Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquito... See more...

Aliases for ADD2 Gene

Aliases for ADD2 Gene

  • Adducin 2 2 3 5
  • Beta-Adducin 2 3 4
  • Erythrocyte Adducin Subunit Beta 3 4
  • Adducin 2 (Beta) 2 3
  • ADDB 3 4

External Ids for ADD2 Gene

Previous GeneCards Identifiers for ADD2 Gene

  • GC02M070898
  • GC02M071100
  • GC02M070863
  • GC02M070800

Summaries for ADD2 Gene

Entrez Gene Summary for ADD2 Gene

  • Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2010]

GeneCards Summary for ADD2 Gene

ADD2 (Adducin 2) is a Protein Coding gene. Diseases associated with ADD2 include Hereditary Elliptocytosis and Capillariasis. Among its related pathways are Activation of cAMP-Dependent PKA and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and actin binding. An important paralog of this gene is ADD3.

UniProtKB/Swiss-Prot Summary for ADD2 Gene

  • Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to the erythrocyte membrane receptor SLC2A1/GLUT1 and may therefore provide a link between the spectrin cytoskeleton to the plasma membrane. Binds to calmodulin. Calmodulin binds preferentially to the beta subunit.

Gene Wiki entry for ADD2 Gene

Additional gene information for ADD2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ADD2 Gene

Genomics for ADD2 Gene

GeneHancer (GH) Regulatory Elements for ADD2 Gene

Promoters and enhancers for ADD2 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
GH02J070766 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 771.6 +0.7 742 3.4 ZBTB40 CTCF L3MBTL2 POU5F1 TEAD4 POLR2A SP1 ZNF148 ZFX MAFK ADD2 lnc-ADD2-1 TIA1 MPHOSPH10 FIGLA lnc-VAX2-5
GH02J070728 Enhancer 0.8 Ensembl ENCODE 47.1 +36.5 36543 9.8 POU5F1 NFIB SP1 RFX1 CEBPB POLR2A ZNF140 ZBTB17 FOSL1 RCOR1 ADD2 TIA1 TEX261 PCBP1-AS1 MPHOSPH10 ZNF638 ENSG00000235035 ANKRD53 CLEC4F VAX2
GH02J070744 Enhancer 0.8 Ensembl 46.3 +22.6 22642 7.2 SMARCE1 HLF MAX MNT ZNF652 SMARCA4 TRIM24 MTA1 IKZF1 DPF2 ADD2 CD207 TEX261 CLEC4F PCBP1-AS1 VAX2 ATP6V1B1-AS1 MCEE TIA1 FIGLA
GH02J069911 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 13.5 +852.9 852905 7.4 SIN3A ZBTB40 SP1 CTCF ZBTB6 MLX RBPJ POLR2A CEBPZ USF2 MXD1 SNRNP27 ASPRV1 AAK1 ADD2 TIA1 CD207 PCBP1-AS1 C2orf42 CLEC4F
GH02J070717 Enhancer 0.8 Ensembl 41.2 +52.4 52442 4.8 SMARCE1 CC2D1A TEAD4 CBFA2T2 SMARCA4 TRIM24 EGR1 DPF2 ZIC2 HDAC1 ADD2 ENSG00000235035 TGFA VAX2 FIGLA ENSG00000233870 piR-38351-254 lnc-VAX2-5 lnc-ADD2-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ADD2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ADD2 gene promoter:
  • c-Ets-1
  • NF-kappaB
  • NF-kappaB1
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Nkx3-1 v4
  • TBP
  • TFIID

Genomic Locations for ADD2 Gene

Genomic Locations for ADD2 Gene
chr2:70,607,618-70,768,243
(GRCh38/hg38)
Size:
160,626 bases
Orientation:
Minus strand
chr2:70,834,750-70,995,375
(GRCh37/hg19)
Size:
160,626 bases
Orientation:
Minus strand

Genomic View for ADD2 Gene

Genes around ADD2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ADD2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ADD2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ADD2 Gene

Proteins for ADD2 Gene

  • Protein details for ADD2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35612-ADDB_HUMAN
    Recommended name:
    Beta-adducin
    Protein Accession:
    P35612
    Secondary Accessions:
    • A8K4P2
    • B4DM17
    • D6W5G7
    • D6W5G8
    • Q13482
    • Q16412
    • Q59G82
    • Q5U5P4
    • Q6P0P2
    • Q6PGQ4
    • Q7Z688
    • Q7Z689
    • Q7Z690
    • Q7Z691

    Protein attributes for ADD2 Gene

    Size:
    726 amino acids
    Molecular mass:
    80854 Da
    Quaternary structure:
    • Heterodimer of an alpha and a beta subunit. Found in a complex with ADD2, DMTN and SLC2A1. Interacts with SLC2A1.
    SequenceCaution:
    • Sequence=BAD92464.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for ADD2 Gene

neXtProt entry for ADD2 Gene

Post-translational modifications for ADD2 Gene

No data available for DME Specific Peptides for ADD2 Gene

Domains & Families for ADD2 Gene

Gene Families for ADD2 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for ADD2 Gene

Suggested Antigen Peptide Sequences for ADD2 Gene

GenScript: Design optimal peptide antigens:
  • Erythrocyte adducin subunit beta (ADDB_HUMAN)
  • cDNA FLJ61313, highly similar to Beta-adducin (B4DM17_HUMAN)
  • ADD2 protein (Q05DK5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P35612

UniProtKB/Swiss-Prot:

ADDB_HUMAN :
  • Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.
  • Belongs to the aldolase class II family. Adducin subfamily.
Domain:
  • Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.
Family:
  • Belongs to the aldolase class II family. Adducin subfamily.
genes like me logo Genes that share domains with ADD2: view

Function for ADD2 Gene

Molecular function for ADD2 Gene

UniProtKB/Swiss-Prot Function:
Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to the erythrocyte membrane receptor SLC2A1/GLUT1 and may therefore provide a link between the spectrin cytoskeleton to the plasma membrane. Binds to calmodulin. Calmodulin binds preferentially to the beta subunit.
GENATLAS Biochemistry:
adducin beta,actin accessory protein,calmodulin binding protein,97kDa,component of the erythrocyte membrane skeleton,also expressed in brain,kidney,liver,intestine,leukocytes,platelets

Phenotypes From GWAS Catalog for ADD2 Gene

Gene Ontology (GO) - Molecular Function for ADD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003779 actin binding IMP 25425738
GO:0005198 structural molecule activity IBA 21873635
GO:0005200 structural constituent of cytoskeleton IEA --
GO:0005516 calmodulin binding IEA --
GO:0019901 protein kinase binding IPI 25425738
genes like me logo Genes that share ontologies with ADD2: view
genes like me logo Genes that share phenotypes with ADD2: view

Animal Models for ADD2 Gene

MGI Knock Outs for ADD2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ADD2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ADD2 Gene

Localization for ADD2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ADD2 Gene

Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side.

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 ADD2 gene
Compartment Confidence
plasma membrane 5
cytoskeleton 5
cytosol 4
nucleus 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Cytosol (2)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ADD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton IEA,IBA 21873635
GO:0005886 plasma membrane IEA --
GO:0008290 F-actin capping protein complex IDA 8626479
genes like me logo Genes that share ontologies with ADD2: view

Pathways & Interactions for ADD2 Gene

genes like me logo Genes that share pathways with ADD2: view

Pathways by source for ADD2 Gene

4 Qiagen pathways for ADD2 Gene
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • cAMP Pathway
  • PKA Signaling

SIGNOR curated interactions for ADD2 Gene

Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for ADD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007416 synapse assembly IEA --
GO:0030036 actin cytoskeleton organization IC 3693401
GO:0030097 hemopoiesis IEA --
GO:0032092 positive regulation of protein binding IDA 3693401
GO:0050900 leukocyte migration IMP 25425738
genes like me logo Genes that share ontologies with ADD2: view

Drugs & Compounds for ADD2 Gene

(3) Drugs for ADD2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for ADD2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ADD2: view

Transcripts for ADD2 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ADD2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ADD2 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b · 9c · 9d · 9e ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^
SP1: - - - - - -
SP2: - - - - - -
SP3: - - - - -
SP4: - - - - - -
SP5: -
SP6: - - - - -
SP7: - - - - -
SP8: - - - -
SP9: - - - -
SP10: - - - - - - -
SP11: - - - - - - -

ExUns: 18 ^ 19a · 19b ^ 20 ^ 21 ^ 22 ^ 23a · 23b
SP1: -
SP2: - -
SP3: - -
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for ADD2 Gene

GeneLoc Exon Structure for
ADD2
ECgene alternative splicing isoforms for
ADD2

Expression for ADD2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ADD2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ADD2 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (x8.0), Brain - Cerebellum (x5.9), Brain - Frontal Cortex (BA9) (x5.2), Brain - Anterior cingulate cortex (BA24) (x4.8), and Brain - Cortex (x4.5).

Protein differential expression in normal tissues from HIPED for ADD2 Gene

This gene is overexpressed in Brain (27.3), Frontal cortex (26.1), and Fetal Brain (8.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ADD2 Gene



Protein tissue co-expression partners for ADD2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ADD2 Gene:

ADD2

SOURCE GeneReport for Unigene cluster for ADD2 Gene:

Hs.188528

mRNA Expression by UniProt/SwissProt for ADD2 Gene:

P35612-ADDB_HUMAN
Tissue specificity: Expressed mainly in brain, spleen, kidney cortex and medulla, and heart. Also expressed in human umbilical vein endothelial cells, human vascular smooth muscle cells, kidney tubular cells and K-562 cell line.

Evidence on tissue expression from TISSUES for ADD2 Gene

  • Nervous system(5)
  • Blood(4.5)
  • Eye(4.4)
  • Bone marrow(4.3)
  • Heart(4.3)
  • Liver(4.2)
genes like me logo Genes that share expression patterns with ADD2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ADD2 Gene

Orthologs for ADD2 Gene

This gene was present in the common ancestor of animals.

Orthologs for ADD2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ADD2 33 32
  • 99.72 (n)
OneToOne
cow
(Bos Taurus)
Mammalia ADD2 33 32
  • 90.88 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ADD2 33
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ADD2 33 32
  • 88 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Add2 32
  • 87.87 (n)
mouse
(Mus musculus)
Mammalia Add2 17 33 32
  • 87.69 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 33
  • 49 (a)
ManyToMany
chicken
(Gallus gallus)
Aves ADD2 33
  • 73 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ADD2 33
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia add2 32
  • 73.95 (n)
zebrafish
(Danio rerio)
Actinopterygii add2 33 32
  • 64.63 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta hts 33 34
  • 13 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea add-1 33
  • 28 (a)
ManyToMany
add-2 33
  • 23 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 28 (a)
OneToMany
Species where no ortholog for ADD2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • 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 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)

Evolution for ADD2 Gene

ENSEMBL:
Gene Tree for ADD2 (if available)
TreeFam:
Gene Tree for ADD2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ADD2: view image

Paralogs for ADD2 Gene

Paralogs for ADD2 Gene

(2) SIMAP similar genes for ADD2 Gene using alignment to 6 proteins:

  • ADDB_HUMAN
  • C9J080_HUMAN
  • C9J299_HUMAN
  • C9JJK3_HUMAN
  • C9JTM0_HUMAN
  • Q05DK5_HUMAN
genes like me logo Genes that share paralogs with ADD2: view

Variants for ADD2 Gene

Sequence variations from dbSNP and Humsavar for ADD2 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs1000023958 -- 70,671,589(-) C/T genic_downstream_transcript_variant, intron_variant
rs1000055079 -- 70,671,379(-) A/G genic_downstream_transcript_variant, intron_variant
rs1000067782 -- 70,755,504(-) G/A/C genic_upstream_transcript_variant, intron_variant
rs1000117222 -- 70,715,453(-) G/A intron_variant
rs1000142601 -- 70,709,102(-) G/A intron_variant

Structural Variations from Database of Genomic Variants (DGV) for ADD2 Gene

Variant ID Type Subtype PubMed ID
esv2659183 CNV deletion 23128226
esv2762674 CNV gain 21179565
esv3429524 CNV insertion 20981092
esv3583858 CNV loss 25503493
esv3591211 CNV loss 21293372
esv3892614 CNV gain 25118596
nsv1146915 OTHER inversion 26484159
nsv2770 CNV insertion 18451855
nsv582192 CNV loss 21841781

Variation tolerance for ADD2 Gene

Residual Variation Intolerance Score: 15.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.42; 63.83% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ADD2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ADD2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ADD2 Gene

Disorders for ADD2 Gene

MalaCards: The human disease database

(8) MalaCards diseases for ADD2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hereditary elliptocytosis
  • congenital elliptocytosis
capillariasis
  • capillaria infection
hereditary spherocytosis
  • spherocytosis, type 1
exhibitionism
hypertension, essential
  • eht
- elite association - COSMIC cancer census association via MalaCards
Search ADD2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ADD2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ADD2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ADD2 Gene

Publications for ADD2 Gene

  1. Primary structure and domain organization of human alpha and beta adducin. (PMID: 1840603) Joshi R … Bennett V (The Journal of cell biology 1991) 2 3 4 23 56
  2. alpha- and beta-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathy. (PMID: 19838659) Ferrandi M … Bianchi G (Journal of molecular medicine (Berlin, Germany) 2010) 3 23 43 56
  3. Arterial properties in relation to genetic variations in the adducin subunits in a white population. (PMID: 18787518) Seidlerová J … Bianchi G (American journal of hypertension 2009) 3 23 43 56
  4. Investigation of Adducin 2 (beta) DNA polymorphisms in genetic predisposition to diabetic nephropathy in Type 1 diabetes. (PMID: 18959617) Currie D … Warren 3/UK GoKinD Study Group (Diabetic medicine : a journal of the British Diabetic Association 2008) 3 23 43 56
  5. Gly460Trp alpha-adducin mutation as a possible mechanism leading to endolymphatic hydrops in Ménière's syndrome. (PMID: 18667944) Teggi R … Bussi M (Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 2008) 3 23 43 56

Products for ADD2 Gene

Sources for ADD2 Gene