NEDD8-activating enzyme E1 regulatory subunit

Details

Name
NEDD8-activating enzyme E1 regulatory subunit
Synonyms
  • Amyloid beta precursor protein-binding protein 1, 59 kDa
  • Amyloid protein-binding protein 1
  • APP-BP1
  • APPBP1
  • Proto-oncogene protein 1
Gene Name
NAE1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000403|NEDD8-activating enzyme E1 regulatory subunit
MAQLGKLLKEQKYDRQLRLWGDHGQEALESAHVCLINATATGTEILKNLVLPGIGSFTII
DGNQVSGEDAGNNFFLQRSSIGKNRAEAAMEFLQELNSDVSGSFVEESPENLLDNDPSFF
CRFTVVVATQLPESTSLRLADVLWNSQIPLLICRTYGLVGYMRIIIKEHPVIESHPDNAL
EDLRLDKPFPELREHFQSYDLDHMEKKDHSHTPWIVIIAKYLAQWYSETNGRIPKTYKEK
EDFRDLIRQGILKNENGAPEDEENFEEAIKNVNTALNTTQIPSSIEDIFNDDRCINITKQ
TPSFWILARALKEFVAKEGQGNLPVRGTIPDMIADSGKYIKLQNVYREKAKKDAAAVGNH
VAKLLQSIGQAPESISEKELKLLCSNSAFLRVVRCRSLAEEYGLDTINKDEIISSMDNPD
NEIVLYLMLRAVDRFHKQQGRYPGVSNYQVEEDIGKLKSCLTGFLQEYGLSVMVKDDYVH
EFCRYGAAEPHTIAAFLGGAAAQEVIKIITKQFVIFNNTYIYSGMSQTSATFQL
Number of residues
534
Molecular Weight
60245.795
Theoretical pI
5.06
GO Classification
Functions
NEDD8 activating enzyme activity / protein heterodimerization activity / ubiquitin protein ligase binding
Processes
mitotic DNA replication checkpoint / neuron apoptotic process / protein neddylation / regulation of apoptotic process / regulation of neuron apoptotic process / signal transduction
Components
cytoplasm / cytosol / nucleus / plasma membrane
General Function
Ubiquitin protein ligase binding
Specific Function
Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010003|NEDD8-activating enzyme E1 regulatory subunit (NAE1)
ATGGATGCTCAGCAAACAAAAACAAATGAAGCCAGGTTGTGGGGTGATCATGGGCAAGAG
GCTTTAGAATCTGCTCATGTTTGCCTAATAAATGCAACAGCCACAGGAACTGAAATTCTT
AAAAACTTGGTACTACCAGGTATTGGTTCGTTTACAATTATTGATGGAAATCAGGTCAGC
GGAGAAGATGCTGGAAACAATTTCTTCCTTCAAAGAAGCAGTATCGGCAAGAACCGAGCT
GAAGCTGCCATGGAATTCTTACAAGAATTAAATAGCGATGTCTCTGGAAGTTTTGTGGAA
GAGAGTCCAGAAAACCTTCTAGACAATGATCCCTCATTTTTCTGTAGGTTTACTGTTGTA
GTTGCAACTCAGCTTCCTGAAAGCACTTCACTACGCTTAGCAGATGTCCTCTGGAATTCC
CAGATTCCTCTTTTGATCTGTAGGACATATGGACTAGTTGGTTATATGAGGATCATTATA
AAAGAACATCCAGTAATAGAATCTCATCCAGATAATGCATTAGAGGATCTACGACTAGAT
AAGCCATTTCCTGAACTGAGAGAACATTTTCAGTCCTATGATTTGGATCATATGGAAAAA
AAGGACCACAGTCATACTCCATGGATTGTGATCATAGCTAAATATTTAGCACAGTGGTAT
AGTGAAACAAATGGACGAATACCTAAAACGTATAAAGAAAAAGAGGACTTCAGAGATTTG
ATTAGACAAGGAATTCTAAAAAATGAAAATGGGGCTCCAGAAGATGAAGAGAATTTTGAA
GAAGCTATTAAAAATGTGAACACAGCACTAAATACAACTCAGATCCCAAGCAGTATTGAA
GATATATTTAATGATGATCGCTGCATAAATATCACCAAACAGACTCCATCATTTTGGATT
TTAGCTCGTGCCTTAAAGGAATTTGTGGCCAAAGAGGGTCAAGGAAATTTACCTGTTCGA
GGCACAATTCCTGATATGATTGCAGATTCAGGCAAATATATAAAACTGCAAAACGTTTAC
CGTGAAAAAGCAAAGAAAGATGCTGCCGCTGTGGGTAATCATGTTGCCAAATTGCTGCAG
TCCATTGGCCAGGCACCAGAGTCCATTTCAGAGAAAGAATTAAAATTACTCTGCAGCAAT
TCTGCATTTCTTCGAGTGGTAAGATGTCGATCCTTAGCTGAAGAATATGGTTTGGATACA
ATTAACAAGGATGAAATTATTTCTAGCATGGACAATCCAGATAATGAAATAGTGTTGTAC
TTAATGTTACGGGCTGTTGATAGATTTCATAAACAACAGGGTAGATATCCAGGAGTATCT
AACTATCAAGTTGAAGAAGATATAGGAAAGTTGAAGTCTTGTCTCACTGGCTTCCTTCAG
GAATATGGTTTATCTGTAATGGTGAAAGATGATTATGTCCACGAATTTTGCCGATATGGA
GCTGCTGAGCCACATACCATTGCTGCATTCTTGGGGGGAGCTGCTGCTCAAGAGGTCATC
AAAATAATCACCAAACAATTTGTAATTTTTAATAATACTTACATTTACAGTGGCATGTCA
CAAACTTCAGCAACTTTCCAGTTGTAG
Chromosome Location
16
Locus
16q22
External Identifiers
ResourceLink
UniProtKB IDQ13564
UniProtKB Entry NameULA1_HUMAN
GenBank Protein ID1314560
GenBank Gene IDU50939
GenAtlas IDAPPBP1
HGNC IDHGNC:621
General References
  1. Chow N, Korenberg JR, Chen XN, Neve RL: APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein. J Biol Chem. 1996 May 10;271(19):11339-46. [Article]
  2. 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]
  3. Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295-308. [Article]
  4. Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A: Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001 Mar;11(3):422-35. [Article]
  5. 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]
  6. 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]
  7. Gong L, Yeh ET: Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem. 1999 Apr 23;274(17):12036-42. [Article]
  8. Chen Y, McPhie DL, Hirschberg J, Neve RL: The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons. J Biol Chem. 2000 Mar 24;275(12):8929-35. [Article]
  9. Bohnsack RN, Haas AL: Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. J Biol Chem. 2003 Jul 18;278(29):26823-30. Epub 2003 May 10. [Article]
  10. Chen Y, Liu W, McPhie DL, Hassinger L, Neve RL: APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain. J Cell Biol. 2003 Oct 13;163(1):27-33. [Article]
  11. Chen Y, Liu W, Naumovski L, Neve RL: ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis. J Neurochem. 2003 May;85(3):801-9. [Article]
  12. Park Y, Yoon SK, Yoon JB: TRIP12 functions as an E3 ubiquitin ligase of APP-BP1. Biochem Biophys Res Commun. 2008 Sep 19;374(2):294-8. doi: 10.1016/j.bbrc.2008.07.019. Epub 2008 Jul 15. [Article]
  13. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  14. 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]
  15. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  16. Walden H, Podgorski MS, Huang DT, Miller DW, Howard RJ, Minor DL Jr, Holton JM, Schulman BA: The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Mol Cell. 2003 Dec;12(6):1427-37. [Article]
  17. Walden H, Podgorski MS, Schulman BA: Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8. Nature. 2003 Mar 20;422(6929):330-4. [Article]
  18. Huang DT, Miller DW, Mathew R, Cassell R, Holton JM, Roussel MF, Schulman BA: A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat Struct Mol Biol. 2004 Oct;11(10):927-35. Epub 2004 Sep 7. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00171ATPinvestigational, nutraceuticalunknownDetails