SECTM1 is a T/NK cell co-stimulatory molecule that is expressed in the peripheral blood by neutrophils and monocytes.Human monocytic cells also displayed a pronounced negative regulation of SECTM1 mRNA expression by LPS, while at the protein level SECTM1 expression was also shown to be regulated by IFN and LPS. This tight regulation of SECTM1 gene expression and rapid upregulation highlights its relevance in the innate immune response.

Secreted and transmembrane 1 (SECTM1), also known as K12, is a transmembrane and secreted protein with characteristics of a type 1a transmembrane protein of SECTM family. It is found in a perinuclear Golgi-like pattern and thought to be involved in hematopoietic and/or immune system processes. The human K12 protein has been shown to be primarily expressed in spleen, prostate, testis, small intestine, and in peripheral blood leukocytes. The K12 protein is expressed on the cell surface in such small amounts as to preclude detection. Alternatively, it may be that K12 on the cell surface is rapidly cleaved to generate a soluble K12 protein. Immunohistochemical analysis of peripheral blood cells shows that K12 is found in leukocytes of the myeloid lineage, with the strongest staining observed in granulocytes and no detectable expression in lymphocytes. May be involved in thymocyte signaling. It had been suggested a role for thymic microenvironment-produced K12 in regulation of thymocyte signaling and cytokine release, particularly in the setting of thymus pathology where IFN-gamma is upregulated such as myasthenia gravis. In addition, as a putative natural CD7 ligand, SECTM1/K12 may be responsible for the costimulatory role it plays in T cell activation.

SECTM1A (secreted and transmembrane 1A), is 192 amino acid (aa) protein, appears to share structural and functional characteristics with other SECTM1 proteins. Human SECTM1 can be found either found as an approximately 27 kDa intracellular type I transmembrane protein that shows a perinuclear, Golgi like staining pattern, or as a 20 kDa soluble, secreted form, and is produced by some myeloid cells and by thymic epithelia and fibroblasts. Stimulation with IFN gamma is often necessary to detect human SECTM1 expression, and it is thought to be an interferon early response gene. Mouse SECTM1A cDNA encodes a signal sequence, an extracellular domain with four potential N linked glycosylation sites, a transmembrane sequence, and a very short (approximately 6 aa) cytoplasmic sequence. SECTM1 proteins from human and mouse show species specific binding of CD7 and co stimulation of T cells, including enhancement of CD3 induced proliferation.