Q9DBI0 (TMPS6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane protease serine 6
EC=3.4.21.-

Alternative name(s):
Matriptase-2

Gene names

Name:

Tmprss6

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	811 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity. May play a specialized role in matrix remodeling processes in liver. Required to sense iron deficiency. Overexpression suppresses activation of the HAMP promoter. Ref.2
Subunit structure	Interacts with HFE2 By similarity.
Subcellular location	Cell membrane; Single-pass type II membrane protein Ref.1.
Tissue specificity	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. Ref.1
Developmental stage	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. Ref.1
Domain	Cytoplasmic domain mediates HAMP suppression via proximal promoter element(s). Ref.2
Post-translational modification	The sigle-chain zymogen undergoes proteolytic processing that results in shedding from the cell surface and conversion into the activated two-chains form By similarity.
Disruption phenotype	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. Ref.2
Sequence similarities	Belongs to the peptidase S1 family. Contains 2 CUB domains. Contains 3 LDL-receptor class A domains. Contains 1 peptidase S1 domain. Contains 1 SEA domain.
Sequence caution	The sequence AAH57674.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fibrinolysis Inferred from sequence or structural similarity. Source: UniProtKB iron ion homeostasis Inferred from electronic annotation. Source: Compara proteolysis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	integral to membrane Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from direct assay Ref.1. Source: MGI
Molecular_function	serine-type endopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9DBI0-1)

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.

Isoform 2 (identifier: Q9DBI0-2)

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

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9DBI0-3)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 811	811	Transmembrane protease serine 6		PRO_0000088697
Regions
	Topological domain	1 – 59	59	Cytoplasmic Potential
	Transmembrane	60 – 80	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	81 – 811	731	Extracellular Potential
	Domain	85 – 186	102	SEA
	Domain	213 – 336	124	CUB 1
	Domain	323 – 440	118	CUB 2
	Domain	445 – 477	33	LDL-receptor class A 1
	Domain	478 – 514	37	LDL-receptor class A 2
	Domain	518 – 555	38	LDL-receptor class A 3
	Domain	577 – 811	235	Peptidase S1
Sites
	Active site	617	1	Charge relay system By similarity
	Active site	668	1	Charge relay system By similarity
	Active site	762	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	138	1	N-linked (GlcNAc...) Potential
	Glycosylation	184	1	N-linked (GlcNAc...) Potential
	Glycosylation	216	1	N-linked (GlcNAc...) Potential
	Glycosylation	338	1	N-linked (GlcNAc...) Potential
	Glycosylation	433	1	N-linked (GlcNAc...) Potential
	Glycosylation	453	1	N-linked (GlcNAc...) Potential
	Glycosylation	518	1	N-linked (GlcNAc...) Potential
	Disulfide bond	335 ↔ 366		By similarity
	Disulfide bond	458 ↔ 470		By similarity
	Disulfide bond	464 ↔ 480		By similarity
	Disulfide bond	474 ↔ 489		By similarity
	Disulfide bond	491 ↔ 503		By similarity
	Disulfide bond	497 ↔ 516		By similarity
	Disulfide bond	510 ↔ 525		By similarity
	Disulfide bond	531 ↔ 543		By similarity
	Disulfide bond	538 ↔ 557		By similarity
	Disulfide bond	551 ↔ 566		By similarity
	Disulfide bond	602 ↔ 618		By similarity
	Disulfide bond	702 ↔ 768		By similarity
	Disulfide bond	733 ↔ 747		By similarity
	Disulfide bond	758 ↔ 787		By similarity
Natural variations
	Alternative sequence	567 – 594	28	DCGLQ…WQASL → AWPPRSCGPCSWERCGRTRA GQARCPSR in isoform 2.		VSP_035564
	Alternative sequence	567 – 581	15	DCGLQ…IVGGT → GPLQPYCGRDRVLRG in isoform 3.		VSP_035565
	Alternative sequence	582 – 811	230	Missing in isoform 3.		VSP_035566
	Alternative sequence	595 – 811	217	Missing in isoform 2.		VSP_035567
Experimental info
	Mutagenesis	762	1	S → A: Protease-dead. Ref.2
	Sequence conflict	690	1	P → PP in BAB23684. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 14, 2008. Version 4. Checksum: 32EB3E7C3127801B	FASTA	811	90,978
	10 20 30 40 50 60 MPRCFQLPCS TRMPTTEVPQ AADGQGDAGD GEEAAEPEGK FKPPKNTKRK NRDYVRFTPL 70 80 90 100 110 120 LLVLAALVSA GVMLWYFLGY KAEVTVSQVY SGSLRVLNRH FSQDLGRRES IAFRSESAKA 130 140 150 160 170 180 QKMLQELVAS TRLGTYYNSS SVYSFGEGPL TCFFWFILDI PEYQRLTLSP EVVRELLVDE 190 200 210 220 230 240 LLSNSSTLAS YKTEYEVDPE GLVILEASVN DIVVLNSTLG CYRYSYVNPG QVLPLKGPDQ 250 260 270 280 290 300 QTTSCLWHLQ GPEDLMIKVR LEWTRVDCRD RVAMYDAAGP LEKRLITSVY GCSRQEPVME 310 320 330 340 350 360 VLASGSVMAV VWKKGMHSYY DPFLLSVKSV AFQDCQVNLT LEGRLDTQGF LRTPYYPSYY 370 380 390 400 410 420 SPSTHCSWHL TVPSLDYGLA LWFDAYALRR QKYNRLCTQG QWMIQNRRLC GFRTLQPYAE 430 440 450 460 470 480 RIPMVASDGV TINFTSQISL TGPGVQVYYS LYNQSDPCPG EFLCSVNGLC VPACDGIKDC 490 500 510 520 530 540 PNGLDERNCV CRAMFQCQED STCISLPRVC DRQPDCLNGS DEEQCQEGVP CGTFTFQCED 550 560 570 580 590 600 RSCVKKPNPE CDGQSDCRDG SDEQHCDCGL QGLSSRIVGG TVSSEGEWPW QASLQIRGRH 610 620 630 640 650 660 ICGGALIADR WVITAAHCFQ EDSMASPKLW TVFLGKMRQN SRWPGEVSFK VSRLFLHPYH 670 680 690 700 710 720 EEDSHDYDVA LLQLDHPVVY SATVRPVCLP ARSHFFEPGQ HCWITGWGAQ REGGPVSNTL 730 740 750 760 770 780 QKVDVQLVPQ DLCSEAYRYQ VSPRMLCAGY RKGKKDACQG DSGGPLVCRE PSGRWFLAGL 790 800 810 VSWGLGCGRP NFFGVYTRVT RVINWIQQVL T
	Isoform 2 [UniParc]. Checksum: 036E77DA7D7DA21D	FASTA	594	66,733
	10 20 30 40 50 60 MPRCFQLPCS TRMPTTEVPQ AADGQGDAGD GEEAAEPEGK FKPPKNTKRK NRDYVRFTPL 70 80 90 100 110 120 LLVLAALVSA GVMLWYFLGY KAEVTVSQVY SGSLRVLNRH FSQDLGRRES IAFRSESAKA 130 140 150 160 170 180 QKMLQELVAS TRLGTYYNSS SVYSFGEGPL TCFFWFILDI PEYQRLTLSP EVVRELLVDE 190 200 210 220 230 240 LLSNSSTLAS YKTEYEVDPE GLVILEASVN DIVVLNSTLG CYRYSYVNPG QVLPLKGPDQ 250 260 270 280 290 300 QTTSCLWHLQ GPEDLMIKVR LEWTRVDCRD RVAMYDAAGP LEKRLITSVY GCSRQEPVME 310 320 330 340 350 360 VLASGSVMAV VWKKGMHSYY DPFLLSVKSV AFQDCQVNLT LEGRLDTQGF LRTPYYPSYY 370 380 390 400 410 420 SPSTHCSWHL TVPSLDYGLA LWFDAYALRR QKYNRLCTQG QWMIQNRRLC GFRTLQPYAE 430 440 450 460 470 480 RIPMVASDGV TINFTSQISL TGPGVQVYYS LYNQSDPCPG EFLCSVNGLC VPACDGIKDC 490 500 510 520 530 540 PNGLDERNCV CRAMFQCQED STCISLPRVC DRQPDCLNGS DEEQCQEGVP CGTFTFQCED 550 560 570 580 590 RSCVKKPNPE CDGQSDCRDG SDEQHCAWPP RSCGPCSWER CGRTRAGQAR CPSR
	Isoform 3 [UniParc]. Checksum: DE658EC33C9B1E03	FASTA	581	65,287
	10 20 30 40 50 60 MPRCFQLPCS TRMPTTEVPQ AADGQGDAGD GEEAAEPEGK FKPPKNTKRK NRDYVRFTPL 70 80 90 100 110 120 LLVLAALVSA GVMLWYFLGY KAEVTVSQVY SGSLRVLNRH FSQDLGRRES IAFRSESAKA 130 140 150 160 170 180 QKMLQELVAS TRLGTYYNSS SVYSFGEGPL TCFFWFILDI PEYQRLTLSP EVVRELLVDE 190 200 210 220 230 240 LLSNSSTLAS YKTEYEVDPE GLVILEASVN DIVVLNSTLG CYRYSYVNPG QVLPLKGPDQ 250 260 270 280 290 300 QTTSCLWHLQ GPEDLMIKVR LEWTRVDCRD RVAMYDAAGP LEKRLITSVY GCSRQEPVME 310 320 330 340 350 360 VLASGSVMAV VWKKGMHSYY DPFLLSVKSV AFQDCQVNLT LEGRLDTQGF LRTPYYPSYY 370 380 390 400 410 420 SPSTHCSWHL TVPSLDYGLA LWFDAYALRR QKYNRLCTQG QWMIQNRRLC GFRTLQPYAE 430 440 450 460 470 480 RIPMVASDGV TINFTSQISL TGPGVQVYYS LYNQSDPCPG EFLCSVNGLC VPACDGIKDC 490 500 510 520 530 540 PNGLDERNCV CRAMFQCQED STCISLPRVC DRQPDCLNGS DEEQCQEGVP CGTFTFQCED 550 560 570 580 RSCVKKPNPE CDGQSDCRDG SDEQHCGPLQ PYCGRDRVLR G

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse matriptase-2: identification, characterization and comparative mRNA expression analysis with mouse hepsin in adult and embryonic tissues." Hooper J.D., Campagnolo L., Goodarzi G., Truong T.N., Stuhlmann H., Quigley J.P. Biochem. J. 373:689-702(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Strain: C57BL/6J. Tissue: Liver.
[2]	"The serine protease TMPRSS6 is required to sense iron deficiency." Du X., She E., Gelbart T., Truksa J., Lee P., Xia Y., Khovananth K., Mudd S., Mann N., Moresco E.M.Y., Beutler E., Beutler B. Science 320:1088-1092(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, DOMAIN, MUTAGENESIS OF SER-762, DISRUPTION PHENOTYPE. Tissue: Liver.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Liver.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N. Tissue: Liver.
[6]	"Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer." Netzel-Arnett S., Hooper J.D., Szabo R., Madison E.L., Quigley J.P., Bugge T.H., Antalis T.M. Cancer Metastasis Rev. 22:237-258(2003) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[7]	"The type II transmembrane serine protease matriptase-2 --identification, structural features, enzymology, expression pattern and potential roles." Ramsay A.J., Reid J.C., Velasco G., Quigley J.P., Hooper J.D. Front. Biosci. 13:569-579(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00173181. IPI00914115. IPI00914127.
RefSeq	NP_082178.2. NM_027902.2.
UniGene	Mm.34056.
3D structure databases
ProteinModelPortal	Q9DBI0.
SMR	Q9DBI0. Positions 460-810.
ModBase	Search...
Proteomic databases
PaxDb	Q9DBI0.
PRIDE	Q9DBI0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000017086; ENSMUSP00000017086; ENSMUSG00000016942.
GeneID	71753.
KEGG	mmu:71753.
UCSC	uc007wpi.1. mouse. uc011zvt.1. mouse.
Organism-specific databases
CTD	164656.
MGI	MGI:1919003. Tmprss6.
Phylogenomic databases
eggNOG	COG5640.
GeneTree	ENSGT00700000104118.
HOGENOM	HOG000136851.
HOVERGEN	HBG108590.
InParanoid	Q9DBI0.
KO	K09637.
OMA	YSPSTHC.
OrthoDB	EOG4W6NVJ.
Gene expression databases
Bgee	Q9DBI0.
CleanEx	MM_TMPRSS6.
Genevestigator	Q9DBI0.
GermOnline	ENSMUSG00000016942. Mus musculus.
Family and domain databases
Gene3D	2.60.120.290. 1 hit. 4.10.400.10. 3 hits.
InterPro	IPR000859. CUB_dom. IPR002172. LDrepeatLR_classA_rpt. IPR017118. Pept_S1A_matriptase-2. IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR000082. SEA. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00057. Ldl_recept_a. 2 hits. PF01390. SEA. 1 hit. PF00089. Trypsin. 1 hit. [Graphical view]
PIRSF	PIRSF037135. Matriptase-2. 1 hit.
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00042. CUB. 1 hit. SM00192. LDLa. 3 hits. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF49854. CUB. 2 hits. SSF57424. LDL_rcpt_classA_cys-rich. 2 hits. SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS01180. CUB. 1 hit. PS01209. LDLRA_1. 2 hits. PS50068. LDLRA_2. 3 hits. PS50024. SEA. False negative. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TMPRSS6. mouse.
NextBio	334409.
SOURCE	Search...

Entry information

Entry name

TMPS6_MOUSE

Accession

Primary (citable) accession number: Q9DBI0
Secondary accession number(s): A8W478 , A8W479, Q3KN88, Q6PF94

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	October 14, 2008
Last modified:	May 1, 2013
This is version 111 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program