ニューロピリン2

WordNet

the complex network of unmyelinated axones, dendrites, and glial branches that form the bulk of the central nervous systems grey matter and in which nerve cell bodies are embedded (同)neuropile

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2018/05/23 01:57:56」(JST)

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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, among 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 (normally plexins) to transduce their signals across a cell membrane. Neuropilins generally work as dimers and different combinations have different affinities for molecules. For example, NRP-1 homodimers have high affinity for Sema3A, whilst NRP-2 homodimers have high affinity for Sema3F. Another ligand for neuropilins is VEGF, a growth factor involved in the regulation of angiogenesis.

The pleiotropic nature of the NRP receptors results in their involvement in multiple signalling pathways, such as axon guidance and angiogenesis, the immune response and remyelination.^[2]

Applications

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.^[3] Also, antagonism of neuropilin-1 has been found to inhibit tumour cell migration and adhesion.^[4]

Structure

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.^[1]

Ramachandran plot.^[5]

References

^ ^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.
^ Mecollari, V; Nieuwenhuis, B; Verhaagen, J (2014). "A perspective on the role of class III semaphorin signaling in central nervous system trauma". Frontiers in Cellular Neuroscience. 8: 328. doi:10.3389/fncel.2014.00328. PMC 4209881 . PMID 25386118.
^ 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. PMC 3298438 . 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.
^ "MolProbity Ramachandran analysis of PDB structure 3I97" (PDF). www.pdb.org.

External links

Neuropilins at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 血管新生阻害剤の概要 overview of angiogenesis inhibitors
2. ヒトTリンパ球好性ウイルスI型：ウイルス学、病因、および疫学 human t lymphotropic virus type i virology pathogenesis and epidemiology
3. 肝線維症の病因 pathogenesis of hepatic fibrosis

English Journal

The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain.

Kanatani S1, Honda T2, Aramaki M2, Hayashi K2, Kubo K2, Ishida M2, Tanaka DH2, Kawauchi T3, Sekine K2, Kusuzawa S2, Kawasaki T4, Hirata T4, Tabata H5, Uhlén P6, Nakajima K7.
Proceedings of the National Academy of Sciences of the United States of America.Proc Natl Acad Sci U S A.2015 Sep 8;112(36):E4985-94. doi: 10.1073/pnas.1420701112. Epub 2015 Aug 24.
The preoptic area (POa) of the rostral diencephalon supplies the neocortex and the amygdala with GABAergic neurons in the developing mouse brain. However, the molecular mechanisms that determine the pathway and destinations of POa-derived neurons have not yet been identified. Here we show that Chick
PMID 26305926

Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons.

Coate TM1, Spita NA2, Zhang KD2, Isgrig KT1, Kelley MW1.
eLife.Elife.2015 Aug 24;4. doi: 10.7554/eLife.07830. [Epub ahead of print]
Auditory function is dependent on the formation of specific innervation patterns between mechanosensory hair cells and afferent spiral ganglion neurons (SGNs). In particular, type I SGNs must precisely connect with inner hair cells (IHCs) while avoiding connections with nearby outer hair cells (OHCs
PMID 26302206

Syndecan-1 up-regulates microRNA-331-3p and mediates epithelial-to-mesenchymal transition in prostate cancer.

Fujii T1, Shimada K1, Tatsumi Y1,2, Tanaka N2, Fujimoto K2, Konishi N1.
Molecular carcinogenesis.Mol Carcinog.2015 Aug 10. doi: 10.1002/mc.22381. [Epub ahead of print]
MicroRNAs (miRNAs) are small noncoding RNAs with a length of approximately 19-24 nucleotides that regulate gene expression through translational inhibition and contribute to the progression of various tumors including prostate cancer. Aberrant expression of miRNAs has been implicated in the progress
PMID 26259043

Japanese Journal

Comprehensive behavioral phenotyping of a new Semaphorin 3 F mutant mouse

Molecular Brain 9, 2016-02-09
NAID 120005758427

Concurrent Expression of VEGF-C and Neuropilin-2 Is Correlated with Poor Prognosis in Glioblastoma

The Tohoku Journal of Experimental Medicine 238(2), 85-91, 2016
NAID 130005118557

Development of the somatosensory cortex, the cerebellum, and the main olfactory system in Semaphorin 3F knockout mice

Neuroscience research : the official journal of the Japan Neuroscience Society 66(3), 321-329, 2010-03-01
NAID 10027501273

「ニューロピリン2」

neuropilin 2
Identifiers
Symbol	NRP2
Entrez	8828
HUGO	8005
OMIM	602070
RefSeq	NM_201279
UniProt	O60462
Other data
Locus	Chr. 2 q34

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

　　[★]

英: neuropilin-2
関: ニューロピリン-2

「ニューロピリン-2」

　　[★]

英: neuropilin-2
関: ニューロピリン2

[pmid20151671-1] 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.

[2] Mecollari, V; Nieuwenhuis, B; Verhaagen, J (2014). "A perspective on the role of class III semaphorin signaling in central nervous system trauma". Frontiers in Cellular Neuroscience. 8: 328. doi:10.3389/fncel.2014.00328. PMC 4209881 . PMID 25386118.

[pmid21063027-3] 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. PMC 3298438 . PMID 21063027.

[pmid20087344-4] 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.

[urlwww.pdb.org-5] "MolProbity Ramachandran analysis of PDB structure 3I97" (PDF). www.pdb.org.

v t e Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1-50	CD1 a-c 1A 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 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

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案内

neuropilin-2