TLL1 tolloid like 1 [Homo sapiens (human)] - Gene

Summary

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

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_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
Characterization of tolloid-mediated cleavage of the GDF8 procomplex.
Title: Characterization of tolloid-mediated cleavage of the GDF8 procomplex.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed
Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

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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

D4S3302 (e-PCR)
- UniSTS:37141

SHGC-59625 (e-PCR)
- UniSTS:47662

SHGC-59832 (e-PCR)
- UniSTS:79709

SHGC4-721 (e-PCR)
- UniSTS:90230

D4S1566 (e-PCR)
- UniSTS:27790

RH119805 (e-PCR)
- UniSTS:133280

SHGC-77747 (e-PCR)
- UniSTS:95940

TLL1__5268 (e-PCR)
- UniSTS:463323

SHGC-50239 (e-PCR)
- UniSTS:60129

Tll (e-PCR), detects polymorphism
- UniSTS:144638

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

EC 3.4.24.-

NP_036596.3

EC 3.4.24.-

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

NG_016278.2 RefSeqGene

Range

4980..236200

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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.
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