Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNIUKC)

• DTT Name: TMPRSS6 messenger RNA (TMPRSS6 mRNA)
• Synonyms: Matriptase-2
• Gene Name: TMPRSS6
• DTT Type: Clinical trial target; [1]
• UniProt ID: TMPS6_HUMAN
• TTD ID: T16087
• EC Number: EC 3.4.21.-
• Sequence:
  MLLLFHSKRMPVAEAPQVAGGQGDGGDGEEAEPEGMFKACEDSKRKARGYLRLVPLFVLL
  ALLVLASAGVLLWYFLGYKAEVMVSQVYSGSLRVLNRHFSQDLTRRESSAFRSETAKAQK
  MLKELITSTRLGTYYNSSSVYSFGEGPLTCFFWFILQIPEHRRLMLSPEVVQALLVEELL
  STVNSSAAVPYRAEYEVDPEGLVILEASVKDIAALNSTLGCYRYSYVGQGQVLRLKGPDH
  LASSCLWHLQGPKDLMLKLRLEWTLAECRDRLAMYDVAGPLEKRLITSVYGCSRQEPVVE
  VLASGAIMAVVWKKGLHSYYDPFVLSVQPVVFQACEVNLTLDNRLDSQGVLSTPYFPSYY
  SPQTHCSWHLTVPSLDYGLALWFDAYALRRQKYDLPCTQGQWTIQNRRLCGLRILQPYAE
  RIPVVATAGITINFTSQISLTGPGVRVHYGLYNQSDPCPGEFLCSVNGLCVPACDGVKDC
  PNGLDERNCVCRATFQCKEDSTCISLPKVCDGQPDCLNGSDEEQCQEGVPCGTFTFQCED
  RSCVKKPNPQCDGRPDCRDGSDEEHCDCGLQGPSSRIVGGAVSSEGEWPWQASLQVRGRH
  ICGGALIADRWVITAAHCFQEDSMASTVLWTVFLGKVWQNSRWPGEVSFKVSRLLLHPYH
  EEDSHDYDVALLQLDHPVVRSAAVRPVCLPARSHFFEPGLHCWITGWGALREGGPISNAL
  QKVDVQLIPQDLCSEVYRYQVTPRMLCAGYRKGKKDACQGDSGGPLVCKALSGRWFLAGL
  VSWGLGCGRPNYFGVYTRITGVISWIQQVVT
• Function: Serine protease which hydrolyzes a range of proteins including type I collagen, fibronectin and fibrinogen. Can also activate urokinase-type plasminogen activator with low efficiency. May play a specialized role in matrix remodeling processes in liver. Through the cleavage of HJV, a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis.
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IONIS-TMPRSS6-LRx	DM7VJE1	Beta thalassemia	3A50.2	Phase 2	[1]
Sapablursen	DM95T5Z	Polycythemia vera	2A20.4	Phase 2	[2]
SLN124	DMIAOU6	Beta thalassemia	3A50.2	Phase 1	[3]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ALN-TMP	DMW7XEU	Beta thalassemia	3A50.2	Preclinical	[4]

References

• [1] Clinical pipeline report, company report or official report of Ionis Pharmaceuticals.
• [2] Clinical pipeline report, company report or official report of Ionis
• [3] SLN124, a GalNAc-siRNA Conjugate Targeting TMPRSS6, Efficiently Prevents Iron Overload in Hereditary Haemochromatosis Type 1. Hemasphere. 2019 Oct 1;3(6):e301.
• [4] Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov. 2017 Jun;16(6):400-423.