Hmdb loader
Survey
Identification
HMDB Protein ID HMDBP09263
Secondary Accession Numbers
  • 15091
Name NEDD4-like E3 ubiquitin-protein ligase WWP2
Synonyms
  1. AIP2
  2. Atrophin-1-interacting protein 2
  3. WW domain-containing protein 2
Gene Name WWP2
Protein Type Enzyme
Biological Properties
General Function Involved in acid-amino acid ligase activity
Specific Function E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells (ESCs) the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation- induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular
Function
binding
catalytic activity
ligase activity
protein binding
ligase activity, forming carbon-nitrogen bonds
acid-amino acid ligase activity
Process
metabolic process
macromolecule metabolic process
macromolecule modification
protein modification process
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location Chromosome:1
Locus 16q22.1
SNPs WWP2
Gene Sequence
>2613 bp
ATGGCATCTGCCAGCTCTAGCCGGGCAGGAGTGGCCCTGCCTTTTGAGAAGTCTCAGCTC
ACTTTGAAAGTGGTGTCCGCAAAGCCCAAGGTGCATAATCGTCAACCTCGAATTAACTCC
TACGTGGAGGTGGCGGTGGATGGACTCCCCAGTGAGACCAAGAAGACTGGGAAGCGCATT
GGGAGCTCTGAGCTTCTCTGGAATGAGATCATCATTTTGAATGTCACGGCACAGAGTCAT
TTAGATTTAAAGGTCTGGAGCTGCCATACCTTGAGAAATGAACTGCTAGGCACCGCATCT
GTCAACCTCTCCAACGTCTTGAAGAACAATGGGGGCAAAATGGAGAACATGCAGCTGACC
CTGAACCTGCAGACGGAGAACAAAGGCAGCGTTGTCTCAGGCGGAGAGCTGACAATTTTC
CTGGACGGGCCAACTGTTGATCTGGGAAATGTGCCTAATGGCAGTGCCCTGACAGATGGA
TCACAGCTGCCTTCGAGAGACTCCAGTGGAACAGCAGTAGCTCCAGAGAACCGGCACCAG
CCCCCCAGCACAAACTGCTTTGGTGGAAGATCCCGGACGCACAGACATTCGGGTGCTTCA
GCCAGAACAACCCCAGCAACCGGCGAGCAAAGCCCCGGTGCTCGGAGCCGGCACCGCCAG
CCCGTCAAGAACTCAGGCCACAGTGGCTTGGCCAATGGCACAGTGAATGATGAACCCACA
ACAGCCACTGATCCCGAAGAACCTTCCGTTGTTGGTGTGACGTCCCCACCTGCTGCACCC
TTGAGTGTGACCCCGAATCCCAACACGACTTCTCTCCCTGCCCCAGCCACACCGGCTGAA
GGAGAGGAACCCAGCACTTCGGGTACACAGCAGCTCCCAGCGGCTGCCCAGGCCCCCGAC
GCTCTGCCTGCTGGATGGGAACAGCGAGAGCTGCCCAACGGACGTGTCTATTATGTTGAC
CACAATACCAAGACCACCACCTGGGAGCGGCCCCTTCCTCCAGGCTGGGAAAAACGCACA
GATCCCCGAGGCAGGTTTTACTATGTGGATCACAATACTCGGACCACCACCTGGCAGCGT
CCGACCGCGGAGTACGTGCGCAACTATGAGCAGTGGCAGTCGCAGCGGAATCAGCTCCAG
GGGGCCATGCAGCACTTCAGCCAAAGATTCCTCTACCAGTCTTCGAGTGCTTCGACTGAC
CATGATCCCCTGGGCCCCCTCCCTCCTGGCTGGGAGAAGAGACAGGACAATGGACGGGTG
TATTACGTGAACCATAACACTCGCACGACCCAGTGGGAGGATCCCCGGACCCAGGGGATG
ATCCAGGAACCAGCTCTGCCCCCAGGATGGGAGATGAAATACACCAGCGAGGGGGTGCGA
TACTTTGTGGACCACAATACCCGCACCACCACCTTTAAGGATCCTCGCCCGGGGTTTGAG
TCGGGGACGAAGCAAGGTTCCCCTGGTGCTTATGACCGCAGTTTTCGGTGGAAGTATCAC
CAGTTCCGTTTCCTCTGCCATTCAAATGCCCTACCTAGCCACGTGAAGATCAGCGTTTCC
AGGCAGACGCTTTTCGAAGATTCCTTCCAACAGATCATGAACATGAAACCCTATGACCTG
CGCCGCCGGCTCTACATCATCATGCGTGGCGAGGAGGGCCTGGACTATGGGGGCATCGCC
AGAGAGTGGTTTTTCCTCCTGTCTCATGAGGTGCTCAACCCTATGTATTGTTTATTTGAA
TATGCCGGAAAGAACAATTACTGCCTGCAGATCAACCCCGCCTCCTCCATCAACCCGGAC
CACCTCACCTACTTTCGCTTTATAGGCAGATTCATCGCCATGGCGCTGTACCATGGAAAG
TTCATCGACACGGGCTTCACCCTCCCTTTCTACAAGCGGATGCTCAATAAGAGACCAACC
CTGAAAGACCTGGAGTCCATTGACCCTGAGTTCTACAACTCCATTGTCTGGATCAAAGAG
AACAACCTGGAAGAATGTGGCCTGGAGCTGTACTTCATCCAGGACATGGAGATACTGGGC
AAGGTGACGACCCACGAGCTGAAGGAGGGCGGCGAGAGCATCCGGGTCACAGAGGAGAAC
AAGGAAGAGTACATCATGCTGCTGACTGACTGGCGTTTCACCCGAGGCGTGGAAGAGCAG
ACCAAAGCCTTCCTGGATGGCTTCAACGAGGTGGCCCCGCTGGAGTGGCTGCGCTACTTT
GACGAGAAAGAGCTGGAGCTGATGCTGTGCGGCATGCAGGAGATAGACATGAGCGACTGG
CAGAAGAGCACCATCTACCGGCACTACACCAAGAACAGCAAGCAGATCCAGTGGTTCTGG
CAGGTGGTGAAGGAGATGGACAACGAGAAGAGGATCCGGCTGCTGCAGTTTGTCACCGGT
ACCTGCCGCCTGCCCGTCGGGGGATTTGCCGAACTCATCGGTAGCAACGGACCACAGAAG
TTTTGCATTGACAAAGTTGGCAAGGAAACCTGGCTGCCCAGAAGCCACACCTGCTTCAAC
CGTCTGGATCTTCCACCCTACAAGAGCTACGAACAGCTGAGAGAGAAGCTGCTGTATGCC
ATTGAGGAGACCGAGGGCTTTGGACAGGAGTAA
Protein Properties
Number of Residues 870
Molecular Weight 98911.4
Theoretical pI 7.13
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>NEDD4-like E3 ubiquitin-protein ligase WWP2
MASASSSRAGVALPFEKSQLTLKVVSAKPKVHNRQPRINSYVEVAVDGLPSETKKTGKRI
GSSELLWNEIIILNVTAQSHLDLKVWSCHTLRNELLGTASVNLSNVLKNNGGKMENMQLT
LNLQTENKGSVVSGGELTIFLDGPTVDLGNVPNGSALTDGSQLPSRDSSGTAVAPENRHQ
PPSTNCFGGRSRTHRHSGASARTTPATGEQSPGARSRHRQPVKNSGHSGLANGTVNDEPT
TATDPEEPSVVGVTSPPAAPLSVTPNPNTTSLPAPATPAEGEEPSTSGTQQLPAAAQAPD
ALPAGWEQRELPNGRVYYVDHNTKTTTWERPLPPGWEKRTDPRGRFYYVDHNTRTTTWQR
PTAEYVRNYEQWQSQRNQLQGAMQHFSQRFLYQSSSASTDHDPLGPLPPGWEKRQDNGRV
YYVNHNTRTTQWEDPRTQGMIQEPALPPGWEMKYTSEGVRYFVDHNTRTTTFKDPRPGFE
SGTKQGSPGAYDRSFRWKYHQFRFLCHSNALPSHVKISVSRQTLFEDSFQQIMNMKPYDL
RRRLYIIMRGEEGLDYGGIAREWFFLLSHEVLNPMYCLFEYAGKNNYCLQINPASSINPD
HLTYFRFIGRFIAMALYHGKFIDTGFTLPFYKRMLNKRPTLKDLESIDPEFYNSIVWIKE
NNLEECGLELYFIQDMEILGKVTTHELKEGGESIRVTEENKEEYIMLLTDWRFTRGVEEQ
TKAFLDGFNEVAPLEWLRYFDEKELELMLCGMQEIDMSDWQKSTIYRHYTKNSKQIQWFW
QVVKEMDNEKRIRLLQFVTGTCRLPVGGFAELIGSNGPQKFCIDKVGKETWLPRSHTCFN
RLDLPPYKSYEQLREKLLYAIEETEGFGQE
GenBank ID Protein 40806207
UniProtKB/Swiss-Prot ID O00308
UniProtKB/Swiss-Prot Entry Name WWP2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_007014.3
GeneCard ID WWP2
GenAtlas ID WWP2
HGNC ID HGNC:16804
References
General References
  1. 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 ]
  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. [PubMed:15489334 ]
  3. 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. [PubMed:19413330 ]
  4. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [PubMed:16964243 ]
  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. [PubMed:15616553 ]
  6. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  7. Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM: Identification of novel human WW domain-containing proteins by cloning of ligand targets. J Biol Chem. 1997 Jun 6;272(23):14611-6. [PubMed:9169421 ]
  8. McDonald FJ, Western AH, McNeil JD, Thomas BC, Olson DR, Snyder PM: Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. Am J Physiol Renal Physiol. 2002 Sep;283(3):F431-6. [PubMed:12167593 ]
  9. Harvey KF, Shearwin-Whyatt LM, Fotia A, Parton RG, Kumar S: N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein. J Biol Chem. 2002 Mar 15;277(11):9307-17. Epub 2001 Dec 17. [PubMed:11748237 ]
  10. Mund T, Pelham HR: Control of the activity of WW-HECT domain E3 ubiquitin ligases by NDFIP proteins. EMBO Rep. 2009 May;10(5):501-7. doi: 10.1038/embor.2009.30. Epub 2009 Apr 3. [PubMed:19343052 ]
  11. Wood JD, Yuan J, Margolis RL, Colomer V, Duan K, Kushi J, Kaminsky Z, Kleiderlein JJ, Sharp AH, Ross CA: Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins. Mol Cell Neurosci. 1998 Jun;11(3):149-60. [PubMed:9647693 ]
  12. Galinier R, Gout E, Lortat-Jacob H, Wood J, Chroboczek J: Adenovirus protein involved in virus internalization recruits ubiquitin-protein ligases. Biochemistry. 2002 Dec 3;41(48):14299-305. [PubMed:12450395 ]
  13. Wiesner S, Ogunjimi AA, Wang HR, Rotin D, Sicheri F, Wrana JL, Forman-Kay JD: Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell. 2007 Aug 24;130(4):651-62. [PubMed:17719543 ]
  14. Xu H, Wang W, Li C, Yu H, Yang A, Wang B, Jin Y: WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells. Cell Res. 2009 May;19(5):561-73. doi: 10.1038/cr.2009.31. [PubMed:19274063 ]
  15. Chen A, Gao B, Zhang J, McEwen T, Ye SQ, Zhang D, Fang D: The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination. Mol Cell Biol. 2009 Oct;29(19):5348-56. doi: 10.1128/MCB.00407-09. Epub 2009 Aug 3. [PubMed:19651900 ]