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

    Gene ID: 23141, updated on 3-Apr-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
    mouse all
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (132725503..132761832, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (132774758..132812890, complement)
    105.20220307 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 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
    2. 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
    3. 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
    4. SIRT2 regulates nuclear envelope reassembly through ANKLE2 deacetylation. Kaufmann T, et al. J Cell Sci, 2016 Dec 15. PMID 27875273, 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 (63) 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
    		Compare labs

    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)

    Genotypes

    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 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 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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein dephosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of protein dephosphorylation 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_2023_10

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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