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Q8IU80 (TMPS6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transmembrane protease serine 6

EC=3.4.21.-
Alternative name(s):
Matriptase-2
Gene names
Name:TMPRSS6
ORF Names:UNQ354/PRO618
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length811 AA.
Sequence statusComplete.
Protein existenceEvidence 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. 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. Ref.1 Ref.15

Subunit structure

Interacts with HFE2. Ref.10 Ref.13

Subcellular location

Cell membrane; Single-pass type II membrane protein Ref.1 Ref.12.

Tissue specificity

Liver specific. Ref.1

Domain

Cytoplasmic domain mediates HAMP suppression via proximal promoter element(s) By similarity.

Post-translational modification

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

Involvement in disease

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.
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 (Ref.19). Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.16 Ref.17 Ref.19 Ref.21 Ref.22

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.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IU80-4)

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: Q8IU80-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.
Isoform 3 (identifier: Q8IU80-2)

The sequence of this isoform differs from the canonical sequence as follows:
     409-461: LCGLRILQPY...YNQSDPCPGE → YHFLSSLWLP...GWGWCQACCP
     462-811: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q8IU80-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.
     714-714: G → ALRADAVALFYGWRNQGSETCCC
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 811811Transmembrane protease serine 6
PRO_0000088696

Regions

Topological domain1 – 5555Cytoplasmic Potential
Transmembrane56 – 7621Helical; Signal-anchor for type II membrane protein; Potential
Topological domain77 – 811735Extracellular Potential
Domain84 – 209126SEA
Domain213 – 336124CUB 1
Domain335 – 452118CUB 2
Domain457 – 48933LDL-receptor class A 1
Domain490 – 52637LDL-receptor class A 2
Domain530 – 56738LDL-receptor class A 3
Domain577 – 811235Peptidase S1

Sites

Active site6171Charge relay system By similarity
Active site6681Charge relay system By similarity
Active site7621Charge relay system By similarity

Amino acid modifications

Glycosylation1361N-linked (GlcNAc...) Potential
Glycosylation1841N-linked (GlcNAc...) Potential
Glycosylation2161N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) Potential
Glycosylation4331N-linked (GlcNAc...) Potential
Glycosylation4531N-linked (GlcNAc...) Potential
Glycosylation5181N-linked (GlcNAc...) Potential
Disulfide bond335 ↔ 366 By similarity
Disulfide bond458 ↔ 470 By similarity
Disulfide bond464 ↔ 480 By similarity
Disulfide bond474 ↔ 489 By similarity
Disulfide bond491 ↔ 503 By similarity
Disulfide bond497 ↔ 516 By similarity
Disulfide bond510 ↔ 525 By similarity
Disulfide bond531 ↔ 543 By similarity
Disulfide bond538 ↔ 557 By similarity
Disulfide bond551 ↔ 566 By similarity
Disulfide bond602 ↔ 618 By similarity
Disulfide bond702 ↔ 768 By similarity
Disulfide bond733 ↔ 747 By similarity
Disulfide bond758 ↔ 787 By similarity

Natural variations

Alternative sequence1 – 99Missing in isoform 2 and isoform 4.
VSP_035562
Alternative sequence409 – 46153LCGLR…PCPGE → YHFLSSLWLPFLPPPPSLPS STVTPSLEAQVPNLRGAARG ASRGWGWCQACCP in isoform 3.
VSP_008379
Alternative sequence462 – 811350Missing in isoform 3.
VSP_008380
Alternative sequence7141G → ALRADAVALFYGWRNQGSET CCC in isoform 4.
VSP_035563
Natural variant1141E → K in IRIDA; does not undergo proteolytic processing; loss of activity. Ref.21
VAR_068665
Natural variant1181A → D in IRIDA; results in reduced inhibition of HAMP promoter. Ref.17
VAR_068666
Natural variant1411Y → C in IRIDA; does not undergo proteolytic processing; able to interact with HFE2; results in reduced inhibition of HAMP promoter. Ref.13 Ref.19
VAR_064075
Natural variant2121I → T in IRIDA; results in reduced inhibition of HAMP promoter. Ref.19
VAR_064076
Natural variant2231R → H in a breast cancer sample; somatic mutation. Ref.14
VAR_036296
Natural variant2281G → D. Ref.18
VAR_068667
Natural variant2341R → S in a breast cancer sample; somatic mutation. Ref.14
VAR_036297
Natural variant2351L → P in IRIDA; does not undergo proteolytic processing; loss of activity. Ref.21
VAR_068668
Natural variant2531K → E. Ref.18 Ref.20
Corresponds to variant rs2235324 [ dbSNP | Ensembl ].
VAR_051841
Natural variant2621E → K.
Corresponds to variant rs2235324 [ dbSNP | Ensembl ].
VAR_044434
Natural variant2711R → Q in IRIDA; does not affect activity. Ref.19
VAR_064077
Natural variant2881S → L.
Corresponds to variant rs5995378 [ dbSNP | Ensembl ].
VAR_051842
Natural variant3041S → L in IRIDA. Ref.16 Ref.19
VAR_064078
Natural variant4181Y → C in IRIDA; does not undergo proteolytic processing; loss of activity. Ref.21
VAR_068669
Natural variant4421G → R in IRIDA; normally targeted to the cell membrane; reduced proteolytic processing; able to interact with HFE2; results in reduced inhibition of HAMP promoter. Ref.10 Ref.15
VAR_044435
Natural variant4461R → W. Ref.18
Corresponds to variant rs117576908 [ dbSNP | Ensembl ].
VAR_068670
Natural variant5101C → S in IRIDA. Ref.19
VAR_064079
Natural variant5211D → N in IRIDA; reduced expression at the cell surface; partially retained in the Golgi apparatus; does not undergo proteolytic processing; able to interact with HFE2; results in reduced inhibition of HAMP promoter. Ref.10 Ref.15
Corresponds to variant rs137853120 [ dbSNP | Ensembl ].
VAR_044436
Natural variant5221E → K in IRIDA; reduced expression at the cell surface; partially retained in the Golgi apparatus; does not undergo proteolytic processing; able to interact with HFE2; results in reduced inhibition of HAMP promoter. Ref.10
VAR_068671
Natural variant6031G → R in IRIDA. Ref.22
VAR_068672
Natural variant6741L → F. Ref.18
VAR_068673
Natural variant7361V → A. Ref.3 Ref.18
Corresponds to variant rs855791 [ dbSNP | Ensembl ].
VAR_051843
Natural variant7631G → D.
Corresponds to variant rs11703011 [ dbSNP | Ensembl ].
VAR_051844
Natural variant7651P → A in IRIDA; severely reduced proteolytic processing; loss of activity. Ref.21
VAR_068674
Natural variant7741R → C in IRIDA. Ref.15
VAR_044437
Natural variant7951V → I. Ref.18
Corresponds to variant rs139105452 [ dbSNP | Ensembl ].
VAR_068675

Experimental info

Mutagenesis5761R → A: Does not undergo proteolytic processing. Ref.21
Mutagenesis7621S → A: Does not undergo proteolytic processing. Ref.12 Ref.21
Sequence conflict1161A → V in CAC85953. Ref.1
Isoform 3:
Sequence conflict4301T → I in CAQ07364. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 14, 2008. Version 3.
Checksum: 7EEF193F655DDE9D

FASTA81190,000
        10         20         30         40         50         60 
MLLLFHSKRM PVAEAPQVAG GQGDGGDGEE AEPEGMFKAC EDSKRKARGY LRLVPLFVLL 

        70         80         90        100        110        120 
ALLVLASAGV LLWYFLGYKA EVMVSQVYSG SLRVLNRHFS QDLTRRESSA FRSETAKAQK 

       130        140        150        160        170        180 
MLKELITSTR LGTYYNSSSV YSFGEGPLTC FFWFILQIPE HRRLMLSPEV VQALLVEELL 

       190        200        210        220        230        240 
STVNSSAAVP YRAEYEVDPE GLVILEASVK DIAALNSTLG CYRYSYVGQG QVLRLKGPDH 

       250        260        270        280        290        300 
LASSCLWHLQ GPKDLMLKLR LEWTLAECRD RLAMYDVAGP LEKRLITSVY GCSRQEPVVE 

       310        320        330        340        350        360 
VLASGAIMAV VWKKGLHSYY DPFVLSVQPV VFQACEVNLT LDNRLDSQGV LSTPYFPSYY 

       370        380        390        400        410        420 
SPQTHCSWHL TVPSLDYGLA LWFDAYALRR QKYDLPCTQG QWTIQNRRLC GLRILQPYAE 

       430        440        450        460        470        480 
RIPVVATAGI TINFTSQISL TGPGVRVHYG LYNQSDPCPG EFLCSVNGLC VPACDGVKDC 

       490        500        510        520        530        540 
PNGLDERNCV CRATFQCKED STCISLPKVC DGQPDCLNGS DEEQCQEGVP CGTFTFQCED 

       550        560        570        580        590        600 
RSCVKKPNPQ CDGRPDCRDG SDEEHCDCGL QGPSSRIVGG AVSSEGEWPW QASLQVRGRH 

       610        620        630        640        650        660 
ICGGALIADR WVITAAHCFQ EDSMASTVLW TVFLGKVWQN SRWPGEVSFK VSRLLLHPYH 

       670        680        690        700        710        720 
EEDSHDYDVA LLQLDHPVVR SAAVRPVCLP ARSHFFEPGL HCWITGWGAL REGGPISNAL 

       730        740        750        760        770        780 
QKVDVQLIPQ DLCSEVYRYQ VTPRMLCAGY RKGKKDACQG DSGGPLVCKA LSGRWFLAGL 

       790        800        810 
VSWGLGCGRP NYFGVYTRIT GVISWIQQVV T 

« Hide

Isoform 2 [UniParc].

Checksum: 5076C9098789F3FA
Show »

FASTA80288,874
Isoform 3 [UniParc].

Checksum: 4344F1E7B4F273A8
Show »

FASTA46151,602
Isoform 4 [UniParc].

Checksum: A74F186406041F7B
Show »

FASTA82491,333

References

« Hide 'large scale' references
[1]"Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins."
Velasco G., Cal S., Quesada V., Sanchez L.M., Lopez-Otin C.
J. Biol. Chem. 277:37637-37646(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Fetal liver.
[2]"TMPRSS6, a new type II transmembrane serine protease."
Hooper J.D., Quigley J.P.
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ALA-736.
[4]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[5]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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 3).
Tissue: Brain.
[7]"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.
[8]"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.
[9]"A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron."
Melis M.A., Cau M., Congiu R., Sole G., Barella S., Cao A., Westerman M., Cazzola M., Galanello R.
Haematologica 93:1473-1479(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IRIDA.
[10]"Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia."
Silvestri L., Guillem F., Pagani A., Nai A., Oudin C., Silva M., Toutain F., Kannengiesser C., Beaumont C., Camaschella C., Grandchamp B.
Blood 113:5605-5608(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HFE2, VARIANTS IRIDA ASN-521 AND LYS-522, CHARACTERIZATION OF VARIANTS IRIDA ARG-442; ASN-521 AND LYS-522.
[11]"A novel splice site mutation c.2278 (-1) G>C in the TMPRSS6 gene causes deletion of the substrate binding site of the serine protease resulting in refractory iron deficiency anaemia."
Edison E.S., Athiyarath R., Rajasekar T., Westerman M., Srivastava A., Chandy M.
Br. J. Haematol. 147:766-769(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IRIDA.
[12]"Proteolytic processing of the serine protease matriptase-2: identification of the cleavage sites required for its autocatalytic release from the cell surface."
Stirnberg M., Maurer E., Horstmeyer A., Kolp S., Frank S., Bald T., Arenz K., Janzer A., Prager K., Wunderlich P., Walter J., Gutschow M.
Biochem. J. 430:87-95(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-762.
[13]"A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA."
Altamura S., D'Alessio F., Selle B., Muckenthaler M.U.
Biochem. J. 431:363-371(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HFE2, VARIANT IRIDA CYS-141, CHARACTERIZATION OF VARIANT IRIDA CYS-141.
[14]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-223 AND SER-234.
[15]"Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)."
Finberg K.E., Heeney M.M., Campagna D.R., Aydinok Y., Pearson H.A., Hartman K.R., Mayo M.M., Samuel S.M., Strouse J.J., Markianos K., Andrews N.C., Fleming M.D.
Nat. Genet. 40:569-571(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IRIDA ARG-442; ASN-521 AND CYS-774, FUNCTION IN IRON HOMEOSTASIS.
[16]"Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemia."
Tchou I., Diepold M., Pilotto P.A., Swinkels D., Neerman-Arbez M., Beris P.
Eur. J. Haematol. 83:595-602(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IRIDA LEU-304.
[17]"Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms."
Ramsay A.J., Quesada V., Sanchez M., Garabaya C., Sarda M.P., Baiget M., Remacha A., Velasco G., Lopez-Otin C.
Hum. Mol. Genet. 18:3673-3683(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IRIDA ASP-118, CHARACTERIZATION OF VARIANT IRIDA ASP-118.
[18]"Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia."
Beutler E., Van Geet C., te Loo D.M., Gelbart T., Crain K., Truksa J., Lee P.L.
Blood Cells Mol. Dis. 44:16-21(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASP-228; GLU-253; TRP-446; PHE-674; ALA-736 AND ILE-795.
[19]"Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA)."
De Falco L., Totaro F., Nai A., Pagani A., Girelli D., Silvestri L., Piscopo C., Campostrini N., Dufour C., Al Manjomi F., Minkov M., Van Vuurden D.G., Feliu A., Kattamis A., Camaschella C., Iolascon A.
Hum. Mutat. 31:E1390-E1405(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IRIDA CYS-141; THR-212; GLN-271; LEU-304 AND SER-510, CHARACTERIZATION OF VARIANTS IRIDA THR-212 AND GLN-271.
[20]"Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia."
Sato T., Iyama S., Murase K., Kamihara Y., Ono K., Kikuchi S., Takada K., Miyanishi K., Sato Y., Takimoto R., Kobune M., Kato J.
Int. J. Hematol. 94:101-103(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLU-253.
[21]"Inactive matriptase-2 mutants found in IRIDA patients still repress hepcidin in a transfection assay despite having lost their serine protease activity."
Guillem F., Kannengiesser C., Oudin C., Lenoir A., Matak P., Donadieu J., Isidor B., Mechinaud F., Aguilar-Martinez P., Beaumont C., Vaulont S., Grandchamp B., Nicolas G.
Hum. Mutat. 33:1388-1396(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IRIDA LYS-114; PRO-235; CYS-418 AND ALA-765, MUTAGENESIS OF ARG-576 AND SER-762, CHARACTERIZATION OF VARIANTS IRIDA LYS-114; PRO-235; CYS-418 AND ALA-765.
[22]"A novel mutation Gly603Arg of TMPRSS6 in a Korean female with iron-refractory iron deficiency anemia."
Choi H.S., Yang H.R., Song S.H., Seo J.Y., Lee K.O., Kim H.J.
Pediatr. Blood Cancer 58:640-642(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IRIDA ARG-603.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ319876 mRNA. Translation: CAC85953.1.
AY055383 Genomic DNA. Translation: AAL16413.1.
AY055384 mRNA. Translation: AAL16414.1.
AY358398 mRNA. Translation: AAQ88764.1.
CR456446 mRNA. Translation: CAG30332.1.
AL022314 Genomic DNA. Translation: CAQ07360.1.
AL022314 Genomic DNA. Translation: CAQ07361.1.
AL022314 Genomic DNA. Translation: CAQ07363.1.
AL022314 Genomic DNA. Translation: CAQ07364.1.
BC039082 mRNA. Translation: AAH39082.1.
CCDSCCDS13941.1. [Q8IU80-4]
RefSeqNP_001275929.1. NM_001289000.1. [Q8IU80-5]
NP_001275930.1. NM_001289001.1. [Q8IU80-1]
NP_705837.1. NM_153609.3. [Q8IU80-4]
XP_006724225.1. XM_006724162.1. [Q8IU80-1]
XP_006724226.1. XM_006724163.1. [Q8IU80-1]
UniGeneHs.370885.

3D structure databases

ProteinModelPortalQ8IU80.
SMRQ8IU80. Positions 460-810.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ8IU80.
ChEMBLCHEMBL1795139.

Protein family/group databases

MEROPSS01.308.

Polymorphism databases

DMDM209572718.

Proteomic databases

PaxDbQ8IU80.
PRIDEQ8IU80.

Protocols and materials databases

DNASU164656.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000346753; ENSP00000334962; ENSG00000187045. [Q8IU80-4]
ENST00000381792; ENSP00000371211; ENSG00000187045. [Q8IU80-5]
ENST00000406725; ENSP00000385453; ENSG00000187045. [Q8IU80-1]
ENST00000406856; ENSP00000384964; ENSG00000187045. [Q8IU80-5]
GeneID164656.
KEGGhsa:164656.
UCSCuc003aqs.1. human. [Q8IU80-4]
uc003aqt.1. human. [Q8IU80-5]
uc003aqu.3. human. [Q8IU80-2]

Organism-specific databases

CTD164656.
GeneCardsGC22M037461.
H-InvDBHIX0138751.
HGNCHGNC:16517. TMPRSS6.
MIM206200. phenotype.
609862. gene.
neXtProtNX_Q8IU80.
Orphanet209981. IRIDA syndrome.
PharmGKBPA134880399.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOVERGENHBG108590.
KOK09637.
OMAWTVFLGK.
OrthoDBEOG75B84T.
PhylomeDBQ8IU80.
TreeFamTF330647.

Gene expression databases

ArrayExpressQ8IU80.
BgeeQ8IU80.
GenevestigatorQ8IU80.

Family and domain databases

Gene3D2.60.120.290. 1 hit.
3.30.70.960. 1 hit.
4.10.400.10. 3 hits.
InterProIPR000859. CUB_dom.
IPR002172. LDrepeatLR_classA_rpt.
IPR017118. Pept_S1A_matriptase-2.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR000082. SEA_dom.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00057. Ldl_recept_a. 2 hits.
PF01390. SEA. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF037135. Matriptase-2. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00042. CUB. 1 hit.
SM00192. LDLa. 3 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF49854. SSF49854. 2 hits.
SSF50494. SSF50494. 1 hit.
SSF57424. SSF57424. 3 hits.
SSF82671. SSF82671. 1 hit.
PROSITEPS01180. 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]
ProtoNetSearch...

Other

GeneWikiTMPRSS6.
GenomeRNAi164656.
NextBio88478.
PROQ8IU80.
SOURCESearch...

Entry information

Entry nameTMPS6_HUMAN
AccessionPrimary (citable) accession number: Q8IU80
Secondary accession number(s): B0QYB4 expand/collapse secondary AC list , B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IUE2, Q8IXV8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: October 14, 2008
Last modified: July 9, 2014
This is version 116 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM