Target Information

Target General Information

Target ID

T86503 (Former ID: TTDI03478)

Target Name

Proprotein convertase subtilisin/kexin type 6 (PCSK6)

Synonyms

Subtilisin/kexin-like protease PACE4; Subtilisin-like proprotein convertase 4; SPC4; Paired basic amino acid cleaving enzyme 4; PACE4

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Gene Name

PCSK6

Target Type

Literature-reported target

[1]

Function

Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive secretory pathway, with unique restricted distribution in both neuroendocrine and non-neuroendocrine tissues.

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UniProt ID

PCSK6_HUMAN

EC Number

EC 3.4.21.-

Sequence

MPPRAPPAPGPRPPPRAAAATDTAAGAGGAGGAGGAGGPGFRPLAPRPWRWLLLLALPAA
CSAPPPRPVYTNHWAVQVLGGPAEADRVAAAHGYLNLGQIGNLEDYYHFYHSKTFKRSTL
SSRGPHTFLRMDPQVKWLQQQEVKRRVKRQVRSDPQALYFNDPIWSNMWYLHCGDKNSRC
RSEMNVQAAWKRGYTGKNVVVTILDDGIERNHPDLAPNYDSYASYDVNGNDYDPSPRYDA
SNENKHGTRCAGEVAASANNSYCIVGIAYNAKIGGIRMLDGDVTDVVEAKSLGIRPNYID
IYSASWGPDDDGKTVDGPGRLAKQAFEYGIKKGRQGLGSIFVWASGNGGREGDYCSCDGY
TNSIYTISVSSATENGYKPWYLEECASTLATTYSSGAFYERKIVTTDLRQRCTDGHTGTS
VSAPMVAGIIALALEANSQLTWRDVQHLLVKTSRPAHLKASDWKVNGAGHKVSHFYGFGL
VDAEALVVEAKKWTAVPSQHMCVAASDKRPRSIPLVQVLRTTALTSACAEHSDQRVVYLE
HVVVRTSISHPRRGDLQIYLVSPSGTKSQLLAKRLLDLSNEGFTNWEFMTVHCWGEKAEG
QWTLEIQDLPSQVRNPEKQGKLKEWSLILYGTAEHPYHTFSAHQSRSRMLELSAPELEPP
KAALSPSQVEVPEDEEDYTAQSTPGSANILQTSVCHPECGDKGCDGPNADQCLNCVHFSL
GSVKTSRKCVSVCPLGYFGDTAARRCRRCHKGCETCSSRAATQCLSCRRGFYHHQEMNTC
VTLCPAGFYADESQKNCLKCHPSCKKCVDEPEKCTVCKEGFSLARGSCIPDCEPGTYFDS
ELIRCGECHHTCGTCVGPGREECIHCAKNFHFHDWKCVPACGEGFYPEEMPGLPHKVCRR
CDENCLSCAGSSRNCSRCKTGFTQLGTSCITNHTCSNADETFCEMVKSNRLCERKLFIQF
CCRTCLLAG

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3D Structure

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AlphaFold

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Similarity Proteins Human Tissue Distribution

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Similarity Proteins

Human Tissue Distribution

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Extracellular matrix organizing protein FRAS1 (FRAS1)	PF16184 ; PF03160 ; PF00093 More >>	32.365 (78/241)	8.41E-24
R-spondin-3 (RSPO3)	PF15913	30.769 (40/130)	1.87E-07
R-spondin-4 (RSPO4)	PF15913	33.663 (34/101)	2.50E-05
Protein disulfide isomerase CRELD1 (CRELD1)	PF11938 ; PF07645	28.696 (33/115)	3.79E-05
Roof plate-specific spondin-1 (RSPO1)	PF15913 ; PF00090	32.075 (34/106)	7.18E-05
Insulin-like growth factor I receptor (IGF1R)	PF00757 ; PF07714 ; PF01030 More >>	26.582 (42/158)	1.00E-03
Scavenger receptor class F member 2 (SCARF2)	PF00053	31.667 (38/120)	2.00E-03
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Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

Chemical Structure based Activity Landscape of Target

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References

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REF 1

Design, synthesis, and structure-activity relationship studies of a potent PACE4 inhibitor. J Med Chem. 2014 Jan 9;57(1):98-109.

REF 2

Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens. J Biol Chem. 2007 Jul 20;282(29):20847-53.

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