TM4SF1

Gene Description

TM4SF1 (tumor-associated antigen L6) is a four-transmembrane glycoprotein of the L6/transmembrane-4 L-six family. It has short cytoplasmic N- and C-termini and a large extracellular loop (EC2) that bears the N-glycosylation site and is exposed at the cell surface (the epitope of the L6 monoclonal antibody). TM4SF1 resides in the plasma membrane, concentrates apically in epithelia, and is found in high-molecular-weight surface complexes; its C-terminal cysteine binds the PDZ protein SDCBP2/SITAC. It is strongly overexpressed in carcinomas and on endothelial cells, where it has been implicated in cell migration and angiogenesis, though its precise molecular function is not established.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005515 protein binding	IPI PMID:11102519 The carboxy-terminal cysteine of the tetraspanin L6 antigen ...	MODIFY	Summary: TM4SF1 C-terminal cysteine binds the PDZ protein SDCBP2/SITAC. Reason: Generic protein binding is uninformative; the paper supports binding to a PDZ-domain protein, better captured as PDZ domain binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:11102519 The carboxy-terminal cysteine of the tetraspanin L6 antigen is required for its interaction with SITAC, a novel PDZ protein
GO:0005886 plasma membrane	IDA PMID:7510285 Membrane topology of the L6 antigen and identification of th...	ACCEPT	Summary: Plasma membrane - L6 antigen is a cell-surface multi-pass membrane protein. Reason: Core location; the L6 mAb epitope is on the surface-exposed extracellular loop. Supporting Evidence: PMID:7510285 four hydrophobic regions, each long enough to span the plasma membrane
GO:0016020 membrane	IBA GO_REF:0000033	MODIFY	Summary: Generic membrane (is_active_in), inherited. Reason: Correct but general; the specific location is the plasma membrane. Proposed replacements: plasma membrane Supporting Evidence: PMID:7510285 four hydrophobic regions, each long enough to span the plasma membrane
GO:0016020 membrane	IEA GO_REF:0000120	MODIFY	Summary: Generic membrane (InterPro/SubCell). Reason: Too general; TM4SF1 is a plasma membrane protein. Proposed replacements: plasma membrane Supporting Evidence: PMID:7510285 four hydrophobic regions, each long enough to span the plasma membrane

Core Functions

Four-transmembrane cell-surface glycoprotein of the L6/TM4SF family, apical in epithelia and part of high-molecular-weight surface complexes; its C-terminus binds the PDZ scaffold SDCBP2/SITAC. Its specific molecular function is not established.

Molecular Function:

PDZ domain binding

Cellular Locations:

plasma membrane

Supporting Evidence:

PMID:11102519
The carboxy-terminal cysteine of the tetraspanin L6 antigen is required for its interaction with SITAC, a novel PDZ protein
PMID:7510285
four hydrophobic regions, each long enough to span the plasma membrane

Gene Description

Existing Annotations Review

Core Functions

Four-transmembrane cell-surface glycoprotein of the L6/TM4SF family, apical in epithelia and part of high-molecular-weight surface complexes; its C-terminus binds the PDZ scaffold SDCBP2/SITAC. Its specific molecular function is not established.

References

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Notes

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