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| Cartoon of NrCAM's structure with fibronectin, immunoglobulin, transmembrane, and intracellular (C-terminal) domains indicated. Arrows indicate sites where splice variants encode additional inserted additional amino acids. These NrCAM structures are conserved in human, mouse, and rat. (from Ishiguro et al., 2006). |
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Description | NrCAM is a cell surface protein of the immunoglobulin superfamily, L1/neurofascin/NgCAM subgroup. The molecule is 200-220kDa transmembrane protein, which contains 5 fibronectin type-III domains, 6 Ig-like C2-type (immunoglobulin-like) domains in the extracellular region and a highly conserved cytoplasmic tail. (Grumet et al., 1991; Kayyem et al., 1992; Lane et al., 1996). Human NrCAM has few alternatively spliced regions: AE19 adds 19 amino acids to the region between Ig domain 2 and 3; AE10 lies clearly between Ig domain 6 and the beginning of the Fn repeats; AE10K2 encompasses part of the G strand of Ig 5 and most of the A strand of Ig 6; AE12 affects the G strand of Fn III domain 4; AE93 corresponds to the entire Fn type III domain (Grumet et al.,1991; Lane et al., 1996; Wang et al., 1998). |
Expression | Central and peripheral nervous system, and other tissues, endothelial cells, and certain tumor cell lines and human cancers including pancreatic cancer, melanoma, renal and colon carcinoma, adrenal gland, placenta, thyroid and testis (Wang et al., 1998; Glienke et al, 2000; Dhodapkar et al., 2001; Aitkenhead et al, 2002; Conacci-Sorrell et al., 2002). Nervous system: NrCAM is expressed in structures in the developing brain. In the floor plate NrCAM has been implicated in axonal guidance trough interaction with TAG-1/axonin-1 (Lustig et al., 2001). Moreover, NrCAM induces neurite outgrowth from dorsal root ganglia neurons. It also operates as a receptor for several different neuronal recognition molecules. NrCAM protein promotes directional signaling during nervous system development in several different regions as the spinal cord, the visual system, and the cerebellum (Lustig et al., 2001; Hutcheson et al., 2004). |
Localisation | Various cell compartments: external side of plasma membrane, integral to plasma membrane, neuron projection, cytoplasm, nucleus. |
Function | NrCAM is engaged in such biological processes as axonal fasciculation, cell-cell adhesion, central nervous system development, clustering of voltage-gated sodium channels, neuron migration, positive regulation of neuron differentiation, regulation of axon extension, and synaptogenesis. It also may play a role in the molecular assembly of the nodes of Ranvier. NrCAM effects are also linked with different recognition processes and signal transduction pathways regulating cell differentiation, proliferation, or migration (Gumbiner, 1996; Cavallaro and Christofori, 2004). |
Homology | - NRCAM, neuronal cell adhesion molecule, Homo sapiens - NRCAM, neuronal cell adhesion molecule, Bos taurus - Nrcam, neuron-glia-CAM-related cell adhesion molecule, Mus musculus - Nrcam, neuron-glia-CAM-related cell adhesion molecule, Rattus norvegicus - NRCAM, neuronal cell adhesion molecule, Gallus gallus - si:dkey-240a12.1, si:dkey-240a12.1, Danio rerio - Nrg, Neuroglian, Drosophila melanogaster - AgaP_AGAP000720, AGAP000720-PA, Anopheles gambiae - lad-2, L1 CAM ADhesion molecule homolog, Caenorhabditis elegans - NRCAM, neuronal cell adhesion molecule, Pan troglodytes - LOC475881, similar to Neuronal cell adhesion m..., Canis lupus familiaris. |
Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM. |
Aitkenhead M, Wang SJ, Nakatsu MN, Mestas J, Heard C, Hughes CC. |
Microvasc Res. 2002 Mar;63(2):159-71. |
PMID 11866539 |
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Mutation screening and association analysis of six candidate genes for autism on chromosome 7q. |
Bonora E, Lamb JA, Barnby G, Sykes N, Moberly T, Beyer KS, Klauck SM, Poustka F, Bacchelli E, Blasi F, Maestrini E, Battaglia A, Haracopos D, Pedersen L, Isager T, Eriksen G, Viskum B, Sorensen EU, Brondum-Nielsen K, Cotterill R, Engeland H, Jonge M, Kemner C, Steggehuis K, Scherpenisse M, Rutter M, Bolton PF, Parr JR, Poustka A, Bailey AJ, Monaco AP; International Molecular Genetic Study of Austism Consortium. |
Eur J Hum Genet. 2005 Feb;13(2):198-207. |
PMID 15523497 |
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Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. |
Borrello MG, Alberti L, Fischer A, Degl'innocenti D, Ferrario C, Gariboldi M, Marchesi F, Allavena P, Greco A, Collini P, Pilotti S, Cassinelli G, Bressan P, Fugazzola L, Mantovani A, Pierotti MA. |
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14825-30. Epub 2005 Oct 3. |
PMID 16203990 |
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Multitasking in tumor progression: signaling functions of cell adhesion molecules. |
Cavallaro U, Christofori G. |
Ann N Y Acad Sci. 2004 Apr;1014:58-66. |
PMID 15153420 |
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The shed ectodomain of Nr-CAM stimulates cell proliferation and motility, and confers cell transformation. |
Conacci-Sorrell M, Kaplan A, Raveh S, Gavert N, Sakurai T, Ben-Ze'ev A. |
Cancer Res. 2005 Dec 15;65(24):11605-12. |
PMID 16357171 |
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Gene expression and the biological phenotype of papillary thyroid carcinomas. |
Delys L, Detours V, Franc B, Thomas G, Bogdanova T, Tronko M, Libert F, Dumont JE, Maenhaut C. |
Oncogene. 2007 Dec 13;26(57):7894-903. Epub 2007 Jul 9. |
PMID 17621275 |
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Differential expression of the cell-adhesion molecule Nr-CAM in hyperplastic and neoplastic human pancreatic tissue. |
Dhodapkar KM, Friedlander D, Scholes J, Grumet M. |
Hum Pathol. 2001 Apr;32(4):396-400. |
PMID 11331956 |
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Differential gene expression by endothelial cells in distinct angiogenic states. |
Glienke J, Schmitt AO, Pilarsky C, Hinzmann B, Weiss B, Rosenthal A, Thierauch KH. |
Eur J Biochem. 2000 May;267(9):2820-30. |
PMID 10785405 |
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NrCAM, a neuronal system cell-adhesion molecule, is induced in papillary thyroid carcinomas. |
Gorka B, Skubis-Zegadlo J, Mikula M, Bardadin K, Paliczka E, Czarnocka B. |
Br J Cancer. 2007 Aug 20;97(4):531-8. Epub 2007 Jul 31. |
PMID 17667921 |
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Structure of a new nervous system glycoprotein, Nr-CAM, and its relationship to subgroups of neural cell adhesion molecules. |
Grumet M, Mauro V, Burgoon MP, Edelman GM, Cunningham BA. |
J Cell Biol. 1991 Jun;113(6):1399-412. |
PMID 2045418 |
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Cell adhesion: the molecular basis of tissue architecture and morphogenesis. |
Gumbiner BM. |
Cell. 1996 Feb 9;84(3):345-57. |
PMID 8608588 |
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Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. |
Hutcheson HB, Olson LM, Bradford Y, Folstein SE, Santangelo SL, Sutcliffe JS, Haines JL. |
BMC Med Genet. 2004 May 5;5:12. |
PMID 15128462 |
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NrCAM in addiction vulnerability: positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice. |
Ishiguro H, Liu QR, Gong JP, Hall FS, Ujike H, Morales M, Sakurai T, Grumet M, Uhl GR. |
Neuropsychopharmacology. 2006 Mar;31(3):572-84. |
PMID 16123759 |
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Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications. |
Jarzab B, Wiench M, Fujarewicz K, Simek K, Jarzab M, Oczko-Wojciechowska M, Wloch J, Czarniecka A, Chmielik E, Lange D, Pawlaczek A, Szpak S, Gubala E, Swierniak A. |
Cancer Res. 2005 Feb 15;65(4):1587-97. |
PMID 15735049 |
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Bravo/Nr-CAM is closely related to the cell adhesion molecules L1 and Ng-CAM and has a similar heterodimer structure. |
Kayyem JF, Roman JM, de la Rosa EJ, Schwarz U, Dreyer WJ. |
J Cell Biol. 1992 Sep;118(5):1259-70. |
PMID 1512296 |
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Characterization of a highly conserved human homolog to the chicken neural cell surface protein Bravo/Nr-CAM that maps to chromosome band 7q31. |
Lane RP, Chen XN, Yamakawa K, Vielmetter J, Korenberg JR, Dreyer WJ. |
Genomics. 1996 Aug 1;35(3):456-65. |
PMID 8812479 |
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Nr-CAM expression in the developing mouse nervous system: ventral midline structures, specific fiber tracts, and neuropilar regions. |
Lustig M, Erskine L, Mason CA, Grumet M, Sakurai T. |
J Comp Neurol. 2001 May 21;434(1):13-28. |
PMID 11329126 |
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Cell adhesion molecule Nr-CAM is over-expressed in human brain tumors. |
Sehgal A, Boynton AL, Young RF, Vermeulen SS, Yonemura KS, Kohler EP, Aldape HC, Simrell CR, Murphy GP. |
Int J Cancer. 1998 May 18;76(4):451-8. |
PMID 9590116 |
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The consensus coding sequences of human breast and colorectal cancers. |
Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. |
Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. |
PMID 16959974 |
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Alternative Splicing of Human NrCAM in Neural and Nonneural Tissues. |
Wang B, Williams H, Du JS, Terrett J, Kenwrick S. |
Mol Cell Neurosci. 1998 Apr;10(5/6):287-95. |
PMID 9618219 |
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