The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its ... See more...

Aliases for WAC Gene

Aliases for WAC Gene

  • WW Domain Containing Adaptor With Coiled-Coil 2 3 5
  • WW Domain-Containing Adapter Protein With Coiled-Coil 3 4
  • PRO1741 2 3
  • BM-016 2 3
  • Wwp4 2 3
  • WW Domain-Containing Adaptor With Coiled Coil 2
  • FLJ31290 2
  • MGC10753 2
  • KIAA1844 4
  • DESSH 3
  • WAC 5

External Ids for WAC Gene

Previous GeneCards Identifiers for WAC Gene

  • GC10P028971
  • GC10P028825
  • GC10P028861

Summaries for WAC Gene

Entrez Gene Summary for WAC Gene

  • The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

GeneCards Summary for WAC Gene

WAC (WW Domain Containing Adaptor With Coiled-Coil) is a Protein Coding gene. Diseases associated with WAC include Desanto-Shinawi Syndrome and Branchial Cleft Anomalies. Among its related pathways are Metabolism of proteins and Protein ubiquitination. Gene Ontology (GO) annotations related to this gene include chromatin binding and RNA polymerase II complex binding.

UniProtKB/Swiss-Prot Summary for WAC Gene

  • Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription (PubMed:21329877). Regulates the cell-cycle checkpoint activation in response to DNA damage (PubMed:21329877). Positive regulator of amino acid starvation-induced autophagy (PubMed:22354037). Also acts as a negative regulator of basal autophagy (PubMed:26812014). Positively regulates MTOR activity by promoting, in an energy-dependent manner, the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex. This leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). May negatively regulate the ubiquitin proteasome pathway (PubMed:21329877).

Gene Wiki entry for WAC Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for WAC Gene

Genomics for WAC Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for WAC Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J028531 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 609.4 +0.6 608 4.6 HNRNPL CREB1 GATAD2A ZNF629 TFE3 LEF1 IKZF1 ZNF692 POLR2A ZNF7 WAC-AS1 WAC BAMBI
GH10J028535 Promoter/Enhancer 0.7 EPDnew ENCODE 600.7 +3.2 3174 0.2 GATA3 TCF7L2 WAC WAC-AS1 SNODB2087 BAMBI
GH10J028592 Enhancer 1.1 Ensembl ENCODE dbSUPER 19.7 +61.6 61627 3.8 ZNF629 JUND REST DPF2 HDAC1 ZNF600 FOXJ2 GATAD2B EP300 CEBPB WAC-AS1 WAC NONHSAG005483.2 MN309158 BAMBI
GH10J028587 Enhancer 1 Ensembl ENCODE dbSUPER 19.7 +54.8 54808 4.2 CEBPG PRDM1 CTCF CEBPB RBM22 JUND NR2F2 IKZF1 RAD21 HNF4A WAC-AS1 WAC NONHSAG005483.2 MN309158 BAMBI
GH10J028675 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 5 +147.0 147038 7.7 RNF2 ARHGAP35 SP1 HNRNPL ZNF629 PRDM10 LEF1 IKZF1 NFKBIZ KDM1A BAMBI WAC-AS1 RNU6-270P LYZL1 WAC piR-50444-041
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around WAC on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for WAC

Top Transcription factor binding sites by QIAGEN in the WAC gene promoter:
  • c-Myb
  • CUTL1
  • GATA-2
  • MZF-1
  • Pax-4a

Genomic Locations for WAC Gene

Genomic Locations for WAC Gene
chr10:28,532,493-28,623,112
(GRCh38/hg38)
Size:
90,620 bases
Orientation:
Plus strand
chr10:28,821,422-28,912,041
(GRCh37/hg19)
Size:
90,620 bases
Orientation:
Plus strand

Genomic View for WAC Gene

Genes around WAC on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
WAC Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for WAC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for WAC Gene

Proteins for WAC Gene

  • Protein details for WAC Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BTA9-WAC_HUMAN
    Recommended name:
    WW domain-containing adapter protein with coiled-coil
    Protein Accession:
    Q9BTA9
    Secondary Accessions:
    • A8K2A9
    • C9JBT9
    • D3DRW5
    • D3DRW6
    • D3DRW7
    • Q53EN9
    • Q5JU75
    • Q5JU77
    • Q5VXK0
    • Q5VXK2
    • Q8TCK1
    • Q96DP3
    • Q96FW6
    • Q96JI3

    Protein attributes for WAC Gene

    Size:
    647 amino acids
    Molecular mass:
    70724 Da
    Quaternary structure:
    • Interacts (via coiled coil domain) with RNF20, RNF40 and UBE2A (PubMed:21329877). Interacts (via WW domain) with RNA polymerase II (PubMed:21329877). Interacts with MTOR and other components of the MTOR pathway including RPTOR, RUVBL1, RUVBL2, TTI1 and TTI2 (PubMed:26812014).
    SequenceCaution:
    • Sequence=AAH04258.2; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAH10356.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB47473.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 3]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Alternative splice isoforms for WAC Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for WAC Gene

Post-translational modifications for WAC Gene

  • Phosphorylated on tyrosine residues.
  • Ubiquitination at Lys466 and Lys486
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for WAC Gene

Domains & Families for WAC Gene

Gene Families for WAC Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for WAC Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for WAC Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ55932, highly similar to Homo sapiens WW domain containing adaptor with coiled-coil (WAC), transcript variant 2, mRNA (B4DMH1_HUMAN)
  • WW domain-containing adapter protein with coiled-coil (WAC_HUMAN)
genes like me logo Genes that share domains with WAC: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for WAC Gene

Function for WAC Gene

Molecular function for WAC Gene

UniProtKB/Swiss-Prot Function:
Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription (PubMed:21329877). Regulates the cell-cycle checkpoint activation in response to DNA damage (PubMed:21329877). Positive regulator of amino acid starvation-induced autophagy (PubMed:22354037). Also acts as a negative regulator of basal autophagy (PubMed:26812014). Positively regulates MTOR activity by promoting, in an energy-dependent manner, the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex. This leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). May negatively regulate the ubiquitin proteasome pathway (PubMed:21329877).

Phenotypes From GWAS Catalog for WAC Gene

Gene Ontology (GO) - Molecular Function for WAC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000993 RNA polymerase II complex binding IDA 21329877
GO:0003682 chromatin binding IDA 21329877
GO:0005515 protein binding IPI 16189514
genes like me logo Genes that share ontologies with WAC: view
genes like me logo Genes that share phenotypes with WAC: view

Human Phenotype Ontology for WAC Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for WAC Gene

MGI Knock Outs for WAC:
  • Wac Wac<tm2b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for WAC Gene

miRTarBase miRNAs that target WAC

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for WAC

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for WAC Gene

Localization for WAC Gene

Subcellular locations from UniProtKB/Swiss-Prot for WAC Gene

Nucleus speckle. Nucleus. Note=In distinct nuclear speckles. Colocalizes with pre-mRNA processing complexes. {ECO:0000250 UniProtKB:Q924H7}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for WAC gene
Compartment Confidence
nucleus 5
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for WAC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,TAS 22354037
GO:0005654 nucleoplasm TAS --
GO:0005681 spliceosomal complex IEA --
GO:0016607 nuclear speck IEA --
genes like me logo Genes that share ontologies with WAC: view

Pathways & Interactions for WAC Gene

genes like me logo Genes that share pathways with WAC: view

Gene Ontology (GO) - Biological Process for WAC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006325 chromatin organization IEA --
GO:0006974 cellular response to DNA damage stimulus IMP 21329877
GO:0010390 histone monoubiquitination IMP 21329877
GO:0016239 positive regulation of macroautophagy IMP 22354037
GO:0016567 protein ubiquitination TAS --
genes like me logo Genes that share ontologies with WAC: view

No data available for SIGNOR curated interactions for WAC Gene

Drugs & Compounds for WAC Gene

No Compound Related Data Available

Transcripts for WAC Gene

mRNA/cDNA for WAC Gene

3 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
24 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for WAC

Alternative Splicing Database (ASD) splice patterns (SP) for WAC Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c ^ 10a · 10b ^ 11a · 11b · 11c ^ 12a · 12b ^ 13 ^ 14a · 14b ^ 15a · 15b ^ 16a · 16b ·
SP1: - - - - - - - - -
SP2: - - - - - -
SP3: - - - - - - - - - -
SP4: - - - - - -
SP5: - - - - - -
SP6: - -
SP7: - - -
SP8: - - - - - - - - - - - - - - - -
SP9:
SP10:
SP11: - - - -
SP12: - -
SP13: - - -
SP14:
SP15:
SP16:
SP17:

ExUns: 16c ^ 17 ^ 18a · 18b · 18c ^ 19a · 19b · 19c ^ 20a · 20b
SP1: - - -
SP2: - - -
SP3:
SP4:
SP5: -
SP6: - - -
SP7: -
SP8:
SP9: - -
SP10: -
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:

Relevant External Links for WAC Gene

GeneLoc Exon Structure for
WAC

Expression for WAC Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for WAC Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for WAC Gene

This gene is overexpressed in Heart (31.6), CD8 Tcells (8.5), and Liver, secretome (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for WAC Gene



Protein tissue co-expression partners for WAC Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for WAC

SOURCE GeneReport for Unigene cluster for WAC Gene:

Hs.743224

Evidence on tissue expression from TISSUES for WAC Gene

  • Nervous system(5)
  • Kidney(4.5)
  • Liver(4.5)
  • Lung(3.5)
  • Blood(3.3)
  • Eye(3.1)
  • Intestine(2.9)
  • Skin(2.7)
  • Heart(2.6)
  • Spleen(2.4)
  • Bone marrow(2.4)
  • Muscle(2.4)
  • Lymph node(2.4)
  • Thyroid gland(2.3)
  • Stomach(2.2)
genes like me logo Genes that share expression patterns with WAC: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for WAC Gene

Orthologs for WAC Gene

This gene was present in the common ancestor of animals.

Orthologs for WAC Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia WAC 30 31
  • 99.74 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia -- 31
  • 97 (a)
OneToMany
-- 31
  • 96 (a)
OneToMany
-- 31
  • 96 (a)
OneToMany
WAC 30
  • 95.63 (n)
-- 31
  • 91 (a)
OneToMany
-- 31
  • 89 (a)
OneToMany
Cow
(Bos Taurus)
Mammalia WAC 30 31
  • 94.96 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia WAC 31
  • 94 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia WAC 31
  • 94 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Wac 30 17 31
  • 92.83 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia RGD1562407 30
  • 92.62 (n)
Chicken
(Gallus gallus)
Aves WAC 30 31
  • 87.78 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia WAC 31
  • 89 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia wac 30
  • 80.78 (n)
Str.2721 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.17846 30
Zebrafish
(Danio rerio)
Actinopterygii waca 30 31
  • 66.67 (n)
OneToMany
wacb 31
  • 61 (a)
OneToMany
WAC (3 of 3) 31
  • 55 (a)
OneToMany
wufc13f04 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG8949 31
  • 18 (a)
OneToOne
Species where no ortholog for WAC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for WAC Gene

ENSEMBL:
Gene Tree for WAC (if available)
TreeFam:
Gene Tree for WAC (if available)
Aminode:
Evolutionary constrained regions (ECRs) for WAC: view image

Paralogs for WAC Gene

No data available for Paralogs for WAC Gene

Variants for WAC Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for WAC Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
642241 Pathogenic: not provided 28,608,424(+) AAATG/A FRAMESHIFT_VARIANT
662757 Pathogenic: not provided 28,533,604(+) C/T NONSENSE,INTRON_VARIANT
668542 Likely Benign: not provided 28,535,760(+) G/A INTRON_VARIANT
709566 Benign: not provided 28,617,776(+) A/G SYNONYMOUS_VARIANT
718173 Benign: not provided 28,616,240(+) G/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for WAC Gene

Structural Variations from Database of Genomic Variants (DGV) for WAC Gene

Variant ID Type Subtype PubMed ID
esv2734606 CNV deletion 23290073
nsv1069036 CNV deletion 25765185
nsv951260 CNV duplication 24416366
nsv951261 CNV duplication 24416366

Variation tolerance for WAC Gene

Residual Variation Intolerance Score: 22.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.75; 66.50% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for WAC Gene

Human Gene Mutation Database (HGMD)
WAC
SNPedia medical, phenotypic, and genealogical associations of SNPs for
WAC

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for WAC Gene

Disorders for WAC Gene

MalaCards: The human disease database

(6) MalaCards diseases for WAC Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search WAC in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

WAC_HUMAN
  • DeSanto-Shinawi syndrome (DESSH) [MIM:616708]: An autosomal dominant syndrome characterized by developmental delay, hypotonia, behavioral problems, eye abnormalities, constipation, feeding difficulties, seizures and sleep problems. Patients exhibit dysmorphic features, including broad/prominent forehead, synophrys and/or bushy eyebrows, depressed nasal bridge and bulbous nasal tip. Additional variable features are posteriorly rotated ears, hirsutism, deep-set eyes, thin upper lip, inverted nipples, hearing loss and branchial cleft anomalies. {ECO:0000269 PubMed:25356899, ECO:0000269 PubMed:26264232}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Note=Defects in WAC are the cause of a form of intellectual disability characterized by hypotonia, behavioral problems and distinctive facial dysmorphisms including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. {ECO:0000269 PubMed:26757981}.
genes like me logo Genes that share disorders with WAC: view

No data available for Genatlas for WAC Gene

Publications for WAC Gene

  1. De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila. (PMID: 26757981) Lugtenberg D … Vissers LE (European journal of human genetics : EJHG 2016) 3 4
  2. WAC loss-of-function mutations cause a recognisable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome. (PMID: 26264232) DeSanto C … Shinawi M (Journal of medical genetics 2015) 3 4
  3. Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. (PMID: 22354037) McKnight NC … Tooze SA (The EMBO journal 2012) 3 4
  4. WAC, a functional partner of RNF20/40, regulates histone H2B ubiquitination and gene transcription. (PMID: 21329877) Zhang F … Yu X (Molecular cell 2011) 3 4
  5. A probability-based approach for high-throughput protein phosphorylation analysis and site localization. (PMID: 16964243) Beausoleil SA … Gygi SP (Nature biotechnology 2006) 3 4

Products for WAC Gene

Sources for WAC Gene