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PMID:15611048

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Citation

Puertollano, R (2005) Interactions of TOM1L1 with the multivesicular body sorting machinery. J. Biol. Chem. 280:9258-64

Abstract

Tom1L1 (Tom1-like1) and related proteins Tom1 (Target of Myb1) and Tom1L2 (Tom1-like2) constitute a new protein family characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. Recently it was demonstrated that the GAT domain of both Tom1 and Tom1L1 binds ubiquitin, suggesting that these proteins might participate in the sorting of ubiquitinated proteins into multivesicular bodies (MVBs). Here we report a novel interaction between Tom1L1 and members of the MVB sorting machinery. Specifically, we found that the VHS domain of Tom1L1 interacts with Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate), whereas a PTAP motif, located between the VHS and GAT domain of Tom1L1, is responsible for binding to TSG101 (tumor susceptibility gene 101). Myc epitope-tagged Tom1L1 showed a cytosolic distribution but was recruited to endosomes following Hrs expression. In addition, Tom1L1 possesses several tyrosine motifs at the C-terminal region that mediate interactions with members of the Src family kinases and other signaling proteins such as Grb2 and p85. We showed that a fraction of Fyn kinase localizes at endosomes and that this distribution becomes more evident after epidermal growth factor internalization. Moreover, expression of a constitutive active form of Fyn also promoted the recruitment of Tom1L1 to enlarged endosomes. Taken together, we propose that Tom1L1 could act as an intermediary between signaling and degradative pathways.

Links

PubMed Online version:10.1074/jbc.M412481200

Keywords

Endosomal Sorting Complexes Required for Transport; Green Fluorescent Proteins/chemistry; Green Fluorescent Proteins/metabolism; Humans; Phosphoproteins/chemistry; Phosphoproteins/metabolism; Polymerase Chain Reaction; Protein Binding; Proteins/chemistry; Proteins/metabolism; Recombinant Fusion Proteins/chemistry; Recombinant Fusion Proteins/metabolism; Recombinant Proteins/chemistry; Recombinant Proteins/metabolism; Saccharomyces cerevisiae/metabolism; Ubiquitin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:HGS

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75674

F

Seeded From UniProt

complete

HUMAN:HGS

located_in

GO:0005768: endosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HGS

involved_in

GO:0042176: regulation of protein catabolic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TM1L1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q99816

F

Seeded From UniProt

complete

HUMAN:TM1L1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14964

F

Seeded From UniProt

complete

HUMAN:TM1L1

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TM1L1

located_in

GO:0005768: endosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TM1L1

enables

GO:0043130: ubiquitin binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TM1L1

involved_in

GO:0043162: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FYN

located_in

GO:0005768: endosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FYN

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TS101

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75674

F

Seeded From UniProt

complete

HUMAN:TS101

enables

GO:0043130: ubiquitin binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TS101

located_in

GO:0005771: multivesicular body

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TS101

involved_in

GO:0043162: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FYN

part_of

GO:0005768: endosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FYN

part_of

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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