PCSK6

PCSK6
Identifiers
AliasesPCSK6, PACE4, SPC4, proprotein convertase subtilisin/kexin type 6
External IDsOMIM: 167405; MGI: 102897; HomoloGene: 20569; GeneCards: PCSK6; OMA:PCSK6 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5046

18553

Ensembl

ENSG00000140479

ENSMUSG00000030513

UniProt

P29122

n/a

RefSeq (mRNA)

NM_001291184
NM_011048

RefSeq (protein)

n/a

Location (UCSC)Chr 15: 101.29 – 101.53 MbChr 7: 65.51 – 65.7 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Proprotein convertase subtilisin/kexin type 6 is an protease that in humans is encoded by the PCSK6 gene which is located in chromosome 15.[5][6] Pcsk6 is a calcium-dependent serine endoprotease that catalyzes the post-translational modification of precursor proteins from its ‘latent’ form to the cleaved ‘active’ form.[5] Active Pcsk6 has been reported to process substrates such as transforming growth factor β,[7] pro-albumin,[8] von Willebrand factor,[9] and corin.[10] Clinically, Pcsk6 is suggested to play a role in left/right asymmetry,[11] structural asymmetry of the brain,[12] handedness,[13][14][15] tumor progression,[16] hemostasis,[9][8][7] and cardiovascular diseases.[10][17]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000140479 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030513 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b KIEFER, MICHAEL C.; TUCKER, JEFFREY E.; JOH, RICHARD; LANDSBERG, KATHERINE E.; SALTMAN, DAVID; BARR, PHILIP J. (December 1991). "Identification of a Second Human Subtilisin-Like Protease Gene in the fes/fps Region of Chromosome 15". DNA and Cell Biology. 10 (10): 757–769. doi:10.1089/dna.1991.10.757. ISSN 1044-5498. PMID 1741956.
  6. ^ "Entrez Gene: PCSK6 proprotein convertase subtilisin/kexin type 6".
  7. ^ a b Constam, Daniel B. (August 2014). "Regulation of TGFβ and related signals by precursor processing". Seminars in Cell & Developmental Biology. 32: 85–97. doi:10.1016/j.semcdb.2014.01.008. ISSN 1084-9521. PMID 24508081.
  8. ^ a b Mori, K.; Imamaki, A.; Nagata, K.; Yonetomi, Y.; Kiyokage-Yoshimoto, R.; Martin, T. J.; Gillespie, M. T.; Nagahama, M.; Tsuji, A.; Matsuda, Y. (1999-03-01). "Subtilisin-Like Proprotein Convertases, PACE4 and PC8, as Well as Furin, are Endogenous Proalbumin Convertases in HepG2 Cells". Journal of Biochemistry. 125 (3): 627–633. doi:10.1093/oxfordjournals.jbchem.a022329. ISSN 0021-924X. PMID 10050053.
  9. ^ a b Rehemtulla, Alnawaz; Barr, Philip J.; Rhodes, Christopher J.; Kaufman, Randal J. (1993-01-26). "PACE4 is a member of the mammalian propeptidase family that has overlapping but not identical substrate specificity to PACE". Biochemistry. 32 (43): 11586–11590. doi:10.1021/bi00094a015. ISSN 0006-2960. PMID 8218226.
  10. ^ a b Chen, Shenghan; Cao, Pengxiu; Dong, Ningzheng; Peng, Jianhao; Zhang, Chunyi; Wang, Hao; Zhou, Tiantian; Yang, Junhua; Zhang, Yue; Martelli, Elizabeth E; Naga Prasad, Sathyamangla V (2015-08-10). "PCSK6-mediated corin activation is essential for normal blood pressure". Nature Medicine. 21 (9): 1048–1053. doi:10.1038/nm.3920. ISSN 1078-8956. PMC 4710517. PMID 26259032.
  11. ^ Constam, D. B.; Robertson, E. J. (2000-05-01). "SPC4/PACE4 regulates a TGFbeta signaling network during axis formation". Genes & Development. 14 (9): 1146–1155. doi:10.1101/gad.14.9.1146. ISSN 0890-9369. PMC 316583. PMID 10809672.
  12. ^ Berretz, Gesa; Arning, Larissa; Gerding, Wanda M.; Friedrich, Patrick; Fraenz, Christoph; Schlüter, Caroline; Epplen, Jörg T.; Güntürkün, Onur; Beste, Christian; Genç, Erhan; Ocklenburg, Sebastian (2019-05-21). "Structural Asymmetry in the Frontal and Temporal Lobes Is Associated with PCSK6 VNTR Polymorphism". Molecular Neurobiology. 56 (11): 7765–7773. doi:10.1007/s12035-019-01646-1. ISSN 0893-7648. PMID 31115778. S2CID 160009569.
  13. ^ Robinson, Kelsey J.; Hurd, Peter L.; Read, Silven; Crespi, Bernard J. (April 2016). "The PCSK6 gene is associated with handedness, the autism spectrum, and magical ideation in a non-clinical population". Neuropsychologia. 84: 205–212. doi:10.1016/j.neuropsychologia.2016.02.020. ISSN 0028-3932. PMID 26921480. S2CID 6142024.
  14. ^ Arning, Larissa; Ocklenburg, Sebastian; Schulz, Stefanie; Ness, Vanessa; Gerding, Wanda M.; Hengstler, Jan G.; Falkenstein, Michael; Epplen, Jörg T.; Güntürkün, Onur; Beste, Christian (2013-06-27). "PCSK6 VNTR Polymorphism Is Associated with Degree of Handedness but Not Direction of Handedness". PLOS ONE. 8 (6): e67251. Bibcode:2013PLoSO...867251A. doi:10.1371/journal.pone.0067251. ISSN 1932-6203. PMC 3695088. PMID 23826248.
  15. ^ Scerri, Thomas S.; Brandler, William M.; Paracchini, Silvia; Morris, Andrew P.; Ring, Susan M.; Richardson, Alex J.; Talcott, Joel B.; Stein, John; Monaco, Anthony P. (2010-11-04). "PCSK6 is associated with handedness in individuals with dyslexia". Human Molecular Genetics. 20 (3): 608–614. doi:10.1093/hmg/ddq475. ISSN 1460-2083. PMC 3016905. PMID 21051773.
  16. ^ Bassi, Daniel E.; Mahloogi, Haleh; Klein-Szanto, Andrés J. P. (2000). "The Proprotein Convertases Furin and PACE4 Play a Significant Role in Tumor Progression". Molecular Carcinogenesis. 28 (2): 63–69. doi:10.1002/1098-2744(200006)28:2<63::aid-mc1>3.0.co;2-c. ISSN 0899-1987. PMID 10900462. S2CID 22849623.
  17. ^ Rykaczewska, Urszula; Suur, Bianca E.; Röhl, Samuel; Razuvaev, Anton; Lengquist, Mariette; Sabater-Lleal, Maria; van der Laan, Sander W.; Miller, Clint L.; Wirka, Robert C.; Kronqvist, Malin; Gonzalez Diez, Maria (2020-02-28). "PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling". Circulation Research. 126 (5): 571–585. doi:10.1161/circresaha.119.316063. hdl:1887/3185300. ISSN 0009-7330. PMID 31893970. S2CID 209539709.