CRLF3

CRLF3
Identifiers
Aliases	CRLF3, CREME-9, CREME9, CRLM9, CYTOR4, FRWS, p48.2, cytokine receptor like factor 3
External IDs	OMIM: 614853 MGI: 1860086 HomoloGene: 9327 GeneCards: CRLF3
Gene location (Human)
Chr.	Chromosome 17 (human)[1]
End	30,824,692 bp[1]
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)[2]
End	79,971,817 bp[2]
RNA expression pattern
	Top expressed in
	cancellous bone; ; monocyte; ; bone marrow; ; blood; ; lymph node; ; thymus; ; bone marrow cells; ; appendix; ; gums; ; cavity of mouth;
	Top expressed in
	spleen; ; blood; ; thymus; ; bone marrow; ; right lung lobe; ; ectoderm; ; otic placode; ; subcutaneous adipose tissue; ; hair follicle; ; left lung;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein binding; identical protein binding; DNA binding;
Cellular component	plasma membrane; cytoplasm; cytosol; nucleus;
Biological process	negative regulation of cell growth; positive regulation of transcription, DNA-templated; positive regulation of transcription by RNA polymerase II; positive regulation of receptor signaling pathway via JAK-STAT; G1/S transition of mitotic cell cycle;
	Sources:Amigo / QuickGO
Orthologs
	51379
	54394
	ENSG00000176390
	ENSMUSG00000017561
	Q8IUI8
	Q9Z2L7
	NM_015986
	NM_001277106; NM_018776
	NP_057070
	NP_001264035; NP_061246
	Wikidata
View/Edit Human	View/Edit Mouse

Cytokine receptor-like factor 3 is a protein that in humans is encoded by the CRLF3 gene.[5]

Model organisms

*Crlf3* knockout mouse phenotype
Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal[6]
Plasma immunoglobulins	Normal
Haematology	Abnormal[7]
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal[8]
Citrobacter infection	Normal[9]
All tests and analysis from[10][11]

Model organisms have been used in the study of CRLF3 function. A conditional knockout mouse line, called Crlf3^{tm1a(KOMP)Wtsi}[12][13] was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[14][15][16] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][17] Twenty six tests were carried out and two significant phenotypes were reported. Homozygous mutant female adults had a significant increase in circulating levels of fructosamine, while mutants of both sexes had decreased platelet cell numbers.[10]

Function

Although CRLF3 signaling pathways have not yet been fully characterized it is very likely that CRLF3 is a neuroprotective erythropoietin receptor.[18]

Origin

Phylogenetic analyses have shown that CRLF3 at first appeared in a common ancestor of Cnidaria and Bilateria and hence emerged with the origin of the nervous system.[19][20]

References

GRCh38: Ensembl release 89: ENSG00000176390 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000017561 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: cytokine receptor-like factor 3".
"Clinical chemistry data for Crlf3". Wellcome Trust Sanger Institute.
"Haematology data for Crlf3". Wellcome Trust Sanger Institute.
"Salmonella infection data for Crlf3". Wellcome Trust Sanger Institute.
"Citrobacter infection data for Crlf3". Wellcome Trust Sanger Institute.
Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
Mouse Resources Portal, Wellcome Trust Sanger Institute.
"International Knockout Mouse Consortium".
"Mouse Genome Informatics".
Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Hahn N, Knorr DY, Liebig J, Wüstefeld L, Peters K, Büscher M, et al. (2017). "The Insect Ortholog of the Human Orphan Cytokine Receptor CRLF3 Is a Neuroprotective Erythropoietin Receptor". Frontiers in Molecular Neuroscience. 10: 223. doi:10.3389/fnmol.2017.00223. PMC 5509957. PMID 28769759.
Hahn N, Büschgens L, Schwedhelm-Domeyer N, Bank S, Geurten BR, Neugebauer P, et al. (2019). "The Orphan Cytokine Receptor CRLF3 Emerged With the Origin of the Nervous System and Is a Neuroprotective Erythropoietin Receptor in Locusts". Frontiers in Molecular Neuroscience. 12: 251. doi:10.3389/fnmol.2019.00251. PMC 6797617. PMID 31680856.
Liongue C, Ward AC (July 2007). "Evolution of Class I cytokine receptors". BMC Evolutionary Biology. 7 (1): 120. doi:10.1186/1471-2148-7-120. PMC 1963337. PMID 17640376.

External links

Human CRLF3 genome location and CRLF3 gene details page in the UCSC Genome Browser.

Visser R, Koelma N, Vijfhuizen L, van der Wielen MJ, Kant SG, Breuning MH, et al. (February 2009). "RNF135 mutations are not present in patients with Sotos syndrome-like features". American Journal of Medical Genetics. Part A. 149A (4): 806–8. doi:10.1002/ajmg.a.32694. PMID 19291764. S2CID 10349510.
Gudbjartsson DF, Walters GB, Thorleifsson G, Stefansson H, Halldorsson BV, Zusmanovich P, et al. (May 2008). "Many sequence variants affecting diversity of adult human height". Nature Genetics. 40 (5): 609–15. doi:10.1038/ng.122. PMID 18391951. S2CID 3005450.
Zhao J, Li M, Bradfield JP, Zhang H, Mentch FD, Wang K, et al. (June 2010). "The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature". BMC Medical Genetics. 11: 96. doi:10.1186/1471-2350-11-96. PMC 2894790. PMID 20546612.
Yang F, Xu YP, Li J, Duan SS, Fu YJ, Zhang Y, et al. (November 2009). "Cloning and characterization of a novel intracellular protein p48.2 that negatively regulates cell cycle progression". The International Journal of Biochemistry & Cell Biology. 41 (11): 2240–50. doi:10.1016/j.biocel.2009.04.022. PMID 19427400.
Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
Johnatty SE, Beesley J, Chen X, Macgregor S, Duffy DL, Spurdle AB, et al. (July 2010). "Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot"". PLOS Genetics. 6 (7): e1001016. doi:10.1371/journal.pgen.1001016. PMC 2900295. PMID 20628624.
Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, et al. (March 2008). "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics. 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
Douglas J, Cilliers D, Coleman K, Tatton-Brown K, Barker K, Bernhard B, et al. (August 2007). "Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth". Nature Genetics. 39 (8): 963–5. doi:10.1038/ng2083. PMID 17632510. S2CID 35797973.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000176390 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000017561 - 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.

[entrez-5] "Entrez Gene: cytokine receptor-like factor 3".

[Clinical_chemistry-6] "Clinical chemistry data for Crlf3". Wellcome Trust Sanger Institute.

[Haematology-7] "Haematology data for Crlf3". Wellcome Trust Sanger Institute.

[''Salmonella''_infection-8] "Salmonella infection data for Crlf3". Wellcome Trust Sanger Institute.

[''Citrobacter''_infection-9] "Citrobacter infection data for Crlf3". Wellcome Trust Sanger Institute.

[mgp_reference-10] Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.

[11] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-12] "International Knockout Mouse Consortium".

[mgi_allele_ref-13] "Mouse Genome Informatics".

[pmid21677750-14] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-15] Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-16] Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.

[pmid21722353-17] van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

[18] Hahn N, Knorr DY, Liebig J, Wüstefeld L, Peters K, Büscher M, et al. (2017). "The Insect Ortholog of the Human Orphan Cytokine Receptor CRLF3 Is a Neuroprotective Erythropoietin Receptor". Frontiers in Molecular Neuroscience. 10: 223. doi:10.3389/fnmol.2017.00223. PMC 5509957. PMID 28769759.

[19] Hahn N, Büschgens L, Schwedhelm-Domeyer N, Bank S, Geurten BR, Neugebauer P, et al. (2019). "The Orphan Cytokine Receptor CRLF3 Emerged With the Origin of the Nervous System and Is a Neuroprotective Erythropoietin Receptor in Locusts". Frontiers in Molecular Neuroscience. 12: 251. doi:10.3389/fnmol.2019.00251. PMC 6797617. PMID 31680856.

[20] Liongue C, Ward AC (July 2007). "Evolution of Class I cytokine receptors". BMC Evolutionary Biology. 7 (1): 120. doi:10.1186/1471-2148-7-120. PMC 1963337. PMID 17640376.