TMPRSS6

Protein identityUniProt · HPA

UniProt accession

Q8IU80

Gene

TMPRSS6

Ensembl

ENSG00000187045

Chromosome

22

Canonical length

811 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

Canonical amino-acid sequenceUniProt

811 residues, UniProt reviewed canonical sequence.

>Q8IU80|TMPRSS6
     1  MLLLFHSKRM PVAEAPQVAG GQGDGGDGEE AEPEGMFKAC EDSKRKARGY LRLVPLFVLL
    61  ALLVLASAGV LLWYFLGYKA EVMVSQVYSG SLRVLNRHFS QDLTRRESSA FRSETAKAQK
   121  MLKELITSTR LGTYYNSSSV YSFGEGPLTC FFWFILQIPE HRRLMLSPEV VQALLVEELL
   181  STVNSSAAVP YRAEYEVDPE GLVILEASVK DIAALNSTLG CYRYSYVGQG QVLRLKGPDH
   241  LASSCLWHLQ GPKDLMLKLR LEWTLAECRD RLAMYDVAGP LEKRLITSVY GCSRQEPVVE
   301  VLASGAIMAV VWKKGLHSYY DPFVLSVQPV VFQACEVNLT LDNRLDSQGV LSTPYFPSYY
   361  SPQTHCSWHL TVPSLDYGLA LWFDAYALRR QKYDLPCTQG QWTIQNRRLC GLRILQPYAE
   421  RIPVVATAGI TINFTSQISL TGPGVRVHYG LYNQSDPCPG EFLCSVNGLC VPACDGVKDC
   481  PNGLDERNCV CRATFQCKED STCISLPKVC DGQPDCLNGS DEEQCQEGVP CGTFTFQCED
   541  RSCVKKPNPQ CDGRPDCRDG SDEEHCDCGL QGPSSRIVGG AVSSEGEWPW QASLQVRGRH
   601  ICGGALIADR WVITAAHCFQ EDSMASTVLW TVFLGKVWQN SRWPGEVSFK VSRLLLHPYH
   661  EEDSHDYDVA LLQLDHPVVR SAAVRPVCLP ARSHFFEPGL HCWITGWGAL REGGPISNAL
   721  QKVDVQLIPQ DLCSEVYRYQ VTPRMLCAGY RKGKKDACQG DSGGPLVCKA LSGRWFLAGL
   781  VSWGLGCGRP NYFGVYTRIT GVISWIQQVV T

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TMPRSS6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

130 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TMPRSS6.

Disease | AllUniProt

Conditions TMPRSS6 is implicated in, by any mechanism.

• Iron-refractory iron deficiency anemia (IRIDA) MIM:206200

Disease | GeneticClinVar

36 pathogenic / likely-pathogenic of 413 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Iron-refractory iron deficiency anemia
• Microcytic anemia
• TMPRSS6-related disorder
• Abnormality of metabolism/homeostasis

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.72

gnomAD pLI

0

gnomAD missense Z

0.21

DepMap mean gene effect

-0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• BMP signaling pathway
• collagen catabolic process
• extracellular matrix disassembly
• intracellular iron ion homeostasis
• membrane protein proteolysis
• multicellular organismal-level iron ion homeostasis
• negative regulation of BMP signaling pathway
• negative regulation of DNA-templated transcription
• negative regulation of transcription by RNA polymerase II
• positive regulation of transcription by RNA polymerase II
• self proteolysis

Molecular functions

• metalloendopeptidase activity
• serine-type endopeptidase activity
• serine-type peptidase activity

Cellular components

• extracellular space
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• SEA domain
• CUB domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• Low-density lipoprotein (LDL) receptor class A repeat
• Peptidase S1, PA clan
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Spermadhesin, CUB domain superfamily
• LDL receptor-like superfamily
• SEA domain superfamily
• Low-density lipoprotein receptor domain class A
• Trypsin
• SEA domain
• Peptidase S1A, matriptase-2

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Hydrolase
• Membrane
• Protease
• Repeat
• Serine protease
• Signal-anchor
• Transmembrane
• Transmembrane helix
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of TMPRSS6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HJV