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Q8IU80

- TMPS6_HUMAN

UniProt

Q8IU80 - TMPS6_HUMAN

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Protein

Transmembrane protease serine 6

Gene

TMPRSS6

Organism
Homo sapiens (Human)
Status
Reviewed - 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. 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. 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
Complete GO annotation...

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5555CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei56 – 7621Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini77 – 811735ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB
  2. plasma membrane Source: UniProtKB
Complete GO annotation...

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

BgeeiQ8IU80.
ExpressionAtlasiQ8IU80. baseline and differential.
GenevestigatoriQ8IU80.

Interactioni

Subunit structurei

Interacts with HFE2.2 Publications

Structurei

3D structure databases

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

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.
GeneTreeiENSGT00760000118962.
HOVERGENiHBG108590.
InParanoidiQ8IU80.
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

        10         20         30         40         50
MLLLFHSKRM PVAEAPQVAG GQGDGGDGEE AEPEGMFKAC EDSKRKARGY
60 70 80 90 100
LRLVPLFVLL ALLVLASAGV LLWYFLGYKA EVMVSQVYSG SLRVLNRHFS
110 120 130 140 150
QDLTRRESSA FRSETAKAQK MLKELITSTR LGTYYNSSSV YSFGEGPLTC
160 170 180 190 200
FFWFILQIPE HRRLMLSPEV VQALLVEELL STVNSSAAVP YRAEYEVDPE
210 220 230 240 250
GLVILEASVK DIAALNSTLG CYRYSYVGQG QVLRLKGPDH LASSCLWHLQ
260 270 280 290 300
GPKDLMLKLR LEWTLAECRD RLAMYDVAGP LEKRLITSVY GCSRQEPVVE
310 320 330 340 350
VLASGAIMAV VWKKGLHSYY DPFVLSVQPV VFQACEVNLT LDNRLDSQGV
360 370 380 390 400
LSTPYFPSYY SPQTHCSWHL TVPSLDYGLA LWFDAYALRR QKYDLPCTQG
410 420 430 440 450
QWTIQNRRLC GLRILQPYAE RIPVVATAGI TINFTSQISL TGPGVRVHYG
460 470 480 490 500
LYNQSDPCPG EFLCSVNGLC VPACDGVKDC PNGLDERNCV CRATFQCKED
510 520 530 540 550
STCISLPKVC DGQPDCLNGS DEEQCQEGVP CGTFTFQCED RSCVKKPNPQ
560 570 580 590 600
CDGRPDCRDG SDEEHCDCGL QGPSSRIVGG AVSSEGEWPW QASLQVRGRH
610 620 630 640 650
ICGGALIADR WVITAAHCFQ EDSMASTVLW TVFLGKVWQN SRWPGEVSFK
660 670 680 690 700
VSRLLLHPYH EEDSHDYDVA LLQLDHPVVR SAAVRPVCLP ARSHFFEPGL
710 720 730 740 750
HCWITGWGAL REGGPISNAL QKVDVQLIPQ DLCSEVYRYQ VTPRMLCAGY
760 770 780 790 800
RKGKKDACQG DSGGPLVCKA LSGRWFLAGL VSWGLGCGRP NYFGVYTRIT
810
GVISWIQQVV T
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:
EMBLi
GenBanki
DDBJi
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]
CCDS74856.1. [Q8IU80-1]
CCDS74857.1. [Q8IU80-5]
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:
EMBLi
GenBanki
DDBJi
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 ]
CCDS74856.1. [Q8IU80-1 ]
CCDS74857.1. [Q8IU80-5 ]
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.
GeneTreei ENSGT00760000118962.
HOVERGENi HBG108590.
InParanoidi Q8IU80.
KOi K09637.
OMAi WTVFLGK.
OrthoDBi EOG75B84T.
PhylomeDBi Q8IU80.
TreeFami TF330647.

Miscellaneous databases

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

Gene expression databases

Bgeei Q8IU80.
ExpressionAtlasi Q8IU80. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 119 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