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Q8IU80

- TMPS6_HUMAN

UniProt

Q8IU80 - TMPS6_HUMAN

Protein

Transmembrane protease serine 6

Gene

TMPRSS6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 3 (14 Oct 2008)
      Previous versions | rss
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    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. 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.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei617 – 6171Charge relay systemBy similarity
    Active sitei668 – 6681Charge relay systemBy similarity
    Active sitei762 – 7621Charge relay systemBy similarity

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. serine-type endopeptidase activity Source: UniProtKB

    GO - Biological processi

    1. angiogenesis Source: UniProtKB
    2. extracellular matrix organization Source: UniProtKB
    3. fibrinolysis Source: UniProtKB
    4. intracellular signal transduction Source: UniProtKB
    5. iron ion homeostasis Source: UniProtKB
    6. proteolysis Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    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
    ORF Names:UNQ354/PRO618
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 22

    Organism-specific databases

    HGNCiHGNC:16517. TMPRSS6.

    Subcellular locationi

    Cell membrane 2 Publications; Single-pass type II membrane protein 2 Publications

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB
    2. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.10 Publications
    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).1 Publication
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti114 – 1141E → K in IRIDA; does not undergo proteolytic processing; loss of activity. 1 Publication
    VAR_068665
    Natural varianti118 – 1181A → D in IRIDA; results in reduced inhibition of HAMP promoter. 1 Publication
    VAR_068666
    Natural varianti141 – 1411Y → C in IRIDA; does not undergo proteolytic processing; able to interact with HFE2; results in reduced inhibition of HAMP promoter. 2 Publications
    VAR_064075
    Natural varianti212 – 2121I → T in IRIDA; results in reduced inhibition of HAMP promoter. 1 Publication
    VAR_064076
    Natural varianti235 – 2351L → P in IRIDA; does not undergo proteolytic processing; loss of activity. 1 Publication
    VAR_068668
    Natural varianti271 – 2711R → Q in IRIDA; does not affect activity. 1 Publication
    VAR_064077
    Natural varianti304 – 3041S → L in IRIDA. 2 Publications
    VAR_064078
    Natural varianti418 – 4181Y → C in IRIDA; does not undergo proteolytic processing; loss of activity. 1 Publication
    VAR_068669
    Natural varianti442 – 4421G → R in IRIDA; normally targeted to the cell membrane; reduced proteolytic processing; able to interact with HFE2; results in reduced inhibition of HAMP promoter. 1 Publication
    VAR_044435
    Natural varianti510 – 5101C → S in IRIDA. 1 Publication
    VAR_064079
    Natural varianti521 – 5211D → 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. 2 Publications
    Corresponds to variant rs137853120 [ dbSNP | Ensembl ].
    VAR_044436
    Natural varianti522 – 5221E → 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. 1 Publication
    VAR_068671
    Natural varianti603 – 6031G → R in IRIDA. 1 Publication
    VAR_068672
    Natural varianti765 – 7651P → A in IRIDA; severely reduced proteolytic processing; loss of activity. 1 Publication
    VAR_068674
    Natural varianti774 – 7741R → C in IRIDA. 1 Publication
    VAR_044437

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi576 – 5761R → A: Does not undergo proteolytic processing. 1 Publication
    Mutagenesisi762 – 7621S → A: Does not undergo proteolytic processing. 2 Publications

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi206200. phenotype.
    Orphaneti209981. IRIDA syndrome.
    PharmGKBiPA134880399.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 811811Transmembrane protease serine 6PRO_0000088696Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi136 – 1361N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi184 – 1841N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi216 – 2161N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi335 ↔ 366By similarity
    Glycosylationi338 – 3381N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi433 – 4331N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi453 – 4531N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi458 ↔ 470By similarity
    Disulfide bondi464 ↔ 480By similarity
    Disulfide bondi474 ↔ 489By similarity
    Disulfide bondi491 ↔ 503By similarity
    Disulfide bondi497 ↔ 516By similarity
    Disulfide bondi510 ↔ 525By similarity
    Glycosylationi518 – 5181N-linked (GlcNAc...)Sequence Analysis
    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 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.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PaxDbiQ8IU80.
    PRIDEiQ8IU80.

    Expressioni

    Tissue specificityi

    Liver specific.1 Publication

    Gene expression databases

    ArrayExpressiQ8IU80.
    BgeeiQ8IU80.
    GenevestigatoriQ8IU80.

    Interactioni

    Subunit structurei

    Interacts with HFE2.2 Publications

    Structurei

    3D structure databases

    ProteinModelPortaliQ8IU80.
    SMRiQ8IU80. Positions 460-810.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 5555CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini77 – 811735ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei56 – 7621Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini84 – 209126SEAPROSITE-ProRule annotationAdd
    BLAST
    Domaini213 – 336124CUB 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini335 – 452118CUB 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini457 – 48933LDL-receptor class A 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini490 – 52637LDL-receptor class A 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini530 – 56738LDL-receptor class A 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini577 – 811235Peptidase S1PROSITE-ProRule annotationAdd
    BLAST

    Domaini

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

    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

    eggNOGiCOG5640.
    HOVERGENiHBG108590.
    KOiK09637.
    OMAiWTVFLGK.
    OrthoDBiEOG75B84T.
    PhylomeDBiQ8IU80.
    TreeFamiTF330647.

    Family and domain databases

    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.
    IPR001254. Peptidase_S1.
    IPR018114. Peptidase_S1_AS.
    IPR001314. Peptidase_S1A.
    IPR000082. SEA_dom.
    IPR009003. Trypsin-like_Pept_dom.
    [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.
    SMARTiSM00042. CUB. 1 hit.
    SM00192. 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 (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8IU80-4) [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

    MLLLFHSKRM PVAEAPQVAG GQGDGGDGEE AEPEGMFKAC EDSKRKARGY    50
    LRLVPLFVLL ALLVLASAGV LLWYFLGYKA EVMVSQVYSG SLRVLNRHFS 100
    QDLTRRESSA FRSETAKAQK MLKELITSTR LGTYYNSSSV YSFGEGPLTC 150
    FFWFILQIPE HRRLMLSPEV VQALLVEELL STVNSSAAVP YRAEYEVDPE 200
    GLVILEASVK DIAALNSTLG CYRYSYVGQG QVLRLKGPDH LASSCLWHLQ 250
    GPKDLMLKLR LEWTLAECRD RLAMYDVAGP LEKRLITSVY GCSRQEPVVE 300
    VLASGAIMAV VWKKGLHSYY DPFVLSVQPV VFQACEVNLT LDNRLDSQGV 350
    LSTPYFPSYY SPQTHCSWHL TVPSLDYGLA LWFDAYALRR QKYDLPCTQG 400
    QWTIQNRRLC GLRILQPYAE RIPVVATAGI TINFTSQISL TGPGVRVHYG 450
    LYNQSDPCPG EFLCSVNGLC VPACDGVKDC PNGLDERNCV CRATFQCKED 500
    STCISLPKVC DGQPDCLNGS DEEQCQEGVP CGTFTFQCED RSCVKKPNPQ 550
    CDGRPDCRDG SDEEHCDCGL QGPSSRIVGG AVSSEGEWPW QASLQVRGRH 600
    ICGGALIADR WVITAAHCFQ EDSMASTVLW TVFLGKVWQN SRWPGEVSFK 650
    VSRLLLHPYH EEDSHDYDVA LLQLDHPVVR SAAVRPVCLP ARSHFFEPGL 700
    HCWITGWGAL REGGPISNAL QKVDVQLIPQ DLCSEVYRYQ VTPRMLCAGY 750
    RKGKKDACQG DSGGPLVCKA LSGRWFLAGL VSWGLGCGRP NYFGVYTRIT 800
    GVISWIQQVV T 811
    Length:811
    Mass (Da):90,000
    Last modified:October 14, 2008 - v3
    Checksum:i7EEF193F655DDE9D
    GO
    Isoform 2 (identifier: Q8IU80-1) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-9: Missing.

    Show »
    Length:802
    Mass (Da):88,874
    Checksum:i5076C9098789F3FA
    GO
    Isoform 3 (identifier: Q8IU80-2) [UniParc]FASTAAdd to Basket

    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.Curated

    Show »
    Length:461
    Mass (Da):51,602
    Checksum:i4344F1E7B4F273A8
    GO
    Isoform 4 (identifier: Q8IU80-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-9: Missing.
         714-714: G → ALRADAVALFYGWRNQGSETCCC

    Note: No experimental confirmation available.

    Show »
    Length:824
    Mass (Da):91,333
    Checksum:iA74F186406041F7B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti116 – 1161A → V in CAC85953. (PubMed:12149247)Curated
    Isoform 3 (identifier: Q8IU80-2)
    Sequence conflicti430 – 4301T → I in CAQ07364. (PubMed:10591208)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti114 – 1141E → K in IRIDA; does not undergo proteolytic processing; loss of activity. 1 Publication
    VAR_068665
    Natural varianti118 – 1181A → D in IRIDA; results in reduced inhibition of HAMP promoter. 1 Publication
    VAR_068666
    Natural varianti141 – 1411Y → C in IRIDA; does not undergo proteolytic processing; able to interact with HFE2; results in reduced inhibition of HAMP promoter. 2 Publications
    VAR_064075
    Natural varianti212 – 2121I → T in IRIDA; results in reduced inhibition of HAMP promoter. 1 Publication
    VAR_064076
    Natural varianti223 – 2231R → H in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036296
    Natural varianti228 – 2281G → D.1 Publication
    VAR_068667
    Natural varianti234 – 2341R → S in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036297
    Natural varianti235 – 2351L → P in IRIDA; does not undergo proteolytic processing; loss of activity. 1 Publication
    VAR_068668
    Natural varianti253 – 2531K → E.2 Publications
    Corresponds to variant rs2235324 [ dbSNP | Ensembl ].
    VAR_051841
    Natural varianti262 – 2621E → K.
    Corresponds to variant rs2235324 [ dbSNP | Ensembl ].
    VAR_044434
    Natural varianti271 – 2711R → Q in IRIDA; does not affect activity. 1 Publication
    VAR_064077
    Natural varianti288 – 2881S → L.
    Corresponds to variant rs5995378 [ dbSNP | Ensembl ].
    VAR_051842
    Natural varianti304 – 3041S → L in IRIDA. 2 Publications
    VAR_064078
    Natural varianti418 – 4181Y → C in IRIDA; does not undergo proteolytic processing; loss of activity. 1 Publication
    VAR_068669
    Natural varianti442 – 4421G → R in IRIDA; normally targeted to the cell membrane; reduced proteolytic processing; able to interact with HFE2; results in reduced inhibition of HAMP promoter. 1 Publication
    VAR_044435
    Natural varianti446 – 4461R → W.1 Publication
    Corresponds to variant rs117576908 [ dbSNP | Ensembl ].
    VAR_068670
    Natural varianti510 – 5101C → S in IRIDA. 1 Publication
    VAR_064079
    Natural varianti521 – 5211D → 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. 2 Publications
    Corresponds to variant rs137853120 [ dbSNP | Ensembl ].
    VAR_044436
    Natural varianti522 – 5221E → 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. 1 Publication
    VAR_068671
    Natural varianti603 – 6031G → R in IRIDA. 1 Publication
    VAR_068672
    Natural varianti674 – 6741L → F.1 Publication
    VAR_068673
    Natural varianti736 – 7361V → A.2 Publications
    Corresponds to variant rs855791 [ dbSNP | Ensembl ].
    VAR_051843
    Natural varianti763 – 7631G → D.
    Corresponds to variant rs11703011 [ dbSNP | Ensembl ].
    VAR_051844
    Natural varianti765 – 7651P → A in IRIDA; severely reduced proteolytic processing; loss of activity. 1 Publication
    VAR_068674
    Natural varianti774 – 7741R → C in IRIDA. 1 Publication
    VAR_044437
    Natural varianti795 – 7951V → I.1 Publication
    Corresponds to variant rs139105452 [ dbSNP | Ensembl ].
    VAR_068675

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 99Missing in isoform 2 and isoform 4. 3 PublicationsVSP_035562
    Alternative sequencei409 – 46153LCGLR…PCPGE → YHFLSSLWLPFLPPPPSLPS STVTPSLEAQVPNLRGAARG ASRGWGWCQACCP in isoform 3. 1 PublicationVSP_008379Add
    BLAST
    Alternative sequencei462 – 811350Missing in isoform 3. 1 PublicationVSP_008380Add
    BLAST
    Alternative sequencei714 – 7141G → ALRADAVALFYGWRNQGSET CCC in isoform 4. 1 PublicationVSP_035563

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS13941.1. [Q8IU80-4]
    RefSeqiNP_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]
    UniGeneiHs.370885.

    Genome annotation databases

    EnsembliENST00000346753; ENSP00000334962; ENSG00000187045. [Q8IU80-4]
    ENST00000381792; ENSP00000371211; ENSG00000187045. [Q8IU80-5]
    ENST00000406725; ENSP00000385453; ENSG00000187045. [Q8IU80-1]
    ENST00000406856; ENSP00000384964; ENSG00000187045. [Q8IU80-5]
    GeneIDi164656.
    KEGGihsa:164656.
    UCSCiuc003aqs.1. human. [Q8IU80-4]
    uc003aqt.1. human. [Q8IU80-5]
    uc003aqu.3. human. [Q8IU80-2]

    Polymorphism databases

    DMDMi209572718.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS13941.1. [Q8IU80-4 ]
    RefSeqi NP_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 ]
    UniGenei Hs.370885.

    3D structure databases

    ProteinModelPortali Q8IU80.
    SMRi Q8IU80. Positions 460-810.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi Q8IU80.
    ChEMBLi CHEMBL1795139.

    Protein family/group databases

    MEROPSi S01.308.

    Polymorphism databases

    DMDMi 209572718.

    Proteomic databases

    PaxDbi Q8IU80.
    PRIDEi Q8IU80.

    Protocols and materials databases

    DNASUi 164656.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000346753 ; ENSP00000334962 ; ENSG00000187045 . [Q8IU80-4 ]
    ENST00000381792 ; ENSP00000371211 ; ENSG00000187045 . [Q8IU80-5 ]
    ENST00000406725 ; ENSP00000385453 ; ENSG00000187045 . [Q8IU80-1 ]
    ENST00000406856 ; ENSP00000384964 ; ENSG00000187045 . [Q8IU80-5 ]
    GeneIDi 164656.
    KEGGi hsa:164656.
    UCSCi uc003aqs.1. human. [Q8IU80-4 ]
    uc003aqt.1. human. [Q8IU80-5 ]
    uc003aqu.3. human. [Q8IU80-2 ]

    Organism-specific databases

    CTDi 164656.
    GeneCardsi GC22M037461.
    H-InvDB HIX0138751.
    HGNCi HGNC:16517. TMPRSS6.
    MIMi 206200. phenotype.
    609862. gene.
    neXtProti NX_Q8IU80.
    Orphaneti 209981. IRIDA syndrome.
    PharmGKBi PA134880399.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5640.
    HOVERGENi HBG108590.
    KOi K09637.
    OMAi WTVFLGK.
    OrthoDBi EOG75B84T.
    PhylomeDBi Q8IU80.
    TreeFami TF330647.

    Miscellaneous databases

    GeneWikii TMPRSS6.
    GenomeRNAii 164656.
    NextBioi 88478.
    PROi Q8IU80.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8IU80.
    Bgeei Q8IU80.
    Genevestigatori Q8IU80.

    Family and domain databases

    Gene3Di 2.60.120.290. 1 hit.
    3.30.70.960. 1 hit.
    4.10.400.10. 3 hits.
    InterProi IPR000859. 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 ]
    Pfami PF00057. Ldl_recept_a. 2 hits.
    PF01390. SEA. 1 hit.
    PF00089. Trypsin. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037135. Matriptase-2. 1 hit.
    PRINTSi PR00722. CHYMOTRYPSIN.
    SMARTi SM00042. CUB. 1 hit.
    SM00192. LDLa. 3 hits.
    SM00020. Tryp_SPc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49854. SSF49854. 2 hits.
    SSF50494. SSF50494. 1 hit.
    SSF57424. SSF57424. 3 hits.
    SSF82671. SSF82671. 1 hit.
    PROSITEi PS01180. 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 ]
    ProtoNeti Search...

    Publicationsi

    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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ALA-736.
    4. 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.
      , 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. Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-223 AND SER-234.
    15. 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. 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.

    Entry informationi

    Entry nameiTMPS6_HUMAN
    AccessioniPrimary (citable) accession number: Q8IU80
    Secondary accession number(s): B0QYB4
    , B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IUE2, Q8IXV8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2003
    Last sequence update: October 14, 2008
    Last modified: October 1, 2014
    This is version 117 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 22
      Human chromosome 22: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3