbage disposal? | journal = Horm. Metab. Res. | volume = 36 | issue = 5 | pages = 261–71 | year = 2005 | pmid = 15156403 | doi = 10.1055/s-2004-814477 | s2cid = 260166901 }}
-*{{cite journal  | author=Hawkes C, Kar S |title=The insulin-like growth factor-II/mannose-6-phosphate receptor: structure, distribution and function in the central nervous system |journal=Brain Res. Brain Res. Rev. |volume=44 |issue= 2–3 |pages= 117–40 |year= 2004 |pmid= 15003389 |doi= 10.1016/j.brainresrev.2003.11.002 }}
+*{{cite journal |vauthors=Antoniades HN, Galanopoulos T, Neville-Golden J, Maxwell M | title = 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 | journal = Int. J. Cancer | volume = 50 | issue = 2 | pages = 215–22 | year = 1992 | pmid = 1370435 | doi = 10.1002/ijc.2910500210 | s2cid = 22632952 }}
-*{{cite journal  | author=Scott CD, Firth SM |title=The role of the M6P/IGF-II receptor in cancer: tumor suppression or garbage disposal? |journal=Horm. Metab. Res. |volume=36 |issue= 5 |pages= 261–71 |year= 2005 |pmid= 15156403 |doi= 10.1055/s-2004-814477 }}
+*{{cite journal |vauthors=Zhou J, Bondy C | title = Insulin-like growth factor-II and its binding proteins in placental development | journal = Endocrinology | volume = 131 | issue = 3 | pages = 1230–40 | year = 1992 | pmid = 1380437 | doi = 10.1210/en.131.3.1230 }}
-*{{cite journal  | author=Antoniades HN, Galanopoulos T, Neville-Golden J, Maxwell M |title=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 |journal=Int. J. Cancer |volume=50 |issue= 2 |pages= 215–22 |year= 1992 |pmid= 1370435 |doi=10.1002/ijc.2910500210  }}
+*{{cite journal |vauthors=Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA, Rutter WJ | title = Insulin-like growth factor II receptor as a multifunctional binding protein | journal = Nature | volume = 329 | issue = 6137 | pages = 301–7 | year = 1987 | pmid = 2957598 | doi = 10.1038/329301a0 | bibcode = 1987Natur.329..301M | s2cid = 4308631 }}
-*{{cite journal  | author=Zhou J, Bondy C |title=Insulin-like growth factor-II and its binding proteins in placental development |journal=Endocrinology |volume=131 |issue= 3 |pages= 1230–40 |year= 1992 |pmid= 1380437 |doi=10.1210/en.131.3.1230  }}
+*{{cite journal |vauthors=Oshima A, Nolan CM, Kyle JW, Grubb JH, Sly WS | title = The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells | journal = J. Biol. Chem. | volume = 263 | issue = 5 | pages = 2553–62 | year = 1988 | doi = 10.1016/S0021-9258(18)69243-9 | pmid = 2963003 | doi-access = free }}
-*{{cite journal  | author=Morgan DO, Edman JC, Standring DN, ''et al.'' |title=Insulin-like growth factor II receptor as a multifunctional binding protein |journal=Nature |volume=329 |issue= 6137 |pages= 301–7 |year= 1987 |pmid= 2957598 |doi= 10.1038/329301a0 }}
+*{{cite journal |vauthors=De Souza AT, Hankins GR, Washington MK, Orton TC, Jirtle RL | title = M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity | journal = Nat. Genet. | volume = 11 | issue = 4 | pages = 447–9 | year = 1996 | pmid = 7493029 | doi = 10.1038/ng1295-447 | s2cid = 21787312 }}
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+*{{cite journal |vauthors=Rao PH, Murty VV, Gaidano G, Hauptschein R, Dalla-Favera R, Chaganti RS | title = Subregional mapping of 8 single copy loci to chromosome 6 by fluorescence in situ hybridization | journal = Cytogenet. Cell Genet. | volume = 66 | issue = 4 | pages = 272–3 | year = 1994 | pmid = 8162705 | doi = 10.1159/000133710 }}
-*{{cite journal  | author=Schmidt B, Kiecke-Siemsen C, Waheed A, ''et al.'' |title=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 |journal=J. Biol. Chem. |volume=270 |issue= 25 |pages= 14975–82 |year= 1995 |pmid= 7797478 |doi=10.1074/jbc.270.25.14975  }}
+*{{cite journal |vauthors=Ishiwata T, Bergmann U, Kornmann M, Lopez M, Beger HG, Korc M | title = Altered expression of insulin-like growth factor II receptor in human pancreatic cancer | journal = Pancreas | volume = 15 | issue = 4 | pages = 367–73 | year = 1997 | pmid = 9361090 | doi = 10.1097/00006676-199711000-00006 | s2cid = 42073680 }}
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+*{{cite journal |vauthors=Tikkanen R, Peltola M, Oinonen C, Rouvinen J, Peltonen L | title = Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase | journal = EMBO J. | volume = 16 | issue = 22 | pages = 6684–93 | year = 1998 | pmid = 9362483 | pmc = 1170273 | doi = 10.1093/emboj/16.22.6684 }}
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+*{{cite journal |vauthors=Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G | title = PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization | journal = Cell | volume = 94 | issue = 2 | pages = 205–16 | year = 1998 | pmid = 9695949 | doi = 10.1016/S0092-8674(00)81420-8 | s2cid = 15027198 | doi-access = free }}
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+*{{cite journal |vauthors=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 | title = Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions | journal = J. Biol. Chem. | volume = 274 | issue = 24 | pages = 17123–31 | year = 1999 | pmid = 10358067 | doi = 10.1074/jbc.274.24.17123 | doi-access = free }}
-*{{cite journal  | author=Killian JK, Jirtle RL |title=Genomic structure of the human M6P/IGF2 receptor |journal=Mamm. Genome |volume=10 |issue= 1 |pages= 74–7 |year= 1999 |pmid= 9892739 |doi=10.1007/s003359900947  }}
-*{{cite journal  | author=Kumar S, Hand AT, Connor JR, ''et al.'' |title=Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions |journal=J. Biol. Chem. |volume=274 |issue= 24 |pages= 17123–31 |year= 1999 |pmid= 10358067 |doi=10.1074/jbc.274.24.17123  }}
-}}
 {{refend}}
@@ Line 60: / Line 59: @@
 {{Clusters of differentiation}}
 {{Growth factor receptors}}
+{{Growth factor receptor modulators}}
 [[Category:Receptors]]
 [[Category:Clusters of differentiation]]
-{{PBB_Controls
-| update_page = yes
-| require_manual_inspection = no
-| update_protein_box = yes
-| update_summary = no
-| update_citations = yes
-}}

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