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    TMPO thymopoietin [ Homo sapiens (human) ]

    Gene ID: 7112, updated on 3-Nov-2024

    Summary

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    Official Symbol
    TMPOprovided by HGNC
    Official Full Name
    thymopoietinprovided by HGNC
    Primary source
    HGNC:HGNC:11875
    See related
    Ensembl:ENSG00000120802 MIM:188380; AllianceGenome:HGNC:11875
    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
    TP; LAP2; CMD1T; LEMD4; PRO0868
    Summary
    Through alternative splicing, this gene encodes several distinct LEM domain containing protein isoforms. LEM domain proteins include inner nuclear membrane and intranuclear proteins, and are involved in a variety of cellular functions including gene expression, chromatin organization, and replication and cell cycle control. The encoded alpha isoform is broadly diffuse in the nucleus and contains a lamin binding domain, while the beta and gamma isoforms are localized to the nuclear membrane and contain an HDAC3 interaction domain. The distinct isoforms may compete with each other when acting to chaperone other proteins and regulate transcription. [provided by RefSeq, Aug 2019]
    Expression
    Ubiquitous expression in lymph node (RPKM 23.3), bone marrow (RPKM 19.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TMPO in Genome Data Viewer
    Location:
    12q23.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (98515573..98550351)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (98488849..98523648)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (98909351..98944129)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 2453 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6841 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6842 Neighboring gene tRNA-Asp (anticodon GTC) 1-1 Neighboring gene tRNA-Trp (anticodon CCA) 4-1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:98902147-98902690 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:98905336-98905836 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6843 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6844 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4752 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4753 Neighboring gene TMPO antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:98922080-98922246 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6845 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:98987254-98987878 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:98987879-98988503 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6847 Neighboring gene peptidylprolyl isomerase A pseudogene 8 Neighboring gene solute carrier family 25 member 3 Neighboring gene small nucleolar RNA, H/ACA box 53

    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 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. Detergent-salt resistance of LAP2alpha in interphase nuclei and phosphorylation-dependent association with chromosomes early in nuclear assembly implies functions in nuclear structure dynamics. Dechat T, et al. EMBO J, 1998 Aug 17. PMID 9707448, Free PMC Article
    2. Lamina-associated polypeptide 2alpha regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway. Dorner D, et al. J Cell Biol, 2006 Apr 10. PMID 16606692, Free PMC Article
    3. Lamina-associated polypeptide 2-alpha forms homo-trimers via its C terminus, and oligomerization is unaffected by a disease-causing mutation. Snyers L, et al. J Biol Chem, 2007 Mar 2. PMID 17213199
    4. Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes. Somech R, et al. Ann Hematol, 2007 Jun. PMID 17364180
    5. Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA. Cai M, et al. EMBO J, 2001 Aug 15. PMID 11500367, Free PMC Article

    See all (302) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. LncRNA TMPO-AS1 promotes esophageal squamous cell carcinoma progression by forming biomolecular condensates with FUS and p300 to regulate TMPO transcription.
      Title: LncRNA TMPO-AS1 promotes esophageal squamous cell carcinoma progression by forming biomolecular condensates with FUS and p300 to regulate TMPO transcription.
    2. LncRNA TMPO-AS1 Aggravates the Development of Hepatocellular Carcinoma via miR-429/GOT1 Axis.
      Title: LncRNA TMPO-AS1 Aggravates the Development of Hepatocellular Carcinoma via miR-429/GOT1 Axis.
    3. TMPO-AS1 contributes to lung carcinogenesis, which may be partially through upregulation TMPO.
      Title: Long noncoding RNA TMPO-AS1 promotes progression of non-small cell lung cancer through regulating its natural antisense transcript TMPO.
    4. Study found TMPO is significantly upregulated in glioblastoma tissues.TMPO knockdown promoted cell apoptosis by upregulation of the cleavage of caspase-3 and PARP protein levels.
      Title: Depletion of thymopoietin inhibits proliferation and induces cell cycle arrest/apoptosis in glioblastoma cells.
    5. Results suggest that TMPObeta and -gamma isoforms could provide a potential reliable diagnostic marker for breast cancer.
      Title: Thymopoietin Beta and Gamma Isoforms as a Potential Diagnostic Molecular Marker for Breast Cancer: Preliminary Data.
    6. The findings unveil a unique mechanism where the nuclear periphery proteins lamin-A/C, LAP2alpha and BAF1 are assembled into a protein complex during mitosis in order to regulate assembly and positioning of the mitotic spindle.
      Title: The lamin-A/C-LAP2α-BAF1 protein complex regulates mitotic spindle assembly and positioning.
    7. The authors find that LAP2alpha (lamina-associated polypeptide-alpha) interacts with lamin A, while its interaction with progerin is significantly reduced.
      Title: Progerin reduces LAP2α-telomere association in Hutchinson-Gilford progeria.
    8. LAP2alpha can regulate extracellular matrix components independently of lamins A/C, which may help explain the proliferation-promoting function of LAP2alpha in cells expressing progerin.
      Title: Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2α (LAP2α) through expression of extracellular matrix proteins.
    9. Results highlight the interactions at the nuclear envelope where mutations in the EMD and TMPO gene in combination with mutations in SUN1 have an impact on several components of the network.
      Title: Contribution of SUN1 mutations to the pathomechanism in muscular dystrophies.
    10. Data indicate that cells lacking either high mobility group protein N5 (HMGN5) and lamina-associated polypeptide 2alpha (LAP2alpha) showed that loss of either protein affects the genome-wide distribution of the remaining partner.
      Title: High mobility group protein N5 (HMGN5) and lamina-associated polypeptide 2α (LAP2α) interact and reciprocally affect their genome-wide chromatin organization.
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    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
    Primary dilated cardiomyopathy
    MedGen: C0007193 GeneReviews: Dilated Cardiomyopathy Overview
    		Compare labs

    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Pr55(Gag) gag Cellular biotinylated lamina-associated polypeptide 2, beta/gamma (LAP2) protein is incorporated into HIV-1 Gag virus-like particles PubMed
    Tat tat Interaction of HIV-1 Tat with lamina-associated polypeptide 2 in T-cells is identified by a proteomic strategy based on affinity chromatography PubMed

    Go to the HIV-1, Human Interaction Database

    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

    • MGC61508

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cadherin binding HDA PubMed 
    enables lamin binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane HDA PubMed 
    located_in nuclear envelope IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear envelope IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nuclear inner membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nuclear membrane IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    thymopoietin
    Names
    LEM domain containing 4
    lamina-associated polypeptide 2

    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_021393.1 RefSeqGene

      Range
      5001..39807
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_443

    mRNA and Protein(s)

    1. NM_001032283.3 → NP_001027454.1  thymopoietin isoform beta

      See identical proteins and their annotated locations for NP_001027454.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs at the 3' end compared to variant 1, resulting in a shorter isoform (beta) with a distinct C-terminus compared to isoform alpha.
      Source sequence(s)
      AA992204, AB209297, AI055921, BC053675, BG676381, BM802949, BQ232508, DB239672
      Consensus CDS
      CCDS31879.1
      UniProtKB/Swiss-Prot
      A2T926, P42167, Q14861
      Related
      ENSP00000450627.1, ENST00000556029.6
      Conserved Domains (2) summary
      cd12940
      Location:111 → 139
      LEM_LAP2_LEMD1; LEM (Lap2/Emerin/Man1) domain found in lamina-associated polypeptide 2 (LAP2), LEM domain-containing protein 1 (LEMP-1) and similar proteins
      pfam08198
      Location:3 → 49
      Thymopoietin; Thymopoietin protein

    2. NM_001032284.3 → NP_001027455.1  thymopoietin isoform gamma

      See identical proteins and their annotated locations for NP_001027455.1

      Status: REVIEWED

      Description
      Transcript Variant: This (3) differs at the 3' end compared to variant 1, resulting in a shorter isoform (gamma) with a distinct C-terminus compared to isoform alpha.
      Source sequence(s)
      AA992204, AB209297, AI055921, BG676381, BM802949, BQ232508, DB239672, U09088
      Consensus CDS
      CCDS31880.1
      UniProtKB/TrEMBL
      Q59G12
      Related
      ENSP00000376773.2, ENST00000393053.6
      Conserved Domains (2) summary
      cd12940
      Location:111 → 139
      LEM_LAP2_LEMD1; LEM (Lap2/Emerin/Man1) domain found in lamina-associated polypeptide 2 (LAP2), LEM domain-containing protein 1 (LEMP-1) and similar proteins
      pfam08198
      Location:2 → 49
      Thymopoietin; Thymopoietin protein

    3. NM_001307975.2 → NP_001294904.1  thymopoietin isoform delta

      See identical proteins and their annotated locations for NP_001294904.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs at the 3' end compared to variant 1, resulting in a shorter isoform (delta) with a distinct C-terminus compared to isoform alpha.
      Source sequence(s)
      AA992204, AC013418, BC050383, BC053675, DB239672
      Consensus CDS
      CCDS76589.1
      UniProtKB/TrEMBL
      G5E972, Q59G12
      Related
      ENSP00000340251.5, ENST00000343315.9
      Conserved Domains (2) summary
      cd12940
      Location:111 → 139
      LEM_LAP2_LEMD1; LEM (Lap2/Emerin/Man1) domain found in lamina-associated polypeptide 2 (LAP2), LEM domain-containing protein 1 (LEMP-1) and similar proteins
      pfam08198
      Location:2 → 49
      Thymopoietin; Thymopoietin protein

    4. NM_003276.2 → NP_003267.1  thymopoietin isoform alpha

      See identical proteins and their annotated locations for NP_003267.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (alpha).
      Source sequence(s)
      BM991833, BP423544, BU932961, DB239672, U09086
      Consensus CDS
      CCDS9064.1
      UniProtKB/Swiss-Prot
      P08918, P08919, P42166, Q14860, Q16295
      Related
      ENSP00000266732.4, ENST00000266732.8
      Conserved Domains (3) summary
      cd12940
      Location:111 → 139
      LEM_LAP2_LEMD1; LEM (Lap2/Emerin/Man1) domain found in lamina-associated polypeptide 2 (LAP2), LEM domain-containing protein 1 (LEMP-1) and similar proteins
      pfam08198
      Location:2 → 49
      Thymopoietin; Thymopoietin protein
      pfam11560
      Location:461 → 693
      LAP2alpha; Lamina-associated polypeptide 2 alpha

    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
      98515573..98550351
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005269132.5 → XP_005269189.1  thymopoietin isoform X2

      UniProtKB/TrEMBL
      Q59G12
      Conserved Domains (2) summary
      cd12940
      Location:111 → 139
      LEM_LAP2_LEMD1; LEM (Lap2/Emerin/Man1) domain found in lamina-associated polypeptide 2 (LAP2), LEM domain-containing protein 1 (LEMP-1) and similar proteins
      pfam08198
      Location:2 → 49
      Thymopoietin; Thymopoietin protein

    2. XM_017019914.3 → XP_016875403.1  thymopoietin isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      98488849..98523648
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054373116.1 → XP_054229091.1  thymopoietin isoform X2

    2. XM_054373115.1 → XP_054229090.1  thymopoietin isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P42166.2 GenPept UniProtKB/Swiss-Prot:P42166
    P42167.2 GenPept UniProtKB/Swiss-Prot:P42167

    Gene LinkOut

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

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