LYPD6B

LY6/PLAUR Domain Containing 6B, also known under the name Cancer/Testis Antigen 116 (CTA116) and LYPD7 is encoded by the LYPD6B gene.^[5] 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.

LYPD6B
Identifiers
Aliases	LYPD6B, CT116, LYPD7, LY6/PLAUR domain containing 6B
External IDs	MGI: 1919147; HomoloGene: 12419; GeneCards: LYPD6B; OMA:LYPD6B - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q23.2 Start 149,038,107 bp[1] End 149,215,262 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 C1.1 Start 49,677,700 bp[2] End 49,838,861 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of abdomen right uterine tube skin of leg gallbladder nasal epithelium right testis left testis olfactory zone of nasal mucosa palpebral conjunctiva mucosa of paranasal sinus Top expressed in medullary collecting duct epithelium of stomach molar skin of abdomen hair follicle anterior horn of spinal cord otolith organ utricle lumbar subsegment of spinal cord urothelium More reference expression data BioGPS n/a
Gene ontology Molecular function acetylcholine receptor regulator activity Cellular component membrane anchored component of membrane extracellular region plasma membrane Biological process regulation of neurotransmitter receptor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 130576 71897 Ensembl ENSG00000150556 ENSMUSG00000026765 UniProt Q8NI32 Q9D7F2 RefSeq (mRNA) NM_177964 NM_001317002 NM_001317003 NM_001317004 NM_001317005 NM_001317006 NM_027990 NM_001379381 NM_001379382 NM_001379383 NM_001379384 NM_001379385 NM_001379386 NM_001379387 RefSeq (protein) NP_001303931 NP_001303932 NP_001303933 NP_001303934 NP_001303935 NP_808879 NP_082266 NP_001366310 NP_001366311 NP_001366312 NP_001366313 NP_001366314 NP_001366315 NP_001366316 Location (UCSC) Chr 2: 149.04 – 149.22 Mb Chr 2: 49.68 – 49.84 Mb PubMed search [3] [4]
Wikidata
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Structure

The protein is 183 amino acids long and its molecular mass is 20.656.^[6] 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.^[7]

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.^[8] LYPD6B is known as a prototoxin due to its structural similarity with the 3-fingered snake venom proteins α-bungarotoxin and cobratoxin.^[9] 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.^[9]

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.^[9] 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.^[10] Additionally, the protein demonstrates high expression in several other normal organs including the testis, lungs, stomach, and prostate.^[11]

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.^[12]

The protein LYPD6 also leads to an increase in Wnt/β-catenin signaling.^[7]

References

1. GRCh38: Ensembl release 89: ENSG00000150556 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026765 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: LY6/PLAUR domain containing 6B". NCBI. Retrieved 21 July 2020.
6. "UniProt, Q8NI32". Retrieved 23 July 2020.
7. Kulbatskii, Dmitrii; Shenkarev, Zakhar; Bychkov, Maxim; Loktyushov, Eugene; Shulepko, Mikhail; Koshelev, Sergey; Povarov, Igor; Popov, Alexander; Peigneur, Steve; Chugunov, Anton (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. PMC 8494132. PMID 34631692.
8. Ni J, Lang Q, Bai M, Zhong C, Chen X, Wan B, Yu L (April 2009). "Cloning and characterization of a human LYPD7, a new member of the Ly-6 superfamily". Molecular Biology Reports. 45 (11): 697–703. doi:10.1007/s11033-008-9231-6. PMID 18360792. S2CID 1772973.
9. Ochoa V, George AA, Nishi R, Whiteaker P (March 2016). "The prototoxin LYPD6B modulates heteromeric α3β4-containing nicotinic acetylcholine receptors, but not α7 homomers". FASEB Journal. 30 (3): 1109–19. doi:10.1096/fj.15-274548. PMC 4750422. PMID 26586467.
10. Chung BH, Mullegama S, Marshall CR, Lionel AC, Weksberg R, Dupuis L, et al. (April 2012). "Severe intellectual disability and autistic features associated with microduplication 2q23.1". European Journal of Human Genetics. 20 (4): 398–403. doi:10.1038/ejhg.2011.199. PMC 3306850. PMID 22085900.
11. Kong HK, Park JH (November 2012). "Characterization and function of human Ly-6/uPAR molecules". BMB Reports. 45 (11): 595–603. doi:10.5483/bmbrep.2012.45.11.210. PMC 4133805. PMID 23186997.
12. Koroknai V, Szász I, Hernandez-Vargas H, Fernandez-Jimenez N, Cuenin C, Herceg Z, et al. (January 2020). "DNA hypermethylation is associated with invasive phenotype of malignant melanoma". Experimental Dermatology. 29 (1): 39–50. doi:10.1111/exd.14047. hdl:2437/278321. PMID 31602702.