WBP4

WBP4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DK1, 2JXW
Identifiers
Aliases	WBP4 , FBP21, WW domain binding protein 4
External IDs	OMIM: 604981; MGI: 109568; HomoloGene: 38287; GeneCards: WBP4; OMA:WBP4 - orthologs
Gene location (Human) Chr. Chromosome 13 (human) [1] Band 13q14.11 Start 41,061,509 bp [1] End 41,084,006 bp [1]
Gene location (Mouse) Chr. Chromosome 14 (mouse) [2] Band 14|14 D3 Start 79,697,377 bp [2] End 79,718,960 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte amniotic fluid tendon biceps brachii Achilles tendon Skeletal muscle tissue of biceps brachii muscle of thigh gastrocnemius muscle vastus lateralis muscle Top expressed in spermatocyte Paneth cell endothelial cell of lymphatic vessel genital tubercle primitive streak tail of embryo dentate gyrus of hippocampal formation granule cell epithelium of lens hair follicle substantia nigra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function zinc ion binding proline-rich region binding protein binding metal ion binding nucleic acid binding Cellular component nuclear speck spliceosomal complex nucleoplasm nucleus U2-type precatalytic spliceosome Biological process mRNA cis splicing, via spliceosome mRNA processing RNA splicing mRNA splicing, via spliceosome Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11193 22380 Ensembl ENSG00000120688 ENSMUSG00000022023 UniProt O75554 Q61048 RefSeq (mRNA) NM_007187 NM_018765 RefSeq (protein) NP_009118 NP_061235 Location (UCSC) Chr 13: 41.06 – 41.08 Mb Chr 14: 79.7 – 79.72 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

WW domain-binding protein 4 is a protein that in humans is encoded by the WBP4 gene. ^{[5] [6]}

This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A. ^[6]

Bi-allelic variants in WBP4 are responsible of spliceosomopathies leading to developmental disorders. Symptoms include hypotonia, global developmental delay, severe intellectual disability, brain, musculoskeletal, and gastrointestinal abnormalities. ^[7] Note that mutations on RNU4-2  ( ia ) gene induce also spliceosomopathies leading to intellectual disability. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000120688 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022023 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bedford MT, Reed R, Leder P (Sep 1998). "WW domain-mediated interactions reveal a spliceosome-associated protein that binds a third class of proline-rich motif: the proline glycine and methionine-rich motif". Proc Natl Acad Sci U S A. 95 (18): 10602–7. Bibcode:1998PNAS...9510602B. doi: 10.1073/pnas.95.18.10602 . PMC   27941 . PMID   9724750.
6. "Entrez Gene: WBP4 WW domain binding protein 4 (formin binding protein 21)".
7. Eden Engal, Kaisa Teele Oja, Reza Maroofian, Katrin Õunap, Maayan Salton, Hagar Mor-Shaked et al., "Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome", AJHG (2023). doi : 10.1016/j.ajhg.2023.10.013
8. Greene, D., Thys, C., Berry, I.R. et al., "Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders". Nat Med (2024). doi : 10.1038/s41591-024-03085-5

Further reading

• Takahara T, Tasic B, Maniatis T, et al. (2005). "Delay in synthesis of the 3' splice site promotes trans-splicing of the preceding 5' splice site". Mol. Cell. 18 (2): 245–51. doi: 10.1016/j.molcel.2005.03.018 . PMID   15837427.
• 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.
• Dunham A, Matthews LH, Burton J, et al. (2004). "The DNA sequence and analysis of human chromosome 13". Nature. 428 (6982): 522–8. Bibcode:2004Natur.428..522D. doi:10.1038/nature02379. PMC   2665288 . PMID   15057823.
• 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.
• 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.
• Bedford MT, Frankel A, Yaffe MB, et al. (2000). "Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains". J. Biol. Chem. 275 (21): 16030–6. doi: 10.1074/jbc.M909368199 . PMID   10748127.
• Chan DC, Bedford MT, Leder P (1996). "Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains". EMBO J. 15 (5): 1045–54. doi:10.1002/j.1460-2075.1996.tb00442.x. PMC   450002 . PMID   8605874.