The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016] See more...

Aliases for NECAB2 Gene

Aliases for NECAB2 Gene

  • N-Terminal EF-Hand Calcium Binding Protein 2 2 3 5
  • N-Terminal EF-Hand Calcium-Binding Protein 2 3 4
  • Synaptotagmin-Interacting Protein 2 3 4
  • Neuronal Calcium-Binding Protein 2 3 4
  • EF-Hand Calcium-Binding Protein 2 3 4
  • EFCBP2 3 4
  • Stip-2 3 4
  • EF-Hand Calcium Binding Protein 2 2
  • Neuronal Calcium Binding 2 3
  • NECAB2 5

External Ids for NECAB2 Gene

Previous HGNC Symbols for NECAB2 Gene

  • EFCBP2

Previous GeneCards Identifiers for NECAB2 Gene

  • GC16P083744
  • GC16P082560
  • GC16P069754

Summaries for NECAB2 Gene

Entrez Gene Summary for NECAB2 Gene

  • The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]

GeneCards Summary for NECAB2 Gene

NECAB2 (N-Terminal EF-Hand Calcium Binding Protein 2) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include calcium ion binding. An important paralog of this gene is NECAB1.

UniProtKB/Swiss-Prot Summary for NECAB2 Gene

  • May act as a signaling scaffold protein that senses intracellular calcium. Can modulate ligand-induced internalization of ADORA2A and coupling efficiency of mGluR5/GRM5; for both receptors may regulate signaling activity such as promoting MAPK1/3 (ERK1/2) activation.

Gene Wiki entry for NECAB2 Gene

Additional gene information for NECAB2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NECAB2 Gene

Genomics for NECAB2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NECAB2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16J083968 Promoter/Enhancer 1.9 EPDnew Ensembl CraniofacialAtlas dbSUPER 606.6 0.0 -33 1.2 CTCF TARDBP MTA2 PKNOX1 MTA1 PATZ1 REST GATAD2B ZNF792 ZNF140 NECAB2 TAF1C ENSG00000261243 KLHL36 MBTPS1 CRISPLD2 MEAK7 ENSG00000260859 HSDL1 LOC654780
GH16J083969 Promoter/Enhancer 0.6 Ensembl dbSUPER 600.7 +0.9 868 0.2 EZH2 NECAB2 RF00001-138 SLC38A8
GH16J083995 Promoter/Enhancer 1.4 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 17.8 +27.2 27164 0.8 RFX1 ZXDB DDX20 BMI1 ESR1 USF1 MYNN ZNF768 SIN3A RFX5 NECAB2 DNAAF1 RNA5SP432 SLC38A8 HSDL1 ADAD2 RF00001-138
GH16J083993 Enhancer 1 ENCODE dbSUPER 25.2 +25.8 25788 1.3 CEBPG GATAD2A ATF7 TFE3 RCOR2 JUND GABPA SOX6 CEBPA SOX13 NECAB2 RNA5SP432 SLC38A8 OSGIN1 MLYCD TAF1C ADAD2 DNAAF1 HSDL1 RF00001-138
GH16J084043 Enhancer 1.4 Ensembl ENCODE CraniofacialAtlas dbSUPER 12.1 +75.2 75169 2.4 CTCF LEF1 JUND PHF21A ZIC2 RXRB ZNF24 REST IRF2 DPF2 SLC38A8 TAF1C NECAB2 OSGIN1 ADAD2 DNAAF1 HSDL1 KCNG4 MBTPS1 ENSG00000285792
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NECAB2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NECAB2

Top Transcription factor binding sites by QIAGEN in the NECAB2 gene promoter:
  • AML1a
  • E47
  • ER-alpha
  • GATA-2
  • HNF-4alpha1
  • HNF-4alpha2
  • HOXA3
  • MyoD
  • MZF-1
  • YY1

Genomic Locations for NECAB2 Gene

Genomic Locations for NECAB2 Gene
chr16:83,968,632-84,002,776
(GRCh38/hg38)
Size:
34,145 bases
Orientation:
Plus strand
chr16:84,002,237-84,036,381
(GRCh37/hg19)
Size:
34,145 bases
Orientation:
Plus strand

Genomic View for NECAB2 Gene

Genes around NECAB2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NECAB2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NECAB2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NECAB2 Gene

Proteins for NECAB2 Gene

  • Protein details for NECAB2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q7Z6G3-NECA2_HUMAN
    Recommended name:
    N-terminal EF-hand calcium-binding protein 2
    Protein Accession:
    Q7Z6G3
    Secondary Accessions:
    • A2RRG3
    • H3BTW2
    • O75547
    • Q6ZSK0

    Protein attributes for NECAB2 Gene

    Size:
    386 amino acids
    Molecular mass:
    43194 Da
    Quaternary structure:
    • Interacts (calcium-dependent) with ADORA2A and GRM5.
    SequenceCaution:
    • Sequence=AAI31616.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC86948.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for NECAB2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NECAB2 Gene

Post-translational modifications for NECAB2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NECAB2 Gene

No data available for DME Specific Peptides for NECAB2 Gene

Domains & Families for NECAB2 Gene

Gene Families for NECAB2 Gene

Protein Domains for NECAB2 Gene

InterPro:
Blocks:
  • Antibiotic biosynthesis monooxygenase
ProtoNet:

Suggested Antigen Peptide Sequences for NECAB2 Gene

GenScript: Design optimal peptide antigens:
  • Synaptotagmin-interacting protein 2 (NECA2_HUMAN)
genes like me logo Genes that share domains with NECAB2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for NECAB2 Gene

Function for NECAB2 Gene

Molecular function for NECAB2 Gene

UniProtKB/Swiss-Prot Function:
May act as a signaling scaffold protein that senses intracellular calcium. Can modulate ligand-induced internalization of ADORA2A and coupling efficiency of mGluR5/GRM5; for both receptors may regulate signaling activity such as promoting MAPK1/3 (ERK1/2) activation.

Phenotypes From GWAS Catalog for NECAB2 Gene

Gene Ontology (GO) - Molecular Function for NECAB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 17689978
GO:0031687 A2A adenosine receptor binding IDA 17689978
GO:0031802 type 5 metabotropic glutamate receptor binding IDA 19694902
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with NECAB2: view
genes like me logo Genes that share phenotypes with NECAB2: view

Animal Models for NECAB2 Gene

MGI Knock Outs for NECAB2:
  • Necab2 Necab2<tm1a(KOMP)Wtsi>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NECAB2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for NECAB2 Gene

Localization for NECAB2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NECAB2 Gene

Cytoplasm. Cell projection, dendrite. Cell projection, axon. Cell membrane. Note=Colocalizes with ADORA2A and/or mGluR5/GRM5 at the plasma membrane (PubMed:17689978, PubMed:19694902). Found in neuronal somata (PubMed:26843217). Detected in the cytoplasm of striatal neurons, at postsynaptic sites, filling dendritic shafts and spines, and at presynaptic sites, filling axon terminals (By similarity). {ECO:0000250 UniProtKB:F1LQY6, ECO:0000269 PubMed:17689978, ECO:0000269 PubMed:19694902, ECO:0000269 PubMed:26843217}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NECAB2 gene
Compartment Confidence
plasma membrane 5
mitochondrion 2
nucleus 2
cytosol 2
cytoskeleton 1
endoplasmic reticulum 1
lysosome 1

Gene Ontology (GO) - Cellular Components for NECAB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005886 plasma membrane IEA,IDA 19694902
GO:0016020 membrane IEA --
GO:0030424 axon IEA --
GO:0030425 dendrite IEA --
genes like me logo Genes that share ontologies with NECAB2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NECAB2 Gene

Pathways & Interactions for NECAB2 Gene

PathCards logo

SuperPathways for NECAB2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for NECAB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0042984 regulation of amyloid precursor protein biosynthetic process IBA 21873635
GO:0060168 positive regulation of adenosine receptor signaling pathway IDA 17689978
GO:0070374 positive regulation of ERK1 and ERK2 cascade IDA 19694902
GO:1900451 positive regulation of glutamate receptor signaling pathway IDA 19694902
GO:1904021 negative regulation of G protein-coupled receptor internalization IDA 17689978
genes like me logo Genes that share ontologies with NECAB2: view

No data available for Pathways by source and SIGNOR curated interactions for NECAB2 Gene

Drugs & Compounds for NECAB2 Gene

No Compound Related Data Available

Transcripts for NECAB2 Gene

mRNA/cDNA for NECAB2 Gene

3 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NECAB2

Alternative Splicing Database (ASD) splice patterns (SP) for NECAB2 Gene

No ASD Table

Relevant External Links for NECAB2 Gene

GeneLoc Exon Structure for
NECAB2

Expression for NECAB2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NECAB2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NECAB2 Gene

This gene is overexpressed in Brain - Nucleus accumbens (basal ganglia) (x7.9), Brain - Amygdala (x7.0), Brain - Caudate (basal ganglia) (x6.5), Brain - Putamen (basal ganglia) (x5.7), Brain - Anterior cingulate cortex (BA24) (x4.9), and Brain - Hypothalamus (x4.1).

Protein differential expression in normal tissues from HIPED for NECAB2 Gene

This gene is overexpressed in Fetal Brain (24.4), Brain (21.2), and Frontal cortex (7.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NECAB2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NECAB2

SOURCE GeneReport for Unigene cluster for NECAB2 Gene:

Hs.140950

mRNA Expression by UniProt/SwissProt for NECAB2 Gene:

Q7Z6G3-NECA2_HUMAN
Tissue specificity: Expressed in brain. Expressed in the spinal dorsal horn with especially strong expression in lamina IIi; found in excitory synaptic boutons and in ependymal cells (at protein level).

Evidence on tissue expression from TISSUES for NECAB2 Gene

  • Nervous system(4.5)
genes like me logo Genes that share expression patterns with NECAB2: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for NECAB2 Gene

Orthologs for NECAB2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NECAB2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NECAB2 30 31
  • 98.53 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NECAB2 30 31
  • 85.77 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NECAB2 30
  • 84.23 (n)
Mouse
(Mus musculus)
Mammalia Necab2 30 17 31
  • 83.68 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Necab2 30
  • 81.85 (n)
Oppossum
(Monodelphis domestica)
Mammalia NECAB2 31
  • 66 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NECAB2 31
  • 60 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NECAB2 30 31
  • 71.87 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NECAB2 31
  • 85 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC101731915 30
  • 70.85 (n)
Zebrafish
(Danio rerio)
Actinopterygii necab2 30 31
  • 67.86 (n)
OneToOne
Species where no ortholog for NECAB2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for NECAB2 Gene

ENSEMBL:
Gene Tree for NECAB2 (if available)
TreeFam:
Gene Tree for NECAB2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NECAB2: view image

Paralogs for NECAB2 Gene

Paralogs for NECAB2 Gene

(2) SIMAP similar genes for NECAB2 Gene using alignment to 5 proteins:

  • NECA2_HUMAN
  • H3BPH6_HUMAN
  • H3BQC7_HUMAN
  • H3BTW2_HUMAN
  • L8E8I4_HUMAN
genes like me logo Genes that share paralogs with NECAB2: view

Variants for NECAB2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NECAB2 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
rs113413576 Benign: not specified 84,001,919(+) A/AG INTRON_VARIANT
rs2271298 - p.Leu353Val
rs2292323 - p.Gly233Ser
rs2292324 - p.Thr235Ser
rs2292329 - p.Gln308His

Additional dbSNP identifiers (rs#s) for NECAB2 Gene

Structural Variations from Database of Genomic Variants (DGV) for NECAB2 Gene

Variant ID Type Subtype PubMed ID
dgv3056n100 CNV loss 25217958
dgv357n27 CNV loss 19166990
dgv5259n54 CNV loss 21841781
dgv5260n54 CNV loss 21841781
esv28321 CNV loss 19812545
esv3572242 CNV gain 25503493
esv3639405 CNV loss 21293372
nsv1065790 CNV loss 25217958
nsv1067050 CNV loss 25217958
nsv1070361 CNV deletion 25765185
nsv1126437 CNV deletion 24896259
nsv1136220 CNV deletion 24896259
nsv457591 CNV loss 19166990
nsv457594 CNV loss 19166990
nsv471106 CNV gain 18288195
nsv517566 CNV gain+loss 19592680
nsv528396 CNV loss 19592680
nsv573409 CNV loss 21841781
nsv573413 CNV loss 21841781
nsv573415 CNV loss 21841781
nsv573417 CNV loss 21841781
nsv573418 CNV loss 21841781
nsv827780 CNV loss 20364138

Variation tolerance for NECAB2 Gene

Residual Variation Intolerance Score: 31.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.05; 90.12% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NECAB2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NECAB2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NECAB2 Gene

Disorders for NECAB2 Gene

Additional Disease Information for NECAB2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform

No disorders were found for NECAB2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for NECAB2 Gene

Publications for NECAB2 Gene

  1. NECABs: a family of neuronal Ca(2+)-binding proteins with an unusual domain structure and a restricted expression pattern. (PMID: 12044471) Sugita S … Südhof TC (Neuroscience 2002) 2 3 4
  2. Comparative anatomical distribution of neuronal calcium-binding protein (NECAB) 1 and -2 in rodent and human spinal cord. (PMID: 26843217) Zhang MD … Hökfelt T (Brain structure & function 2016) 3 4
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  4. The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function. (PMID: 19694902) Canela L … Ciruela F (Journal of neurochemistry 2009) 3 4
  5. Molecular genetics of successful smoking cessation: convergent genome-wide association study results. (PMID: 18519826) Uhl GR … Lerman C (Archives of general psychiatry 2008) 3 41

Products for NECAB2 Gene

Sources for NECAB2 Gene