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    FHL3 four and a half LIM domains 3 [ Homo sapiens (human) ]

    Gene ID: 2275, updated on 2-Nov-2024

    Summary

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    Official Symbol
    FHL3provided by HGNC
    Official Full Name
    four and a half LIM domains 3provided by HGNC
    Primary source
    HGNC:HGNC:3704
    See related
    Ensembl:ENSG00000183386 MIM:602790; AllianceGenome:HGNC:3704
    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
    SLIM2
    Summary
    The protein encoded by this gene is a member of a family of proteins containing a four-and-a-half LIM domain, which is a highly conserved double zinc finger motif. The encoded protein has been shown to interact with the cancer developmental regulators SMAD2, SMAD3, and SMAD4, the skeletal muscle myogenesis protein MyoD, and the high-affinity IgE beta chain regulator MZF-1. This protein may be involved in tumor suppression, repression of MyoD expression, and repression of IgE receptor expression. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
    Expression
    Ubiquitous expression in esophagus (RPKM 21.3), endometrium (RPKM 16.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FHL3 in Genome Data Viewer
    Location:
    1p34.3
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (37996770..38005514, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (37863951..37872693, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (38462442..38471186, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene splicing factor 3a subunit 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 780 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 781 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38456307-38456852 Neighboring gene RNA, U6 small nuclear 510, pseudogene Neighboring gene Sharpr-MPRA regulatory region 8264 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38463160-38464081 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38465171-38465958 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38465959-38466746 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38469196-38470004 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 684 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 685 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 782 Neighboring gene UTP11 small subunit processome component Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:38491775-38492274 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38492441-38492993 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38492994-38493545 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 783 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 784 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 785 Neighboring gene Sharpr-MPRA regulatory region 3132 Neighboring gene POU class 3 homeobox 1

    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. Ribotrap analysis of proteins associated with FHL3 3'untranslated region in glioma cells. Han W, et al. Chin Med Sci J, 2014 Jun. PMID 24998228
    2. Chromosomal mapping of a skeletal muscle specific LIM-only protein FHL3 to the distal end of the short arm of human chromosome 1. Lee SM, et al. Somat Cell Mol Genet, 1998 May. PMID 10226657
    3. The four and a half LIM family members are novel interactants of the human T-cell leukemia virus type 1 Tax oncoprotein. McCabe Á, et al. J Virol, 2013 Jul. PMID 23616667, Free PMC Article
    4. Downregulation and antiproliferative role of FHL3 in breast cancer. Niu C, et al. IUBMB Life, 2011 Sep. PMID 22362714
    5. Identification of the transactivation domain of the human FHL3. Huang X, et al. Mol Biol (Mosk), 2010 Mar-Apr. PMID 20586194

    See all (88) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Upregulation of FHL1, SPNS3, and MPZL2 predicts poor prognosis in pediatric acute myeloid leukemia patients with FLT3-ITD mutation.
      Title: Upregulation of FHL1, SPNS3, and MPZL2 predicts poor prognosis in pediatric acute myeloid leukemia patients with FLT3-ITD mutation.
    2. PCBP2 promotes the development of glioma by regulating FHL3/TGF-beta/Smad signaling pathway.
      Title: PCBP2 promotes the development of glioma by regulating FHL3/TGF-β/Smad signaling pathway.
    3. these findings highlight the role of FHL3 as a stemness-suppressor in regulation of the Smad2/3-SOX4-SOX2 axis in glioma
      Title: FHL3 links cell growth and self-renewal by modulating SOX4 in glioma.
    4. the present study established a link between Ang and FHL3 proteins and identifies a new pathway for regulating astrocytoma progression.
      Title: Angiogenin promotes U87MG cell proliferation by activating NF-κB signaling pathway and downregulating its binding partner FHL3.
    5. These findings suggest that functional interactions between FHL3 and MT-1X may provide some clues to the mechanisms of FHL3-regulated cell proliferation.
      Title: Identification and characterization of MT-1X as a novel FHL3-binding partner.
    6. PCBP2 could bind to FHL3 mRNA 3'UTR-A and inhibited the expression of FHL3 in T98G glioms cells
      Title: Ribotrap analysis of proteins associated with FHL3 3'untranslated region in glioma cells.
    7. FHL3 enhances Tax1-mediated activation of the Human T-cell leukemia virus type 1 long terminal repeat (LTR) without affecting basal activity and regulates NF-kappaB activation by Tax1 in a cell-specific manner.
      Title: The four and a half LIM family members are novel interactants of the human T-cell leukemia virus type 1 Tax oncoprotein.
    8. findings suggest that the interaction between Ang and FHL3 may provide some clues to the mechanisms of Ang-regulated cell growth and apoptosis
      Title: Identification and characterization of FHL3 as a novel angiogenin-binding partner.
    9. FHL3 suppressed anchorage-dependent and -independent growth of human breast cancer cells.
      Title: Downregulation and antiproliferative role of FHL3 in breast cancer.
    10. FHL3 does not bind to HIF-1alpha or p300, indicating that it regulates transactivation by a novel molecular mechanism.
      Title: Four-and-a-half LIM domain proteins inhibit transactivation by hypoxia-inducible factor 1.
    Submit: New GeneRIF Correction See all GeneRIFs (16)

    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

    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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    Replication interactions

    Interaction Pubs
    Knockdown of four and a half LIM domains 3 (FHL3) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC8696, MGC19547, MGC23614

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables actin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription coregulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in actin cytoskeleton organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in muscle organ development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in Z disc IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in focal adhesion HDA PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in stress fiber IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    four and a half LIM domains protein 3
    Names
    FHL-3
    LIM-only protein FHL3
    SLIM-2
    skeletal muscle LIM-protein 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.

    mRNA and Protein(s)

    1. NM_001243878.2 → NP_001230807.1  four and a half LIM domains protein 3 isoform 2

      See identical proteins and their annotated locations for NP_001230807.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AL603790
      UniProtKB/TrEMBL
      Q96C98
      Related
      ENST00000485803.5
      Conserved Domains (3) summary
      cd09346
      Location:54 → 105
      LIM3_FHL; The third LIM domain of Four and a half LIM domains protein (FHL)
      cd09434
      Location:113 → 168
      LIM4_FHL3; The fourth LIM domain of Four and a half LIM domains protein 3 (FHL3)
      cl02475
      Location:1 → 47
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    2. NM_004468.5 → NP_004459.2  four and a half LIM domains protein 3 isoform 1

      See identical proteins and their annotated locations for NP_004459.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AL603790
      Consensus CDS
      CCDS30678.1
      UniProtKB/Swiss-Prot
      D3DPT6, Q13643, Q6I9T0, Q9BVA2
      UniProtKB/TrEMBL
      Q9P100
      Related
      ENSP00000362107.3, ENST00000373016.4
      Conserved Domains (5) summary
      cd09346
      Location:162 → 213
      LIM3_FHL; The third LIM domain of Four and a half LIM domains protein (FHL)
      cd09423
      Location:36 → 94
      LIM1_FHL3; The first LIM domain of Four and a half LIM domains protein 3 (FHL3)
      cd09427
      Location:98 → 155
      LIM2_FHL3; The second LIM domain of Four and a half LIM domains protein 3 (FHL3)
      cd09434
      Location:221 → 276
      LIM4_FHL3; The fourth LIM domain of Four and a half LIM domains protein 3 (FHL3)
      cl02475
      Location:5 → 33
      LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      37996770..38005514 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      37863951..37872693 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13643.4 GenPept UniProtKB/Swiss-Prot:Q13643

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