PCSK6

Protein identityUniProt · HPA

UniProt accession

P29122

Gene

PCSK6

Ensembl

ENSG00000140479

Chromosome

15

Canonical length

969 aa

Protein class

Enzymes, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]

Canonical amino-acid sequenceUniProt

969 residues, UniProt reviewed canonical sequence.

>P29122|PCSK6
     1  MPPRAPPAPG PRPPPRAAAA TDTAAGAGGA GGAGGAGGPG FRPLAPRPWR WLLLLALPAA
    61  CSAPPPRPVY TNHWAVQVLG GPAEADRVAA AHGYLNLGQI GNLEDYYHFY HSKTFKRSTL
   121  SSRGPHTFLR MDPQVKWLQQ QEVKRRVKRQ VRSDPQALYF NDPIWSNMWY LHCGDKNSRC
   181  RSEMNVQAAW KRGYTGKNVV VTILDDGIER NHPDLAPNYD SYASYDVNGN DYDPSPRYDA
   241  SNENKHGTRC AGEVAASANN SYCIVGIAYN AKIGGIRMLD GDVTDVVEAK SLGIRPNYID
   301  IYSASWGPDD DGKTVDGPGR LAKQAFEYGI KKGRQGLGSI FVWASGNGGR EGDYCSCDGY
   361  TNSIYTISVS SATENGYKPW YLEECASTLA TTYSSGAFYE RKIVTTDLRQ RCTDGHTGTS
   421  VSAPMVAGII ALALEANSQL TWRDVQHLLV KTSRPAHLKA SDWKVNGAGH KVSHFYGFGL
   481  VDAEALVVEA KKWTAVPSQH MCVAASDKRP RSIPLVQVLR TTALTSACAE HSDQRVVYLE
   541  HVVVRTSISH PRRGDLQIYL VSPSGTKSQL LAKRLLDLSN EGFTNWEFMT VHCWGEKAEG
   601  QWTLEIQDLP SQVRNPEKQG KLKEWSLILY GTAEHPYHTF SAHQSRSRML ELSAPELEPP
   661  KAALSPSQVE VPEDEEDYTA QSTPGSANIL QTSVCHPECG DKGCDGPNAD QCLNCVHFSL
   721  GSVKTSRKCV SVCPLGYFGD TAARRCRRCH KGCETCSSRA ATQCLSCRRG FYHHQEMNTC
   781  VTLCPAGFYA DESQKNCLKC HPSCKKCVDE PEKCTVCKEG FSLARGSCIP DCEPGTYFDS
   841  ELIRCGECHH TCGTCVGPGR EECIHCAKNF HFHDWKCVPA CGEGFYPEEM PGLPHKVCRR
   901  CDENCLSCAG SSRNCSRCKT GFTQLGTSCI TNHTCSNADE TFCEMVKSNR LCERKLFIQF
   961  CCRTCLLAG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PCSK6 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

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

149 nTPM

Expression across tissuesHPA

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)

0.73

gnomAD pLI

0

gnomAD missense Z

1.41

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• determination of left/right symmetry
• glycoprotein metabolic process
• nerve growth factor production
• peptide hormone processing
• plasma lipoprotein particle remodeling
• protein processing
• regulation of BMP signaling pathway
• secretion by cell
• zygotic determination of anterior/posterior axis, embryo

Molecular functions

• endopeptidase activity
• heparin binding
• nerve growth factor binding
• serine-type endopeptidase activity

Cellular components

• cell surface
• endoplasmic reticulum
• extracellular matrix
• extracellular region
• extracellular space
• Golgi lumen
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Peptidase S8/S53 domain
• EGF-like domain
• P domain
• Furin-like repeat
• Galactose-binding-like domain superfamily
• Growth factor receptor cysteine-rich domain superfamily
• PLAC
• Peptidase S8, subtilisin-related
• Peptidase S8, subtilisin, His-active site
• Peptidase S8, subtilisin, Asp-active site
• Peptidase S8, subtilisin, Ser-active site
• Growth factor receptor domain 4
• Peptidase S8, pro-domain
• Kexin/furin catalytic domain
• Peptidase S8/S53 domain superfamily
• Peptidase S8, pro-domain superfamily
• Subtilase family
• Proprotein convertase P-domain
• PLAC (protease and lacunin) domain
• Growth factor receptor domain IV
• Peptidase S8 pro-domain

KeywordsUniProt

• Calcium
• Cleavage on pair of basic residues
• Endoplasmic reticulum
• Glycoprotein
• Hydrolase
• Membrane
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of PCSK6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RCN3