PLXNB1 (plexin B1)

2009-03-01   José 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


Atlas Image


Atlas Image


Functioning gene. 21.00 kb; 37 Exons.


7097.00 bp; Number of transcripts: 1; Type: Messenger.
Two alternatively truncated spliced variant, coding secreted proteins (lacking the part of the extracellular domains).





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.


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.


Three isoforms have been identified: The isoform 1 is located in cell membrane and the isoforms 2 and 3 are secreted proteins.


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.
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Plexin B1 policlonal antibody in foetal human central nervous system. Positive staining in developing neurons.


It belongs to the plexin family and it contains 3 IPT/TIG domains and one Sema domain.



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

Entity name
Breast cancer
Loss of protein Plexin B1 expression is associated with poor outcome in breast cancer ER (estrogen positive) patients.
Entity name
Renal cell carcinoma
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.
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Plexin B1 in normal kidney tissue.
Tubular cortical and medular cells reactive.
The same immunostaining after blocking peptide incubation.
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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 name
Prostate carcinoma
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 name
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.
Degenerative bone disease.


Pubmed IDLast YearTitleAuthors
160557032005Semaphorin 4D/plexin-B1 induces endothelial cell migration through the activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway.Basile JR et al
178553502007Plexin-B1 utilizes RhoA and Rho kinase to promote the integrin-dependent activation of Akt and ERK and endothelial cell motility.Basile JR et al
183215272008Compensatory 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 et al
156322042005Sema4D induces angiogenesis through Met recruitment by Plexin B1.Conrotto P et al
119598162002Caenorhabditis elegans PlexinA, PLX-1, interacts with transmembrane semaphorins and regulates epidermal morphogenesis.Fujii T et al
182798122008Plexin B1 is downregulated in renal cell carcinomas and modulates cell growth.Gómez Román JJ et al
173836492007Human uterine epithelial RL95-2 and HEC-1A cell-line adhesiveness: the role of plexin B1.Harduf H et al
124609232002Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion.Lorenzato A et al
85706141996A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor.Maestrini E et al
152976732004The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras.Oinuma I et al
127302352003Direct 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 et al
180250832008ErbB-2 and met reciprocally regulate cellular signaling via plexin-B1.Swiercz JM et al
179165602007Binding of Rac1, Rnd1, and RhoD to a novel Rho GTPase interaction motif destabilizes dimerization of the plexin-B1 effector domain.Tong Y et al
182758162008Insights into oncogenic mutations of plexin-B1 based on the solution structure of the Rho GTPase binding domain.Tong Y et al
152399592004Semaphorin-plexin signaling guides patterning of the developing vasculature.Torres-Vázquez J et al
125599622003Plexin-A1 and plexin-B1 specifically interact at their cytoplasmic domains.Usui H et al
180245972007Plexin-B1 mutations in prostate cancer.Wong OG et al

Other Information

Locus ID:

NCBI: 5364
MIM: 601053
HGNC: 9103
Ensembl: ENSG00000164050


dbSNP: 5364
ClinVar: 5364
TCGA: ENSG00000164050


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Axon guidanceKEGGko04360
Axon guidanceKEGGhsa04360
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (12/13) signalling eventsREACTOMER-HSA-416482
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
Semaphorin interactionsREACTOMER-HSA-373755
Sema4D in semaphorin signalingREACTOMER-HSA-400685
Sema4D mediated inhibition of cell attachment and migrationREACTOMER-HSA-416550
Sema4D induced cell migration and growth-cone collapseREACTOMER-HSA-416572

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
208772822010Structural basis of semaphorin-plexin signalling.83
156322042005Sema4D induces angiogenesis through Met recruitment by Plexin B1.70
121966282002The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG.63
180250832008ErbB-2 and met reciprocally regulate cellular signaling via plexin-B1.62
151848882004Interplay between scatter factor receptors and B plexins controls invasive growth.60
152107332004Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2.54
160557032005Semaphorin 4D/plexin-B1 induces endothelial cell migration through the activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway.51
179165602007Binding of Rac1, Rnd1, and RhoD to a novel Rho GTPase interaction motif destabilizes dimerization of the plexin-B1 effector domain.51
119374912002The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding.41
180245972007Plexin-B1 mutations in prostate cancer.41


José Javier Gómez-Román ; Montserrat Nicolas Martínez ; Servando Lazuén Fernández ; José Fernando Val-Bernal

PLXNB1 (plexin B1)

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

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