FAD-linked sulfhydryl oxidase ALR

Details

Name
FAD-linked sulfhydryl oxidase ALR
Synonyms
  • 1.8.3.2
  • ALR
  • Augmenter of liver regeneration
  • Hepatopoietin
  • HERV1
  • HPO
Gene Name
GFER
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009501|FAD-linked sulfhydryl oxidase ALR
MAAPGERGRFHGGNLFFLPGGARSEMMDDLATDARGRGAGRRDAAASASTPAQAPTSDSP
VAEDASRRRPCRACVDFKTWMRTQQKRDTKFREDCPPDREELGRHSWAVLHTLAAYYPDL
PTPEQQQDMAQFIHLFSKFYPCEECAEDLRKRLCRNHPDTRTRACFTQWLCHLHNEVNRK
LGKPDFDCSKVDERWRDGWKDGSCD
Number of residues
205
Molecular Weight
23448.95
Theoretical pI
Not Available
GO Classification
Functions
flavin adenine dinucleotide binding / protein disulfide oxidoreductase activity / thiol oxidase activity
Processes
cellular protein metabolic process / protein targeting to mitochondrion
Components
cytoplasm / extracellular region / mitochondrial intermembrane space / mitochondrion
General Function
Thiol oxidase activity
Specific Function
Isoform 1: FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen.Isoform 2: May act as an autocrine hepatotrophic growth factor promoting liver regeneration.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion intermembrane space
Gene sequence
>lcl|BSEQ0013200|FAD-linked sulfhydryl oxidase ALR (GFER)
ATGGCGGCGCCCGGCGAGCGGGGCCGCTTCCACGGCGGGAACCTCTTCTTCCTGCCGGGG
GGCGCGCGCTCCGAGATGATGGACGACCTGGCGACCGACGCGCGGGGCCGGGGCGCGGGG
CGGAGAGACGCGGCCGCCTCGGCCTCGACGCCAGCCCAGGCGCCGACCTCCGATTCTCCT
GTCGCCGAGGACGCCTCCCGGAGGCGGCCGTGCCGGGCCTGCGTCGACTTCAAGACGTGG
ATGCGGACGCAGCAGAAGCGGGACACCAAGTTTAGGGAGGACTGCCCGCCGGATCGCGAG
GAACTGGGCCGCCACAGCTGGGCTGTCCTCCACACCCTGGCCGCCTACTACCCCGACCTG
CCCACCCCAGAACAGCAGCAAGACATGGCCCAGTTCATACATTTATTTTCTAAGTTTTAC
CCCTGTGAGGAGTGTGCTGAAGACCTAAGAAAAAGGCTGTGCAGGAACCACCCAGACACC
CGCACCCGGGCATGCTTCACACAGTGGCTGTGCCACCTGCACAATGAAGTGAACCGCAAG
CTGGGCAAGCCTGACTTCGACTGCTCAAAAGTGGATGAGCGCTGGCGCGACGGCTGGAAG
GATGGCTCCTGTGACTAG
Chromosome Location
16
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP55789
UniProtKB Entry NameALR_HUMAN
HGNC IDHGNC:4236
General References
  1. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. [Article]
  2. 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]
  3. Cheng J, Zhong Y: [Cloning and sequence analysis of human genomic DNA of augmenter of liver regeneration hepatitis]. Zhonghua Gan Zang Bing Za Zhi. 2000 Feb;8(1):12-4. [Article]
  4. Lisowsky T, Weinstat-Saslow DL, Barton N, Reeders ST, Schneider MC: A new human gene located in the PKD1 region of chromosome 16 is a functional homologue to ERV1 of yeast. Genomics. 1995 Oct 10;29(3):690-7. [Article]
  5. Li Y, Wei K, Lu C, Li Y, Li M, Xing G, Wei H, Wang Q, Chen J, Wu C, Chen H, Yang S, He F: Identification of hepatopoietin dimerization, its interacting regions and alternative splicing of its transcription. Eur J Biochem. 2002 Aug;269(16):3888-93. [Article]
  6. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  7. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  8. Daithankar VN, Farrell SR, Thorpe C: Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space. Biochemistry. 2009 Jun 9;48(22):4828-37. doi: 10.1021/bi900347v. [Article]
  9. Sztolsztener ME, Brewinska A, Guiard B, Chacinska A: Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic. 2013 Mar;14(3):309-20. doi: 10.1111/tra.12030. Epub 2012 Dec 16. [Article]
  10. 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]
  11. Daithankar VN, Schaefer SA, Dong M, Bahnson BJ, Thorpe C: Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy . Biochemistry. 2010 Aug 10;49(31):6737-45. doi: 10.1021/bi100912m. [Article]
  12. Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K: Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4811-6. doi: 10.1073/pnas.1014542108. Epub 2011 Mar 7. [Article]
  13. Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K: An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. J Am Chem Soc. 2012 Jan 25;134(3):1442-5. doi: 10.1021/ja209881f. Epub 2012 Jan 6. [Article]
  14. Di Fonzo A, Ronchi D, Lodi T, Fassone E, Tigano M, Lamperti C, Corti S, Bordoni A, Fortunato F, Nizzardo M, Napoli L, Donadoni C, Salani S, Saladino F, Moggio M, Bresolin N, Ferrero I, Comi GP: The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency. Am J Hum Genet. 2009 May;84(5):594-604. doi: 10.1016/j.ajhg.2009.04.004. Epub 2009 Apr 30. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03147Flavin adenine dinucleotideapprovedunknownDetails