<i>CELSR1</i> | Adhesion Class GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

CELSR1

Target id: 178

Nomenclature: CELSR1

Family: Adhesion Class GPCRs

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for CELSR1 in GtoImmuPdb

Gene and Protein Information
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 3014 22q13.31 CELSR1 cadherin EGF LAG seven-pass G-type receptor 1 11
Mouse 7 3034 15 E2 Celsr1 cadherin, EGF LAG seven-pass G-type receptor 1 12
Rat 7 3064 7q34 Celsr1 cadherin, EGF LAG seven-pass G-type receptor 1
Previous and Unofficial Names
crash | ADGRC1 (adhesion G protein-coupled receptor C1)
Database Links
Specialist databases
GPCRDB celr1_human (Hs), celr1_mouse (Mm)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Agonist Comments
No ligands identified: orphan receptor.
Primary Transduction Mechanisms
Transducer Effector/Response
Other - See Comments
Comments:  Evidence suggests that in the developing chicken embryo, Celsr1 cooperates with Dishevelled, DAAM1, and PDZ-RhoGEF to upregulate Rho kinase, which subsequently induces anisotropic contraction of the adherens junctions and results in bending of the neural plate contributing towards neural-tube closure,a critical step during embryogenesis [14].
References: 
Tissue Distribution
Epidermis.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  3,6
Lung.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  23
Central nervous system.
Species:  Mouse
Technique:  In situ hybridization, immunohistochemistry.
References:  7-8,11-12,15,18-20
Celsr1–3 expression was initiated broadly in the nervous system at early developmental stages, and each paralog showed characteristic expression patterns in the developing CNS. These genes were also expressed in several other organs, including the cochlea, where hair cells develop planar polarity, the kidney, and the whisker.
Species:  Mouse
Technique:  Immunocytochemistry.
References:  18
Celsr1-3 is expressed in the developing brain following a specific pattern, suggesting that they serve distinct functions.
Species:  Mouse
Technique:  In situ hybridisation.
References:  19
Inner ear.
Species:  Mouse
Technique:  In situ hybridization.
References:  5
Kidney.
Species:  Mouse
Technique:  In situ hybridization.
References:  22
Pancreas.
Species:  Mouse
Technique:  In situ hybridization.
References:  4
Testis
Species:  Rat
Technique:  In situ hybridization.
References:  2
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Physiological Consequences of Altering Gene Expression
Mice with receptor knockout exhibit defects in the orientation of hair outgrowth in the adult. Tissue specific PGK promotor-driven gene knockout results in the epidermis being affected.
Species:  Mouse
Tissue:  Epidermis.
Technique:  Gene knockout.
References:  16
Mice with ethylnitrosourea (ENU)-induced missense mutation develop lung branching defects.
Species:  Mouse
Tissue:  Full body, lung.
Technique:  Induced mutation.
References:  23
Mice with ethylnitrosourea (ENU)-induced missense mutations develop inner ear defects
Species:  Mouse
Tissue:  Full-body, inner ear affected
Technique:  Induced mutation.
References:  5
Mice with ethylnitrosourea (ENU)-induced missense mutations develop the severe neural tube defect, craniorachischisis
Species:  Mouse
Tissue:  Full-body, neural tube affected
Technique:  Induced mutation.
References:  5
Mice with receptor knockout exhibit defects in hindbrain neuron migration. Tissue-specific PGK promotor-driven gene knockout mouse and ENU-induced missense mutation (Celsr1 crash allele) resulting in the phenotype of aberrant tangential neuron migration.
Species:  Mouse
Tissue:  Central nervous system.
Technique:  Gene knockout.
References:  15
Mice with ethylnitrosourea (ENU)-induced missense mutation exhibit defects in hair follicle development with mis-alligned hair follicles.
Species:  Mouse
Tissue:  Full-body, epidermis affected
Technique:  Induced mutation.
References:  6
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Celsr1Crsh Celsr1Crsh/Celsr1Crsh
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0003308 abnormal cochlear sensory epithelium morphology PMID: 12842012 
Celsr1+|Celsr1Crsh Celsr1Crsh/Celsr1+
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0003308 abnormal cochlear sensory epithelium morphology PMID: 12842012 
Celsr1+|Celsr1Scy Celsr1Scy/Celsr1+
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0003308 abnormal cochlear sensory epithelium morphology PMID: 12842012 
Celsr1Scy Celsr1Scy/Celsr1Scy
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0003308 abnormal cochlear sensory epithelium morphology PMID: 12842012 
Celsr1tm1.1Fati Celsr1tm1.1Fati/Celsr1tm1.1Fati
involves: 129S1/Sv * 129X1/SvJ
MGI:1100883  MP:0000383 abnormal hair follicle orientation PMID: 19357712 
Celsr1+|Celsr1Scy Celsr1Scy/Celsr1+
involves: BALB/c * C3H/HeN
MGI:1100883  MP:0003492 abnormal involuntary movement PMID: 10932191 
Celsr1tm1.1Fati Celsr1tm1.1Fati/Celsr1tm1.1Fati
involves: 129S1/Sv * 129X1/SvJ
MGI:1100883  MP:0003720 abnormal neural tube closure PMID: 19357712 
Celsr1+|Celsr1Scy Celsr1Scy/Celsr1+
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0004300 abnormal organ of Corti supporting cell morphology PMID: 12842012 
Celsr1Crsh Celsr1Crsh/Celsr1Crsh
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0004491 abnormal orientation of outer hair cell stereociliary bundles PMID: 12842012 
Celsr1+|Celsr1Crsh Celsr1Crsh/Celsr1+
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0004491 abnormal orientation of outer hair cell stereociliary bundles PMID: 12842012 
Celsr1+|Celsr1Scy Celsr1Scy/Celsr1+
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0004491 abnormal orientation of outer hair cell stereociliary bundles PMID: 12842012 
Celsr1Scy Celsr1Scy/Celsr1Scy
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0004491 abnormal orientation of outer hair cell stereociliary bundles PMID: 12842012 
Celsr1Crsh Celsr1Crsh/Celsr1Crsh
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0001341 absent eyelids PMID: 12842012 
Celsr1Scy Celsr1Scy/Celsr1Scy
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0001341 absent eyelids PMID: 12842012 
Celsr1+|Celsr1Scy Celsr1Scy/Celsr1+
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0004404 cochlear outer hair cell degeneration PMID: 12842012 
Celsr1Crsh Celsr1Crsh/Celsr1Crsh
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0008784 craniorachischisis PMID: 12842012 
Celsr1Scy Celsr1Scy/Celsr1Scy
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0008784 craniorachischisis PMID: 12842012 
Celsr1Crsh|Celsr1Scy Celsr1Crsh/Celsr1Scy
involves: 101/H * BALB/c * C3H/He * C3H/HeH
MGI:1100883  MP:0008784 craniorachischisis PMID: 12842012 
Celsr1tm1.1Fati Celsr1tm1.1Fati/Celsr1tm1.1Fati
involves: 129S1/Sv * 129X1/SvJ
MGI:1100883  MP:0000919 cranioschisis PMID: 19357712 
Celsr1+|Celsr1Scy Celsr1Scy/Celsr1+
involves: BALB/c * C3H/HeN
MGI:1100883  MP:0001410 head bobbing PMID: 10932191 
Celsr1+|Celsr1Crsh Celsr1Crsh/Celsr1+
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0002730 head shaking PMID: 12842012 
Celsr1+|Celsr1Scy Celsr1Scy/Celsr1+
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0002730 head shaking PMID: 12842012 
Celsr1Crsh Celsr1Crsh/Celsr1Crsh
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0000928 incomplete cephalic closure PMID: 12842012 
Celsr1Scy Celsr1Scy/Celsr1Scy
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0000928 incomplete cephalic closure PMID: 12842012 
Celsr1tm1.1Fati Celsr1tm1.1Fati/Celsr1tm1.1Fati
involves: 129S1/Sv * 129X1/SvJ
MGI:1100883  MP:0000585 kinked tail PMID: 19357712 
Celsr1Crsh Celsr1Crsh/Celsr1Crsh
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0002081 perinatal lethality PMID: 12842012 
Celsr1Scy Celsr1Scy/Celsr1Scy
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0002081 perinatal lethality PMID: 12842012 
Celsr1tm1.1Fati Celsr1tm1.1Fati/Celsr1tm1.1Fati
involves: 129S1/Sv * 129X1/SvJ
MGI:1100883  MP:0002080 prenatal lethality PMID: 19357712 
Celsr1+|Celsr1Crsh|Ptk7+|Ptk7chz Celsr1Crsh/Celsr1+,Ptk7chz/Ptk7+
involves: 101/H * BALB/c * BALB/cAnN * C3H/HeH
MGI:1100883  MGI:1918711  MP:0003054 spina bifida PMID: 20704721 
Celsr1+|Celsr1Crsh Celsr1Crsh/Celsr1+
involves: 101/H * BALB/c * C3H/HeH
MGI:1100883  MP:0001411 spinning PMID: 12842012 
Celsr1+|Celsr1Scy Celsr1Scy/Celsr1+
involves: BALB/cAnN * C3H/He * C3H/HeH
MGI:1100883  MP:0001411 spinning PMID: 12842012 
Celsr1tm1.1Fati Celsr1tm1.1Fati/Celsr1tm1.1Fati
involves: 129S1/Sv * 129X1/SvJ
MGI:1100883  MP:0009457 whorled hair PMID: 19357712 
Celsr1tm1Fati|Emx1+|Emx1tm1(cre)Krj Celsr1tm1Fati/Celsr1tm1Fati,Emx1tm1(cre)Krj/Emx1+
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ
MGI:1100883  MGI:95387  MP:0009457 whorled hair PMID: 19357712 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Caudal agenesis type II
References:  1
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Type Species Amino acid change Nucleotide change Description Reference
Deletion Human c.8887_8898del12 12 bp in frame deletion in exon 34 1
Disease:  Chiari II malformation
References:  1
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Type Species Amino acid change Nucleotide change Description Reference
Nonsense Human Q834X c.2502C>T Nonsense mutation which is predicted to truncate protein 1
Disease:  Craniorachischisis
References:  5,17
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Type Species Amino acid change Nucleotide change Description Reference
Missense Human A773V Protein expressed but mis-localised 17
Missense Human R2312P Protein expressed at cell surface 17
Missense Human N2739T Protein expressed at cell surface 17
Missense Human S2964L Protein expressed but mis-localised 17
Missense Human P2983A Protein expressed but mis-localised 17
Disease:  Hydrocephalus
Disease Ontology: DOID:10908
References:  1
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Type Species Amino acid change Nucleotide change Description Reference
Nonsense Human Q834X c.2502C>T Nonsense mutation which is predicted to truncate protein 1
Disease:  Hydromyelia
References:  1
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Type Species Amino acid change Nucleotide change Description Reference
Nonsense Human Q834X c.2502C>T Nonsense mutation which is predicted to truncate protein 1
Disease:  Lipoma
Disease Ontology: DOID:3315
References:  1
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Type Species Amino acid change Nucleotide change Description Reference
Missense Human R836C c.2506C>T exon 1 1
Missense Human S2190L c.6569C>T exon 19 1
Missense Human A2228V c.6683C>T exon 19 1
Disease:  Lipomyelocele
References:  1
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Type Species Amino acid change Nucleotide change Description Reference
Missense Human V551M c.1651G>A exon 1 1
Missense Human R2359C c.7075C>T exon 21 1
Disease:  Lipomyelomeningocele
References:  1
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Type Species Amino acid change Nucleotide change Description Reference
Missense Human T1443P c.4327A>C exon 3 1
Disease:  Myelomeningocele
References:  1
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Type Species Amino acid change Nucleotide change Description Reference
Missense Human R541W c.1621C>T exon 1 1
Missense Human D1401G c.4202A>G exon 3 1
Missense Human R1526W c.4576C>T exon 5 1
Missense Human R1835C c.5503C>T exon 11 1
Nonsense Human Q834X c.2502C>T Nonsense mutation occuring in exon 1 which is predicted to truncate the protein, leading to myelomeningocele localize in D12-L1 intervertebral disc of spine. 1
Disease:  Stroke, ischemic
Synonyms: Cerebral infarction
Cerebrovascular accident [Disease Ontology: DOID:3455]
Disease Ontology: DOID:3455
OMIM: 601367
References:  10,21
Biologically Significant Variants
Type:  Missense mutation
Species:  Mouse
Description:  Missense mutation in exon 2 associated with craniorachischisis. The protein is expressed but mis-localised. This mutation is referred to as the spin-cycle mutation in the reference.
Amino acid change:  N1110K
Nucleotide change:  c.3337T>A
References:  5
Type:  Missense mutation
Species:  Mouse
Description:  Missense mutation associated with craniorachischisis. The protein is expressd but mis-localised. The mutation is referred to as the crash mutation in the reference.
Amino acid change:  D1040G
Nucleotide change:  c.3126A>G
References:  5
General Comments
Known ligand interactions: Vangl2 (core PCP protein) [6], VhaPRR (accessory unit of the proton pump V-ATPase) via HRM domain of CELSR1 [13].

CELSR1 (cadherin, EGF LAG seven-pass G-type receptor 1) is an orphan receptor that belongs to Family IV Adhesion-GPCRs together with CELSR2 and 3 [9]. The gene is localized on human chromosome 22 and mouse chromosome 15. Family IV Adhesion-GPCRs have orthologs in vertebrate and invertebrate species.

References

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1. Allache R, De Marco P, Merello E, Capra V, Kibar Z. (2012) Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis. Birth Defects Res. Part A Clin. Mol. Teratol., 94 (3): 176-81. [PMID:22371354]

2. Beall SA, Boekelheide K, Johnson KJ. (2005) Hybrid GPCR/cadherin (Celsr) proteins in rat testis are expressed with cell type specificity and exhibit differential Sertoli cell-germ cell adhesion activity. J. Androl., 26 (4): 529-38. [PMID:15955893]

3. Caddy J, Wilanowski T, Darido C, Dworkin S, Ting SB, Zhao Q, Rank G, Auden A, Srivastava S, Papenfuss TA, Murdoch JN, Humbert PO, Parekh V, Boulos N, Weber T, Zuo J, Cunningham JM, Jane SM. (2010) Epidermal wound repair is regulated by the planar cell polarity signaling pathway. Dev. Cell, 19 (1): 138-47. [PMID:20643356]

4. Cortijo C, Gouzi M, Tissir F, Grapin-Botton A. (2012) Planar cell polarity controls pancreatic Beta cell differentiation and glucose homeostasis. Cell Rep, 2 (6): 1593-606. [PMID:23177622]

5. Curtin JA, Quint E, Tsipouri V, Arkell RM, Cattanach B, Copp AJ, Henderson DJ, Spurr N, Stanier P, Fisher EM, Nolan PM, Steel KP, Brown SD, Gray IC, Murdoch JN. (2003) Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr Biol, 13: 1129-1133. [PMID:12842012]

6. Devenport D, Fuchs E. (2008) Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat. Cell Biol., 10 (11): 1257-68. [PMID:18849982]

7. Formstone CJ, Little PF. (2001) The flamingo-related mouse Celsr family (Celsr1-3) genes exhibit distinct patterns of expression during embryonic development. Mech Dev, 109: 91-94. [PMID:11677057]

8. Formstone CJ, Moxon C, Murdoch J, Little P, Mason I. (2010) Basal enrichment within neuroepithelia suggests novel function(s) for Celsr1 protein. Mol. Cell. Neurosci., 44 (3): 210-22. [PMID:20353824]

9. Fredriksson R, Gloriam DE, Höglund PJ, Lagerström MC, Schiöth HB. (2003) There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem. Biophys. Res. Commun., 301 (3): 725-34. [PMID:12565841]

10. Gouveia LO, Sobral J, Vicente AM, Ferro JM, Oliveira SA. (2011) Replication of the CELSR1 association with ischemic stroke in a Portuguese case-control cohort. Atherosclerosis, 217 (1): 260-2. [PMID:21511255]

11. Hadjantonakis AK, Formstone CJ, Little PF. (1998) mCelsr1 is an evolutionarily conserved seven-pass transmembrane receptor and is expressed during mouse embryonic development. Mech Dev, 78: 91-95. [PMID:9858697]

12. Hadjantonakis AK, Sheward WJ, Harmar AJ, de Galan L, Hoovers JM, Little PF. (1997) Celsr1, a neural-specific gene encoding an unusual seven-pass transmembrane receptor, maps to mouse chromosome 15 and human chromosome 22qter. Genomics, 45: 97-104. [PMID:9339365]

13. Hermle T, Guida MC, Beck S, Helmstädter S, Simons M. (2013) Drosophila ATP6AP2/VhaPRR functions both as a novel planar cell polarity core protein and a regulator of endosomal trafficking. EMBO J., 32 (2): 245-59. [PMID:23292348]

14. Nishimura T, Honda H, Takeichi M. (2012) Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell, 149 (5): 1084-97. [PMID:22632972]

15. Qu Y, Glasco DM, Zhou L, Sawant A, Ravni A, Fritzsch B, Damrau C, Murdoch JN, Evans S, Pfaff SL, Formstone C, Goffinet AM, Chandrasekhar A, Tissir F. (2010) Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice. J. Neurosci., 30 (28): 9392-401. [PMID:20631168]

16. Ravni A, Qu Y, Goffinet AM, Tissir F. (2009) Planar cell polarity cadherin Celsr1 regulates skin hair patterning in the mouse. J. Invest. Dermatol., 129 (10): 2507-9. [PMID:19357712]

17. Robinson A, Escuin S, Doudney K, Vekemans M, Stevenson RE, Greene ND, Copp AJ, Stanier P. (2012) Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. Hum. Mutat., 33 (2): 440-7. [PMID:22095531]

18. Shima Y, Copeland NG, Gilbert DJ, Jenkins NA, Chisaka O, Takeichi M, Uemura T. (2002) Differential expression of the seven-pass transmembrane cadherin genes Celsr1-3 and distribution of the Celsr2 protein during mouse development. Dev Dyn, 223: 321-332. [PMID:11891983]

19. Tissir F, De-Backer O, Goffinet AM, Lambert de Rouvroit C. (2002) Developmental expression profiles of Celsr (Flamingo) genes in the mouse. Mech Dev, 112: 157-160. [PMID:11850187]

20. Tissir F, Goffinet AM. (2006) Expression of planar cell polarity genes during development of the mouse CNS. Eur. J. Neurosci., 23 (3): 597-607. [PMID:16487141]

21. Yamada Y, Fuku N, Tanaka M, Aoyagi Y, Sawabe M, Metoki N, Yoshida H, Satoh K, Kato K, Watanabe S, Nozawa Y, Hasegawa A, Kojima T. (2009) Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study. Atherosclerosis, 207 (1): 144-9. [PMID:19403135]

22. Yates LL, Papakrivopoulou J, Long DA, Goggolidou P, Connolly JO, Woolf AS, Dean CH. (2010) The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation. Hum. Mol. Genet., 19 (23): 4663-76. [PMID:20843830]

23. Yates LL, Schnatwinkel C, Murdoch JN, Bogani D, Formstone CJ, Townsend S, Greenfield A, Niswander LA, Dean CH. (2010) The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis. Hum. Mol. Genet., 19 (11): 2251-67. [PMID:20223754]

Contributors

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How to cite this page

Caroline Formstone, Tom I. Bonner.
Adhesion Class GPCRs: CELSR1. Last modified on 03/03/2017. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=178.