The following text describes a protein:
Function:
An immunogenic protein essential for bacterial spreading, it elicits polar deposition of filamentous actin (actin-based motility). Inside the host (human) cell mediates nucleation and polymerization of actin molecules on the bacterial surface, which provides the propulsive force for intracellular movement and intercellular dissemination of the bacterium. During invasion of mammalian cells, triggers autophagy by binding to host ATG5. Interaction with IcsB leads to escape from the host autophagy defense system. Binds ATP and displays weak ATPase activity. Mediates polar adhesion to host cells and their invasion. The bile salt deoxycholate activates adhesion and invasion of host cells, possibly by altering IcsA's conformation. The adhesion and intercellular dissemination phenotypes can be separated.
Miscellaneous:
MISCELLANEOUS: Different strains accumulate different amounts of the intact autotransporter protein; MISCELLANEOUS: Secretion across inner membrane is dependent on the SecA and SecYEG apparatus. Intracellular polar localization precedes secretion and is independent of SecA.
Subcellular Localization:
[Outer membrane autotransporter IcsA]: Periplasm. Cell outer membrane. Cell surface. Note=This protein can be detected in infected (human) MK2 cells; [IcsA alpha domain]: Secreted. Cell surface. Note=The alpha domain is localized as a cap over the old pole of the bacterial surface. Cleavage of this fragment requires genes controlled by virB. This protein fragment can be detected in infected (human) MK2 cells. Colocalizes with SepA at the old cell pole; [Outer membrane protein IcsA translocator domain]: Cell outer membrane; Multi-pass membrane protein. Note=The cleaved C-terminal fragment (autotransporter domain) is localized in the outer membrane. This protein fragment can be detected in infected (human) MK2 cells.
Domain:
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Insertion of the C-terminal translocator domain (beta domain) in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain (alpha domain) to the bacterial cell surface, where IcsA is cleaved by IcsP (SopA) and released into the extracellular medium. This cleavage is important for the maintenance of the sharply polarized distribution of IcsA but is not a prerequisite for intracellular spreading; The N-terminus has 5 copies of an approximately 34 amino acid repeat sequence that are enriched for Gly residues (together called the GRR). The GRR interacts with the host WASL CRIB domain; Domain deletion experiments show that amino acids 1-104, and 507-620 are independently sufficient for polar localization for polar localization and that amino acids 320-433 are responsible for interaction with host ATG5 and IcsB. Other experiments show residues 1-104 are not required for polar targeting. Domain deletion experiments show that residues 103-507 are required for assembly of F-actin and for vinculin binding; Insertion mutations in the probable autochaperone domain (residues 634-735) alter protein conformation and stability. Insertion mutations in the GRR domain and IcsB-interacting domain are unable to recruit N-WASP and do not form F-actin comet tails. Combined insertion mutations (at residues 149 and 387) decrease adhesion and invasion of host cells but do not affect intercellular spreading once bacteria are inside cells. Thus the adhesion and spreading phenotypes can be separated.
Sequence:
MNQIHKFFCNMTQCSQGGAGELPTVKEKTCKLSFSPFVVGASLLLGGPIAFATPLSGTQELHFSEDNYEKLLTPVDGLSPLGAGEDGMDAWYITSSNPSHASRTKLRINSDIMISAGHGGAGDNNDGNSCGGNGGDSITGSDLSIINQGMILGGSGGSGADHNGDGGEAVTGDNLFIINGEIISGGHGGDSYSDSDGGNGGDAVTGVNLPIINKGTISGGNGGNNYGEGDGGNGGDAITGSSLSVINKGTFAGGNGGAAYGYGYDGYGGNAITGDNLSVINNGAILGGNGGHWGDAINGSNMTIANSGYIISGKEDDGTQNVAGNAIHITGGNNSLILHEGSVITGDVQVNNSSILKIINNDYTGTTPTIEGDLCAGDCTTVSLSGNKFTVSGDVSFGENSSLNLAGISSLEASGNMSFGNNVKVEAIINNWAQKDYKLLSADKGITGFSVSNISIINPLLTTGAIDYTKSYISDQNKLIYGLSWNDTDGDSHGEFNLKENAELTVSTILADNLSHHNINSWDGKSLTKSGEGTLILAEKNTYSGFTNINAGILKMGTVEAMTRTAGVIVNKGATLNFSGMNQTVNTLLNSGTVLINNINAPFLPDPVIVTGNMTLEKNGHVILNNSSSNVGQTYVQKGNWHGKGGILSLGAVLGNDNSKTDRLEIAGHASGITYVAVTNEGGSGDKTLEGVQIISTDSSDKNAFIQKGRIVAGSYDYRLKQGTVSGLNTNKWYLTSQMDNQESKQMSNQESTQMSSRRASSQLVSSLNLGEGSIHTWRPEAGSYIANLIAMNTMFSPSLYDRHGSTIVDPTTGQLSETTMWIRTVGGHNEHNLADRQLKTTANRMVYQIGGDILKTNFTDHDGLHVGIMGAYGYQDSKTHNKYTSYSSRGTVSGYTAGLYSSWFQDEKERTGLYMDAWLQYSWFNNTVKGDGLTGEKYSSKGITGALEAGYIYPTIRWTAHNNIDNALYLNPQVQITRHGVKANDYIEHNGTMVTSSGGNNIQAKLGLRTSLISQSCIDKETLRKFEPFLEVNWKWSSKQYGVIMNGMSNHQIGNRNVIELKTGVGGRLADNLSIWGNVSQQLGNNSYRDTQGILGVKYTF