Alpha-1-antichymotrypsin

Details

Name
Alpha-1-antichymotrypsin
Synonyms
  • AACT
  • ACT
  • Cell growth-inhibiting gene 24/25 protein
  • Serpin A3
Gene Name
SERPINA3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0049889|Alpha-1-antichymotrypsin
MERMLPLLALGLLAAGFCPAVLCHPNSPLDEENLTQENQDRGTHVDLGLASANVDFAFSL
YKQLVLKAPDKNVIFSPLSISTALAFLSLGAHNTTLTEILKGLKFNLTETSEAEIHQSFQ
HLLRTLNQSSDELQLSMGNAMFVKEQLSLLDRFTEDAKRLYGSEAFATDFQDSAAAKKLI
NDYVKNGTRGKITDLIKDLDSQTMMVLVNYIFFKAKWEMPFDPQDTHQSRFYLSKKKWVM
VPMMSLHHLTIPYFRDEELSCTVVELKYTGNASALFILPDQDKMEEVEAMLLPETLKRWR
DSLEFREIGELYLPKFSISRDYNLNDILLQLGIEEAFTSKADLSGITGARNLAVSQVVHK
AVLDVFEEGTEASAATAVKITLLSALVETRTIVRFNRPFLMIIVPTDTQNIFFMSKVTNP
KQA
Number of residues
423
Molecular Weight
47650.36
Theoretical pI
Not Available
GO Classification
Functions
DNA binding / serine-type endopeptidase inhibitor activity
Processes
acute-phase response / inflammatory response / maintenance of gastrointestinal epithelium / neutrophil degranulation / platelet degranulation / regulation of lipid metabolic process
Components
azurophil granule lumen / blood microparticle / extracellular exosome / extracellular region / extracellular space / intracellular / nucleus / platelet alpha granule lumen / secretory granule lumen
General Function
Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.
Specific Function
Dna binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0049890|Alpha-1-antichymotrypsin (SERPINA3)
ATGGAGAGAATGTTACCTCTCCTGGCTCTGGGGCTCTTGGCGGCTGGGTTCTGCCCTGCT
GTCCTCTGCCACCCTAACAGCCCACTTGACGAGGAGAATCTGACCCAGGAGAACCAAGAC
CGAGGGACACACGTGGACCTCGGATTAGCCTCCGCCAACGTGGACTTCGCTTTCAGCCTG
TACAAGCAGTTAGTCCTGAAGGCCCCTGATAAGAATGTCATCTTCTCCCCACTGAGCATC
TCCACCGCCTTGGCCTTCCTGTCTCTGGGGGCCCATAATACCACCCTGACAGAGATTCTC
AAAGGCCTCAAGTTCAACCTCACGGAGACTTCTGAGGCAGAAATTCACCAGAGCTTCCAG
CACCTCCTGCGCACCCTCAATCAGTCCAGCGATGAGCTGCAGCTGAGTATGGGAAATGCC
ATGTTTGTCAAAGAGCAACTCAGTCTGCTGGACAGGTTCACGGAGGATGCCAAGAGGCTG
TATGGCTCCGAGGCCTTTGCCACTGACTTTCAGGACTCAGCTGCAGCTAAGAAGCTCATC
AACGACTACGTGAAGAATGGAACTAGGGGGAAAATCACAGATCTGATCAAGGACCTTGAC
TCGCAGACAATGATGGTCCTGGTGAATTACATCTTCTTTAAAGCCAAATGGGAGATGCCC
TTTGACCCCCAAGATACTCATCAGTCAAGGTTCTACTTGAGCAAGAAAAAGTGGGTAATG
GTGCCCATGATGAGTTTGCATCACCTGACTATACCTTACTTCCGGGACGAGGAGCTGTCC
TGCACCGTGGTGGAGCTGAAGTACACAGGCAATGCCAGCGCACTCTTCATCCTCCCTGAT
CAAGACAAGATGGAGGAAGTGGAAGCCATGCTGCTCCCAGAGACCCTGAAGCGGTGGAGA
GACTCTCTGGAGTTCAGAGAGATAGGTGAGCTCTACCTGCCAAAGTTTTCCATCTCGAGG
GACTATAACCTGAACGACATACTTCTCCAGCTGGGCATTGAGGAAGCCTTCACCAGCAAG
GCTGACCTGTCAGGGATCACAGGGGCCAGGAACCTAGCAGTCTCCCAGGTGGTCCATAAG
GCTGTGCTTGATGTATTTGAGGAGGGCACAGAAGCATCTGCTGCCACAGCAGTCAAAATC
ACCCTCCTTTCTGCATTAGTGGAGACAAGGACCATTGTGCGTTTCAACAGGCCCTTCCTG
ATGATCATTGTCCCTACAGACACCCAGAACATCTTCTTCATGAGCAAAGTCACCAATCCC
AAGCAAGCCTAG
Chromosome Location
14
Locus
14q32.13
External Identifiers
ResourceLink
UniProtKB IDP01011
UniProtKB Entry NameAACT_HUMAN
HGNC IDHGNC:16
General References
  1. Chandra T, Stackhouse R, Kidd VJ, Robson KJ, Woo SL: Sequence homology between human alpha 1-antichymotrypsin, alpha 1-antitrypsin, and antithrombin III. Biochemistry. 1983 Oct 25;22(22):5055-61. [PubMed:6606438]
  2. Poller W, Faber JP, Weidinger S, Tief K, Scholz S, Fischer M, Olek K, Kirchgesser M, Heidtmann HH: A leucine-to-proline substitution causes a defective alpha 1-antichymotrypsin allele associated with familial obstructive lung disease. Genomics. 1993 Sep;17(3):740-3. [PubMed:8244391]
  3. 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. [PubMed:14702039]
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  5. Abraham CR, Selkoe DJ, Potter H: Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease. Cell. 1988 Feb 26;52(4):487-501. [PubMed:3257719]
  6. Hwang SR, Steineckert B, Kohn A, Palkovits M, Hook VY: Molecular studies define the primary structure of alpha1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver. J Biol Chem. 1999 Jan 15;274(3):1821-7. [PubMed:9880565]
  7. Lindmark B, Lilja H, Alm R, Eriksson S: The microheterogeneity of desialylated alpha 1-antichymotrypsin: the occurrence of two amino-terminal isoforms, one lacking a His-Pro dipeptide. Biochim Biophys Acta. 1989 Jul 27;997(1-2):90-5. [PubMed:2787670]
  8. Korzus E, Luisetti M, Travis J: Interactions of alpha-1-antichymotrypsin, alpha-1-proteinase inhibitor, and alpha-2-macroglobulin with the fungal enzyme, seaprose. Biol Chem Hoppe Seyler. 1994 May;375(5):335-41. [PubMed:7521171]
  9. Morii M, Travis J: Structural alterations in alpha 1-antichymotrypsin from normal and acute phase human plasma. Biochem Biophys Res Commun. 1983 Mar 16;111(2):438-43. [PubMed:6687683]
  10. Pinczower GD, Williams RP, Gianello RD, Robinson HC, Preston BN, Linnane AW: Characterisation of the tumour-associated carbohydrate epitope recognised by monoclonal antibody 4D3. Int J Cancer. 1996 May 29;66(5):636-44. [PubMed:8647626]
  11. Rubin H, Wang ZM, Nickbarg EB, McLarney S, Naidoo N, Schoenberger OL, Johnson JL, Cooperman BS: Cloning, expression, purification, and biological activity of recombinant native and variant human alpha 1-antichymotrypsins. J Biol Chem. 1990 Jan 15;265(2):1199-207. [PubMed:2404007]
  12. Hill RE, Shaw PH, Boyd PA, Baumann H, Hastie ND: Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions. Nature. 1984 Sep 13-19;311(5982):175-7. [PubMed:6547997]
  13. Morii M, Travis J: Amino acid sequence at the reactive site of human alpha 1-antichymotrypsin. J Biol Chem. 1983 Nov 10;258(21):12749-52. [PubMed:6556193]
  14. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed:12754519]
  15. Kroczynska B, Evangelista CM, Samant SS, Elguindi EC, Blond SY: The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human homologue interacts with alpha1-antichymotrypsin and kinetically interferes with its serpin inhibitory activity. J Biol Chem. 2004 Mar 19;279(12):11432-43. Epub 2003 Dec 10. [PubMed:14668352]
  16. Horvath AJ, Forsyth SL, Coughlin PB: Expression patterns of murine antichymotrypsin-like genes reflect evolutionary divergence at the Serpina3 locus. J Mol Evol. 2004 Oct;59(4):488-97. [PubMed:15638460]
  17. Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wisniewski JR: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. Proteomics. 2004 Feb;4(2):454-65. [PubMed:14760718]
  18. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [PubMed:16335952]
  19. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  20. 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. [PubMed:23234360]
  21. Baumann U, Huber R, Bode W, Grosse D, Lesjak M, Laurell CB: Crystal structure of cleaved human alpha 1-antichymotrypsin at 2.7 A resolution and its comparison with other serpins. J Mol Biol. 1991 Apr 5;218(3):595-606. [PubMed:2016749]
  22. Lukacs CM, Zhong JQ, Plotnick MI, Rubin H, Cooperman BS, Christianson DW: Arginine substitutions in the hinge region of antichymotrypsin affect serpin beta-sheet rearrangement. Nat Struct Biol. 1996 Oct;3(10):888-93. [PubMed:8836107]
  23. Lukacs CM, Rubin H, Christianson DW: Engineering an anion-binding cavity in antichymotrypsin modulates the "spring-loaded" serpin-protease interaction. Biochemistry. 1998 Mar 10;37(10):3297-304. [PubMed:9521649]
  24. Gooptu B, Hazes B, Chang WS, Dafforn TR, Carrell RW, Read RJ, Lomas DA: Inactive conformation of the serpin alpha(1)-antichymotrypsin indicates two-stage insertion of the reactive loop: implications for inhibitory function and conformational disease. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):67-72. [PubMed:10618372]
  25. Tsuda M, Sei Y, Yamamura M, Yamamoto M, Shinohara Y: Detection of a new mutant alpha-1-antichymotrypsin in patients with occlusive-cerebrovascular disease. FEBS Lett. 1992 Jun 8;304(1):66-8. [PubMed:1618300]
  26. Poller W, Faber JP, Scholz S, Weidinger S, Bartholome K, Olek K, Eriksson S: Mis-sense mutation of alpha 1-antichymotrypsin gene associated with chronic lung disease. Lancet. 1992 Jun 20;339(8808):1538. [PubMed:1351206]
  27. Tachikawa H, Tsuda M, Onoe K, Ueno M, Takagi S, Shinohara Y: alpha-1-Antichymotrypsin gene A1252G variant (ACT Isehara-1) is associated with a lacunar type of ischemic cerebrovascular disease. J Hum Genet. 2001;46(1):45-7. [PubMed:11289720]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01593Zincapproved, investigationalunknownDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownDetails