neuropilin 1 Crystallographic structure of the dimeric B1 domain of human neuropilin 1. Identifiers Symbol NRP1 Entrez 8829 HUGO 8004 OMIM 602069 PDB 3I97 RefSeq NM_001024628 UniProt O14786 Other data Locus Chr. 10 p12 neuropilin 2 Identifiers Symbol NRP2 Entrez 8828 HUGO 8005 OMIM 602070 RefSeq NM_201279 UniProt O60462 Other data Locus Chr. 2 q34
Neuropilin is a protein receptor active in neurons.
There are two forms of Neuropilins, NRP-1 and NRP-2. They are transmembrane glycoproteins, and predominantly co-receptors for another class of proteins known as semaphorins. Of the semaphorins, NRP-1 and NRP-2 are specifically receptors for class-3 semaphorins, which, amongst many things, are responsible for axon guidance during the development of the nervous system in vertebrates.
Neuropilins work as co-receptors as they have a very small cytoplasmic domain and thus rely upon other molecules to transduce their signals across a cell membrane, normally plexins. Neuropilins generally work as dimers and different combinations have different affinities for molecules. For example, NRP-1 homodimers have high affinity for Sema-3A, whilst NRP-2 homodimers have high affinity for Sema-3F.
Another ligand for neuropilins is VEGF, a growth factor involved in the regulation of angiogenesis.
Neuropilin-1 is a therapeutic target protein in the treatment for leukemia and lymphoma, since It has been shown that there is increased expression in neuropilin-1 in leukemia and lymphoma cell lines. Also, antagonism of neuropilin-1 has been found to inhibit tumour cell migration and adhesion.
Neuropilins contain the following four domains:
- N-terminal CUB domain (for complement C1r/C1s, Uegf, Bmp1)
- Coagulation factor 5/8 type, C-terminal (discoidin domain)
- MAM domain (for meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu)
- C-terminal neuropilin
The structure of B1 domain (coagulation factor 5/8 type) of neuropilin-1 was determined through X-Ray Diffraction with a resolution of 2.90 Å. The secondary structure of this domain is 5% alpha helical and 46% beta sheet.
- ^ a b PDB 3I97; Jarvis A, Allerston CK, Jia H, Herzog B, Garza-Garcia A, Winfield N, Ellard K, Aqil R, Lynch R, Chapman C, Hartzoulakis B, Nally J, Stewart M, Cheng L, Menon M, Tickner M, Djordjevic S, Driscoll PC, Zachary I, Selwood DL (March 2010). "Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction". J. Med. Chem. 53 (5): 2215–26. doi:10.1021/jm901755g. PMC 2841442. PMID 20151671. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2841442.
- ^ Karjalainen K, Jaalouk DE, Bueso-Ramos CE, Zurita AJ, Kuniyasu A, Eckhardt BL, Marini FC, Lichtiger B, O'Brien S, Kantarjian HM, Cortes JE, Koivunen E, Arap W, Pasqualini R (November 2010). "Targeting neuropilin-1 in human leukemia and lymphoma". Blood 117 (3): 920–927. doi:10.1182/blood-2010-05-282921. PMID 21063027.
- ^ Jia H, Cheng L, Tickner M, Bagherzadeh A, Selwood D, Zachary I (February 2010). "Neuropilin-1 antagonism in human carcinoma cells inhibits migration and enhances chemosensitivity". Br. J. Cancer 102 (3): 541–52. doi:10.1038/sj.bjc.6605539. PMC 2822953. PMID 20087344. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2822953.
- ^ "MolProbity Ramachandran analysis of PDB structure 3I97". www.pdb.org. http://www.pdb.org/pdb/images/3I97_ram_m_500.pdf.
Membrane proteins, receptors: cell surface receptors G protein-coupled receptorClass AClass BClass CClass DPheromone receptorClass EcAMP receptorClass F Ligand-gated ion channel Enzyme-linked receptor Other/ungroupedAsialoglycoprotein receptor · Tumor necrosis factor receptor · Immunoglobulin superfamily · N-Acetylglucosamine receptor · Neuropilins · Transferrin receptor · EDAR · Lipoprotein receptor-related protein see also cell surface receptor deficiencies
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)Categories:
- Genes on chromosome 10
- Genes on chromosome 2
- Transmembrane receptors
- Biochemistry stubs
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