InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TMPRSS6

Summary

InnateDB Protein

IDBP-6333.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TMPRSS6

Protein Name

transmembrane protease, serine 6

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000334962

InnateDB Gene

IDBG-6331 (TMPRSS6)

Protein Structure

UniProt Annotation

Function

Serine protease which hydrolyzes a range of proteins including type I collagen, fibronectin and fibrinogen. Can also activate urokinase-type plasminogen activator with low efficiency. May play a specialized role in matrix remodeling processes in liver. Plays a role in the regulation of iron homeostasis, a process involving HAMP. Required to sense iron deficiency and suppress activation of the HAMP promoter. {ECO:0000269PubMed:12149247, ECO:0000269PubMed:18408718}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:12149247, ECO:0000269PubMed:20518742}; Single-pass type II membrane protein {ECO:0000269PubMed:12149247, ECO:0000269PubMed:20518742}.

Disease Associations

Iron-refractory iron deficiency anemia (IRIDA) [MIM:206200]: Key features include congenital hypochromic microcytic anemia, very low mean corpuscular erythrocyte volume, low transferrin saturation, abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron, and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron. {ECO:0000269PubMed:18408718, ECO:0000269PubMed:18603562, ECO:0000269PubMed:19357398, ECO:0000269PubMed:19592582, ECO:0000269PubMed:19708871, ECO:0000269PubMed:19747362, ECO:0000269PubMed:20232450, ECO:0000269PubMed:20704562, ECO:0000269PubMed:21618415, ECO:0000269PubMed:22581667}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations leading to abrogation of TMPRSS6 activity are associated with IRIDA due to elevated levels of hepcidin, a negative regulator of plasma iron pool (PubMed:20232450). {ECO:0000269PubMed:20232450}.

Tissue Specificity

Liver specific. {ECO:0000269PubMed:12149247}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003824	catalytic activity
GO:0004252	serine-type endopeptidase activity
GO:0005515	protein binding

Biological Process

GO:0001525	angiogenesis
GO:0006508	proteolysis
GO:0030198	extracellular matrix organization
GO:0035556	intracellular signal transduction
GO:0042730	fibrinolysis
GO:0055072	iron ion homeostasis

Cellular Component

GO:0005886	plasma membrane
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000082 SEA domain
IPR000859 CUB domain
IPR001254 Peptidase S1
IPR001314 Peptidase S1A, chymotrypsin-type
IPR002172 Low-density lipoprotein (LDL) receptor class A repeat
IPR009003 Trypsin-like cysteine/serine peptidase domain
IPR015420 Peptidase S1A, nudel
IPR017118 Peptidase S1A, matriptase-2

PFAM

PF01390
PF00431
PF00089
PF00057
PF09342

PRINTS

PR00722
PR00261

PIRSF

PIRSF037135

SMART

SM00200
SM00042
SM00020
SM00192

TIGRFAMs

Post-translational Modifications

Modification

Cross-References