title: The ulcerative colitis marker protein WAFL interacts with accessory proteins in endocytosis.
abstract: Ulcerative colitis (UC) is one of the major forms of inflammatory bowel disease with unknown cause. A molecular marker, WAFL, has recently been found to be up-regulated in the inflamed colonic mucosa of UC patients. Towards understanding biological function of WAFL, we analyzed proteins interacting with WAFL in HEK-293 cells by immunoprecipitation and mass spectrometry. Among four proteins found to specifically interact with WAFL, both KIAA0196 and KIAA1033 bind to alpha-appendage of the adaptor protein complex 2 (AP2), which acts as an interaction hub for accessory proteins in endocytosis mediated by clathrin-coated vesicle (CCV). The specific interaction between WAFL and KIAA0196 was also confirmed in human colorectal carcinoma HCT-116 cells by co-immunoprecipitation with specific antibodies. Meta-analyses of the databases of expressed genes suggest that the three genes are co-expressed in many tissues and cell types, and that their molecular function may be classified in the category of 'membrane traffic protein'. Therefore, these results suggest that WAFL may play an important role in endocytosis and subsequent membrane trafficking by interacting with AP2 through KIAA0196 and KIAA1033.
authors.affiliation: Genome Institute of Singapore, Singapore.
authors.forename: You Fu
authors.initials: YF
authors.lastname: Pan
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Viklund
authors.forename: Heng Hang
authors.initials: HH
authors.lastname: Tsai
authors.forename: Sven
authors.initials: S
authors.lastname: Pettersson
authors.forename: Ichiro N
authors.initials: IN
authors.lastname: Maruyama
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000379:methods; D003093:Colitis, Ulcerative / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology; D004705:Endocytosis; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
chemical_list: C540489:FKBP15 protein, human; D011506:Proteins; D050656:Transcription Factor AP-2; C495767:WAS protein, human; C517003:WASHC5 protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D051300:Wiskott-Aldrich Syndrome Protein Family; D022021:Tacrolimus Binding Proteins