ANK2 ankyrin 2, neuronal [Homo sapiens (human)] - Gene

Summary

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Official Symbol: ANK2provided by HGNC
Official Full Name: ankyrin 2, neuronalprovided by HGNC
Primary source: HGNC:493
See related: Ensembl:ENSG00000145362; HPRD:00110; MIM:106410; Vega:OTTHUMG00000132912
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LQT4; ANK-2; brank-2
Summary: This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]

Genomic context

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Location :: 4q25-q27

Sequence :: Chromosome: 4; NC_000004.11 (113739239..114304896)

See ANK2 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Residues 63-73 of cdB3 is also essential for ankyrin binding.
Title: Identification of contact sites between ankyrin and band 3 in the human erythrocyte membrane.
Ankyrin-B protein in heart failure: identification of a new component of metazoan cardioprotection.
Title: Ankyrin-B protein in heart failure: identification of a new component of metazoan cardioprotection.
Reduced ankyrin-B expression or mutations in ankyrin 2 are associated with atrial fibrillation.
Title: Defects in ankyrin-based membrane protein targeting pathways underlie atrial fibrillation.
Data show that DAnk2-binding is critical for beta spectrin function in vivo.
Title: Transgene rescue identifies an essential function for Drosophila beta spectrin in the nervous system and a selective requirement for ankyrin-2-binding activity.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
This protein has been found differentially expressed in thalami from patients with schizophrenia.
Title: Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers candidates for schizophrenia.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
The common genetic variation in the ANK2 gene is modified the physiological variability of the QT interval in the general population.
Title: Common genetic variants in ANK2 modulate QT interval: results from the KORA study.
ANK2 mutations were not found to directly cause long QT syndrome.
Title: Mutation analysis of candidate genes SCN1B, KCND3 and ANK2 in patients with clinical diagnosis of long QT syndrome.
Exon organization and novel alternative splicing of the human ANK2 gene: implications for cardiac function and human cardiac disease
Title: Exon organization and novel alternative splicing of the human ANK2 gene: implications for cardiac function and human cardiac disease.

Submit: New GeneRIF Correction See all (27)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Cardiac arrhythmia, ankyrin B-related

MIM: 600919

Genetic Testing Registry

NHGRI GWAS Catalog

A genome-wide search for loci interacting with known prostate cancer risk-associated genetic variants.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_066187.2	NP_000416.1	L1CAM	BIND	PubMed	L1CAM interacts with Ankyrin. This interaction was modelled on a demonstrated interaction between human L1CAM and drosophila ankyrin.
Q01484	P25685	DNAJB1	HPRD	PubMed
Q01484	P32004	L1CAM	HPRD	PubMed
Q01484	Q92823	NRCAM	HPRD	PubMed
Q01484	Q5VST9	OBSCN	HPRD	PubMed
Q01484	Q99720	SIGMAR1	HPRD	PubMed
Q01484	Q01082	SPTBN1	HPRD	PubMed
BioGRID:106784	BioGRID:108352	EPB42	BioGRID	PubMed	Reconstituted Complex
BioGRID:106784	BioGRID:116966	KIAA0368	BioGRID	PubMed	Two-hybrid
BioGRID:106784	BioGRID:123527	NDEL1	BioGRID	PubMed	Two-hybrid
BioGRID:106784	BioGRID:115569	SIGMAR1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106784	BioGRID:116682	TNIK	BioGRID	PubMed	Two-hybrid
BioGRID:106784	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Axon guidance, organism-specific biosystem (from REACTOME)
Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
Interaction between L1 and Ankyrins, organism-specific biosystem (from REACTOME)
Interaction between L1 and Ankyrins, organism-specific biosystemAnkyrins are a family of adaptor proteins that couple membrane proteins such as voltage gated Na+ channels and the Na+/K+ anion exchanger to the spectrin actin cytoskeleton. Ankyrins are encoded by t...
L1CAM interactions, organism-specific biosystem (from REACTOME)
L1CAM interactions, organism-specific biosystemThe L1 family of cell adhesion molecules (L1CAMs) are a subfamily of the immunoglobulin superfamily of transmembrane receptors, comprised of four structurally related proteins: L1, Close Homolog of L...
Proteoglycans in cancer, organism-specific biosystem (from KEGG)
Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
Proteoglycans in cancer, conserved biosystem (from KEGG)
Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...

General gene information

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Markers

D4S2542E (e-PCR)
- UniSTS:23040

D11S2921 (e-PCR)
- UniSTS:152074

NoName (e-PCR)
- UniSTS:9484

AFM186xb4 (e-PCR), detects polymorphism
- UniSTS:84752

SHGC-59287 (e-PCR)
- UniSTS:3352

SHGC-132360 (e-PCR)
- UniSTS:170793

SHGC-83197 (e-PCR)
- UniSTS:95789

WIAF-2193 (e-PCR)
- UniSTS:5702

SHGC-24748 (e-PCR)
- UniSTS:83025

SHGC-11962 (e-PCR)
- UniSTS:14677

L18426 (e-PCR)
- UniSTS:34648

SHGC-82082 (e-PCR)
- UniSTS:103011

SHGC-23907 (e-PCR)
- UniSTS:74347

D4S2309 (e-PCR)
- UniSTS:149363

SHGC-81181 (e-PCR)
- UniSTS:102006

SHGC-59553 (e-PCR)
- UniSTS:79233

RH119774 (e-PCR)
- UniSTS:133250

WI-19148 (e-PCR)
- UniSTS:64392

SHGC-14389 (e-PCR)
- UniSTS:71608

SHGC-148725 (e-PCR)
- UniSTS:176582

SHGC-50779 (e-PCR)
- UniSTS:38343

ANK2_3170 (e-PCR)
- UniSTS:462025

SHGC-83104 (e-PCR)
- UniSTS:101330

SHGC-23852 (e-PCR)
- UniSTS:74974

SHGC-67324 (e-PCR)
- UniSTS:85726

SHGC-84192 (e-PCR)
- UniSTS:104688

NIB1562 (e-PCR)
- UniSTS:13305

SHGC-79494 (e-PCR)
- UniSTS:103417

Genotypes

See ANK2 SNP Geneview Report
See ANK2 SNP Genotype Report
See ANK2 SNP Variation Viewer Report

Homology

Homologs of the ANK2 gene: The ANK2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, and mosquito.
Map Viewer (Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

FLJ11832, FLJ38277, FLJ46169, DKFZp686P0948, DKFZp686M09125

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATPase binding	ISS Inferred from Sequence or Structural Similarity more info
enzyme binding	IPI Inferred from Physical Interaction more info
ion channel binding	IPI Inferred from Physical Interaction more info
ion channel binding	ISS Inferred from Sequence or Structural Similarity more info
potassium channel regulator activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding, bridging	ISS Inferred from Sequence or Structural Similarity more info
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
spectrin binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
SA node cell to atrial cardiac muscle cell communication	IMP Inferred from Mutant Phenotype more info	PubMed
T-tubule organization	ISS Inferred from Sequence or Structural Similarity more info
atrial cardiac muscle cell to AV node cell communication	ISS Inferred from Sequence or Structural Similarity more info
atrial septum development	IMP Inferred from Mutant Phenotype more info	PubMed
axon guidance	TAS Traceable Author Statement more info
cardiac muscle contraction	IEA Inferred from Electronic Annotation more info
cellular calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
cellular protein localization	IGI Inferred from Genetic Interaction more info	PubMed
membrane depolarization involved in regulation of SA node cell action potential	TAS Traceable Author Statement more info	PubMed
positive regulation of calcium ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of calcium ion transport	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cation channel activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of potassium ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of potassium ion transport	ISS Inferred from Sequence or Structural Similarity more info
protein localization to M-band	ISS Inferred from Sequence or Structural Similarity more info
protein localization to T-tubule	ISS Inferred from Sequence or Structural Similarity more info
protein localization to cell surface	ISS Inferred from Sequence or Structural Similarity more info
protein localization to endoplasmic reticulum	IGI Inferred from Genetic Interaction more info	PubMed
protein localization to organelle	IGI Inferred from Genetic Interaction more info	PubMed
protein localization to plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
protein localization to plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
protein stabilization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
protein targeting to plasma membrane	IEA Inferred from Electronic Annotation more info
regulation of SA node cell action potential	ISS Inferred from Sequence or Structural Similarity more info
regulation of atrial cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of calcium ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
regulation of calcium ion transport	IGI Inferred from Genetic Interaction more info	PubMed
regulation of cardiac muscle cell contraction	IGI Inferred from Genetic Interaction more info	PubMed
regulation of cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of cardiac muscle contraction by calcium ion signaling	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	IGI Inferred from Genetic Interaction more info	PubMed
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	ISS Inferred from Sequence or Structural Similarity more info
regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of heart rate by cardiac conduction	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of heart rate by cardiac conduction	ISS Inferred from Sequence or Structural Similarity more info
regulation of protein stability	IC Inferred by Curator more info	PubMed
regulation of release of sequestered calcium ion into cytosol	IGI Inferred from Genetic Interaction more info	PubMed
regulation of ventricular cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of ventricular cardiac muscle cell membrane repolarization	IMP Inferred from Mutant Phenotype more info	PubMed
sarcoplasmic reticulum calcium ion transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
A band	ISS Inferred from Sequence or Structural Similarity more info
M band	ISS Inferred from Sequence or Structural Similarity more info
T-tubule	ISS Inferred from Sequence or Structural Similarity more info
Z disc	ISS Inferred from Sequence or Structural Similarity more info
apical plasma membrane	IEA Inferred from Electronic Annotation more info
basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
costamere	ISS Inferred from Sequence or Structural Similarity more info
cytoskeleton	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
integral to plasma membrane	IEA Inferred from Electronic Annotation more info
intercalated disc	ISS Inferred from Sequence or Structural Similarity more info
intracellular	IGI Inferred from Genetic Interaction more info	PubMed
perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
postsynaptic membrane	IEA Inferred from Electronic Annotation more info
sarcolemma	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: ankyrin-2

Names: ankyrin-2; ankyrin B; ankyrin, brain; non-erythroid ankyrin; ankyrin-2, nonerythrocytic

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009006.2 RefSeqGene

Range

5001..570658

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_327

mRNA and Protein(s)

NM_001127493.1 → NP_001120965.1 ankyrin-2 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding region, compared to variant 1, resulting in a shorter isoform (3) that has a distinct N-terminus.

Source sequence(s)

AC004057, AC017007, AC093900

Consensus CDS

CCDS54796.1

UniProtKB/Swiss-Prot

Q01484

Related

ENSP00000421067, OTTHUMP00000220392, ENST00000506722, OTTHUMT00000365336

Conserved Domains (6) summary

cd00204
Location:206 – 331
Blast Score: 347

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

smart00218
Location:957 – 1094
Blast Score: 377

ZU5; Domain present in ZO-1 and Unc5-like netrin receptors

cd08804
Location:1473 – 1556
Blast Score: 443

Death_ank2; Death domain of Ankyrin-2

pfam00023
Location:508 – 533
Blast Score: 96

Ank; Ankyrin repeat

pfam12796
Location:216 – 307
Blast Score: 258

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:16 – 63
Blast Score: 108

Ank_4; Ankyrin repeats (many copies)
NM_001148.4 → NP_001139.3 ankyrin-2 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC004057, AC093879, AC093900

Consensus CDS

CCDS3702.1

UniProtKB/Swiss-Prot

Q01484

Related

ENSP00000349588, OTTHUMP00000163833, ENST00000357077, OTTHUMT00000256422

Conserved Domains (7) summary

cd00204
Location:227 – 352
Blast Score: 377

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

smart00218
Location:966 – 1103
Blast Score: 374

ZU5; Domain present in ZO-1 and Unc5-like netrin receptors

cd08804
Location:3567 – 3650
Blast Score: 436

Death_ank2; Death domain of Ankyrin-2

pfam00023
Location:529 – 554
Blast Score: 103

Ank; Ankyrin repeat

pfam12737
Location:1764 – 1936
Blast Score: 119

Mating_C; C-terminal domain of homeodomain 1

pfam12796
Location:237 – 328
Blast Score: 277

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:37 – 84
Blast Score: 118

Ank_4; Ankyrin repeats (many copies)
NM_020977.3 → NP_066187.2 ankyrin-2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. It encodes isoform 2 which is shorter than isoform 1. Isoform 2 is the major form of ankyrin in adult brain.

Source sequence(s)

AC004057, AC093879, AC093900

Consensus CDS

CCDS43261.1

UniProtKB/Swiss-Prot

Q01484

Conserved Domains (6) summary

cd00204
Location:227 – 352
Blast Score: 348

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

smart00218
Location:966 – 1103
Blast Score: 379

ZU5; Domain present in ZO-1 and Unc5-like netrin receptors

cd08804
Location:1482 – 1565
Blast Score: 443

Death_ank2; Death domain of Ankyrin-2

pfam00023
Location:529 – 554
Blast Score: 96

Ank; Ankyrin repeat

pfam12796
Location:237 – 328
Blast Score: 258

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:37 – 84
Blast Score: 109

Ank_4; Ankyrin repeats (many copies)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p10 Primary Assembly

Range

113739239..114304896

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

109467190..110033212

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018915.1 Alternate CHM1_1.0

Range

113534355..114099491

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01063822.1 (35546..56916)	None
genomic	ABBA01063823.1	None
genomic	ABBA01063824.1	None
genomic	ABBA01063825.1	None
genomic	ABBA01063826.1	None
genomic	ABBA01063827.1	None
genomic	ABBA01063828.1	None
genomic	ABBA01063829.1	None
genomic	ABBA01063830.1	None
genomic	ABBA01063831.1	None
genomic	ABBA01063832.1	None
genomic	AC004057.1 (7362..135785)	None
genomic	AC017007.9 (87279..173710)	None
genomic	AC093617.2	None
genomic	AC093879.3 (126238..214870)	None
genomic	AC093900.3 (3049..75534)	None
genomic	AC108042.4	None
genomic	AMYH01014471.1 (7915..40341)	None
genomic	AMYH01014472.1	None
genomic	AMYH01014473.1	None
genomic	AMYH01014474.1	None
genomic	CH471057.1	EAX06287.1
		EAX06288.1
		EAX06289.1
		EAX06290.1
		EAX06291.1
		EAX06292.1
genomic	M37123.1	AAA62828.1
mRNA	AF131823.1	None
mRNA	AK021894.1	None
mRNA	AK095596.1	None
mRNA	AK128049.1	None
mRNA	AK294720.1	BAH11860.1
mRNA	AK299767.1	BAH13122.1
mRNA	AK299815.1	BAH13137.1
mRNA	AK299893.1	BAH13164.1
mRNA	AK307601.1	None
mRNA	AL706912.1	None
mRNA	BC017986.1	None
mRNA	BC047498.1	None
mRNA	BC125235.1	AAI25236.1
mRNA	BC125236.1	AAI25237.1
mRNA	BQ716903.1	None
mRNA	BQ890406.1	None
mRNA	BX537758.1	CAD97827.1
mRNA	BX538132.1	CAD98033.1
mRNA	BX538239.1	CAD98077.1
mRNA	CN259048.1	None
mRNA	DQ925692.1	ABL59919.1
mRNA	DQ925693.1	ABL59920.1
mRNA	X56957.1	CAA40278.1
mRNA	X56958.2	CAA40279.2
mRNA	Z26634.2	CAB42644.1