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PLXNB1 (plexin B1)

Written2009-03José Javier Gómez-Román, Montserrat Nicolas Martínez, Servando Lazuén Fernández, José Fernando Val-Bernal
Department of Anatomical Pathology, Marques de Valdecilla University Hospital, Medical Faculty, University of Cantabria, Santander, Spain

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPLXN5
Alias_symbol (synonym)SEP
KIAA0407
Other aliasMGC149167
OTTHUMP00000164806
PLEXIN-B1
HGNC (Hugo) PLXNB1
LocusID (NCBI) 5364
Atlas_Id 43413
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 48403854 and ends at 48430051 bp from pter ( according to hg19-Feb_2009)  [Mapping PLXNB1.png]
Local_order The Plexin B1 gene is located between FBXW12 and CCDC51 genes.
 
Fusion genes
(updated 2016)
COPE (19p13.11) / PLXNB1 (3p21.31)NCL (2q37.1) / PLXNB1 (3p21.31)PLXNB1 (3p21.31) / ANKLE2 (12q24.33)
PLXNB1 (3p21.31) / PLXNB1 (3p21.31)PLXNB1 (3p21.31) / SLC25A1 (22q11.21)
Note Size: 26,200 bases.
Orientation: minus strand.

DNA/RNA

Note [Annexed document]
 
Description Functioning gene. 21.00 kb; 37 Exons.
Transcription 7097.00 bp; Number of transcripts: 1; Type: Messenger.
Two alternatively truncated spliced variant, coding secreted proteins (lacking the part of the extracellular domains).
Pseudogene No.

Protein

Description 2135 Amino acids (AA). Plexins are receptors for axon molecular guidance molecules semaphorins. Plexin signalling is important in pathfinding and patterning of both neurons and developing blood vessels. Plexin-B1 is a surface cell receptor. When it binds to its ligand SEMA4D it activates several pathways by binding of cytoplasmic ligands, like RHOA activation and subsequent changes of the actin cytoskeleton, axon guidance, invasive growth and cell migration.
It monomers and heterodimers with PLXNB2 after proteolytic processing. Binds RAC1 that has been activated by GTP binding.
It binds PLXNA1 and by similarity ARHGEF11, ARHGEF12, ERBB2, MET, MST1R, RND1, NRP1 and NRP2.
This family features the C-terminal regions of various plexins. The cytoplasmic region, which has been called a SEX domain in some members of this family is involved in downstream signalling pathways, by interaction with proteins such as Rac1, RhoD, Rnd1 and other plexins.
Three copies of a cysteine rich repeat are found in Plexin. The function of the repeat is unknown.
Expression It is highly expressed in fetal kidney, digestive system (from esophagus to colon), thyroid, prostate and trachea and at slightly lower levels in fetal brain, lung, female reproductive system (breast, uterus and ovary) and liver.
Localisation Three isoforms have been identified: The isoform 1 is located in cell membrane and the isoforms 2 and 3 are secreted proteins.
Function Plexin B1 has several molecular functions, like a receptor activity, transmembrane receptor activity, protein binding, semaphorin receptor and semaphorin receptor binding. It is implicated in the next biological processes: Signal transduction, intracellular signalling cascade, multicellular organismal development, cell migration and positive regulation of axonogenesis.
 
  Plexin B1 policlonal antibody in foetal human central nervous system. Positive staining in developing neurons.
Homology It belongs to the plexin family and it contains 3 IPT/TIG domains and one Sema domain.

Mutations

Somatic Wong et al. (2007) identified 13 different somatic mutations in the cytoplasmic domain of the PLXNB1 gene in prostate cancer tissue. Mutations were found in 8 (89%) of 9 prostate cancer bone metastases, in 7 (41%) of 17 lymph node metastases, and in 41 (46%) of 89 primary cancers. Forty percent of prostate cancers contained the same mutation, and the majority of the primary tumors showed overexpression of the plexin-B1 protein. In vitro functional expression studies of the 3 most common mutations showed that the mutant proteins resulted in increased cell motility, invasion, adhesion, and lamellipodia extension compared to wildtype. The mutations acted by hindering RAC1 and RRAS binding and GTP activity.

Implicated in

Note
  
Entity Breast cancer
Prognosis Loss of protein Plexin B1 expression is associated with poor outcome in breast cancer ER (estrogen positive) patients.
  
  
Entity Renal cell carcinoma
Note By reverse transcription-polymerase chain reaction plexin B1 is expressed in nonneoplastic renal tissue, and it is severely downregulated in clear cell renal carcinomas. By immunohistochemistry on tissue microarrays it was shown that plexin B1 protein is absent in more than 80% of renal cell carcinomas. Otherwise, all kinds of renal tubules showed strong membrane reactivity.
When plexin B1 expression is induced with an expression vector in the renal adenocarcinoma cell line ACHN, a marked reduction in proliferation rate is found.
 
Plexin B1 in normal kidney tissue.
Tubular cortical and medular cells reactive.
The same immunostaining after blocking peptide incubation.
 
Plexin B1 loss of expression in three cases of renal cell carcinoma (clear cell upper right and left), and papillary (bottom right). One case of renal clear cell carcinoma with PlexinB1 expression (bottom left).
  
  
Entity Prostate carcinoma
Note 13 somatic missense mutations in the cytoplasmic domain of the Plexin-B1 gene have been reported. Mutations were found in cancer bone metastases, lymph node metastases, and in primary cancers. Forty percent of prostate cancers contained the same mutation. Overexpression of the Plexin-B1 protein was found in the majority of primary tumors. The mutations hinder Rac and R-Ras binding and R-RasGAP activity, resulting in an increase in cell motility, invasion, adhesion, and lamellipodia.
  
  
Entity Osteoarthritis
Note Using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, plexin B1 (PLXNB1) was confirmed to be consistently expressed at lower levels in osteoarthritis.
Disease Degenerative bone disease.
  

Bibliography

Semaphorin 4D/plexin-B1 induces endothelial cell migration through the activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway.
Basile JR, Afkhami T, Gutkind JS.
Mol Cell Biol. 2005 Aug;25(16):6889-98.
PMID 16055703
 
Plexin-B1 utilizes RhoA and Rho kinase to promote the integrin-dependent activation of Akt and ERK and endothelial cell motility.
Basile JR, Gavard J, Gutkind JS.
J Biol Chem. 2007 Nov 30;282(48):34888-95. Epub 2007 Sep 12.
PMID 17855350
 
Compensatory and long-range changes in picosecond-nanosecond main-chain dynamics upon complex formation: 15N relaxation analysis of the free and bound states of the ubiquitin-like domain of human plexin-B1 and the small GTPase Rac1.
Bouguet-Bonnet S, Buck M.
J Mol Biol. 2008 Apr 11;377(5):1474-87. Epub 2008 Feb 4.
PMID 18321527
 
Sema4D induces angiogenesis through Met recruitment by Plexin B1.
Conrotto P, Valdembri D, Corso S, Serini G, Tamagnone L, Comoglio PM, Bussolino F, Giordano S.
Blood. 2005 Jun 1;105(11):4321-9. Epub 2005 Jan 4.
PMID 15632204
 
Caenorhabditis elegans PlexinA, PLX-1, interacts with transmembrane semaphorins and regulates epidermal morphogenesis
Fujii T, Nakao F, Shibata Y, Shioi G, Kodama E, Fujisawa H, Takagi S.
Development. 2002 May;129(9):2053-63.
PMID 11959816
 
Plexin B1 is downregulated in renal cell carcinomas and modulates cell growth.
Gomez Roman JJ, Garay GO, Saenz P, Escuredo K, Sanz Ibayondo C, Gutkind S, Junquera C, Simon L, Martinez A, Fernandez Luna JL, Val-Bernal JF.
Transl Res. 2008 Mar;151(3):134-40. Epub 2008 Jan 7.
PMID 18279812
 
Human uterine epithelial RL95-2 and HEC-1A cell-line adhesiveness: the role of plexin B1.
Harduf H, Goldman S, Shalev E.
Fertil Steril. 2007 Jun;87(6):1419-27. Epub 2007 Mar 26.
PMID 17383649
 
Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion.
Lorenzato A, Olivero M, Patane S, Rosso E, Oliaro A, Comoglio PM, Di Renzo MF.
Cancer Res. 2002 Dec 1;62(23):7025-30.
PMID 12460923
 
A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor.
Maestrini E, Tamagnone L, Longati P, Cremona O, Gulisano M, Bione S, Tamanini F, Neel BG, Toniolo D, Comoglio PM.
Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):674-8.
PMID 8570614
 
The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras.
Oinuma I, Ishikawa Y, Katoh H, Negishi M.
Science. 2004 Aug 6;305(5685):862-5.
PMID 15297673
 
Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells.
Oinuma I, Katoh H, Harada A, Negishi M.
J Biol Chem. 2003 Jul 11;278(28):25671-7. Epub 2003 May 1.
PMID 12730235
 
ErbB-2 and met reciprocally regulate cellular signaling via plexin-B1.
Swiercz JM, Worzfeld T, Offermanns S.
J Biol Chem. 2008 Jan 25;283(4):1893-901. Epub 2007 Nov 19.
PMID 18025083
 
Binding of Rac1, Rnd1, and RhoD to a novel Rho GTPase interaction motif destabilizes dimerization of the plexin-B1 effector domain.
Tong Y, Chugha P, Hota PK, Alviani RS, Li M, Tempel W, Shen L, Park HW, Buck M.
J Biol Chem. 2007 Dec 21;282(51):37215-24. Epub 2007 Oct 4.
PMID 17916560
 
Insights into oncogenic mutations of plexin-B1 based on the solution structure of the Rho GTPase binding domain.
Tong Y, Hota PK, Hamaneh MB, Buck M.
Structure. 2008 Feb;16(2):246-58.
PMID 18275816
 
Semaphorin-plexin signaling guides patterning of the developing vasculature.
Torres-Vazquez J, Gitler AD, Fraser SD, Berk JD, Van N Pham, Fishman MC, Childs S, Epstein JA, Weinstein BM.
Dev Cell. 2004 Jul;7(1):117-23.
PMID 15239959
 
Plexin-A1 and plexin-B1 specifically interact at their cytoplasmic domains.
Usui H, Taniguchi M, Yokomizo T, Shimizu T.
Biochem Biophys Res Commun. 2003 Jan 24;300(4):927-31.
PMID 12559962
 
Plexin-B1 mutations in prostate cancer.
Wong OG, Nitkunan T, Oinuma I, Zhou C, Blanc V, Brown RS, Bott SR, Nariculam J, Box G, Munson P, Constantinou J, Feneley MR, Klocker H, Eccles SA, Negishi M, Freeman A, Masters JR, Williamson M.
Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19040-5. Epub 2007 Nov 16.
PMID 18024597
 

Citation

This paper should be referenced as such :
Gòmez-Roman, JJ ; Nicolas, Martinez M ; Lazuén, Fernandez S ; Val-Bernal, JF
PLXNB1 (plexin B1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(3):249-253.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PLXNB1ID43413ch3p21.html


External links

Nomenclature
HGNC (Hugo)PLXNB1   9103
Cards
AtlasPLXNB1ID43413ch3p21
Entrez_Gene (NCBI)PLXNB1  5364  plexin B1
AliasesPLEXIN-B1; PLXN5; SEP
GeneCards (Weizmann)PLXNB1
Ensembl hg19 (Hinxton)ENSG00000164050 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000164050 [Gene_View]  chr3:48403854-48430051 [Contig_View]  PLXNB1 [Vega]
ICGC DataPortalENSG00000164050
TCGA cBioPortalPLXNB1
AceView (NCBI)PLXNB1
Genatlas (Paris)PLXNB1
WikiGenes5364
SOURCE (Princeton)PLXNB1
Genetics Home Reference (NIH)PLXNB1
Genomic and cartography
GoldenPath hg38 (UCSC)PLXNB1  -     chr3:48403854-48430051 -  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PLXNB1  -     3p21.31   [Description]    (hg19-Feb_2009)
EnsemblPLXNB1 - 3p21.31 [CytoView hg19]  PLXNB1 - 3p21.31 [CytoView hg38]
Mapping of homologs : NCBIPLXNB1 [Mapview hg19]  PLXNB1 [Mapview hg38]
OMIM601053   
Gene and transcription
Genbank (Entrez)AB007867 AJ011414 AJ011415 AK091832 AK092609
RefSeq transcript (Entrez)NM_001130082 NM_002673
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PLXNB1
Cluster EST : UnigeneHs.476209 [ NCBI ]
CGAP (NCI)Hs.476209
Alternative Splicing GalleryENSG00000164050
Gene ExpressionPLXNB1 [ NCBI-GEO ]   PLXNB1 [ EBI - ARRAY_EXPRESS ]   PLXNB1 [ SEEK ]   PLXNB1 [ MEM ]
Gene Expression Viewer (FireBrowse)PLXNB1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5364
GTEX Portal (Tissue expression)PLXNB1
Protein : pattern, domain, 3D structure
UniProt/SwissProtO43157   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO43157  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO43157
Splice isoforms : SwissVarO43157
PhosPhoSitePlusO43157
Domaine pattern : Prosite (Expaxy)SEMA (PS51004)   
Domains : Interpro (EBI)Ig-like_fold    Ig_E-set    IPT    Plexin    Plexin_cytoplasmic_RasGAP_dom    Plexin_repeat    PSI    Rho_GTPase_activation_prot    Semap_dom    WD40/YVTN_repeat-like_dom   
Domain families : Pfam (Sanger)Plexin_cytopl (PF08337)    PSI (PF01437)    Sema (PF01403)    TIG (PF01833)   
Domain families : Pfam (NCBI)pfam08337    pfam01437    pfam01403    pfam01833   
Domain families : Smart (EMBL)IPT (SM00429)  PSI (SM00423)  Sema (SM00630)  
Conserved Domain (NCBI)PLXNB1
DMDM Disease mutations5364
Blocks (Seattle)PLXNB1
PDB (SRS)2JPH    2OS6    2R2O    2REX    3HM6    3OL2    3SU8    3SUA    5B4W   
PDB (PDBSum)2JPH    2OS6    2R2O    2REX    3HM6    3OL2    3SU8    3SUA    5B4W   
PDB (IMB)2JPH    2OS6    2R2O    2REX    3HM6    3OL2    3SU8    3SUA    5B4W   
PDB (RSDB)2JPH    2OS6    2R2O    2REX    3HM6    3OL2    3SU8    3SUA    5B4W   
Structural Biology KnowledgeBase2JPH    2OS6    2R2O    2REX    3HM6    3OL2    3SU8    3SUA    5B4W   
SCOP (Structural Classification of Proteins)2JPH    2OS6    2R2O    2REX    3HM6    3OL2    3SU8    3SUA    5B4W   
CATH (Classification of proteins structures)2JPH    2OS6    2R2O    2REX    3HM6    3OL2    3SU8    3SUA    5B4W   
SuperfamilyO43157
Human Protein AtlasENSG00000164050
Peptide AtlasO43157
HPRD03032
IPIIPI00455329   IPI00006644   IPI00384195   IPI00828142   IPI01013449   
Protein Interaction databases
DIP (DOE-UCLA)O43157
IntAct (EBI)O43157
FunCoupENSG00000164050
BioGRIDPLXNB1
STRING (EMBL)PLXNB1
ZODIACPLXNB1
Ontologies - Pathways
QuickGOO43157
Ontology : AmiGOsemaphorin receptor complex  semaphorin receptor complex  receptor activity  transmembrane signaling receptor activity  GTPase activator activity  protein binding  extracellular region  intracellular  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  negative regulation of cell adhesion  signal transduction  regulation of cell shape  positive regulation of phosphatidylinositol 3-kinase signaling  cell migration  semaphorin receptor activity  semaphorin receptor activity  semaphorin receptor binding  GTPase activating protein binding  negative regulation of osteoblast proliferation  intracellular signal transduction  regulation of GTPase activity  positive regulation of GTPase activity  ossification involved in bone maturation  axon extension  neuron projection morphogenesis  positive regulation of axonogenesis  regulation of cytoskeleton organization  semaphorin-plexin signaling pathway  semaphorin-plexin signaling pathway involved in bone trabecula morphogenesis  
Ontology : EGO-EBIsemaphorin receptor complex  semaphorin receptor complex  receptor activity  transmembrane signaling receptor activity  GTPase activator activity  protein binding  extracellular region  intracellular  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  negative regulation of cell adhesion  signal transduction  regulation of cell shape  positive regulation of phosphatidylinositol 3-kinase signaling  cell migration  semaphorin receptor activity  semaphorin receptor activity  semaphorin receptor binding  GTPase activating protein binding  negative regulation of osteoblast proliferation  intracellular signal transduction  regulation of GTPase activity  positive regulation of GTPase activity  ossification involved in bone maturation  axon extension  neuron projection morphogenesis  positive regulation of axonogenesis  regulation of cytoskeleton organization  semaphorin-plexin signaling pathway  semaphorin-plexin signaling pathway involved in bone trabecula morphogenesis  
Pathways : KEGGAxon guidance   
REACTOMEO43157 [protein]
REACTOME PathwaysR-HSA-416572 [pathway]   
NDEx NetworkPLXNB1
Atlas of Cancer Signalling NetworkPLXNB1
Wikipedia pathwaysPLXNB1
Orthology - Evolution
OrthoDB5364
GeneTree (enSembl)ENSG00000164050
Phylogenetic Trees/Animal Genes : TreeFamPLXNB1
HOVERGENO43157
HOGENOMO43157
Homologs : HomoloGenePLXNB1
Homology/Alignments : Family Browser (UCSC)PLXNB1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPLXNB1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PLXNB1
dbVarPLXNB1
ClinVarPLXNB1
1000_GenomesPLXNB1 
Exome Variant ServerPLXNB1
ExAC (Exome Aggregation Consortium)PLXNB1 (select the gene name)
Genetic variants : HAPMAP5364
Genomic Variants (DGV)PLXNB1 [DGVbeta]
DECIPHERPLXNB1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPLXNB1 
Mutations
ICGC Data PortalPLXNB1 
TCGA Data PortalPLXNB1 
Broad Tumor PortalPLXNB1
OASIS PortalPLXNB1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPLXNB1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPLXNB1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PLXNB1
DgiDB (Drug Gene Interaction Database)PLXNB1
DoCM (Curated mutations)PLXNB1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PLXNB1 (select a term)
intoGenPLXNB1
NCG5 (London)PLXNB1
Cancer3DPLXNB1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601053   
Orphanet
MedgenPLXNB1
Genetic Testing Registry PLXNB1
NextProtO43157 [Medical]
TSGene5364
GENETestsPLXNB1
Target ValidationPLXNB1
Huge Navigator PLXNB1 [HugePedia]
snp3D : Map Gene to Disease5364
BioCentury BCIQPLXNB1
ClinGenPLXNB1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5364
Chemical/Pharm GKB GenePA33429
Clinical trialPLXNB1
Miscellaneous
canSAR (ICR)PLXNB1 (select the gene name)
Probes
Litterature
PubMed68 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePLXNB1
EVEXPLXNB1
GoPubMedPLXNB1
iHOPPLXNB1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon May 22 09:20:07 CEST 2017

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