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Protein

Transmembrane protease serine 6

Gene

TMPRSS6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine protease which hydrolyzes a range of proteins including type I collagen, fibronectin and fibrinogen. Can also activate urokinase-type plasminogen activator with low efficiency. May play a specialized role in matrix remodeling processes in liver. Through the cleavage of HFE2, a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis.1 Publication2 Publications

Sites

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

GO - Molecular functioni

  • metalloendopeptidase activity Source: Reactome
  • serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • cellular iron ion homeostasis Source: BHF-UCL
  • collagen catabolic process Source: Reactome
  • extracellular matrix disassembly Source: Reactome
  • extracellular matrix organization Source: UniProtKB
  • fibrinolysis Source: UniProtKB
  • intracellular signal transduction Source: UniProtKB
  • iron ion homeostasis Source: UniProtKB
  • membrane protein proteolysis Source: UniProtKB
  • negative regulation of BMP signaling pathway Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • proteolysis Source: UniProtKB
  • self proteolysis Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.109 2681
ReactomeiR-HSA-1442490 Collagen degradation
R-HSA-1474228 Degradation of the extracellular matrix

Protein family/group databases

MEROPSiS01.308

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane protease serine 6 (EC:3.4.21.-)
Alternative name(s):
Matriptase-2
Gene namesi
Name:TMPRSS6
ORF Names:UNQ354/PRO618
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000187045.16
HGNCiHGNC:16517 TMPRSS6
MIMi609862 gene
neXtProtiNX_Q8IU80

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 55CytoplasmicSequence analysisAdd BLAST55
Transmembranei56 – 76Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini77 – 811ExtracellularSequence analysisAdd BLAST735

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Iron-refractory iron deficiency anemia (IRIDA)12 Publications
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
Disease descriptionKey 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.
See also OMIM:206200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068665114E → K in IRIDA; does not undergo proteolytic processing; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs199474803Ensembl.1
Natural variantiVAR_068666118A → D in IRIDA; results in reduced inhibition of HAMP promoter. 1 PublicationCorresponds to variant dbSNP:rs267607121EnsemblClinVar.1
Natural variantiVAR_064075141Y → C in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; does not undergo proteolytic processing; impaired localization to the cell membrane; able to interact with HFE2. 3 Publications1
Natural variantiVAR_064076212I → T in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; no effect on catalytic activity. 2 PublicationsCorresponds to variant dbSNP:rs776877803Ensembl.1
Natural variantiVAR_068668235L → P in IRIDA; does not undergo proteolytic processing; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs199474802Ensembl.1
Natural variantiVAR_072901247W → C in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_064077271R → Q in IRIDA; no effect on HFE2-mediated inhibition of HAMP transcription; no effect on localization to the cell membrane; no effect on catalytic activity; HFE2 processing is not affected. 2 PublicationsCorresponds to variant dbSNP:rs776180387Ensembl.1
Natural variantiVAR_072902287T → N in IRIDA; no effect on HFE2-mediated inhibition of HAMP transcription; no effect on catalytic activity; autoproteolytic and HFE2 processing are not affected. 1 Publication1
Natural variantiVAR_064078304S → L in IRIDA. 3 Publications1
Natural variantiVAR_072903335C → F in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_068669418Y → C in IRIDA; does not undergo proteolytic processing; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs199474804Ensembl.1
Natural variantiVAR_044435442G → R in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; altered catalytic activity; autoproteolytic processing is reduced but it retains the ability to process HFE2; able to interact with HFE2. 3 PublicationsCorresponds to variant dbSNP:rs137853119EnsemblClinVar.1
Natural variantiVAR_072904510C → R in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_064079510C → S in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; loss of catalytic activity; no ability to process HFE2. 2 Publications1
Natural variantiVAR_072905521D → G in IRIDA. 1 Publication1
Natural variantiVAR_044436521D → 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 PublicationsCorresponds to variant dbSNP:rs137853120EnsemblClinVar.1
Natural variantiVAR_068671522E → 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 PublicationCorresponds to variant dbSNP:rs387907018EnsemblClinVar.1
Natural variantiVAR_072906590W → R in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 PublicationCorresponds to variant dbSNP:rs770897887Ensembl.1
Natural variantiVAR_072907597R → W in IRIDA; slightly reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are significantly reduced. 1 PublicationCorresponds to variant dbSNP:rs773272073Ensembl.1
Natural variantiVAR_068672603G → R in IRIDA. 1 PublicationCorresponds to variant dbSNP:rs769083817Ensembl.1
Natural variantiVAR_072908605A → G in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_072909606L → R in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_072910623S → T in IRIDA. 1 Publication1
Natural variantiVAR_068674765P → A in IRIDA; severely reduced proteolytic processing; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs199474805Ensembl.1
Natural variantiVAR_044437774R → C in IRIDA. 1 PublicationCorresponds to variant dbSNP:rs776069764Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi576R → A: Does not undergo proteolytic processing. 1 Publication1
Mutagenesisi762S → A: Does not undergo proteolytic processing. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi164656
MalaCardsiTMPRSS6
MIMi206200 phenotype
OpenTargetsiENSG00000187045
Orphaneti209981 IRIDA syndrome
PharmGKBiPA134880399

Chemistry databases

ChEMBLiCHEMBL1795139
GuidetoPHARMACOLOGYi2422

Polymorphism and mutation databases

BioMutaiTMPRSS6
DMDMi209572718

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000886961 – 811Transmembrane protease serine 6Add BLAST811

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi136N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi184N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi216N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi335 ↔ 366By similarity
Glycosylationi338N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi433N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi453N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi458 ↔ 470By similarity
Disulfide bondi464 ↔ 480By similarity
Disulfide bondi474 ↔ 489By similarity
Disulfide bondi491 ↔ 503By similarity
Disulfide bondi497 ↔ 516By similarity
Disulfide bondi510 ↔ 525By similarity
Glycosylationi518N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi531 ↔ 543By similarity
Disulfide bondi538 ↔ 557By similarity
Disulfide bondi551 ↔ 566By similarity
Disulfide bondi602 ↔ 618By similarity
Disulfide bondi702 ↔ 768By similarity
Disulfide bondi733 ↔ 747By similarity
Disulfide bondi758 ↔ 787By similarity

Post-translational modificationi

The single-chain zymogen undergoes autoproteolytic processing. This results in TMPRSS6 shedding from the cell surface and conversion into an activated two-chains form which is released extracellularly. The process involves a trans-activation mechanism that requires TMPRSS6 oligomerization.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ8IU80
PeptideAtlasiQ8IU80
PRIDEiQ8IU80

PTM databases

iPTMnetiQ8IU80
PhosphoSitePlusiQ8IU80

Expressioni

Tissue specificityi

Liver specific.1 Publication

Gene expression databases

BgeeiENSG00000187045
ExpressionAtlasiQ8IU80 baseline and differential
GenevisibleiQ8IU80 HS

Interactioni

Subunit structurei

Interacts with HFE2.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HFE2Q6ZVN83EBI-11686560,EBI-10900704

Protein-protein interaction databases

IntActiQ8IU80, 1 interactor
STRINGi9606.ENSP00000334962

Chemistry databases

BindingDBiQ8IU80

Structurei

3D structure databases

ProteinModelPortaliQ8IU80
SMRiQ8IU80
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini84 – 209SEAPROSITE-ProRule annotationAdd BLAST126
Domaini213 – 336CUB 1PROSITE-ProRule annotationAdd BLAST124
Domaini335 – 452CUB 2PROSITE-ProRule annotationAdd BLAST118
Domaini457 – 489LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST33
Domaini490 – 526LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST37
Domaini530 – 567LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST38
Domaini577 – 811Peptidase S1PROSITE-ProRule annotationAdd BLAST235

Domaini

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

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118962
HOVERGENiHBG108590
InParanoidiQ8IU80
KOiK09637
OMAiWTVFLGK
OrthoDBiEOG091G0DF7
PhylomeDBiQ8IU80
TreeFamiTF330647

Family and domain databases

CDDicd00041 CUB, 1 hit
cd00112 LDLa, 3 hits
cd00190 Tryp_SPc, 1 hit
Gene3Di2.60.120.290, 1 hit
3.30.70.960, 1 hit
InterProiView protein in InterPro
IPR000859 CUB_dom
IPR036055 LDL_receptor-like_sf
IPR002172 LDrepeatLR_classA_rpt
IPR017118 Pept_S1A_matriptase-2
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR000082 SEA_dom
IPR036364 SEA_dom_sf
IPR035914 Sperma_CUB_dom_sf
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00057 Ldl_recept_a, 2 hits
PF01390 SEA, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF037135 Matriptase-2, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00192 LDLa, 3 hits
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF49854 SSF49854, 2 hits
SSF50494 SSF50494, 1 hit
SSF57424 SSF57424, 3 hits
SSF82671 SSF82671, 1 hit
PROSITEiView protein in PROSITE
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

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti116A → V in CAC85953 (PubMed:12149247).Curated1
Isoform 3 (identifier: Q8IU80-2)
Sequence conflicti430T → I in CAQ07364 (PubMed:10591208).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068665114E → K in IRIDA; does not undergo proteolytic processing; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs199474803Ensembl.1
Natural variantiVAR_068666118A → D in IRIDA; results in reduced inhibition of HAMP promoter. 1 PublicationCorresponds to variant dbSNP:rs267607121EnsemblClinVar.1
Natural variantiVAR_064075141Y → C in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; does not undergo proteolytic processing; impaired localization to the cell membrane; able to interact with HFE2. 3 Publications1
Natural variantiVAR_064076212I → T in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; no effect on catalytic activity. 2 PublicationsCorresponds to variant dbSNP:rs776877803Ensembl.1
Natural variantiVAR_036296223R → H in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs749106338Ensembl.1
Natural variantiVAR_068667228G → D1 PublicationCorresponds to variant dbSNP:rs754848810Ensembl.1
Natural variantiVAR_036297234R → S in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_068668235L → P in IRIDA; does not undergo proteolytic processing; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs199474802Ensembl.1
Natural variantiVAR_072901247W → C in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_051841253K → E2 PublicationsCorresponds to variant dbSNP:rs2235324EnsemblClinVar.1
Natural variantiVAR_044434262E → K. Corresponds to variant dbSNP:rs2235324EnsemblClinVar.1
Natural variantiVAR_064077271R → Q in IRIDA; no effect on HFE2-mediated inhibition of HAMP transcription; no effect on localization to the cell membrane; no effect on catalytic activity; HFE2 processing is not affected. 2 PublicationsCorresponds to variant dbSNP:rs776180387Ensembl.1
Natural variantiVAR_072902287T → N in IRIDA; no effect on HFE2-mediated inhibition of HAMP transcription; no effect on catalytic activity; autoproteolytic and HFE2 processing are not affected. 1 Publication1
Natural variantiVAR_051842288S → L. Corresponds to variant dbSNP:rs5995378EnsemblClinVar.1
Natural variantiVAR_064078304S → L in IRIDA. 3 Publications1
Natural variantiVAR_072903335C → F in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_068669418Y → C in IRIDA; does not undergo proteolytic processing; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs199474804Ensembl.1
Natural variantiVAR_044435442G → R in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; altered catalytic activity; autoproteolytic processing is reduced but it retains the ability to process HFE2; able to interact with HFE2. 3 PublicationsCorresponds to variant dbSNP:rs137853119EnsemblClinVar.1
Natural variantiVAR_068670446R → W1 PublicationCorresponds to variant dbSNP:rs117576908EnsemblClinVar.1
Natural variantiVAR_072904510C → R in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_064079510C → S in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; loss of catalytic activity; no ability to process HFE2. 2 Publications1
Natural variantiVAR_072905521D → G in IRIDA. 1 Publication1
Natural variantiVAR_044436521D → 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 PublicationsCorresponds to variant dbSNP:rs137853120EnsemblClinVar.1
Natural variantiVAR_068671522E → 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 PublicationCorresponds to variant dbSNP:rs387907018EnsemblClinVar.1
Natural variantiVAR_072906590W → R in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 PublicationCorresponds to variant dbSNP:rs770897887Ensembl.1
Natural variantiVAR_072907597R → W in IRIDA; slightly reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are significantly reduced. 1 PublicationCorresponds to variant dbSNP:rs773272073Ensembl.1
Natural variantiVAR_068672603G → R in IRIDA. 1 PublicationCorresponds to variant dbSNP:rs769083817Ensembl.1
Natural variantiVAR_072908605A → G in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_072909606L → R in IRIDA; reduced HFE2-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HFE2 processing are impaired. 1 Publication1
Natural variantiVAR_072910623S → T in IRIDA. 1 Publication1
Natural variantiVAR_068673674L → F1 Publication1
Natural variantiVAR_051843736V → A2 PublicationsCorresponds to variant dbSNP:rs855791EnsemblClinVar.1
Natural variantiVAR_051844763G → D. Corresponds to variant dbSNP:rs11703011Ensembl.1
Natural variantiVAR_068674765P → A in IRIDA; severely reduced proteolytic processing; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs199474805Ensembl.1
Natural variantiVAR_044437774R → C in IRIDA. 1 PublicationCorresponds to variant dbSNP:rs776069764Ensembl.1
Natural variantiVAR_068675795V → I1 PublicationCorresponds to variant dbSNP:rs139105452EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0355621 – 9Missing in isoform 2 and isoform 4. 3 Publications9
Alternative sequenceiVSP_008379409 – 461LCGLR…PCPGE → YHFLSSLWLPFLPPPPSLPS STVTPSLEAQVPNLRGAARG ASRGWGWCQACCP in isoform 3. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_008380462 – 811Missing in isoform 3. 1 PublicationAdd BLAST350
Alternative sequenceiVSP_035563714G → ALRADAVALFYGWRNQGSET CCC in isoform 4. 1 Publication1

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]
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.3 human [Q8IU80-4]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTMPS6_HUMAN
AccessioniPrimary (citable) accession number: Q8IU80
Secondary accession number(s): B0QYB4
, B0QYB7, B0QYB8, Q5TI06, Q6ICC2, Q6UXD8, Q8IUE2, Q8IXV8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: October 14, 2008
Last modified: March 28, 2018
This is version 148 of the entry and version 3 of the sequence. See 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

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