NameE3 ubiquitin-protein ligase Midline-1
Synonyms
  • 6.3.2.-
  • FXY
  • Midin
  • Putative transcription factor XPRF
  • RING finger protein 59
  • RING finger protein Midline-1
  • RNF59
  • TRIM18
  • Tripartite motif-containing protein 18
  • XPRF
Gene NameMID1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009861|E3 ubiquitin-protein ligase Midline-1
METLESELTCPICLELFEDPLLLPCAHSLCFNCAHRILVSHCATNESVESITAFQCPTCR
HVITLSQRGLDGLKRNVTLQNIIDRFQKASVSGPNSPSETRRERAFDANTMTSAEKVLCQ
FCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEPIPDSHIRGLMCLEHED
EKVNMYCVTDDQLICALCKLVGRHRDHQVAALSERYDKLKQNLESNLTNLIKRNTELETL
LAKLIQTCQHVEVNASRQEAKLTEECDLLIEIIQQRRQIIGTKIKEGKVMRLRKLAQQIA
NCKQCIERSASLISQAEHSLKENDHARFLQTAKNITERVSMATASSQVLIPEINLNDTFD
TFALDFSREKKLLECLDYLTAPNPPTIREELCTASYDTITVHWTSDDEFSVVSYELQYTI
FTGQANVVSLCNSADSWMIVPNIKQNHYTVHGLQSGTKYIFMVKAINQAGSRSSEPGKLK
TNSQPFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGR
HYWEVVISGSTWYAIGLAYKSAPKHEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPH
LRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVCPTFTVWNKCLTIITGLPIPDHL
DCTEQLP
Number of residues667
Molecular Weight75249.94
Theoretical pINot Available
GO Classification
Functions
  • protein homodimerization activity
  • identical protein binding
  • protein heterodimerization activity
  • ubiquitin protein ligase binding
  • phosphoprotein binding
  • microtubule binding
  • zinc ion binding
  • ligase activity
Processes
  • negative regulation of microtubule depolymerization
  • cytokine-mediated signaling pathway
  • interferon-gamma-mediated signaling pathway
  • positive regulation of stress-activated MAPK cascade
  • microtubule cytoskeleton organization
  • pattern specification process
  • protein localization to microtubule
Components
  • microtubule associated complex
  • cytosol
  • spindle
  • microtubule
General FunctionZinc ion binding
Specific FunctionHas E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDO15344
UniProtKB Entry NameTRI18_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0013956|E3 ubiquitin-protein ligase Midline-1 (MID1)
ATGGAAACACTGGAGTCAGAACTGACCTGCCCTATTTGTCTGGAGCTCTTTGAGGACCCT
CTTCTACTGCCCTGCGCACACAGCCTCTGCTTCAACTGCGCCCACCGCATCCTAGTATCA
CACTGTGCCACCAACGAGTCTGTGGAGTCCATCACCGCCTTCCAGTGCCCCACCTGCCGG
CATGTCATCACCCTCAGCCAGCGAGGTCTAGACGGGCTCAAGCGCAACGTCACCCTACAG
AACATCATCGACAGGTTCCAGAAAGCATCAGTGAGCGGGCCCAACTCTCCCAGCGAGACC
CGTCGGGAGCGGGCCTTTGACGCCAACACCATGACCTCCGCCGAGAAGGTCCTCTGCCAG
TTTTGTGACCAGGATCCTGCCCAGGACGCTGTGAAGACCTGTGTCACTTGTGAAGTATCC
TACTGTGACGAGTGCCTGAAAGCCACTCACCCGAATAAGAAGCCCTTTACAGGCCATCGT
CTGATTGAGCCAATTCCGGACTCTCACATCCGGGGGCTGATGTGCTTGGAGCATGAGGAT
GAGAAGGTGAATATGTACTGTGTGACCGATGACCAGTTAATCTGTGCCTTGTGTAAACTG
GTTGGGCGGCACCGCGATCATCAGGTGGCAGCTTTGAGTGAGCGCTATGACAAATTGAAG
CAAAACTTAGAGAGTAACCTCACCAACCTTATTAAGAGGAACACAGAACTGGAGACCCTT
TTGGCTAAACTCATCCAAACCTGTCAACATGTTGAAGTCAATGCATCACGTCAAGAAGCC
AAATTGACAGAGGAGTGTGATCTTCTCATTGAGATCATTCAGCAAAGACGACAGATTATT
GGAACCAAGATCAAAGAAGGGAAGGTGATGAGGCTTCGCAAACTGGCTCAGCAGATTGCA
AACTGCAAACAGTGCATTGAGCGGTCAGCATCACTCATCTCCCAAGCGGAACACTCTCTG
AAGGAGAATGATCATGCGCGTTTCCTACAGACTGCTAAGAATATCACCGAGAGAGTCTCC
ATGGCAACTGCATCCTCCCAGGTTCTAATTCCTGAAATCAACCTCAATGACACATTTGAC
ACCTTTGCCTTAGATTTTTCCCGAGAGAAGAAACTGCTAGAATGTCTGGATTACCTTACA
GCTCCCAACCCTCCCACAATTAGAGAAGAGCTCTGCACAGCTTCATATGACACCATCACT
GTGCATTGGACCTCCGATGATGAGTTCAGCGTGGTCTCCTACGAGCTCCAGTACACCATA
TTCACCGGACAAGCCAACGTCGTTAGTCTGTGTAATTCGGCTGATAGCTGGATGATAGTA
CCCAACATCAAGCAGAACCACTACACGGTGCACGGTCTGCAGAGCGGCACCAAGTACATC
TTCATGGTCAAGGCCATCAACCAGGCGGGCAGCCGCAGCAGTGAGCCTGGGAAGTTGAAG
ACAAACAGCCAACCATTTAAACTGGATCCCAAATCTGCTCATCGAAAACTGAAGGTGTCC
CATGATAACTTGACAGTAGAACGTGATGAGTCATCATCCAAGAAGAGTCACACACCTGAA
CGCTTCACCAGCCAGGGGAGCTATGGAGTAGCTGGAAATGTGTTTATTGATAGTGGCCGG
CATTATTGGGAAGTGGTCATAAGTGGAAGCACATGGTATGCCATTGGTCTTGCTTACAAA
TCAGCCCCGAAGCATGAATGGATTGGGAAGAACTCTGCTTCCTGGGCGCTCTGCCGCTGC
AACAATAACTGGGTGGTGAGACACAATAGCAAGGAAATCCCCATTGAGCCTGCCCCCCAC
CTCCGGCGCGTGGGCATCCTGCTGGACTATGATAACGGCTCTATCGCCTTTTATGATGCT
TTGAACTCCATCCACCTCTACACCTTCGACGTCGCATTTGCGCAGCCTGTTTGCCCCACC
TTCACCGTGTGGAACAAGTGTCTGACGATTATCACTGGGCTCCCTATCCCAGACCATTTG
GACTGCACAGAGCAGCTGCCGTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:7095
Chromosome LocationX
LocusNot Available
References
  1. Quaderi NA, Schweiger S, Gaudenz K, Franco B, Rugarli EI, Berger W, Feldman GJ, Volta M, Andolfi G, Gilgenkrantz S, Marion RW, Hennekam RC, Opitz JM, Muenke M, Ropers HH, Ballabio A: Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Nat Genet. 1997 Nov;17(3):285-91. 9354791
  2. Perry J, Feather S, Smith A, Palmer S, Ashworth A: The human FXY gene is located within Xp22.3: implications for evolution of the mammalian X chromosome. Hum Mol Genet. 1998 Feb;7(2):299-305. 9425238
  3. Van den Veyver IB, Cormier TA, Jurecic V, Baldini A, Zoghbi HY: Characterization and physical mapping in human and mouse of a novel RING finger gene in Xp22. Genomics. 1998 Jul 15;51(2):251-61. 9722948
  4. Cox TC, Allen LR, Cox LL, Hopwood B, Goodwin B, Haan E, Suthers GK: New mutations in MID1 provide support for loss of function as the cause of X-linked Opitz syndrome. Hum Mol Genet. 2000 Oct 12;9(17):2553-62. 11030761
  5. Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A: The tripartite motif family identifies cell compartments. EMBO J. 2001 May 1;20(9):2140-51. 11331580
  6. 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
  7. 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. 15489334
  8. Cainarca S, Messali S, Ballabio A, Meroni G: Functional characterization of the Opitz syndrome gene product (midin): evidence for homodimerization and association with microtubules throughout the cell cycle. Hum Mol Genet. 1999 Aug;8(8):1387-96. 10400985
  9. Schweiger S, Foerster J, Lehmann T, Suckow V, Muller YA, Walter G, Davies T, Porter H, van Bokhoven H, Lunt PW, Traub P, Ropers HH: The Opitz syndrome gene product, MID1, associates with microtubules. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2794-9. 10077590
  10. Trockenbacher A, Suckow V, Foerster J, Winter J, Krauss S, Ropers HH, Schneider R, Schweiger S: MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Nat Genet. 2001 Nov;29(3):287-94. 11685209
  11. Short KM, Hopwood B, Yi Z, Cox TC: MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders. BMC Cell Biol. 2002;3:1. Epub 2002 Jan 4. 11806752
  12. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  13. 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. 18669648
  14. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  15. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  16. Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR, Kraemer BC, Schweiger S, Spiller BW, Wadzinski BE: Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit alpha4, altering PP2A stability and microtubule-associated protein phosphorylation. J Biol Chem. 2012 Jul 13;287(29):24207-15. doi: 10.1074/jbc.M112.368613. Epub 2012 May 21. 22613722
  17. 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. 24275569
  18. Massiah MA, Simmons BN, Short KM, Cox TC: Solution structure of the RBCC/TRIM B-box1 domain of human MID1: B-box with a RING. J Mol Biol. 2006 Apr 28;358(2):532-45. Epub 2006 Feb 20. 16529770
  19. Gaudenz K, Roessler E, Quaderi N, Franco B, Feldman G, Gasser DL, Wittwer B, Horst J, Montini E, Opitz JM, Ballabio A, Muenke M: Opitz G/BBB syndrome in Xp22: mutations in the MID1 gene cluster in the carboxy-terminal domain. Am J Hum Genet. 1998 Sep;63(3):703-10. 9718340
  20. So J, Suckow V, Kijas Z, Kalscheuer V, Moser B, Winter J, Baars M, Firth H, Lunt P, Hamel B, Meinecke P, Moraine C, Odent S, Schinzel A, van der Smagt JJ, Devriendt K, Albrecht B, Gillessen-Kaesbach G, van der Burgt I, Petrij F, Faivre L, McGaughran J, McKenzie F, Opitz JM, Cox T, Schweiger S: Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1 mutations. Am J Med Genet A. 2005 Jan 1;132A(1):1-7. 15558842