Introduction of CELSR2
CELSR2, encoded by CELSR2 gene, is a member of the flamingo subfamily, one of the cadherin superfamily. The extracellular domain of flamingo cadherins is very large, consist of nine N-terminal repeated cadherin domains, seven epidermal growth factor-like repeats, two laminin A G-type repeats, a hormone receptor motif and a G-protein-coupled receptor proteolytic site. The flamingo cadherins also have seven transmembrane domains which are unique structural feature of the subfamily.
Basic Information of CELSR2 | |
Protein Name | Cadherin EGF LAG seven-pass G-type receptor 2 |
Gene Name | CELSR2 |
Aliases | EGFL2, MEGF3, ADGRC2, CDHF10, Flamingo1 |
Organism | Homo sapiens (Human) |
UniProt ID | Q9HCU4 |
Transmembrane Times | 7 |
Length (aa) | 2923 |
Sequence |
MRSPATGVPLPTPPPPLLLLLLLLLPPPLLGDQVGPCRSLGSRGRGSSGACAPMGWLCPS SASNLWLYTSRCRDAGTELTGHLVPHHDGLRVWCPESEAHIPLPPAPEGCPWSCRLLGIG GHLSPQGKLTLPEEHPCLKAPRLRCQSCKLAQAPGLRAGERSPEESLGGRRKRNVNTAPQ FQPPSYQATVPENQPAGTPVASLRAIDPDEGEAGRLEYTMDALFDSRSNQFFSLDPVTGA VTTAEELDRETKSTHVFRVTAQDHGMPRRSALATLTILVTDTNDHDPVFEQQEYKESLRE NLEVGYEVLTVRATDGDAPPNANILYRLLEGSGGSPSEVFEIDPRSGVIRTRGPVDREEV ESYQLTVEASDQGRDPGPRSTTAAVFLSVEDDNDNAPQFSEKRYVVQVREDVTPGAPVLR VTASDRDKGSNAVVHYSIMSGNARGQFYLDAQTGALDVVSPLDYETTKEYTLRVRAQDGG RPPLSNVSGLVTVQVLDINDNAPIFVSTPFQATVLESVPLGYLVLHVQAIDADAGDNARL EYRLAGVGHDFPFTINNGTGWISVAAELDREEVDFYSFGVEARDHGTPALTASASVSVTV LDVNDNNPTFTQPEYTVRLNEDAAVGTSVVTVSAVDRDAHSVITYQITSGNTRNRFSITS QSGGGLVSLALPLDYKLERQYVLAVTASDGTRQDTAQIVVNVTDANTHRPVFQSSHYTVN VNEDRPAGTTVVLISATDEDTGENARITYFMEDSIPQFRIDADTGAVTTQAELDYEDQVS YTLAITARDNGIPQKSDTTYLEILVNDVNDNAPQFLRDSYQGSVYEDVPPFTSVLQISAT DRDSGLNGRVFYTFQGGDDGDGDFIVESTSGIVRTLRRLDRENVAQYVLRAYAVDKGMPP ARTPMEVTVTVLDVNDNPPVFEQDEFDVFVEENSPIGLAVARVTATDPDEGTNAQIMYQI VEGNIPEVFQLDIFSGELTALVDLDYEDRPEYVLVIQATSAPLVSRATVHVRLLDRNDNP PVLGNFEILFNNYVTNRSSSFPGGAIGRVPAHDPDISDSLTYSFERGNELSLVLLNASTG ELKLSRALDNNRPLEAIMSVLVSDGVHSVTAQCALRVTIITDEMLTHSITLRLEDMSPER FLSPLLGLFIQAVAATLATPPDHVVVFNVQRDTDAPGGHILNVSLSVGQPPGPGGGPPFL PSEDLQERLYLNRSLLTAISAQRVLPFDDNICLREPCENYMRCVSVLRFDSSAPFIASSS VLFRPIHPVGGLRCRCPPGFTGDYCETEVDLCYSRPCGPHGRCRSREGGYTCLCRDGYTG EHCEVSARSGRCTPGVCKNGGTCVNLLVGGFKCDCPSGDFEKPYCQVTTRSFPAHSFITF RGLRQRFHFTLALSFATKERDGLLLYNGRFNEKHDFVALEVIQEQVQLTFSAGESTTTVS PFVPGGVSDGQWHTVQLKYYNKPLLGQTGLPQGPSEQKVAVVTVDGCDTGVALRFGSVLG NYSCAAQGTQGGSKKSLDLTGPLLLGGVPDLPESFPVRMRQFVGCMRNLQVDSRHIDMAD FIANNGTVPGCPAKKNVCDSNTCHNGGTCVNQWDAFSCECPLGFGGKSCAQEMANPQHFL GSSLVAWHGLSLPISQPWYLSLMFRTRQADGVLLQAITRGRSTITLQLREGHVMLSVEGT GLQASSLRLEPGRANDGDWHHAQLALGASGGPGHAILSFDYGQQRAEGNLGPRLHGLHLS NITVGGIPGPAGGVARGFRGCLQGVRVSDTPEGVNSLDPSHGESINVEQGCSLPDPCDSN PCPANSYCSNDWDSYSCSCDPGYYGDNCTNVCDLNPCEHQSVCTRKPSAPHGYTCECPPN YLGPYCETRIDQPCPRGWWGHPTCGPCNCDVSKGFDPDCNKTSGECHCKENHYRPPGSPT CLLCDCYPTGSLSRVCDPEDGQCPCKPGVIGRQCDRCDNPFAEVTTNGCEVNYDSCPRAI EAGIWWPRTRFGLPAAAPCPKGSFGTAVRHCDEHRGWLPPNLFNCTSITFSELKGFAERL QRNESGLDSGRSQQLALLLRNATQHTAGYFGSDVKVAYQLATRLLAHESTQRGFGLSATQ DVHFTENLLRVGSALLDTANKRHWELIQQTEGGTAWLLQHYEAYASALAQNMRHTYLSPF TIVTPNIVISVVRLDKGNFAGAKLPRYEALRGEQPPDLETTVILPESVFRETPPVVRPAG PGEAQEPEELARRQRRHPELSQGEAVASVIIYRTLAGLLPHNYDPDKRSLRVPKRPIINT PVVSISVHDDEELLPRALDKPVTVQFRLLETEERTKPICVFWNHSILVSGTGGWSARGCE VVFRNESHVSCQCNHMTSFAVLMDVSRRENGEILPLKTLTYVALGVTLAALLLTFFFLTL LRILRSNQHGIRRNLTAALGLAQLVFLLGINQADLPFACTVIAILLHFLYLCTFSWALLE ALHLYRALTEVRDVNTGPMRFYYMLGWGVPAFITGLAVGLDPEGYGNPDFCWLSIYDTLI WSFAGPVAFAVSMSVFLYILAARASCAAQRQGFEKKGPVSGLQPSFAVLLLLSATWLLAL LSVNSDTLLFHYLFATCNCIQGPFIFLSYVVLSKEVRKALKLACSRKPSPDPALTTKSTL TSSYNCPSPYADGRLYQPYGDSAGSLHSTSRSGKSQPSYIPFLLREESALNPGQGPPGLG DPGSLFLEGQDQQHDPDTDSDSDLSLEDDQSGSYASTHSSDSEEEEEEEEEEAAFPGEQG WDSLLGPGAERLPLHSTPKDGGPGPGKAPWPGDFGTTAKESSGNGAPEERLRENGDALSR EGSLGPLPGSSAQPHKGILKKKCLPTISEKSSLLRLPLEQCTGSSRGSSASEGSRGGPPP RPPPRQSLQEQLNGVMPIAMSIKAGTVDEDSSGSEFLFFNFLH |
Function of CELSR2 Membrane Protein
CELSR2 plays an essential role in the contact-mediated communication, involving in cell adhesion and receptor-ligand interactions. Studies have been shown that CELSR2 is involved in the development of nervous system through regulating neural migration, axon guidance, and cilium polarity. During the development of brain, CELSR2 regulates ciliogenesis via PCP signaling. In mice, CELSR2 knockout and CELSR2/ CELSR3 double-knockout impair the development of ependymal cilia and give rise to the fatal hydrocephalus. Moreover, CELSR2 also functions as a mediator in glucose homeostasis. In mice, the deficiency of CELSR2/3 could reduce the pancreatic β cells differentiation, leading to a decreased glucose eliminate. Besides, some variants of CELSR2 in humans are associated with the low-density lipoprotein and higher high-density lipoprotein cholesterol levels, implicating the functions of CELSR2 in the coronary artery disease (CAD) and ischemic stroke. Additionally, CELSR2 is also involved in the progress of breast cancer.
Fig.1 Cadherin mediates the cell-cell adhesion.
Application of CELSR2 Membrane Protein in Literature
1. Jiang L., et al. Differential cellular localization of CELSR2 and ING4 and correlations with hormone receptor status in breast cancer. Histology & Histopathology. 2018, 33(8): 835-842. PMID: 29489009
Jiang’s study analyzes the expression of CELSR2 and ING4 protein in breast tumors and benign epithelial cells by means of Immunohistochemistry. And the result showed that both CELSR2 and ING4 cytoplasmic expression was significantly stronger in breast cancer cells than in benign epithelial cells, which suggests the two genes may play important roles in the pathogenesis of human breast cancer.
2. Einarsdottir E., et al. CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. Plos One. 2017, 12(12): e0189591. PubMed ID: 29240829
This study reveals that a rare variant in CELSR2 is found as causative for idiopathic scoliosis in a family with dominant segregation. Moreover, the common variations in the highly conserved GAIN protein domain of CELSR2 are susceptible factors for idiopathic scoliosis in the Swedish-Danish population.
3. Vilboux T., et al. CELSR2, encoding a planar cell polarity protein, is a putative gene in Joubert syndrome with cortical heterotopia, microophthalmia, and growth hormone deficiency. American Journal of Medical Genetics Part A. 2017, 173(3): 661-666. PMID: 28052552
CELSR2, a planar cell polarity protein, plays an important role in neural development. The study reports that the bi-allelic mutations in CELSR2 in Joubert syndrome with cortical heterotopia, microophthalmia, and growth hormone deficiency.
4. Zhou Y J., et al. Association of variants in CELSR2-PSRC1-SORT1 with risk of serum lipid traits, coronary artery disease and ischemic stroke. International Journal of Clinical & Experimental Pathology. 2015, 8(8): 9543-51. PMID: 26464717
The study suggests that the minor G alleles of rs599839 and rs464218 SNPs are significantly associated with higher high-density lipoprotein cholesterol concentrations in the southern Chinese patients with coronary artery disease (CAD) and ischemic stroke (IS). However, the SNPs of rs599839, rs464218, and rs6698843 at the CELSR2-PSRC1-SORT1 are not related to the risk of CAD or IS.
5. Qu Y., et al. Genetic evidence that Celsr3 and Celsr2, together with Fzd3, regulate forebrain wiring in a Vangl-independent manner. Proceedings of the National Academy of Sciences of the United States of America. 2014, 111(29): E2996. PMID: 25002511
The study shows that Celsr2 and Celsr 3, as well as Fzd3, regulate axon guidance in the forebrain in an independent manner. The mechanism is different from classical epithelial PCP signaling mediation.
CELSR2 Preparation Options
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