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Protein

Transmembrane protease serine 6

Gene

Tmprss6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Through the cleavage of HFE2, a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei617Charge relay systemBy similarity1
Active sitei668Charge relay systemBy similarity1
Active sitei762Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cellular iron ion homeostasis Source: BHF-UCL
  • fibrinolysis Source: UniProtKB
  • iron ion homeostasis Source: MGI
  • membrane protein proteolysis Source: UniProtKB
  • negative regulation of BMP signaling pathway Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • proteolysis Source: UniProtKB
  • self proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.109. 3474.
ReactomeiR-MMU-1442490. Collagen degradation.
R-MMU-1474228. Degradation of the extracellular matrix.

Protein family/group databases

MEROPSiS01.308.

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane protease serine 6 (EC:3.4.21.-)
Alternative name(s):
Matriptase-2
Gene namesi
Name:Tmprss6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1919003. Tmprss6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 59CytoplasmicSequence analysisAdd BLAST59
Transmembranei60 – 80Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini81 – 811ExtracellularSequence analysisAdd BLAST731

GO - Cellular componenti

  • extracellular space Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice display the phenotype named mask, characterized by progressive loss of body (but not facial) hair, microcytic anemia and female infertility, all reversible by dietary iron supplementation. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi762S → A: Protease-dead. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000886971 – 811Transmembrane protease serine 6Add BLAST811

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi138N-linked (GlcNAc...)Sequence analysis1
Glycosylationi184N-linked (GlcNAc...)Sequence analysis1
Glycosylationi216N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi335 ↔ 366By similarity
Glycosylationi338N-linked (GlcNAc...)Sequence analysis1
Glycosylationi433N-linked (GlcNAc...)Sequence analysis1
Glycosylationi453N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi458 ↔ 470By similarity
Disulfide bondi464 ↔ 480By similarity
Disulfide bondi474 ↔ 489By similarity
Disulfide bondi491 ↔ 503By similarity
Disulfide bondi497 ↔ 516By similarity
Disulfide bondi510 ↔ 525By similarity
Glycosylationi518N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi531 ↔ 543By similarity
Disulfide bondi538 ↔ 557By similarity
Disulfide bondi551 ↔ 566By similarity
Disulfide bondi602 ↔ 618By similarity
Disulfide bondi702 ↔ 768By similarity
Disulfide bondi733 ↔ 747By similarity
Disulfide bondi758 ↔ 787By similarity

Post-translational modificationi

The single-chain zymogen undergoes autoproteolytic processing. This results in TMPRSS6 shedding from the cell surface and conversion into an activated two-chains form which is released extracellularly. The process involves a trans-activation mechanism that requires TMPRSS6 oligomerization.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ9DBI0.
PeptideAtlasiQ9DBI0.
PRIDEiQ9DBI0.

PTM databases

PhosphoSitePlusiQ9DBI0.

Expressioni

Tissue specificityi

Expressed at highest levels in adult mice liver, kidney and uterus. Also strongly expressed within the nasal cavity by olfactory epithelial cells. A weak, but detectable, signal in adult mice tissues analyzed including brain, lung, heart, kidney, spleen, muscle, intestine, thymus and pancreas. No signal in residual embryonic yolk sac, developing kidney tubules or in embryonic tissues analyzed including lung, heart, gastrointestinal tract and epithelium of the oral cavity.1 Publication

Developmental stagei

Expressed at higher levels from 12.5 dpc to 15.5 dpc with a peak at 13.5 dpc. Expressed in the developing liver and at lower levels in developing pharyngo-tympanic tubes.1 Publication

Gene expression databases

BgeeiENSMUSG00000016942.
CleanExiMM_TMPRSS6.
GenevisibleiQ9DBI0. MM.

Interactioni

Subunit structurei

Interacts with HFE2.By similarity

Protein-protein interaction databases

IntActiQ9DBI0. 1 interactor.
STRINGi10090.ENSMUSP00000017086.

Structurei

3D structure databases

ProteinModelPortaliQ9DBI0.
SMRiQ9DBI0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini86 – 209SEAPROSITE-ProRule annotationAdd BLAST124
Domaini213 – 336CUB 1PROSITE-ProRule annotationAdd BLAST124
Domaini323 – 440CUB 2PROSITE-ProRule annotationAdd BLAST118
Domaini445 – 477LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST33
Domaini478 – 514LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST37
Domaini518 – 555LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST38
Domaini577 – 811Peptidase S1PROSITE-ProRule annotationAdd BLAST235

Domaini

Cytoplasmic domain mediates HAMP suppression via proximal promoter element(s).1 Publication

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 2 CUB domains.PROSITE-ProRule annotation
Contains 3 LDL-receptor class A domains.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation
Contains 1 SEA domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118962.
HOGENOMiHOG000136851.
HOVERGENiHBG108590.
InParanoidiQ9DBI0.
KOiK09637.
OMAiQGQWIIQ.
OrthoDBiEOG091G0DF7.
PhylomeDBiQ9DBI0.
TreeFamiTF330647.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di2.60.120.290. 1 hit.
3.30.70.960. 1 hit.
4.10.400.10. 3 hits.
InterProiIPR000859. CUB_dom.
IPR002172. LDrepeatLR_classA_rpt.
IPR017118. Pept_S1A_matriptase-2.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR000082. SEA_dom.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00057. Ldl_recept_a. 2 hits.
PF01390. SEA. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF037135. Matriptase-2. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00192. LDLa. 3 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 2 hits.
SSF50494. SSF50494. 1 hit.
SSF57424. SSF57424. 3 hits.
SSF82671. SSF82671. 1 hit.
PROSITEiPS01180. CUB. 1 hit.
PS01209. LDLRA_1. 2 hits.
PS50068. LDLRA_2. 3 hits.
PS50024. SEA. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9DBI0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPRCFQLPCS TRMPTTEVPQ AADGQGDAGD GEEAAEPEGK FKPPKNTKRK
60 70 80 90 100
NRDYVRFTPL LLVLAALVSA GVMLWYFLGY KAEVTVSQVY SGSLRVLNRH
110 120 130 140 150
FSQDLGRRES IAFRSESAKA QKMLQELVAS TRLGTYYNSS SVYSFGEGPL
160 170 180 190 200
TCFFWFILDI PEYQRLTLSP EVVRELLVDE LLSNSSTLAS YKTEYEVDPE
210 220 230 240 250
GLVILEASVN DIVVLNSTLG CYRYSYVNPG QVLPLKGPDQ QTTSCLWHLQ
260 270 280 290 300
GPEDLMIKVR LEWTRVDCRD RVAMYDAAGP LEKRLITSVY GCSRQEPVME
310 320 330 340 350
VLASGSVMAV VWKKGMHSYY DPFLLSVKSV AFQDCQVNLT LEGRLDTQGF
360 370 380 390 400
LRTPYYPSYY SPSTHCSWHL TVPSLDYGLA LWFDAYALRR QKYNRLCTQG
410 420 430 440 450
QWMIQNRRLC GFRTLQPYAE RIPMVASDGV TINFTSQISL TGPGVQVYYS
460 470 480 490 500
LYNQSDPCPG EFLCSVNGLC VPACDGIKDC PNGLDERNCV CRAMFQCQED
510 520 530 540 550
STCISLPRVC DRQPDCLNGS DEEQCQEGVP CGTFTFQCED RSCVKKPNPE
560 570 580 590 600
CDGQSDCRDG SDEQHCDCGL QGLSSRIVGG TVSSEGEWPW QASLQIRGRH
610 620 630 640 650
ICGGALIADR WVITAAHCFQ EDSMASPKLW TVFLGKMRQN SRWPGEVSFK
660 670 680 690 700
VSRLFLHPYH EEDSHDYDVA LLQLDHPVVY SATVRPVCLP ARSHFFEPGQ
710 720 730 740 750
HCWITGWGAQ REGGPVSNTL QKVDVQLVPQ DLCSEAYRYQ VSPRMLCAGY
760 770 780 790 800
RKGKKDACQG DSGGPLVCRE PSGRWFLAGL VSWGLGCGRP NFFGVYTRVT
810
RVINWIQQVL T
Length:811
Mass (Da):90,978
Last modified:October 14, 2008 - v4
Checksum:i32EB3E7C3127801B
GO
Isoform 2 (identifier: Q9DBI0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     567-594: DCGLQGLSSRIVGGTVSSEGEWPWQASL → AWPPRSCGPCSWERCGRTRAGQARCPSR
     595-811: Missing.

Note: No experimental confirmation available.
Show »
Length:594
Mass (Da):66,733
Checksum:i036E77DA7D7DA21D
GO
Isoform 3 (identifier: Q9DBI0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     567-581: DCGLQGLSSRIVGGT → GPLQPYCGRDRVLRG
     582-811: Missing.

Note: No experimental confirmation available.
Show »
Length:581
Mass (Da):65,287
Checksum:iDE658EC33C9B1E03
GO

Sequence cautioni

The sequence AAH57674 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti690P → PP in BAB23684 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035564567 – 594DCGLQ…WQASL → AWPPRSCGPCSWERCGRTRA GQARCPSR in isoform 2. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_035565567 – 581DCGLQ…IVGGT → GPLQPYCGRDRVLRG in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_035566582 – 811Missing in isoform 3. 1 PublicationAdd BLAST230
Alternative sequenceiVSP_035567595 – 811Missing in isoform 2. 1 PublicationAdd BLAST217

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY240929 mRNA. Translation: AAP69827.1.
EU190436 mRNA. Translation: ABW38782.1.
EU190437 mRNA. Translation: ABW38783.1.
AK004939 mRNA. Translation: BAB23684.2.
AL590144 Genomic DNA. No translation available.
BC029645 mRNA. Translation: AAH29645.2.
BC057674 mRNA. Translation: AAH57674.1. Different initiation.
BK000520 Genomic DNA. Translation: DAA00246.1.
CCDSiCCDS37133.1. [Q9DBI0-1]
RefSeqiNP_082178.2. NM_027902.2. [Q9DBI0-1]
XP_006521479.1. XM_006521416.2.
UniGeneiMm.34056.

Genome annotation databases

EnsembliENSMUST00000017086; ENSMUSP00000017086; ENSMUSG00000016942. [Q9DBI0-1]
GeneIDi71753.
KEGGimmu:71753.
UCSCiuc007wpi.1. mouse. [Q9DBI0-1]
uc011zvt.1. mouse. [Q9DBI0-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY240929 mRNA. Translation: AAP69827.1.
EU190436 mRNA. Translation: ABW38782.1.
EU190437 mRNA. Translation: ABW38783.1.
AK004939 mRNA. Translation: BAB23684.2.
AL590144 Genomic DNA. No translation available.
BC029645 mRNA. Translation: AAH29645.2.
BC057674 mRNA. Translation: AAH57674.1. Different initiation.
BK000520 Genomic DNA. Translation: DAA00246.1.
CCDSiCCDS37133.1. [Q9DBI0-1]
RefSeqiNP_082178.2. NM_027902.2. [Q9DBI0-1]
XP_006521479.1. XM_006521416.2.
UniGeneiMm.34056.

3D structure databases

ProteinModelPortaliQ9DBI0.
SMRiQ9DBI0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9DBI0. 1 interactor.
STRINGi10090.ENSMUSP00000017086.

Protein family/group databases

MEROPSiS01.308.

PTM databases

PhosphoSitePlusiQ9DBI0.

Proteomic databases

PaxDbiQ9DBI0.
PeptideAtlasiQ9DBI0.
PRIDEiQ9DBI0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000017086; ENSMUSP00000017086; ENSMUSG00000016942. [Q9DBI0-1]
GeneIDi71753.
KEGGimmu:71753.
UCSCiuc007wpi.1. mouse. [Q9DBI0-1]
uc011zvt.1. mouse. [Q9DBI0-2]

Organism-specific databases

CTDi164656.
MGIiMGI:1919003. Tmprss6.

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118962.
HOGENOMiHOG000136851.
HOVERGENiHBG108590.
InParanoidiQ9DBI0.
KOiK09637.
OMAiQGQWIIQ.
OrthoDBiEOG091G0DF7.
PhylomeDBiQ9DBI0.
TreeFamiTF330647.

Enzyme and pathway databases

BRENDAi3.4.21.109. 3474.
ReactomeiR-MMU-1442490. Collagen degradation.
R-MMU-1474228. Degradation of the extracellular matrix.

Miscellaneous databases

ChiTaRSiTmprss6. mouse.
PROiQ9DBI0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000016942.
CleanExiMM_TMPRSS6.
GenevisibleiQ9DBI0. MM.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di2.60.120.290. 1 hit.
3.30.70.960. 1 hit.
4.10.400.10. 3 hits.
InterProiIPR000859. CUB_dom.
IPR002172. LDrepeatLR_classA_rpt.
IPR017118. Pept_S1A_matriptase-2.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR000082. SEA_dom.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00057. Ldl_recept_a. 2 hits.
PF01390. SEA. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF037135. Matriptase-2. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00192. LDLa. 3 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 2 hits.
SSF50494. SSF50494. 1 hit.
SSF57424. SSF57424. 3 hits.
SSF82671. SSF82671. 1 hit.
PROSITEiPS01180. CUB. 1 hit.
PS01209. LDLRA_1. 2 hits.
PS50068. LDLRA_2. 3 hits.
PS50024. SEA. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTMPS6_MOUSE
AccessioniPrimary (citable) accession number: Q9DBI0
Secondary accession number(s): A8W478
, A8W479, Q3KN88, Q6PF94
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: October 14, 2008
Last modified: November 30, 2016
This is version 144 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.