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TLL2 tolloid like 2 [ Homo sapiens (human) ]

Gene ID: 7093, updated on 7-Apr-2025

Summary

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Official Symbol
TLL2provided by HGNC
Official Full Name
tolloid like 2provided by HGNC
Primary source
HGNC:HGNC:11844
See related
Ensembl:ENSG00000095587 MIM:606743; AllianceGenome:HGNC:11844
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. Unlike other family members, a similar protein in mice does not cleave procollagen C-propeptides or chordin. [provided by RefSeq, Jul 2008]
Expression
Low expression observed in reference dataset See more
Orthologs
mouse all
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Genomic context

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See TLL2 in Genome Data Viewer
Location:
10q24.1
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (96364608..96513926, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (97243944..97395061, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (98124365..98273683, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:98068473-98069311 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:98069312-98070152 Neighboring gene NANOG hESC enhancer GRCh37_chr10:98084017-98084578 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2653 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:98104629-98105395 Neighboring gene DNA nucleotidylexotransferase Neighboring gene oligodendrocytic myelin paranodal and inner loop protein Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:98138703-98139212 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:98156871-98157399 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:98201903-98202541 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:98210491-98210992 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:98246593-98247092 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:98262485-98262985 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:98265857-98266640 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:98271755-98272274 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3827 Neighboring gene transmembrane 9 superfamily member 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:98331950-98332450 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:98332451-98332951 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:98339518-98340092 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2654 Neighboring gene uncharacterized LOC105378443 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3828 Neighboring gene nucleophosmin 1 pseudogene 26 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2655 Neighboring gene phosphoinositide-3-kinase adaptor protein 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. Genomic analysis of a spinal muscular atrophy (SMA) discordant family identifies a novel mutation in TLL2, an activator of growth differentiation factor 8 (myostatin): a case report. Jiang J, et al. BMC Med Genet, 2019 Dec 30. PMID 31888525, Free PMC Article
  2. Cross-species genetics converge to TLL2 for mouse avoidance behavior and human bipolar disorder. de Mooij-van Malsen JG, et al. Genes Brain Behav, 2013 Aug. PMID 23777486
  3. Cloning of the chick BMP1/Tolloid cDNA and expression in skeletal tissues. Reynolds SD, et al. Gene, 2000 May 2. PMID 10806368
  4. Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases. Mac Sweeney A, et al. J Mol Biol, 2008 Dec 5. PMID 18824173
  5. Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival. Xu Y, et al. Mol Carcinog, 2018 Jan. PMID 28796414, Free PMC Article

See all (22) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. genomic analysis identified compound heterozygous mutations at TLL2 on the male patient's genome, and compound heterozygous mutations at VPS13A and the de novo mutation at AGAP5 on female patient's genome
    Title: Genomic analysis of a spinal muscular atrophy (SMA) discordant family identifies a novel mutation in TLL2, an activator of growth differentiation factor 8 (myostatin): a case report.
  2. Findings suggest that these MMP16 rs10090371, ADAMTS3 rs788935, TLL2 rs10882807 and MMP9 rs3918251 may be promising prognostic biomarkers for cutaneous melanoma specific survival (CMSS).
    Title: Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival.
  3. By means of a cross-species comparative genetic strategy we describe an association for TLL2 with bipolar disorder.
    Title: Cross-species genetics converge to TLL2 for mouse avoidance behavior and human bipolar disorder.
  4. Observational study of gene-disease association. (HuGE Navigator)
    Title: A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
  5. The crystal structures of the protease domains of human BMP-1 and the closely related Tolloid-like protease 1 (TLL-1), are reported.
    Title: Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases.
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

EBI GWAS Catalog

Description
Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies.
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)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0932, MGC133312, MGC133313

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables metalloendopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metalloendopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables metallopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables peptidase activity IEA
Inferred from Electronic Annotation
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
  
acts_upstream_of_or_within negative regulation of skeletal muscle tissue growth IEA
Inferred from Electronic Annotation
more info
  
involved_in protein processing IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in extracellular region IEA
Inferred from Electronic Annotation
more info
  
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 2
NP_036597.1

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_012465.4 → NP_036597.1  tolloid-like protein 2 precursor

    See identical proteins and their annotated locations for NP_036597.1

    Status: VALIDATED

    Source sequence(s)
    AB023149, AL136181, AW452288, BC112341, DA716349
    Consensus CDS
    CCDS7449.1
    UniProtKB/Swiss-Prot
    A6NDK0, Q2M1H1, Q6PJN5, Q9UQ00, Q9Y6L7
    Related
    ENSP00000350630.3, ENST00000357947.4
    Conserved Domains (4) summary
    cd04281
    Location:150 → 349
    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:464 → 573
    CUB; CUB domain
    pfam01400
    Location:157 → 350
    Astacin; Astacin (Peptidase family M12A)
    pfam14670
    Location:736 → 771
    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_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    96364608..96513926 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    97243944..97395061 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y6L7.1 GenPept UniProtKB/Swiss-Prot:Q9Y6L7

Gene LinkOut

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