Tmprss6 transmembrane serine protease 6 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tmprss6provided by MGI
Official Full Name: transmembrane serine protease 6provided by MGI
Primary source: MGI:MGI:1919003
See related: Ensembl:ENSMUSG00000016942 AllianceGenome:MGI:1919003
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: 1300008A22Rik
Summary: Predicted to enable serine-type endopeptidase activity. Involved in cellular iron ion homeostasis; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Acts upstream of or within iron ion homeostasis and negative regulation of BMP signaling pathway. Located in plasma membrane. Is expressed in several structures, including cerebral cortex; gut; hemolymphoid system gland; sensory organ; and uterus. Human ortholog(s) of this gene implicated in microcytic anemia. Orthologous to human TMPRSS6 (transmembrane serine protease 6). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in liver adult (RPKM 178.1) and liver E18 (RPKM 39.2) See more
Orthologs: human all
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Genomic context

Location:: 15 E1; 15 37.49 cM

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (78323867..78352848, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (78439667..78468648, complement)

Chromosome 15 - NC_000081.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Transmembrane serine protease 6, a novel target for inhibition of neuronal tumor growth.
Title: Transmembrane serine protease 6, a novel target for inhibition of neuronal tumor growth.
Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies in Mask Mice.
Title: Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies in Mask Mice.
Correcting beta-thalassemia by combined therapies that restrict iron and modulate erythropoietin activity.
Title: Correcting β-thalassemia by combined therapies that restrict iron and modulate erythropoietin activity.
The ectodomain of matriptase-2 plays an important nonproteolytic role in suppressing hepcidin expression in mice.
Title: The ectodomain of matriptase-2 plays an important nonproteolytic role in suppressing hepcidin expression in mice.
Genetic loss of Tmprss6 alters terminal erythroid differentiation in a mouse model of beta-thalassemia intermedia.
Title: Genetic loss of Tmprss6 alters terminal erythroid differentiation in a mouse model of β-thalassemia intermedia.
our results highlight the importance of understanding the precise function of each TMPRSS6 isoforms both in human and in mouse
Title: Transcriptome analysis reveals TMPRSS6 isoforms with distinct functionalities.
The study describes a role for C and hepcidin in obesity and highlights the relevance of iron regulation in the control of adipose tissue function.
Title: Matriptase-2 deficiency protects from obesity by modulating iron homeostasis.
Erythroferrone and matriptase-2 independently regulate hepcidin expression.
Title: Erythroferrone and matriptase-2 independently regulate hepcidin expression.
Data (including data from studies using knockout mice) suggest that Mt2/Tmprss6 suppresses hepcidin expression in hepatocytes independently of Hjv; Mt2/Tmprss6 cleaves Alk2, Alk3, ActRIIA, Bmpr2, Hfe, and, to a lesser extent, Hjv and Tfr2; thus, Mt2/Tmprss6 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway. (Mt2/Tmprss6 = matriptase-2; Hjv = hemojuvelin)
Title: Matriptase-2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway.
The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6.
Title: Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (5) 1 citation
Chemically induced (ENU) (6) 1 citation
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables peptidase activity	IEA Inferred from Electronic Annotation more info
enables serine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables serine-type peptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of BMP signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in intracellular iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane protein proteolysis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within multicellular organismal-level iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in multicellular organismal-level iron ion homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of BMP signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within proteolysis	ISO Inferred from Sequence Orthology more info
involved_in self proteolysis	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: transmembrane protease serine 6

Names: matriptase 2; transmembrane protease, serine 6; type II transmembrane serine protease 6

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)

NM_001355601.1 → NP_001342530.1 transmembrane protease serine 6 isoform 2

Status: VALIDATED

Source sequence(s)

AL590144

Consensus CDS

CCDS88800.1

UniProtKB/TrEMBL

A0A2R8W6T9

Related

ENSMUSP00000155401.2, ENSMUST00000230226.2

Conserved Domains (4) summary

cd00112
Location:483 → 513

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:565 → 797

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:517 → 554

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:76 → 180

SEA; SEA domain
NM_027902.2 → NP_082178.2 transmembrane protease serine 6 isoform 1

See identical proteins and their annotated locations for NP_082178.2

Status: VALIDATED

Source sequence(s)

AY240929, BB872026

Consensus CDS

CCDS37133.1

UniProtKB/Swiss-Prot

A8W478, A8W479, Q3KN88, Q6PF94, Q9DBI0

Related

ENSMUSP00000017086.4, ENSMUST00000017086.5

Conserved Domains (5) summary

smart00020
Location:576 → 806

Tryp_SPc; Trypsin-like serine protease

cd00112
Location:495 → 525

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:577 → 809

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:529 → 566

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:88 → 185

SEA; SEA domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000081.7 Reference GRCm39 C57BL/6J

Range

78323867..78352848 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006521417.3 → XP_006521480.1 transmembrane protease serine 6 isoform X1

Conserved Domains (4) summary

cd00112
Location:481 → 511

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:563 → 795

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00057
Location:515 → 552

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam01390
Location:88 → 145

SEA; SEA domain