Protein-coding gene in the species Homo sapiens
WDR5 Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CNX , 2CO0 , 2G99 , 2G9A , 2GNQ , 2H13 , 2H14 , 2H68 , 2H6K , 2H6N , 2H6Q , 2H9L , 2H9M , 2H9N , 2H9P , 2O9K , 3EG6 , 3EMH , 3MXX , 3N0D , 3N0E , 3P4F , 3PSL , 3SMR , 3UR4 , 3UVK , 3UVL , 3UVM , 3UVN , 3UVO , 4A7J , 4CY1 , 4CY2 , 4ERQ , 4ERY , 4ERZ , 4ES0 , 4ESG , 4EWR , 4GM3 , 4GM8 , 4GM9 , 4GMB , 4IA9 , 4O45 , 4QL1 , 4Y7R , 5EAL , 5EAP , 5EAR , 4QQE , 5EAM
Identifiers Aliases WDR5 , BIG-3, CFAP89, SWD3, WD repeat-containing protein 5, WD repeat domain 5External IDs OMIM : 609012 ; MGI : 2155884 ; HomoloGene : 59931 ; GeneCards : WDR5 ; OMA :WDR5 - orthologs Wikidata
WD repeat-containing protein 5 is a protein that in humans is encoded by the WDR5 gene .[ 5] [ 6]
This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 7 WD repeats. Alternatively spliced transcript variants encoding the same protein have been identified.[ 6]
Interactions
WDR5 has been shown to interact with Host cell factor C1 [ 7] [ 8] and MLL .[ 7] It also interacts with the long non-coding RNA HOTTIP and to the lncRNA NeST .[ 9] [ 10]
WDR5 is a key determinant for MYC recruitment to chromatin [ 11]
References
^ a b c GRCh38: Ensembl release 89: ENSG00000196363 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026917 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Gori F, Divieti P, Demay MB (Dec 2001). "Cloning and characterization of a novel WD-40 repeat protein that dramatically accelerates osteoblastic differentiation" . J Biol Chem . 276 (49): 46515– 22. doi :10.1074/jbc.M105757200 . PMID 11551928 .
^ a b "Entrez Gene: WDR5 WD repeat domain 5" .
^ a b Yokoyama, Akihiko; Wang Zhong; Wysocka Joanna; Sanyal Mrinmoy; Aufiero Deborah J; Kitabayashi Issay; Herr Winship; Cleary Michael L (Jul 2004). "Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression" . Mol. Cell. Biol . 24 (13): 5639– 49. doi :10.1128/MCB.24.13.5639-5649.2004 . ISSN 0270-7306 . PMC 480881 . PMID 15199122 .
^ Wysocka, Joanna; Myers Michael P; Laherty Carol D; Eisenman Robert N; Herr Winship (Apr 2003). "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1" . Genes Dev . 17 (7): 896– 911. doi :10.1101/gad.252103 . ISSN 0890-9369 . PMC 196026 . PMID 12670868 .
^ Wells, Alexandria C.; Pobezinskaya, Elena L.; Pobezinsky, Leonid A. (April 2020). "Non-coding RNAs in CD8 T cell biology" . Molecular Immunology . 120 : 67– 73. doi :10.1016/j.molimm.2020.01.023 . ISSN 1872-9142 . PMC 7093237 . PMID 32085976 .
^ Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, et al. (2011). "A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression" . Nature . 472 (7341): 120– 4. Bibcode :2011Natur.472..120W . doi :10.1038/nature09819 . PMC 3670758 . PMID 21423168 .
^ Thomas, L. R.; Tansey, W. P. (2015). "Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC" . Molecular Cell . 58 (3): 1– 13. doi :10.1016/j.molcel.2015.02.028 . PMC 4427524 . PMID 25818646 .
Further reading
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899– 903. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 . PMC 139241 . PMID 12477932 .
Wysocka J, Myers MP, Laherty CD, et al. (2003). "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1" . Genes Dev . 17 (7): 896– 911. doi :10.1101/gad.252103 . PMC 196026 . PMID 12670868 .
Gori F, Demay MB (2004). "BIG-3, a novel WD-40 repeat protein, is expressed in the developing growth plate and accelerates chondrocyte differentiation in vitro" . Endocrinology . 145 (3): 1050– 4. doi :10.1210/en.2003-1314 . PMID 14657013 .
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs" . Nat. Genet . 36 (1): 40– 5. doi :10.1038/ng1285 . PMID 14702039 .
Yokoyama A, Wang Z, Wysocka J, et al. (2004). "Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression" . Mol. Cell. Biol . 24 (13): 5639– 49. doi :10.1128/MCB.24.13.5639-5649.2004 . PMC 480881 . PMID 15199122 .
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121– 7. doi :10.1101/gr.2596504 . PMC 528928 . PMID 15489334 .
Andersen JS, Lam YW, Leung AK, et al. (2005). "Nucleolar proteome dynamics". Nature . 433 (7021): 77– 83. Bibcode :2005Natur.433...77A . doi :10.1038/nature03207 . PMID 15635413 . S2CID 4344740 .
Wysocka J, Swigut T, Milne TA, et al. (2005). "WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development" . Cell . 121 (6): 859– 72. doi :10.1016/j.cell.2005.03.036 . PMID 15960974 . S2CID 17521631 .
Dou Y, Milne TA, Tackett AJ, et al. (2005). "Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF" . Cell . 121 (6): 873– 85. doi :10.1016/j.cell.2005.04.031 . PMID 15960975 . S2CID 14717470 .
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173– 8. Bibcode :2005Natur.437.1173R . doi :10.1038/nature04209 . PMID 16189514 . S2CID 4427026 .
Gori F, Friedman L, Demay MB (2006). "Wdr5, a novel WD repeat protein, regulates osteoblast and chondrocyte differentiation in vivo". Journal of Musculoskeletal & Neuronal Interactions . 5 (4): 338– 9. PMID 16340128 .
Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration" . Cell . 125 (4): 801– 14. doi :10.1016/j.cell.2006.03.032 . PMID 16713569 . S2CID 13709685 .
Ruthenburg AJ, Wang W, Graybosch DM, et al. (2006). "Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex" . Nat. Struct. Mol. Biol . 13 (8): 704– 12. doi :10.1038/nsmb1119 . PMC 4698793 . PMID 16829959 .
Couture JF, Collazo E, Trievel RC (2006). "Molecular recognition of histone H3 by the WD40 protein WDR5". Nat. Struct. Mol. Biol . 13 (8): 698– 703. doi :10.1038/nsmb1116 . PMID 16829960 . S2CID 26165068 .
Dou Y, Milne TA, Ruthenburg AJ, et al. (2006). "Regulation of MLL1 H3K4 methyltransferase activity by its core components". Nat. Struct. Mol. Biol . 13 (8): 713– 9. doi :10.1038/nsmb1128 . PMID 16878130 . S2CID 12849159 .
Schuetz A, Allali-Hassani A, Martín F, et al. (2006). "Structural basis for molecular recognition and presentation of histone H3 by WDR5" . EMBO J . 25 (18): 4245– 52. doi :10.1038/sj.emboj.7601316 . PMC 1570438 . PMID 16946699 .
Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry" . Mol. Syst. Biol . 3 (1): 89. doi :10.1038/msb4100134 . PMC 1847948 . PMID 17353931 .
Bryan AF, Wang J, Howard GC, et al. (2020). "WDR5 is a conserved regulator of protein synthesis gene expression" . Nucleic Acids Research . 48 (6): 2924– 2941. doi :10.1093/nar/gkaa051 . PMC 7102967 . PMID 31996893 .
PDB gallery
2cnx : WDR5 AND HISTONE H3 LYSINE 4 DIMETHYL COMPLEX AT 2.1 ANGSTROM
2co0 : WDR5 AND UNMODIFIED HISTONE H3 COMPLEX AT 2.25 ANGSTROM
2g99 : Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5
2g9a : Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5
2gnq : Structure of wdr5
2h13 : Crystal structure of WDR5/histone H3 complex
2h14 : Crystal of WDR5 (apo-form)
2h68 : Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex
2h6k : Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex
2h6n : Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex
2h6q : Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex
2h9l : WDR5delta23
2h9m : WDR5 in complex with unmodified H3K4 peptide
2h9n : WDR5 in complex with monomethylated H3K4 peptide
2h9p : WDR5 in complex with trimethylated H3K4 peptide
2o9k : WDR5 in Complex with Dimethylated H3K4 Peptide