Recombinant Human Plexin-A1 (PLXNA1), partial

Function

Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm. Acts as coreceptor of TREM2 for SEMA6D in dendritic cells and is involved in the generation of immune responses and skeletal homeostasis

Subcellular Location

Cell membrane (Single-pass type I membrane protein)

Disease Association

Dworschak-Punetha neurodevelopmental syndrome (DWOPNED) : An autosomal recessive disorder characterized by global developmental delay, mildly impaired intellectual development, speech delay, and behavioral abnormalities including autism spectrum disorder and hyperactivity. Additional variable additional features include optic disk hypoplasia, ptosis, hypo- or hyperpigmented skin lesions, non-specific facial dysmorphism, and abnormalities of the ventricles or corpus callosum seen on brain imaging. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Detected in fetal brain, lung, liver and kidney

Subunit

Interacts directly with NRP1 and NRP2. Interacts with PLXN1B. Interacts with FARP2, RND1 and KDR/VEGFR2. Binding of SEMA3A leads to dissociation of FARP2. Interacts with CRMP1, DPYSL2/CRMP2, DPYSL3/CRMP3 and DPYSL4/CRMP4. Interacts (via TIG domains) with TREM2; the interaction mediates SEMA6D binding and signaling through TYROBP

• Muzny D.M. et al. The DNA sequence, annotation and analysis of human chromosome 3. — Nature (2006)
• Maestrini E. et al. A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor. — Proc. Natl. Acad. Sci. U.S.A. (1996)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Wollscheid B. et al. Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. — Nat. Biotechnol. (2009)
• Burkard T.R. et al. Initial characterization of the human central proteome. — BMC Syst. Biol. (2011)
• Dworschak G.C. et al. Biallelic and monoallelic variants in PLXNA1 are implicated in a novel neurodevelopmental disorder with variable cerebral and eye anomalies. — Genet. Med. (2021)