SPN
This gene encodes a highly sialylated glycoprotein that functions in antigen-specific activation of T cells, and is found on the surface of thymocytes, T lymphocytes, monocytes, granulocytes, and some B lymphocytes. It contains a mucin-like extracellular domain, a transmembrane region and a carboxy-terminal intracellular region. The extracellular domain has a high proportion of serine and threonine residues, allowing extensive O-glycosylation, and has one potential N-glycosylation site, while the carboxy-terminal region has potential phosphorylation sites that may mediate transduction of activation signals. Different glycoforms of this protein have been described. In stimulated immune cells, proteolytic cleavage of the extracellular domain occurs in some cell types, releasing a soluble extracellular fragment. Defects in expression of this gene are associated with Wiskott-Aldrich syndrome. [provided by RefSeq, Sep 2017]
Function
Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN) (By similarity).
Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression of IFN-gamma by CD4+ T-cells and to a lesser extent by CD8+ T-cells (PubMed:18036228).
Plays a role in preparing T-cells for cytokine sensing and differentiation into effector cells by inducing the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR and IL4R signaling and by mediating the clustering of IFNGR with TCR (PubMed:24328034).
Acts as a major E-selectin ligand responsible for Th17 cell rolling on activated vasculature and recruitment during inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-selectin. Acts as a T-cell counter-receptor for SIGLEC1 (By similarity).
CD43 cytoplasmic tail
Protects cells from apoptotic signals, promoting cell survival.
Biological Process
Biological Process cell surface receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cellular defense responseManual Assertion Based On ExperimentTAS:ProtInc
Biological Process chemotaxisManual Assertion Based On ExperimentTAS:ProtInc
Biological Process defense response to bacteriumManual Assertion Based On ExperimentIDA:MGI
Biological Process establishment or maintenance of cell polarityManual Assertion Based On ExperimentTAS:ProtInc
Biological Process immune responseManual Assertion Based On ExperimentTAS:ProtInc
Biological Process leukocyte tethering or rollingISS:UniProtKB
Biological Process negative regulation of cell adhesionManual Assertion Based On ExperimentTAS:ProtInc
Biological Process negative regulation of T cell proliferationISS:UniProtKB
Biological Process positive regulation of T cell migrationISS:UniProtKB
Biological Process positive regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIDA:MGI
Biological Process regulation of immune responseManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of T cell migrationISS:UniProtKB
Biological Process signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Biological Process T-helper 1 cell lineage commitmentManual Assertion Based On ExperimentIDA:UniProtKB
Cellular Location
Membrane
Cell projection, microvillus
Cell projection, uropodium
Localizes to the uropodium and microvilli via its interaction with ERM proteins (EZR, RDX and MSN).
CD43 cytoplasmic tail
Nucleus
Nucleus, PML body
The sumoylated form localizes to the PML body.
Topology
Extracellular: 20-253
Helical: 254-276
Cytoplasmic: 277-400
PTM
Glycosylated; has a high content of sialic acid and O-linked carbohydrate structures.
Phosphorylation at Ser-355 is regulated by chemokines, requires its association with ERM proteins (EZR, RDX and MSN) and is essential for its function in the regulation of T-cell trafficking to lymph nodes.
Has a high content of sialic acid and O-linked carbohydrate structures.
Cleavage by CTSG releases its extracellular domain and triggers its intramembrane proteolysis by gamma-secretase releasing the CD43 cytoplasmic tail chain (CD43-ct) which translocates to the nucleus.
CD43 cytoplasmic tail
Sumoylated.
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Datasheet