PABPC4

Poly(A) binding protein, cytoplasmic 4 (inducible form)
PDB rendering based on 1cvj.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1cvj​
Identifiers
Symbols	PABPC4 ; APP-1; APP1; PABP4; iPABP
External IDs	OMIM: 603407 MGI: 2385206 HomoloGene: 37855 ChEMBL: 5333 GeneCards: PABPC4 Gene
Gene ontology Molecular function • nucleotide binding • protein binding • poly(A) binding • poly(U) RNA binding • poly(C) RNA binding • poly(A) RNA binding Cellular component • nucleus • cytoplasm • cytoplasmic stress granule • ribonucleoprotein complex Biological process • RNA processing • RNA catabolic process • translation • blood coagulation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8761	230721
Ensembl	ENSG00000090621	ENSMUSG00000011257
UniProt	Q13310	Q6PHQ9
RefSeq (mRNA)	NM_001135653	NM_130881
RefSeq (protein)	NP_001129125	NP_570951
Location (UCSC)	Chr 1: 39.56 – 39.58 Mb	Chr 4: 123.26 – 123.3 Mb
PubMed search

Polyadenylate-binding protein 4 is a protein that in humans is encoded by the PABPC4 gene.^[1][2]

Function

Poly(A)-binding proteins (PABPs) bind to the poly(A) tail present at the 3-prime ends of most eukaryotic mRNAs. PABPC4 or IPABP (inducible PABP) was isolated as an activation-induced T-cell mRNA encoding a protein. Activation of T cells increased PABPC4 mRNA levels in T cells approximately 5-fold. PABPC4 contains 4 RNA-binding domains and proline-rich C terminus. PABPC4 is localized primarily to the cytoplasm. It is suggested that PABPC4 might be necessary for regulation of stability of labile mRNA species in activated T cells. PABPC4 was also identified as an antigen, APP1 (activated-platelet protein-1), expressed on thrombin-activated rabbit platelets. PABPC4 may also be involved in the regulation of protein translation in platelets and megakaryocytes or may participate in the binding or stabilization of polyadenylates in platelet dense granules.^[2]

Model organisms

Pabpc4 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Abnormal[3]
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
All tests and analysis from[4][5]

Model organisms have been used in the study of PABPC4 function. A conditional knockout mouse line, called Pabpc4^{tm1a(KOMP)Wtsi[6][7]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[8][9][10]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[4][11] Twenty tests were carried out on mutant mice and one significant abnormality was observed: female homozygous mutants displayed impaired glucose tolerance.^[4]

Interactions

PABPC4 has been shown to interact with PHLDA1.^[12]

References

1. Féral C, Mattéi MG, Pawlak A, Guellaën G (Nov 1999). "Chromosomal localization of three human poly(A)-binding protein genes and four related pseudogenes". Hum Genet 105 (4): 347–53. doi:10.1007/s004390051113. PMC 1865476. PMID 10543404.
2. "Entrez Gene: PABPC4 poly(A) binding protein, cytoplasmic 4 (inducible form)".
3. "Glucose tolerance test data for Pabpc4". Wellcome Trust Sanger Institute.
4. Gerdin, AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
5. Mouse Resources Portal, Wellcome Trust Sanger Institute.
6. "International Knockout Mouse Consortium".
7. "Mouse Genome Informatics".
8. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
9. Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
10. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
11. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
12. Hinz T, Flindt S, Marx A, Janssen O, Kabelitz D (May 2001). "Inhibition of protein synthesis by the T cell receptor-inducible human TDAG51 gene product". Cell. Signal. 13 (5): 345–52. doi:10.1016/S0898-6568(01)00141-3. PMID 11369516.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Yang H, Duckett CS, Lindsten T (1996). "iPABP, an inducible poly(A)-binding protein detected in activated human T cells". Mol. Cell. Biol. 15 (12): 6770–6. PMC 230930. PMID 8524242.
• Houng AK, Maggini L, Clement CY, Reed GL (1997). "Identification and structure of activated-platelet protein-1, a protein with RNA-binding domain motifs that is expressed by activated platelets". Eur. J. Biochem. 243 (1–2): 209–18. doi:10.1111/j.1432-1033.1997.0209a.x. PMID 9030741.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T (1999). "The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3'-Poly(A) tail of mRNA. Direct association of erf3/GSPT with polyadenylate-binding protein". J. Biol. Chem. 274 (24): 16677–80. doi:10.1074/jbc.274.24.16677. PMID 10358005.
• Hinz T, Flindt S, Marx A, Janssen O, Kabelitz D (2001). "Inhibition of protein synthesis by the T cell receptor-inducible human TDAG51 gene product". Cell. Signal. 13 (5): 345–52. doi:10.1016/S0898-6568(01)00141-3. PMID 11369516.
• Li J, Hawkins IC, Harvey CD, Jennings JL, Link AJ, Patton JG (2003). "Regulation of Alternative Splicing by SRrp86 and Its Interacting Proteins". Mol. Cell. Biol. 23 (21): 7437–47. doi:10.1128/MCB.23.21.7437-7447.2003. PMC 207616. PMID 14559993.
• Lehner B, Sanderson CM (2004). "A Protein Interaction Framework for Human mRNA Degradation". Genome Res. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (2004). "Functional Proteomics Mapping of a Human Signaling Pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U, Droege A, Lindenberg KS, Knoblich M, Haenig C, Herbst M, Suopanki J, Scherzinger E, Abraham C, Bauer B, Hasenbank R, Fritzsche A, Ludewig AH, Büssow K, Buessow K, Coleman SH, Gutekunst CA, Landwehrmeyer BG, Lehrach H, Wanker EE (2004). "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease". Mol. Cell 15 (6): 853–65. doi:10.1016/j.molcel.2004.09.016. PMID 15383276.
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455.
• Ong SE, Mittler G, Mann M (2005). "Identifying and quantifying in vivo methylation sites by heavy methyl SILAC". Nat. Methods 1 (2): 119–26. doi:10.1038/nmeth715. PMID 15782174.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (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.