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ANKLE2 ankyrin repeat and LEM domain containing 2 [ Homo sapiens (human) ]

Gene ID: 23141, updated on 27-Nov-2024

Summary

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Official Symbol
ANKLE2provided by HGNC
Official Full Name
ankyrin repeat and LEM domain containing 2provided by HGNC
Primary source
HGNC:HGNC:29101
See related
Ensembl:ENSG00000176915 MIM:616062; AllianceGenome:HGNC:29101
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
Lem4; LEMD7; MCPH16; KIAA0692
Summary
This gene encodes a member of the LEM family of inner nuclear membrane proteins. The encoded protein functions as a mitotic regulator through postmitotic formation of the nuclear envelope. Mutations in this gene cause morphology defects in the nuclear envelope and BAF hyperphosphorylation. [provided by RefSeq, Mar 2014]
Expression
Ubiquitous expression in testis (RPKM 31.1), lymph node (RPKM 13.1) and 25 other tissues See more
Orthologs
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Genomic context

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See ANKLE2 in Genome Data Viewer
Location:
12q24.33
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (132725503..132761832, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (132774758..132812890, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (133302089..133338418, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5124 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5125 Neighboring gene PGAM family member 5, mitochondrial serine/threonine protein phosphatase Neighboring gene RNA, 5S ribosomal pseudogene 379 Neighboring gene TPD52 like 2 pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr12:133334029-133334208 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:133337764-133338632 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7387 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7388 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7389 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_26051 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7390 Neighboring gene golgin A3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:133365291-133365792 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_26074 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7391 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5128 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5129 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7392 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5130 Neighboring gene ribosomal protein S11 pseudogene 5 Neighboring gene RNA, U6 small nuclear 327, pseudogene Neighboring gene checkpoint with forkhead and ring finger domains

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. LEM4/ANKLE-2 deficiency impairs post-mitotic re-localization of BAF, LAP2α and LaminA to the nucleus, causes nuclear envelope instability in telophase and leads to hyperploidy in HeLa cells. Snyers L, et al. Eur J Cell Biol, 2018 Jan. PMID 29254732
  2. LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway. Gao A, et al. Nat Commun, 2018 Oct 9. PMID 30301939, Free PMC Article
  3. SIRT2 regulates nuclear envelope reassembly through ANKLE2 deacetylation. Kaufmann T, et al. J Cell Sci, 2016 Dec 15. PMID 27875273, Free PMC Article
  4. ANKLE2-related microcephaly: A variable microcephaly syndrome resembling Zika infection. Thomas AX, et al. Ann Clin Transl Neurol, 2022 Aug. PMID 35871307, Free PMC Article
  5. LEM-domain proteins are lost during human spermiogenesis but BAF and BAF-L persist. Elkhatib RA, et al. Reproduction, 2017 Oct. PMID 28684548

See all (75) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. ANKLE2-related microcephaly: A variable microcephaly syndrome resembling Zika infection.
    Title: ANKLE2-related microcephaly: A variable microcephaly syndrome resembling Zika infection.
  2. that NS4A, ANKLE2, VRK1, and LLGL1 define a pathway impinging on asymmetric determinants of neural stem cell division
    Title: Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly.
  3. LEM4 represents a prognostic marker and an attractive target for breast cancer therapeutics.
    Title: LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway.
  4. Absence of ANKLE2 severely compromises the post mitotic re-association of the nuclear proteins BAF, LAP2alpha and LaminA to chromosomes. These defects give rise to a strong mechanical instability of the nuclear envelope in telophase and to a chromosomal instability leading to increased number of hyperploid cells.
    Title: LEM4/ANKLE-2 deficiency impairs post-mitotic re-localization of BAF, LAP2α and LaminA to the nucleus, causes nuclear envelope instability in telophase and leads to hyperploidy in HeLa cells.
  5. ANKLE2 acetylation at K302 and phosphorylation at S662 are dynamically regulated throughout the cell cycle by SIRT2 and are essential for normal nuclear envelope reassembly.
    Title: SIRT2 regulates nuclear envelope reassembly through ANKLE2 deacetylation.
  6. By coordinating VRK-1- and PP2A-mediated signaling on BAF, Lem4 and LEM-4L (Y55F3BR.8) controls postmitotic nuclear envelope formation in a function conserved from worms to humans.
    Title: Coordination of kinase and phosphatase activities by Lem4 enables nuclear envelope reassembly during mitosis.
Submit: New GeneRIF Correction

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

Associated conditions

Description Tests
Microcephaly 16, primary, autosomal recessive
MedGen: C4225249 OMIM: 616681 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association study of antibody response to smallpox vaccine.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ22280, FLJ36132, KIAA0692

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein phosphatase 2A binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein phosphatase 2A binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein phosphatase regulator activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell division IEA
Inferred from Electronic Annotation
more info
  
involved_in central nervous system development IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in mitotic nuclear membrane reassembly IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitotic nuclear membrane reassembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of catalytic activity TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in membrane HDA PubMed 

General protein information

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Preferred Names
ankyrin repeat and LEM domain-containing protein 2
Names
LEM domain containing 7
LEM domain-containing protein 4
LEM-domain protein 4

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

  1. NG_034022.1 RefSeqGene

    Range
    5057..41386
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_015114.3 → NP_055929.1  ankyrin repeat and LEM domain-containing protein 2

    See identical proteins and their annotated locations for NP_055929.1

    Status: REVIEWED

    Source sequence(s)
    AB014592, AC135586, AK293028, BC043157, BC062373, DB451935, DB453975, R59085
    Consensus CDS
    CCDS41869.1
    UniProtKB/Swiss-Prot
    A8KAG3, B3KN97, B3KSF8, O75176, Q6P6A5, Q86XL3, Q8TAZ9, Q96DH4
    UniProtKB/TrEMBL
    A0A220T1R9
    Related
    ENSP00000350686.5, ENST00000357997.10
    Conserved Domains (5) summary
    cd00204
    Location:334 → 464
    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 ...
    cd12944
    Location:71 → 113
    LEM_ANKL2; LEM (Lap2/Emerin/Man1) domain found in ankyrin repeat and LEM domain-containing protein 2 (ANKL2)
    pfam01693
    Location:218 → 249
    Cauli_VI; Caulimovirus viroplasmin
    pfam12796
    Location:356 → 435
    Ank_2; Ankyrin repeats (3 copies)
    sd00045
    Location:410 → 443
    ANK; ANK repeat [structural motif]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    132725503..132761832 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006719735.2 → XP_006719798.1  ankyrin repeat and LEM domain-containing protein 2 isoform X2

    Conserved Domains (5) summary
    cd00204
    Location:334 → 464
    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 ...
    cd12944
    Location:71 → 113
    LEM_ANKL2; LEM (Lap2/Emerin/Man1) domain found in ankyrin repeat and LEM domain-containing protein 2 (ANKL2)
    pfam01693
    Location:218 → 249
    Cauli_VI; Caulimovirus viroplasmin
    pfam12796
    Location:356 → 435
    Ank_2; Ankyrin repeats (3 copies)
    sd00045
    Location:410 → 443
    ANK; ANK repeat [structural motif]

  2. XM_005266159.4 → XP_005266216.1  ankyrin repeat and LEM domain-containing protein 2 isoform X1

    See identical proteins and their annotated locations for XP_005266216.1

    UniProtKB/TrEMBL
    A0A220T1R9
    Conserved Domains (5) summary
    cd00204
    Location:272 → 402
    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 ...
    cd12944
    Location:9 → 51
    LEM_ANKL2; LEM (Lap2/Emerin/Man1) domain found in ankyrin repeat and LEM domain-containing protein 2 (ANKL2)
    pfam01693
    Location:156 → 187
    Cauli_VI; Caulimovirus viroplasmin
    pfam12796
    Location:294 → 373
    Ank_2; Ankyrin repeats (3 copies)
    sd00045
    Location:348 → 381
    ANK; ANK repeat [structural motif]

  3. XM_024448899.2 → XP_024304667.1  ankyrin repeat and LEM domain-containing protein 2 isoform X5

  4. XM_011534787.4 → XP_011533089.1  ankyrin repeat and LEM domain-containing protein 2 isoform X3

    See identical proteins and their annotated locations for XP_011533089.1

    UniProtKB/Swiss-Prot
    Q86XL3
    Conserved Domains (5) summary
    cd00204
    Location:334 → 464
    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 ...
    cd12944
    Location:71 → 113
    LEM_ANKL2; LEM (Lap2/Emerin/Man1) domain found in ankyrin repeat and LEM domain-containing protein 2 (ANKL2)
    pfam01693
    Location:218 → 249
    Cauli_VI; Caulimovirus viroplasmin
    pfam12796
    Location:356 → 435
    Ank_2; Ankyrin repeats (3 copies)
    sd00045
    Location:410 → 443
    ANK; ANK repeat [structural motif]

  5. XM_011534788.2 → XP_011533090.1  ankyrin repeat and LEM domain-containing protein 2 isoform X3

    See identical proteins and their annotated locations for XP_011533090.1

    UniProtKB/Swiss-Prot
    Q86XL3
    Conserved Domains (5) summary
    cd00204
    Location:334 → 464
    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 ...
    cd12944
    Location:71 → 113
    LEM_ANKL2; LEM (Lap2/Emerin/Man1) domain found in ankyrin repeat and LEM domain-containing protein 2 (ANKL2)
    pfam01693
    Location:218 → 249
    Cauli_VI; Caulimovirus viroplasmin
    pfam12796
    Location:356 → 435
    Ank_2; Ankyrin repeats (3 copies)
    sd00045
    Location:410 → 443
    ANK; ANK repeat [structural motif]

  6. XM_047428585.1 → XP_047284541.1  ankyrin repeat and LEM domain-containing protein 2 isoform X4

  7. XM_047428586.1 → XP_047284542.1  ankyrin repeat and LEM domain-containing protein 2 isoform X6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    132774758..132812890 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054371538.1 → XP_054227513.1  ankyrin repeat and LEM domain-containing protein 2 isoform X2

  2. XM_054371537.1 → XP_054227512.1  ankyrin repeat and LEM domain-containing protein 2 isoform X1

  3. XM_054371542.1 → XP_054227517.1  ankyrin repeat and LEM domain-containing protein 2 isoform X5

  4. XM_054371540.1 → XP_054227515.1  ankyrin repeat and LEM domain-containing protein 2 isoform X3

  5. XM_054371539.1 → XP_054227514.1  ankyrin repeat and LEM domain-containing protein 2 isoform X3

  6. XM_054371541.1 → XP_054227516.1  ankyrin repeat and LEM domain-containing protein 2 isoform X4

  7. XM_054371543.1 → XP_054227518.1  ankyrin repeat and LEM domain-containing protein 2 isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q86XL3.4 GenPept UniProtKB/Swiss-Prot:Q86XL3

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