Biology:LYPD6B
 Generic protein structure example |
LY6/PLAUR Domain Containing 6B, also known under the name Cancer/Testis Antigen 116 (CTA116) and LYPD7 is encoded by the LYPD6B gene.[1] LYPD6B is a member of the lymphocyte antigen 6 (LY6) protein family. It is expressed in the testis, lungs, stomach, prostate and in the nervous system where it acts as a modulator of nicotinic acetylcholine receptor (nAChRs) activity.
Structure
The protein is 183 amino acids long and its molecular mass is 20.656.[2] The gene LYPD6B encoding the protein is located on chromosome 2 in humans.
As a member of the Ly-6/uPAR family, the protein contains a disulfide β-structural core and three protruding loops.[3]
Background
The protein was discovered for the first time in a 2009 study; its presence was detected in the cytoplasm and it was associated with activation of the AP-1 transcription factor.[4] LYPD6B is known as a prototoxin due to its structural similarity with the 3-fingered snake venom proteins α-bungarotoxin and cobratoxin.[5] As a prototoxin, LYPD6B also belongs to the protein family of Ly-6/urokinase plasminogen activator receptor (Ly6/uPAR). It has a 3-fingered motif secondary structure which appears due to the presence of 8–10 cysteine residues that facilitate disulfide bond formation.[5]
Role
The protein is expressed in the nervous system where it acts as an enhancer of the activity of the neurotransmitter acetylcholine certain α7-containing nicotinic acetylcholine receptors, which have a role in learning.[5] A duplication of the gene has been detected in a case study of two individuals with severe intellectual disability, suggesting its role in proper brain development and cognitive function.[6] Additionally, the protein demonstrates high expression in several other normal organs including the testis, lungs, stomach, and prostate.[7]
Hypermethylation of the gene and a subsequent decreased expression has been demonstrated as one of the contributors to the invasive capacity of cancer cells in melanoma.[8]
The protein LYPD6 also leads to an increase in Wnt/β-catenin signaling.[3]
References
- ↑ "Entrez Gene: LY6/PLAUR domain containing 6B". NCBI. https://www.ncbi.nlm.nih.gov/gene/130576.
- ↑ "UniProt, Q8NI32". http://www.uniprot.org/uniprot/Q8NI32#sequences.
- ↑ 3.0 3.1 Kulbatskii, Dmitrii; Shenkarev, Zakhar; Bychkov, Maxim; Loktyushov, Eugene; Shulepko, Mikhail; Koshelev, Sergey; Povarov, Igor; Popov, Alexander et al. (21 September 2021). "Human Three-Finger Protein Lypd6 Is a Negative Modulator of the Cholinergic System in the Brain". Front Cell Dev Biol 9 (21): 662227. doi:10.3389/fcell.2021.662227. PMID 34631692.
- ↑ "Cloning and characterization of a human LYPD7, a new member of the Ly-6 superfamily". Molecular Biology Reports 45 (11): 697–703. April 2009. doi:10.1007/s11033-008-9231-6. PMID 18360792.
- ↑ 5.0 5.1 5.2 "The prototoxin LYPD6B modulates heteromeric α3β4-containing nicotinic acetylcholine receptors, but not α7 homomers". FASEB Journal 30 (3): 1109–19. March 2016. doi:10.1096/fj.15-274548. PMID 26586467.
- ↑ "Severe intellectual disability and autistic features associated with microduplication 2q23.1". European Journal of Human Genetics 20 (4): 398–403. April 2012. doi:10.1038/ejhg.2011.199. PMID 22085900.
- ↑ "Characterization and function of human Ly-6/uPAR molecules". BMB Reports 45 (11): 595–603. November 2012. doi:10.5483/bmbrep.2012.45.11.210. PMID 23186997.
- ↑ "DNA hypermethylation is associated with invasive phenotype of malignant melanoma". Experimental Dermatology 29 (1): 39–50. January 2020. doi:10.1111/exd.14047. PMID 31602702.
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