Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

WDR5 (P61964) - Overview - Molecular Target Synopsis

Protein


WDR5, WD repeat-containing protein 5
UniProt P61964

Also Known as WDR5_HUMAN, WDR5, BIG3

Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation. Interacts with PAXBP1; the interaction is direct and links a WDR5-containing histone methyltransferase complex to PAX7 and PAX3. Interacts with HCFC1. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30. Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7. Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts with KMT2A/MLL1 and RBBP5; the interaction is direct. Component ofthe ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1. In the complex, it probably interacts directly with KAT2A, MBIP and KAT14. Interacts with histone H3. Interacts with SETD1A. Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with PER1.

6E23
DISPLACEMENT OF WDR5 FROM CHROMATIN BY A PHARMACOLOGICAL WIN SITE INHIBITOR WITH PICOMOLAR AFFINITY
RCSB/PDB
Inspect Structure
See all 3D Structures for WDR5

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
103ENSG00000196363ENST00000608739ENSP00000477449
62ENSG00000196363ENST00000608937ENSP00000477000

Sub-cellular localization


UniProt: WDR5 is active in the following subcellular-locations: nucleus.
GO terms: WDR5 is active in the following subcellular-locations: Ada2/Gcn5/Ada3 transcription activator complex, histone acetyltransferase complex, histone methyltransferase complex, MLL1 complex, MLL3/4 complex, nucleoplasm, nucleus, Set1C/COMPASS complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project WDR5 has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, SR, COLO205

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: PE/CA-PJ15, FaDu, NCI-H1882

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HeLa-S3, HSMM

(see details)

3D Structures


For WDR5 there are:
71 structures (115 chains) solved
25 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


WDR5 has been screened with 158 compounds (205 bioactivities), 37 compounds have bioactivities that show binding affinity of <= 500nM (49 bioactivities). (see details)