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    TLL1 tolloid like 1 [ Homo sapiens (human) ]

    Gene ID: 7092, updated on 3-Nov-2024

    Summary

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    Official Symbol
    TLL1provided by HGNC
    Official Full Name
    tolloid like 1provided by HGNC
    Primary source
    HGNC:HGNC:11843
    See related
    Ensembl:ENSG00000038295 MIM:606742; AllianceGenome:HGNC:11843
    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
    TLL; ASD6
    Summary
    This gene encodes an astacin-like, zinc-dependent, metalloprotease that belongs to the peptidase M12A family. This protease processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Studies in mice suggest that this gene plays multiple roles in the development of mammalian heart, and is essential for the formation of the interventricular septum. Allelic variants of this gene are associated with atrial septal defect type 6. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
    Expression
    Broad expression in placenta (RPKM 2.3), gall bladder (RPKM 1.2) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TLL1 in Genome Data Viewer
    Location:
    4q32.3
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (165873237..166104457)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (169219854..169450476)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (166794389..167025609)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101928131 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:166664283-166664783 Neighboring gene long intergenic non-protein coding RNA 1179 Neighboring gene uncharacterized LOC105377521 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:166888016-166889215 Neighboring gene Sharpr-MPRA regulatory region 2915 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr4:166963784-166964983 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22120 Neighboring gene RNA, 5S ribosomal pseudogene 170 Neighboring gene Sharpr-MPRA regulatory region 13283 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_75833 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_75852 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_75875 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_75970 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_75989 Neighboring gene Sharpr-MPRA regulatory region 523 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_76035 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:167490745-167491404 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:167491405-167492062 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22121 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:167636733-167637577 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:167637578-167638421 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:167642620-167643500 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22122 Neighboring gene SPARC (osteonectin), cwcv and kazal like domains proteoglycan 3 Neighboring gene NANOG hESC enhancer GRCh37_chr4:167796983-167797484 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15787 Neighboring gene RNA, 5S ribosomal pseudogene 171 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22123 Neighboring gene RNA, 7SL, cytoplasmic 776, pseudogene

    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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Assessment of TLL1 variant and risk of hepatocellular carcinoma in Latin Americans and Europeans.
      Title: Assessment of TLL1 variant and risk of hepatocellular carcinoma in Latin Americans and Europeans.
    2. Klebsiella pneumoniae activates the TGF-beta signaling pathway to adhere to and invade intestinal epithelial cells via enhancing TLL1 expression.
      Title: Klebsiella pneumoniae activates the TGF-β signaling pathway to adhere to and invade intestinal epithelial cells via enhancing TLL1 expression.
    3. Chitinase 3-like-1, Tolloid-like protein 1, and intergenic gene polymorphisms are predictors for hepatocellular carcinoma development after hepatitis C virus eradication by direct-acting antivirals.
      Title: Chitinase 3-like-1, Tolloid-like protein 1, and intergenic gene polymorphisms are predictors for hepatocellular carcinoma development after hepatitis C virus eradication by direct-acting antivirals.
    4. Characterization of tolloid-mediated cleavage of the GDF8 procomplex.
      Title: Characterization of tolloid-mediated cleavage of the GDF8 procomplex.
    5. Proteinase bone morphogenetic protein 1, but not tolloid-like 1, plays a dominant role in maintaining periodontal homeostasis.
      Title: Proteinase bone morphogenetic protein 1, but not tolloid-like 1, plays a dominant role in maintaining periodontal homeostasis.
    6. Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients.
      Title: Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients.
    7. Genetic variation in the TLL1 gene is not associated with fibrosis in patients with metabolic associated fatty liver disease.
      Title: Genetic variation in the TLL1 gene is not associated with fibrosis in patients with metabolic associated fatty liver disease.
    8. The incidence of hepatocellular carcinoma was not influenced by TLL1 genotypes even when considering an additional group of 348 noncirrhotic patients, being 2% in AA vs 1% AT/TT patients (P = 0.58). In a large cohort of Caucasian hepatitis C cirrhotics treated with direct-acting antiviral, TLL1 variants do not predict hepatocellular carcinoma development.
      Title: TLL1 variants do not predict hepatocellular carcinoma development in HCV cirrhotic patients treated with direct-acting antivirals.
    9. The TLL1 variant was independently associated with hepatocellular carcinoma after hepatitis C virus eradication by interferon-free regimen; it might be involved in hepatic fibrogenesis and thereby carcinogenesis
      Title: TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus by interferon-free therapy.
    10. TLL-1 genetic variants determined fibrotic improvement in chronic hepatitis C with curative antivirals, particularly in patients with mild liver disease.
      Title: Tolloid-like 1 genetic variants determine fibrosis regression in chronic hepatitis C patients with curative antivirals.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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
    Atrial septal defect 6
    MedGen: C2751315 OMIM: 613087 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    A genome-wide association study of brain lesion distribution in multiple sclerosis.
    EBI GWAS Catalog
    Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See Variation Viewer (GRCh37.p13)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    capsid gag Depletion of the TLL1 expression upregulates HIV-1 CA A92E mutant infectivity in CsA-untreated HeLa cells and downregulates its infectivity in CsA-treated HeLa 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloendopeptidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables serine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in collagen fibril organization TAS
    Traceable Author Statement
    more info
    		  
    involved_in dorsal/ventral pattern formation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in skeletal system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    tolloid-like protein 1
    NP_001191689.1
    NP_036596.3

    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_016278.2 RefSeqGene

      Range
      4980..236200
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001204760.2 → NP_001191689.1  tolloid-like protein 1 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001191689.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is missing many exons from the 3' end, and contains a novel 3' terminal exon compared to variant 1. This results in a frame-shift, and a much shorter isoform (2) with a distinct C-terminus compared to isoform 1. This isoform lacks experimental support.
      Source sequence(s)
      AC097502, BC016922, U91963
      Consensus CDS
      CCDS56342.1
      UniProtKB/Swiss-Prot
      O43897
      Related
      ENSP00000422937.1, ENST00000513213.5
      Conserved Domains (2) summary
      cd04281
      Location:148 → 347
      ZnMc_BMP1_TLD; Zinc-dependent metalloprotease; BMP1/TLD-like subfamily. BMP1 (Bone morphogenetic protein 1) and TLD (tolloid)-like metalloproteases play vital roles in extracellular matrix formation, by cleaving precursor proteins such as enzymes, structural proteins, ...
      cl00049
      Location:349 → 390
      CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

    2. NM_012464.5 → NP_036596.3  tolloid-like protein 1 isoform 1 precursor

      See identical proteins and their annotated locations for NP_036596.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AC093874, AC097502, AC097507, AF282732, AK021908, BC144085, BU753788, U91963
      Consensus CDS
      CCDS3811.1
      UniProtKB/Swiss-Prot
      B2RMU2, O43897, Q96AN3, Q9NQS4
      UniProtKB/TrEMBL
      E9PD25
      Related
      ENSP00000061240.2, ENST00000061240.7
      Conserved Domains (4) summary
      cd04281
      Location:148 → 347
      ZnMc_BMP1_TLD; Zinc-dependent metalloprotease; BMP1/TLD-like subfamily. BMP1 (Bone morphogenetic protein 1) and TLD (tolloid)-like metalloproteases play vital roles in extracellular matrix formation, by cleaving precursor proteins such as enzymes, structural proteins, ...
      pfam00431
      Location:462 → 571
      CUB; CUB domain
      pfam01400
      Location:155 → 348
      Astacin; Astacin (Peptidase family M12A)
      pfam14670
      Location:734 → 769
      FXa_inhibition; Coagulation Factor Xa inhibitory site

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      165873237..166104457
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      169219854..169450476
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43897.1 GenPept UniProtKB/Swiss-Prot:O43897

    Gene LinkOut

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

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