afadin; ALL1 fused gene from chromosome 6 protein; protein AF-6 (MLLT4 AF6)

Function

• component of adhesion system
• associated with adherens junctions
• connects nectin to the actin cytoskeleton
• interacts with F-actin & nectin
• essential for the association of nectin & E-cadherin
• isoform 2/s-afadin does not interact with F-actin
• interacts with ZO-1 & occludin, probably indirecty
• interacts with RIT1 & RIT2 (putative)
• interacts with NRXN1 & BCR
• isoform 3 is phosphorylated on Ser-1718
• isoform 4 is phosphorylated on Ser-1799
• isoform 5 is phosphorylated on Ser-1809

Structure

• homodimer
• PDZ/DHR domain interacts with the C-terminus of nectin
• Pro-rich N-terminus domain interacts with F-actin
• contains 1 dilute domain
• contains 1 FHA domain
• contains 1 PDZ domain (DHR domain)
• contains 2 Ras-associating domains

Compartment

cell membrane; cell-cell junction, adherens junction

Alternative splicing

named isoforms=3

Pathology

• chromosomal aberration of MLLT4 associated with acute leukemias - translocation t(6;11)(q27;q23) with MLL, resulting in a rogue activator protein

More general terms

• cytoskeletal protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4301
• OMIM: https://mirror.omim.org/entry/159559
• UniProt: http://www.uniprot.org/uniprot/P55196.html