Argininosuccinate synthase

Details

Name
Argininosuccinate synthase
Synonyms
  • 6.3.4.5
  • ASS
  • Citrulline--aspartate ligase
Gene Name
ASS1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016170|Argininosuccinate synthase
MSSKGSVVLAYSGGLDTSCILVWLKEQGYDVIAYLANIGQKEDFEEARKKALKLGAKKVF
IEDVSREFVEEFIWPAIQSSALYEDRYLLGTSLARPCIARKQVEIAQREGAKYVSHGATG
KGNDQVRFELSCYSLAPQIKVIAPWRMPEFYNRFKGRNDLMEYAKQHGIPIPVTPKNPWS
MDENLMHISYEAGILENPKNQAPPGLYTKTQDPAKAPNTPDILEIEFKKGVPVKVTNVKD
GTTHQTSLELFMYLNEVAGKHGVGRIDIVENRFIGMKSRGIYETPAGTILYHAHLDIEAF
TMDREVRKIKQGLGLKFAELVYTGFWHSPECEFVRHCIAKSQERVEGKVQVSVLKGQVYI
LGRESPLSLYNEELVSMNVQGDYEPTDATGFININSLRLKEYHRLQSKVTAK
Number of residues
412
Molecular Weight
46530.055
Theoretical pI
8.18
GO Classification
Functions
amino acid binding / argininosuccinate synthase activity / ATP binding / identical protein binding / poly(A) RNA binding / toxic substance binding
Processes
acute-phase response / aging / arginine biosynthetic process / argininosuccinate metabolic process / aspartate metabolic process / cellular nitrogen compound metabolic process / cellular response to amine stimulus / cellular response to amino acid stimulus / cellular response to ammonium ion / cellular response to cAMP / cellular response to dexamethasone stimulus / cellular response to glucagon stimulus / cellular response to interferon-gamma / cellular response to laminar fluid shear stress / cellular response to lipopolysaccharide / cellular response to oleic acid / cellular response to tumor necrosis factor / citrulline metabolic process / diaphragm development / kidney development / liver development / midgut development / negative regulation of leukocyte cell-cell adhesion / polyamine metabolic process / positive regulation of nitric oxide biosynthetic process / response to drug / response to estradiol / response to growth hormone / response to mycotoxin / response to nutrient / response to zinc ion / small molecule metabolic process / urea cycle
Components
cell body fiber / cytoplasm / cytosol / endoplasmic reticulum / extracellular exosome / lysosome / mitochondrial outer membrane / nucleus / perikaryon
General Function
Toxic substance binding
Specific Function
Is indirectly involved in the control of blood pressure.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0016171|Argininosuccinate synthase (ASS1)
ATGTCCAGCAAAGGCTCCGTGGTTCTGGCCTACAGTGGCGGCCTGGACACCTCGTGCATC
CTCGTGTGGCTGAAGGAACAAGGCTATGACGTCATTGCCTATCTGGCCAACATTGGCCAG
AAGGAAGACTTCGAGGAAGCCAGGAAGAAGGCACTGAAGCTTGGGGCCAAAAAGGTGTTC
ATTGAGGATGTCAGCAGGGAGTTTGTGGAGGAGTTCATCTGGCCGGCCATCCAGTCCAGC
GCACTGTATGAGGACCGCTACCTCCTGGGCACCTCTCTTGCCAGGCCCTGCATCGCCCGC
AAACAAGTGGAAATCGCCCAGCGGGAGGGGGCCAAGTATGTGTCCCACGGCGCCACAGGA
AAGGGGAACGATCAGGTCCGGTTTGAGCTCAGCTGCTACTCACTGGCCCCCCAGATAAAG
GTCATTGCTCCCTGGAGGATGCCTGAATTCTACAACCGGTTCAAGGGCCGCAATGACCTG
ATGGAGTACGCAAAGCAACACGGGATTCCCATCCCGGTCACTCCCAAGAACCCGTGGAGC
ATGGATGAGAACCTCATGCACATCAGCTACGAGGCTGGAATCCTGGAGAACCCCAAGAAC
CAAGCGCCTCCAGGTCTCTACACGAAGACCCAGGACCCAGCCAAAGCCCCCAACACCCCT
GACATTCTCGAGATCGAGTTCAAAAAAGGGGTCCCTGTGAAGGTGACCAACGTCAAGGAT
GGCACCACCCACCAGACCTCCTTGGAGCTCTTCATGTACCTGAACGAAGTCGCGGGCAAG
CATGGCGTGGGCCGTATTGACATCGTGGAGAACCGCTTCATTGGAATGAAGTCCCGAGGT
ATCTACGAGACCCCAGCAGGCACCATCCTTTACCATGCTCATTTAGACATCGAGGCCTTC
ACCATGGACCGGGAAGTGCGCAAAATCAAACAAGGCCTGGGCTTGAAATTTGCTGAGCTG
GTGTATACCGGTTTCTGGCACAGCCCTGAGTGTGAATTTGTCCGCCACTGCATCGCCAAG
TCCCAGGAGCGAGTGGAAGGGAAAGTGCAGGTGTCCGTCCTCAAGGGCCAGGTGTACATC
CTCGGCCGGGAGTCCCCACTGTCTCTCTACAATGAGGAGCTGGTGAGCATGAACGTGCAG
GGTGATTATGAGCCAACTGATGCCACCGGGTTCATCAACATCAATTCCCTCAGGCTGAAG
GAATATCATCGTCTCCAGAGCAAGGTCACTGCCAAATAG
Chromosome Location
9
Locus
9q34.1
External Identifiers
ResourceLink
UniProtKB IDP00966
UniProtKB Entry NameASSY_HUMAN
GenBank Protein ID28872
GenBank Gene IDX01630
GenAtlas IDASS1
HGNC IDHGNC:758
General References
  1. Bock HG, Su TS, O'Brien WE, Beaudet AL: Sequence for human argininosuccinate synthetase cDNA. Nucleic Acids Res. 1983 Sep 24;11(18):6505-12. [Article]
  2. Freytag SO, Bock HG, Beaudet AL, O'Brien WE: Molecular structures of human argininosuccinate synthetase pseudogenes. Evolutionary and mechanistic implications. J Biol Chem. 1984 Mar 10;259(5):3160-6. [Article]
  3. Haberle J, Pauli S, Linnebank M, Kleijer WJ, Bakker HD, Wanders RJ, Harms E, Koch HG: Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. Hum Genet. 2002 Apr;110(4):327-33. Epub 2002 Mar 1. [Article]
  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. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Jinno Y, Nomiyama H, Matuo S, Shimada K, Matsuda I, Saheki T: Structure of the 5' end region of the human argininosuccinate synthetase gene. J Inherit Metab Dis. 1985;8(3):157-9. [Article]
  7. Isashiki Y, Noda T, Kobayashi K, Sase M, Saheki T, Titani K: Identification of essential arginine residue(s) for Mg-ATP binding of human argininosuccinate synthetase. Protein Seq Data Anal. 1989 Jul;2(4):283-7. [Article]
  8. Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ: A two-dimensional gel database of human colon carcinoma proteins. Electrophoresis. 1997 Mar-Apr;18(3-4):605-13. [Article]
  9. Zheng X, Dai X, Zhao Y, Chen Q, Lu F, Yao D, Yu Q, Liu X, Zhang C, Gu X, Luo M: Restructuring of the dinucleotide-binding fold in an NADP(H) sensor protein. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8809-14. Epub 2007 May 11. [Article]
  10. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  11. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  12. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  13. Karlberg T, Collins R, van den Berg S, Flores A, Hammarstrom M, Hogbom M, Holmberg Schiavone L, Uppenberg J: Structure of human argininosuccinate synthetase. Acta Crystallogr D Biol Crystallogr. 2008 Mar;64(Pt 3):279-86. doi: 10.1107/S0907444907067455. Epub 2008 Feb 20. [Article]
  14. Engel K, Hohne W, Haberle J: Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene. Hum Mutat. 2009 Mar;30(3):300-7. doi: 10.1002/humu.20847. [Article]
  15. Kobayashi K, Jackson MJ, Tick DB, O'Brien WE, Beaudet AL: Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. J Biol Chem. 1990 Jul 5;265(19):11361-7. [Article]
  16. Kobayashi K, Rosenbloom C, Beaudet AL, O'Brien WE: Additional mutations in argininosuccinate synthetase causing citrullinemia. Mol Biol Med. 1991 Feb;8(1):95-100. [Article]
  17. Kobayashi K, Shaheen N, Terazono H, Saheki T: Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia. Am J Hum Genet. 1994 Dec;55(6):1103-12. [Article]
  18. Shaheen N, Kobayashi K, Terazono H, Fukushige T, Horiuchi M, Saheki T: Characterization of human wild-type and mutant argininosuccinate synthetase proteins expressed in bacterial cells. Enzyme Protein. 1994-1995;48(5-6):251-64. [Article]
  19. Vilaseca MA, Kobayashi K, Briones P, Lambruschini N, Campistol J, Tabata A, Alomar A, Rodes M, Lluch M, Saheki T: Phenotype and genotype heterogeneity in Mediterranean citrullinemia. Mol Genet Metab. 2001 Nov;74(3):396-8. [Article]
  20. Gao HZ, Kobayashi K, Tabata A, Tsuge H, Iijima M, Yasuda T, Kalkanoglu HS, Dursun A, Tokatli A, Coskun T, Trefz FK, Skladal D, Mandel H, Seidel J, Kodama S, Shirane S, Ichida T, Makino S, Yoshino M, Kang JH, Mizuguchi M, Barshop BA, Fuchinoue S, Seneca S, Zeesman S, Knerr I, Rodes M, Wasant P, Yoshida I, De Meirleir L, Abdul Jalil M, Begum L, Horiuchi M, Katunuma N, Nakagawa S, Saheki T: Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients. Hum Mutat. 2003 Jul;22(1):24-34. [Article]
  21. Haberle J, Pauli S, Schmidt E, Schulze-Eilfing B, Berning C, Koch HG: Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1). Mol Genet Metab. 2003 Nov;80(3):302-6. [Article]
  22. Kleijer WJ, Garritsen VH, van der Sterre ML, Berning C, Haberle J, Huijmans JG: Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia. Prenat Diagn. 2006 Mar;26(3):242-7. [Article]
  23. Kimani JK, Wei T, Chol K, Li Y, Yu P, Ye S, Huang X, Qi M: Functional analysis of novel splicing and missense mutations identified in the ASS1 gene in classical citrullinemia patients. Clin Chim Acta. 2015 Jan 1;438:323-9. doi: 10.1016/j.cca.2014.08.028. Epub 2014 Aug 30. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00125Arginineinvestigational, nutraceuticalunknownDetails
DB00128Aspartic acidapproved, nutraceuticalunknownDetails
DB00155Citrullineinvestigational, nutraceuticalunknownDetails
DB00171ATPinvestigational, nutraceuticalunknownDetails