Neuroendocrine convertase 1

NameNeuroendocrine convertase 1
Synonyms
  • 3.4.21.93
  • NEC 1
  • NEC1
  • PC1
  • Prohormone convertase 1
  • Proprotein convertase 1
Gene NamePCSK1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004168|Neuroendocrine convertase 1
MERRAWSLQCTAFVLFCAWCALNSAKAKRQFVNEWAAEIPGGPEAASAIAEELGYDLLGQ
IGSLENHYLFKHKNHPRRSRRSAFHITKRLSDDDRVIWAEQQYEKERSKRSALRDSALNL
FNDPMWNQQWYLQDTRMTAALPKLDLHVIPVWQKGITGKGVVITVLDDGLEWNHTDIYAN
YDPEASYDFNDNDHDPFPRYDPTNENKHGTRCAGEIAMQANNHKCGVGVAYNSKVGGIRM
LDGIVTDAIEASSIGFNPGHVDIYSASWGPNDDGKTVEGPGRLAQKAFEYGVKQGRQGKG
SIFVWASGNGGRQGDNCDCDGYTDSIYTISISSASQQGLSPWYAEKCSSTLATSYSSGDY
TDQRITSADLHNDCTETHTGTSASAPLAAGIFALALEANPNLTWRDMQHLVVWTSEYDPL
ANNPGWKKNGAGLMVNSRFGFGLLNAKALVDLADPRTWRSVPEKKECVVKDNDFEPRALK
ANGEVIIEIPTRACEGQENAIKSLEHVQFEATIEYSRRGDLHVTLTSAAGTSTVLLAERE
RDTSPNGFKNWDFMSVHTWGENPIGTWTLRITDMSGRIQNEGRIVNWKLILHGTSSQPEH
MKQPRVYTSYNTVQNDRRGVEKMVDPGEEQPTQENPKENTLVSKSPSSSSVGGRRDELEE
GAPSQAMLRLLQSAFSKNSPPKQSPKKSPSAKLNIPYENFYEALEKLNKPSQLKDSEDSL
YNDYVDVFYNTKPYKHRDDRLLQALVDILNEEN
Number of residues753
Molecular Weight84150.92
Theoretical pI5.84
GO Classification
Functions
  • serine-type endopeptidase activity
Processes
  • regulation of insulin secretion
  • metabolic process
  • peptide hormone processing
  • peptide biosynthetic process
  • proteolysis
  • cell-cell signaling
  • cellular protein metabolic process
Components
  • secretory granule lumen
  • transport vesicle
  • extracellular space
  • Golgi apparatus
General FunctionSerine-type endopeptidase activity
Specific FunctionInvolved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin and AGRP.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID35318
UniProtKB IDP29120
UniProtKB Entry NameNEC1_HUMAN
Cellular LocationCytoplasmic vesicle
Gene sequence
>lcl|BSEQ0016688|Neuroendocrine convertase 1 (PCSK1)
ATGGAGCGAAGAGCCTGGAGTCTGCAGTGCACTGCTTTCGTCCTCTTTTGCGCTTGGTGT
GCACTGAACAGTGCAAAAGCGAAAAGGCAATTTGTCAATGAATGGGCAGCGGAGATCCCC
GGGGGCCCGGAAGCAGCCTCGGCCATCGCCGAGGAGCTGGGCTATGACCTTTTGGGTCAG
ATTGGTTCACTTGAAAATCACTACTTATTCAAACATAAAAACCACCCCAGAAGGTCTCGA
AGGAGTGCCTTTCATATCACTAAGAGATTATCTGATGATGATCGTGTGATATGGGCTGAA
CAACAGTATGAAAAAGAAAGAAGTAAACGTTCAGCTCTAAGGGACTCAGCACTAAATCTC
TTCAATGATCCCATGTGGAATCAGCAATGGTACTTGCAAGATACCAGGATGACGGCAGCC
CTGCCCAAGCTGGACCTTCATGTGATACCTGTTTGGCAAAAAGGCATTACGGGCAAAGGA
GTTGTTATCACCGTACTGGATGATGGTTTGGAGTGGAATCACACGGACATTTATGCCAAC
TATGATCCAGAGGCTAGCTATGATTTTAATGATAATGACCATGATCCATTTCCCCGATAT
GATCCCACAAACGAGAACAAACACGGGACCAGATGTGCAGGAGAAATTGCCATGCAAGCA
AATAATCACAAATGCGGGGTTGGAGTTGCATACAATTCCAAAGTTGGAGGCATAAGAATG
CTGGATGGCATTGTGACGGATGCTATTGAGGCCAGTTCAATTGGATTCAATCCTGGACAC
GTGGATATTTACAGTGCAAGCTGGGGCCCTAATGATGATGGGAAAACTGTGGAGGGGCCT
GGCCGGCTAGCCCAGAAGGCTTTTGAATATGGTGTCAAACAGGGGAGACAGGGGAAGGGG
TCCATCTTCGTCTGGGCTTCGGGAAACGGGGGGCGTCAGGGAGATAATTGTGACTGTGAT
GGCTACACAGACAGCATCTACACCATCTCCATCAGCAGTGCCTCCCAGCAAGGCCTATCC
CCCTGGTACGCTGAGAAGTGCTCCTCCACACTGGCCACCTCTTACAGCAGCGGAGATTAC
ACCGACCAGAGAATCACGAGCGCTGACCTGCACAATGACTGCACGGAGACGCACACAGGC
ACCTCGGCCTCTGCACCTCTGGCTGCTGGCATCTTCGCTCTGGCCCTGGAAGCAAACCCA
AATCTCACCTGGCGAGATATGCAGCACCTGGTTGTCTGGACCTCTGAGTATGACCCGCTG
GCCAATAACCCTGGATGGAAAAAGAATGGAGCAGGCTTGATGGTGAATAGTCGATTTGGA
TTTGGCTTGCTAAATGCCAAAGCTCTGGTGGATTTAGCTGACCCCAGGACCTGGAGGAGC
GTGCCTGAGAAGAAAGAGTGTGTTGTAAAGGACAATGACTTTGAGCCCAGAGCCCTGAAA
GCTAATGGAGAAGTTATCATTGAAATTCCAACAAGAGCTTGTGAAGGACAAGAAAATGCT
ATCAAGTCCCTGGAGCATGTACAATTTGAAGCAACAATTGAATATTCCCGAAGAGGAGAC
CTTCATGTCACACTTACTTCTGCTGCTGGAACTAGCACTGTGCTCTTGGCTGAAAGAGAA
CGGGATACATCTCCTAATGGCTTTAAGAATTGGGACTTCATGTCTGTTCACACATGGGGA
GAGAACCCTATAGGTACTTGGACTTTGAGAATTACAGACATGTCTGGAAGAATTCAAAAT
GAAGGAAGAATTGTGAACTGGAAGCTGATTTTGCACGGGACCTCTTCTCAGCCAGAGCAT
ATGAAGCAGCCTCGTGTGTACACGTCCTACAACACTGTTCAGAATGACAGAAGAGGGGTG
GAGAAGATGGTGGATCCAGGGGAGGAGCAGCCCACACAAGAGAACCCTAAGGAGAACACC
CTGGTGTCCAAAAGCCCCAGCAGCAGCAGCGTAGGGGGCCGGAGGGATGAGTTGGAGGAG
GGAGCCCCTTCCCAGGCCATGCTGCGACTCCTGCAAAGTGCTTTCAGTAAAAACTCACCG
CCAAAGCAATCACCAAAGAAGTCCCCAAGTGCAAAGCTCAACATCCCTTATGAAAACTTC
TACGAAGCCCTGGAAAAGCTGAACAAACCTTCCCAGCTTAAAGACTCTGAAGACAGTCTG
TATAATGACTATGTTGATGTTTTTTATAACACTAAACCTTACAAGCACAGAGACGACCGG
CTGCTTCAAGCTCTGGTGGACATTCTGAATGAGGAAAATTAA
GenBank Gene IDX64810
GeneCard IDNot Available
GenAtlas IDPCSK1
HGNC IDHGNC:8743
Chromosome Location5
Locus5q15-q21
References
  1. Creemers JW, Roebroek AJ, Van de Ven WJ: Expression in human lung tumor cells of the proprotein processing enzyme PC1/PC3. Cloning and primary sequence of a 5 kb cDNA. FEBS Lett. 1992 Mar 23;300(1):82-8. 1547893
  2. Seidah NG, Hamelin J, Gaspar AM, Day R, Chretien M: The cDNA sequence of the human pro-hormone and pro-protein convertase PC1. DNA Cell Biol. 1992 May;11(4):283-9. 1605851
  3. Ohagi S, Sakaguchi H, Sanke T, Tatsuta H, Hanabusa T, Nanjo K: Human prohormone convertase 3 gene: exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM. Diabetes. 1996 Jul;45(7):897-901. 8666140
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  5. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. 15372022
  6. Jansen E, Ayoubi TA, Meulemans SM, Van de Ven WJ: Neuroendocrine-specific expression of the human prohormone convertase 1 gene. Hormonal regulation of transcription through distinct cAMP response elements. J Biol Chem. 1995 Jun 23;270(25):15391-7. 7797529
  7. Halim A, Ruetschi U, Larson G, Nilsson J: LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins. J Proteome Res. 2013 Feb 1;12(2):573-84. doi: 10.1021/pr300963h. Epub 2013 Jan 11. 23234360
  8. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, Montague CT, Hutton JC, O'Rahilly S: Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet. 1997 Jul;16(3):303-6. 9207799
  9. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. 10391209
  10. Jackson RS, Creemers JW, Farooqi IS, Raffin-Sanson ML, Varro A, Dockray GJ, Holst JJ, Brubaker PL, Corvol P, Polonsky KS, Ostrega D, Becker KL, Bertagna X, Hutton JC, White A, Dattani MT, Hussain K, Middleton SJ, Nicole TM, Milla PJ, Lindley KJ, O'Rahilly S: Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest. 2003 Nov;112(10):1550-60. 14617756
  11. Farooqi IS, Volders K, Stanhope R, Heuschkel R, White A, Lank E, Keogh J, O'Rahilly S, Creemers JW: Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab. 2007 Sep;92(9):3369-73. Epub 2007 Jun 26. 17595246
  12. Benzinou M, Creemers JW, Choquet H, Lobbens S, Dina C, Durand E, Guerardel A, Boutin P, Jouret B, Heude B, Balkau B, Tichet J, Marre M, Potoczna N, Horber F, Le Stunff C, Czernichow S, Sandbaek A, Lauritzen T, Borch-Johnsen K, Andersen G, Kiess W, Korner A, Kovacs P, Jacobson P, Carlsson LM, Walley AJ, Jorgensen T, Hansen T, Pedersen O, Meyre D, Froguel P: Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet. 2008 Aug;40(8):943-5. doi: 10.1038/ng.177. Epub 2008 Jul 6. 18604207