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Identification
HMDB Protein ID HMDBP01820
Secondary Accession Numbers
  • 7181
Name Proprotein convertase subtilisin/kexin type 6
Synonyms
  1. Paired basic amino acid cleaving enzyme 4
  2. SPC4
  3. Subtilisin-like proprotein convertase 4
  4. Subtilisin/kexin-like protease PACE4
Gene Name PCSK6
Protein Type Unknown
Biological Properties
General Function Involved in serine-type endopeptidase activity
Specific Function Likely to represent an endoprotease activity within the constitutive secretory pathway, with unique restricted distribution in both neuroendocrine and non-neuroendocrine tissues and capable of cleavage at the RX(K/R)R consensus motif
Pathways Not Available
Reactions Not Available
GO Classification
Function
endopeptidase activity
serine-type endopeptidase activity
catalytic activity
hydrolase activity
peptidase activity
peptidase activity, acting on l-amino acid peptides
Process
metabolic process
macromolecule metabolic process
protein metabolic process
proteolysis
Cellular Location
  1. Isoform PACE4B:Secreted
Gene Properties
Chromosome Location Chromosome:1
Locus 15q26.3
SNPs PCSK6
Gene Sequence
>2910 bp
ATGCCTCCGCGCGCGCCGCCTGCGCCCGGGCCCCGGCCGCCGCCCCGGGCCGCCGCCGCC
ACCGACACCGCCGCGGGCGCGGGGGGCGCGGGGGGCGCGGGGGGCGCCGGCGGGCCCGGG
TTCCGGCCGCTCGCGCCGCGTCCCTGGCGCTGGCTGCTGCTGCTGGCGCTGCCTGCCGCC
TGCTCCGCGCCCCCGCCGCGCCCCGTCTACACCAACCACTGGGCGGTGCAAGTGCTGGGC
GGCCCGGCCGAGGCGGACCGCGTGGCGGCGGCGCACGGGTACCTCAACTTGGGCCAGATT
GGAAACCTGGAAGATTACTACCATTTTTATCACAGCAAAACCTTTAAAAGATCAACCTTG
AGTAGCAGAGGCCCTCACACCTTCCTCAGAATGGACCCCCAGGTGAAATGGCTCCAGCAA
CAGGAAGTGAAACGAAGGGTGAAGAGACAGGTGCGAAGTGACCCGCAGGCCCTTTACTTC
AACGACCCCATTTGGTCCAACATGTGGTACCTGCATTGTGGCGACAAGAACAGTCGCTGC
CGGTCGGAAATGAATGTCCAGGCAGCGTGGAAGAGGGGCTACACAGGAAAAAACGTGGTG
GTCACCATCCTTGATGATGGCATAGAGAGAAATCACCCTGACCTGGCCCCAAATTATGAT
TCCTACGCCAGCTACGACGTGAACGGCAATGATTATGACCCATCTCCACGATATGATGCC
AGCAATGAAAATAAACACGGCACTCGTTGTGCGGGAGAAGTTGCTGCTTCAGCAAACAAT
TCCTACTGCATCGTGGGCATAGCGTACAATGCCAAAATAGGAGGCATCCGCATGCTGGAC
GGCGATGTCACAGATGTGGTCGAGGCAAAGTCGCTGGGCATCAGACCCAACTACATCGAC
ATTTACAGTGCCAGCTGGGGGCCGGACGACGACGGCAAGACGGTGGACGGGCCCGGCCGA
CTGGCTAAGCAGGCTTTCGAGTATGGCATTAAAAAGGGCCGGCAGGGCCTGGGCTCCATT
TTCGTCTGGGCATCTGGGAATGGCGGGAGAGAGGGGGACTACTGCTCGTGCGATGGCTAC
ACCAACAGCATCTACACCATCTCCGTCAGCAGCGCCACCGAGAATGGCTACAAGCCCTGG
TACCTGGAAGAGTGTGCCTCCACCCTGGCCACCACCTACAGCAGTGGGGCCTTTTATGAG
CGAAAAATCGTCACCACGGATCTGCGTCAGCGCTGTACCGATGGCCACACTGGGACCTCA
GTCTCTGCCCCCATGGTGGCGGGCATCATCGCCTTGGCTCTAGAAGCAAACAGCCAGTTA
ACCTGGAGGGACGTCCAGCACCTGCTAGTGAAGACATCCCGGCCGGCCCACCTGAAAGCG
AGCGACTGGAAAGTGAACGGCGCGGGTCATAAAGTTAGCCATTTCTATGGATTTGGTTTG
GTGGACGCAGAAGCTCTCGTTGTGGAGGCAAAGAAGTGGACAGCAGTGCCATCGCAGCAC
ATGTGCGTGGCCGCCTCGGACAAGAGACCCAGGAGCATCCCCTTAGTGCAGGTGCTGCGG
ACTACGGCCCTGACCAGCGCCTGCGCGGAGCACTCGGACCAGCGGGTGGTCTACTTGGAG
CACGTGGTGGTTCGCACCTCCATCTCACACCCACGCCGAGGAGACCTCCAGATCTACCTG
GTTTCTCCCTCGGGAACCAAGTCTCAACTTTTGGCAAAGAGGTTGCTGGATCTTTCCAAT
GAAGGGTTTACAAACTGGGAATTCATGACTGTCCACTGCTGGGGAGAAAAGGCTGAAGGG
CAGTGGACCTTGGAAATCCAAGATCTGCCATCCCAGGTCCGCAACCCGGAGAAGCAAGGG
AAGTTGAAAGAATGGAGCCTCATACTGTATGGCACAGCAGAGCACCCGTACCACATCTTC
AGTGCCCATCAGTCCCGCTCGCGGATGCTGGAGCTCTCAGCCCCAGAGCTGGAGCCACCC
AAGGCTGCCCTGTCACCCTCCCAGGTGGAAGTTCCTGAAGATGAGGAAGATTACACAGCT
CAATCCACCCCAGGCTCTGCTAATATTTTACAGACCAGTGTGTGCCATCCGGAGTGTGGT
GACAAAGGCTGTGATGGCCCCAATGCAGACCAGTGCTTGAACTGCGTCCACTTCAGCCTG
GGGAGTGTCAAGACCAGCAGGAAGTGCGTGAGTGTGTGCCCCTTGGGCTACTTTGGGGAC
ACAGCAGCAAGACGCTGTCGCCGGTGCCACAAGGGGTGTGAGACCTGCTCCAGCAGAGCT
GCGACGCAGTGCCTGTCTTGCCGCCGCGGGTTCTATCACCACCAGGAGATGAACACCTGT
GTGACCCTCTGTCCTGCAGGATTTTATGCTGATGAAAGTCAGAAAAATTGCCTTAAATGC
CACCCAAGCTGTAAAAAGTGCGTGGATGAACCTGAGAAATGTACTGTCTGTAAAGAAGGA
TTCAGCCTTGCACGGGGCAGCTGCATTCCTGACTGTGAGCCAGGCACCTACTTTGACTCA
GAGCTGATCAGATGTGGGGAATGCCATCACACCTGCGGAACCTGCGTGGGGCCAGGCAGA
GAAGAGTGCATTCACTGTGCGAAAAACTTCCACTTCCACGACTGGAAGTGTGTGCCAGCC
TGTGGTGAGGGCTTCTACCCAGAAGAGATGCCGGGCTTGCCCCACAAAGTGTGTCGAAGG
TGTGACGAGAACTGCTTGAGCTGTGCAGGCTCCAGCAGGAACTGTAGCAGGTGTAAGACG
GGCTTCACACAGCTGGGGACCTCCTGCATCACCAACCACACGTGCAGCAACGCTGACGAG
ACATTCTGCGAGATGGTGAAGTCCAACCGGCTGTGCGAACGGAAGCTCTTCATTCAGTTC
TGCTGCCGCACGTGCCTCCTGGCCGGGTAA
Protein Properties
Number of Residues 969
Molecular Weight 106419.2
Theoretical pI 7.7
Pfam Domain Function
Signals
  • 1-63
Transmembrane Regions
  • None
Protein Sequence
>Proprotein convertase subtilisin/kexin type 6
MPPRAPPAPGPRPPPRAAAATDTAAGAGGAGGAGGAGGPGFRPLAPRPWRWLLLLALPAA
CSAPPPRPVYTNHWAVQVLGGPAEADRVAAAHGYLNLGQIGNLEDYYHFYHSKTFKRSTL
SSRGPHTFLRMDPQVKWLQQQEVKRRVKRQVRSDPQALYFNDPIWSNMWYLHCGDKNSRC
RSEMNVQAAWKRGYTGKNVVVTILDDGIERNHPDLAPNYDSYASYDVNGNDYDPSPRYDA
SNENKHGTRCAGEVAASANNSYCIVGIAYNAKIGGIRMLDGDVTDVVEAKSLGIRPNYID
IYSASWGPDDDGKTVDGPGRLAKQAFEYGIKKGRQGLGSIFVWASGNGGREGDYCSCDGY
TNSIYTISVSSATENGYKPWYLEECASTLATTYSSGAFYERKIVTTDLRQRCTDGHTGTS
VSAPMVAGIIALALEANSQLTWRDVQHLLVKTSRPAHLKASDWKVNGAGHKVSHFYGFGL
VDAEALVVEAKKWTAVPSQHMCVAASDKRPRSIPLVQVLRTTALTSACAEHSDQRVVYLE
HVVVRTSISHPRRGDLQIYLVSPSGTKSQLLAKRLLDLSNEGFTNWEFMTVHCWGEKAEG
QWTLEIQDLPSQVRNPEKQGKLKEWSLILYGTAEHPYHTFSAHQSRSRMLELSAPELEPP
KAALSPSQVEVPEDEEDYTAQSTPGSANILQTSVCHPECGDKGCDGPNADQCLNCVHFSL
GSVKTSRKCVSVCPLGYFGDTAARRCRRCHKGCETCSSRAATQCLSCRRGFYHHQEMNTC
VTLCPAGFYADESQKNCLKCHPSCKKCVDEPEKCTVCKEGFSLARGSCIPDCEPGTYFDS
ELIRCGECHHTCGTCVGPGREECIHCAKNFHFHDWKCVPACGEGFYPEEMPGLPHKVCRR
CDENCLSCAGSSRNCSRCKTGFTQLGTSCITNHTCSNADETFCEMVKSNRLCERKLFIQF
CCRTCLLAG
GenBank ID Protein 2281775
UniProtKB/Swiss-Prot ID P29122
UniProtKB/Swiss-Prot Entry Name PCSK6_HUMAN
PDB IDs Not Available
GenBank Gene ID AB001914
GeneCard ID PCSK6
GenAtlas ID PCSK6
HGNC ID HGNC:8569
References
General References
  1. Kiefer MC, Tucker JE, Joh R, Landsberg KE, Saltman D, Barr PJ: Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15. DNA Cell Biol. 1991 Dec;10(10):757-69. [PubMed:1741956 ]
  2. Tsuji A, Higashine K, Hine C, Mori K, Tamai Y, Nagamune H, Matsuda Y: Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms. Biochem Biophys Res Commun. 1994 Apr 29;200(2):943-50. [PubMed:8179631 ]
  3. Tsuji A, Higashine K, Hine C, Mori K, Tamai Y, Nagamune H, Matsuda Y: "Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms.". Biochem Biophys Res Commun. 1994 Nov 15;204(3):1381-2. [PubMed:7980617 ]
  4. Mori K, Kii S, Tsuji A, Nagahama M, Imamaki A, Hayashi K, Akamatsu T, Nagamune H, Matsuda Y: A novel human PACE4 isoform, PACE4E is an active processing protease containing a hydrophobic cluster at the carboxy terminus. J Biochem. 1997 May;121(5):941-8. [PubMed:9192737 ]
  5. Tsuji A, Hine C, Tamai Y, Yonemoto K, Mori K, Yoshida S, Bando M, Sakai E, Mori K, Akamatsu T, Matsuda Y: Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease. J Biochem. 1997 Aug;122(2):438-52. [PubMed:9378725 ]
  6. Zhong M, Benjannet S, Lazure C, Munzer S, Seidah NG: Functional analysis of human PACE4-A and PACE4-C isoforms: identification of a new PACE4-CS isoform. FEBS Lett. 1996 Oct 28;396(1):31-6. [PubMed:8906861 ]
  7. Sucic JF, Moehring JM, Inocencio NM, Luchini JW, Moehring TJ: Endoprotease PACE4 is Ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain. Biochem J. 1999 May 1;339 ( Pt 3):639-47. [PubMed:10215603 ]
  8. Nagahama M, Taniguchi T, Hashimoto E, Imamaki A, Mori K, Tsuji A, Matsuda Y: Biosynthetic processing and quaternary interactions of proprotein convertase SPC4 (PACE4). FEBS Lett. 1998 Aug 28;434(1-2):155-9. [PubMed:9738469 ]