G2Cdb::Gene report

Gene id
G00001902
Gene symbol
NCAM2 (HGNC)
Species
Homo sapiens
Description
neural cell adhesion molecule 2
Orthologue
G00000653 (Mus musculus)

Databases (7)

Gene
ENSG00000154654 (Ensembl human gene)
4685 (Entrez Gene)
1068 (G2Cdb plasticity & disease)
NCAM2 (GeneCards)
Literature
602040 (OMIM)
Marker Symbol
HGNC:7657 (HGNC)
Protein Sequence
O15394 (UniProt)

Synonyms (2)

  • MGC51008
  • NCAM21

Literature (9)

Pubmed - other

  • Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.

    Gratacòs M, Costas J, de Cid R, Bayés M, González JR, Baca-García E, de Diego Y, Fernández-Aranda F, Fernández-Piqueras J, Guitart M, Martín-Santos R, Martorell L, Menchón JM, Roca M, Sáiz-Ruiz J, Sanjuán J, Torrens M, Urretavizcaya M, Valero J, Vilella E, Estivill X, Carracedo A and Psychiatric Genetics Network Group

    CIBER en Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.

    A fundamental difficulty in human genetics research is the identification of the spectrum of genetic variants that contribute to the susceptibility to common/complex disorders. We tested here the hypothesis that functional genetic variants may confer susceptibility to several related common disorders. We analyzed five main psychiatric diagnostic categories (substance-abuse, anxiety, eating, psychotic, and mood disorders) and two different control groups, representing a total of 3,214 samples, for 748 promoter and non-synonymous single nucleotide polymorphisms (SNPs) at 306 genes involved in neurotransmission and/or neurodevelopment. We identified strong associations to individual disorders, such as growth hormone releasing hormone (GHRH) with anxiety disorders, prolactin regulatory element (PREB) with eating disorders, ionotropic kainate glutamate receptor 5 (GRIK5) with bipolar disorder and several SNPs associated to several disorders, that may represent individual and related disease susceptibility factors. Remarkably, a functional SNP, rs945032, located in the promoter region of the bradykinin receptor B2 gene (BDKRB2) was associated to three disorders (panic disorder, substance abuse, and bipolar disorder), and two additional BDKRB2 SNPs to obsessive-compulsive disorder and major depression, providing evidence for common variants of susceptibility to several related psychiatric disorders. The association of BDKRB2 (odd ratios between 1.65 and 3.06) to several psychiatric disorders supports the view that a common genetic variant could confer susceptibility to clinically related phenotypes, and defines a new functional hint in the pathophysiology of psychiatric diseases.

    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2009;150B;6;808-16

  • Crystal structure of the Ig1 domain of the neural cell adhesion molecule NCAM2 displays domain swapping.

    Rasmussen KK, Kulahin N, Kristensen O, Poulsen JC, Sigurskjold BW, Kastrup JS, Berezin V, Bock E, Walmod PS and Gajhede M

    Protein Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.

    The crystal structure of the first immunoglobulin (Ig1) domain of neural cell adhesion molecule 2 (NCAM2/OCAM/RNCAM) is presented at a resolution of 2.7 A. NCAM2 is a member of the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). In the structure, two Ig domains interact by domain swapping, as the two N-terminal beta-strands are interchanged. beta-Strand swapping at the terminal domain is the accepted mechanism of homophilic interactions amongst the cadherins, another class of CAMs, but it has not been observed within the IgCAM superfamily. Gel-filtration chromatography demonstrated the ability of NCAM2 Ig1 to form dimers in solution. Taken together, these observations suggest that beta-strand swapping could have a role in the molecular mechanism of homophilic binding for NCAM2.

    Journal of molecular biology 2008;382;5;1113-20

  • Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1.

    Carroll JS, Liu XS, Brodsky AS, Li W, Meyer CA, Szary AJ, Eeckhoute J, Shao W, Hestermann EV, Geistlinger TR, Fox EA, Silver PA and Brown M

    Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.

    Estrogen plays an essential physiologic role in reproduction and a pathologic one in breast cancer. The completion of the human genome has allowed the identification of the expressed regions of protein-coding genes; however, little is known concerning the organization of their cis-regulatory elements. We have mapped the association of the estrogen receptor (ER) with the complete nonrepetitive sequence of human chromosomes 21 and 22 by combining chromatin immunoprecipitation (ChIP) with tiled microarrays. ER binds selectively to a limited number of sites, the majority of which are distant from the transcription start sites of regulated genes. The unbiased sequence interrogation of the genuine chromatin binding sites suggests that direct ER binding requires the presence of Forkhead factor binding in close proximity. Furthermore, knockdown of FoxA1 expression blocks the association of ER with chromatin and estrogen-induced gene expression demonstrating the necessity of FoxA1 in mediating an estrogen response in breast cancer cells.

    Funded by: NCI NIH HHS: F32 CA108380-02; NHGRI NIH HHS: K22 HG02488-01A1; NIDDK NIH HHS: T90 DK070078-01

    Cell 2005;122;1;33-43

  • Time-controlled transcardiac perfusion cross-linking for the study of protein interactions in complex tissues.

    Schmitt-Ulms G, Hansen K, Liu J, Cowdrey C, Yang J, DeArmond SJ, Cohen FE, Prusiner SB and Baldwin MA

    Institute for Neurodegenerative Disease, San Francisco, California 94143, USA. g.schmittulms@utoronto.ca

    Because of their sensitivity to solubilizing detergents, membrane protein assemblies are difficult to study. We describe a protocol that covalently conserves protein interactions through time-controlled transcardiac perfusion cross-linking (tcTPC) before disruption of tissue integrity. To validate tcTPC for identifying protein-protein interactions, we established that tcTPC allowed stringent immunoaffinity purification of the gamma-secretase complex in high salt concentrations and detergents and was compatible with mass spectrometric identification of cross-linked aph-1, presenilin-1 and nicastrin. We then applied tcTPC to identify more than 20 proteins residing in the vicinity of the cellular prion protein (PrPC), suggesting that PrP is embedded in specialized membrane regions with a subset of molecules that, like PrP, use a glycosylphosphatidylinositol anchor for membrane attachment. Many of these proteins have been implicated in cell adhesion/neuritic outgrowth, and harbor immunoglobulin C2 and fibronectin type III-like motifs.

    Funded by: NCRR NIH HHS: NCRR RR01614; NIA NIH HHS: AG010770, AG02132

    Nature biotechnology 2004;22;6;724-31

  • Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry.

    Zhang H, Li XJ, Martin DB and Aebersold R

    Institute for Systems Biology, 1441 N 34th Street, Seattle, Washington 98103-8904, USA.

    Quantitative proteome profiling using stable isotope protein tagging and automated tandem mass spectrometry (MS/MS) is an emerging technology with great potential for the functional analysis of biological systems and for the detection of clinical diagnostic or prognostic marker proteins. Owing to the enormous complexity of proteomes, their comprehensive analysis is an as-yet-unresolved technical challenge. However, biologically or clinically important information can be obtained if specific, information-rich protein classes, or sub-proteomes, are isolated and analyzed. Glycosylation is the most common post-translational modification. Here we describe a method for the selective isolation, identification and quantification of peptides that contain N-linked carbohydrates. It is based on the conjugation of glycoproteins to a solid support using hydrazide chemistry, stable isotope labeling of glycopeptides and the specific release of formerly N-linked glycosylated peptides via peptide- N-glycosidase F (PNGase F). The recovered peptides are then identified and quantified by MS/MS. We applied the approach to the analysis of plasma membrane proteins and proteins contained in human blood serum.

    Funded by: NCI NIH HHS: K08CA97282-01, R33 CA93302

    Nature biotechnology 2003;21;6;660-6

  • Differential function of RNCAM isoforms in precise target selection of olfactory sensory neurons.

    Alenius M and Bohm S

    Department of Molecular Biology, Umeå University, Umeå, S-901 87, Sweden.

    Olfactory sensory neurons (OSNs) are individually specified to express one odorant receptor (OR) gene among approximately 1000 different and project with precision to topographically defined convergence sites, the glomeruli, in the olfactory bulb. Although ORs partially determine the location of convergence sites, the mechanism ensuring that axons with different OR identities do not co-converge is unknown. RNCAM (OCAM, NCAM2) is assumed to regulate a broad zonal segregation of projections by virtue of being a homophilic cell adhesion molecule that is selectively expressed on axons terminating in a defined olfactory bulb region. We have identified NADPH diaphorase activity as being an independent marker for RNCAM-negative axons. Analyses of transgenic mice that ectopically express RNCAM in NADPH diaphorase-positive OSNs show that the postulated function of RNCAM in mediating zone-specific segregation of axons is unlikely. Instead, analyses of one OR-specific OSN subpopulation (P2) reveal that elevated RNCAM levels result in an increased number of P2 axons that incorrectly co-converge with axons of other OR identities. Both Gpi-anchored and transmembrane-bound RNCAM isoforms are localized on axons in the nerve layer, while the transmembrane-bound RNCAM is the predominant isoform on axon terminals within glomeruli. Overexpressing transmembrane-bound RNCAM results in co-convergence events close to the correct target glomeruli. By contrast, overexpression of Gpi-anchored RNCAM results in axons that can bypass the correct target before co-converging on glomeruli located at a distance. The phenotype specific for Gpi-anchored RNCAM is suppressed in mice overexpressing both isoforms, which suggests that two distinct RNCAM isoform-dependent activities influence segregation of OR-defined axon subclasses.

    Development (Cambridge, England) 2003;130;5;917-27

  • The DNA sequence of human chromosome 21.

    Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML and Chromosome 21 mapping and sequencing consortium

    RIKEN, Genomic Sciences Center, Sagamihara, Japan.

    Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

    Nature 2000;405;6784;311-9

  • Cloning of a novel human neural cell adhesion molecule gene (NCAM2) that maps to chromosome region 21q21 and is potentially involved in Down syndrome.

    Paoloni-Giacobino A, Chen H and Antonarakis SE

    Department of Genetics and Microbiology, Geneva University Medical School, Switzerland.

    To contribute to the development of the transcription map of human chromosome 21 (HC21), we have used exon trapping to identify portions of HC21 genes. One trapped exon showed strong homology with members of the neural cell adhesion molecule (NCAM) family of genes from different species. We subsequently cloned the complete coding sequence from a human fetal brain cDNA library and determined its nucleotide sequence and predicted amino acid sequence. The predicted polypeptide of this novel NCAM2 gene contains 837 amino acids and shows 62% similarity to the NCAM homologs. It contains five immunoglobulin-like domains, two fibronectin type III domains, a transmembrane domain and a cytoplasmic domain. The gene is expressed most strongly in human adult and fetal brain. Using somatic cell hybrids, we mapped NCAM2 to 21q21, between markers D21S18 and D21S282. Radiation hybrid mapping localized this novel gene between polymorphic markers D21S1914 and D21S265. NCAMs are members of the immunoglobulin superfamily and are essential in the formation and maintenance of tissue structure. To date there are no candidate human disorders on HC21 that could be associated with mutations in NCAM2. In addition, the role of NCAM2 in the pathophysiology of Down syndrome is unknown. However, it is a good candidate for involvement in certain Down syndrome phenotypes because a slight overexpression of NCAMs increases many-fold the homotypic adhesion properties of cells.

    Genomics 1997;43;1;43-51

Gene lists (6)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000061 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus (ortho) 984
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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