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SB0097 : Insulin-like growth factor binding protein 2

[ CaMP Format ]

* Basic Information

OrganismHomo sapiens (human)
Protein Namesinsulin-like growth factor-binding protein 2 precursor [Homo sapiens]; insulin-like growth factor-binding protein 2 precursor; insulin-like growth factor-binding protein 2; IBP-2; IGFBP-2; IGF-binding protein 2; Insulin-like growth factor-binding protein 2
Gene NamesIGFBP2; BP2, IBP2; BP2; IBP2; insulin-like growth factor binding protein 2, 36kDa
Gene Locus2q35; chromosome 2
GO FunctionNot available
Entrez Protein Entrez Nucleotide Entrez Gene UniProt OMIM HGNC HPRD KEGG
NP_000588 NM_000597 3485 P18065 146731 HGNC:5471 N/A hsa:3485

* Information From OMIM

Function: Png et al. (2012) demonstrated that endogenous miR126 (OMIM:611767), a miRNA silenced in a variety of human cancers, non-cell-autonomously regulates endothelial cell recruitment to metastatic breast cancer cells, in vitro and in vivo. It suppresses metastatic endothelial recruitment, metastatic angiogenesis, and metastatic colonization through coordinate targeting of IGFBP2, PITPNC1 (OMIM:605134), and MERTK (OMIM:604705), novel proangiogenic genes and biomarkers of human metastasis. Insulin-like growth factor binding protein-2 (IGFBP2) secreted by metastatic cells recruits endothelia by modulating IGF1 (OMIM:147440)-mediated activation of the IGF type-I receptor (OMIM:147370) on endothelial cells, whereas c-Mer tyrosine kinase (MERTK) receptor cleaved from metastatic cells promotes endothelial recruitment by competitively antagonizing the binding of its ligand GAS6 (OMIM:600441) to endothelial MERTK receptors. Coinjection of endothelial cells with breast cancer cells non-cell-autonomously rescued their miR126-induced metastatic defect, revealing a novel and important role for endothelial interactions in metastatic initiation. Through loss-of-function and epistasis experiments, Png et al. (2012) delineated a miRNA regulator network's individual components as novel and cell-extrinsic regulators of endothelial recruitment, angiogenesis, and metastatic colonization. The authors also identified the IGFBP2/IGF1/IGF1R and GAS6/MERTK signaling pathways as regulators of cancer-mediated endothelial recruitment.

* Structure Information

1. Primary Information

Length: 328 aa

Average Mass: 35.137 kDa

Monoisotopic Mass: 35.114 kDa

2. Domain Information

Annotated Domains: interpro / pfam / smart / prosite

Computationally Assigned Domains (Pfam+HMMER):

domain namebeginendscoree-value
Cysteine-rich CWC 1. 869320.04.7
Thyroglobulin type-1 repeat 1. 10110921.00.0
--- cleavage 202 ---
Insulin-like growth factor binding protein 1. 27128811.00.7

3. Sequence Information

Fasta Sequence: SB0097.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 2H7T (NMR; -; A=220-325)

* Cleavage Information

1 [sites] cleaved by Calpain 2

Source Reference: [PubMed ID: 17655506] Berg U, Bang P, Carlsson-Skwirut C, Calpain proteolysis of insulin-like growth factor binding protein (IGFBP) -2 and -3, but not of IGFBP-1. Biol Chem. 2007 Aug;388(8):859-63.

Cleavage sites (±10aa)

[Site 1] VFREKVTEQH202-RQMGKGGKHH

His202 Arg

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Val193Phe194Arg195Glu196Lys197Val198Thr199Glu200Gln201His202
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Arg203Gln204Met205Gly206Lys207Gly208Gly209Lys210His211His212

Sequence conservation (by blast)

* References

[PubMed ID: 24682597] Hu Q, Huang L, Kuang X, Zhang H, Ling G, Chen X, Li K, Deng Z, Zhou J, Is insulin-like growth factor binding protein 2 associated with metastasis in lung cancer? Clin Exp Metastasis. 2014 Jun;31(5):535-41. doi: 10.1007/s10585-014-9647-4. Epub

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