Cell-surface receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. Mediates the chemorepulsant activity of semaphorins ( ). Recognizes a C-end rule (CendR) motif R/KXXR/K on its ligands which causes cellular internalization and vascular leakage . It binds to semaphorin 3A, the PLGF-2 isoform of PGF, the VEGF165 isoform of VEGFA and VEGFB ( , ). Coexpression with KDR results in increased VEGF165 binding to KDR as well as increased chemotaxis. Regulates VEGF-induced angiogenesis. Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). Regulates mitochondrial iron transport via interaction with ABCB8/MITOSUR .
(Microbial infection) Acts as a host factor for human coronavirus SARS-CoV-2 infection. Recognizes and binds to CendR motif RRAR on SARS-CoV-2 spike protein S1 which enhances SARS-CoV-2 infection.
Binds VEGF-165 and may inhibit its binding to cells (, ). May induce apoptosis by sequestering VEGF-165 . May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity.
Subcellular locations: Secreted
Subcellular locations: Mitochondrion membrane, Cell membrane, Cytoplasm
The expression of isoforms 1 and 2 does not seem to overlap. Expressed in olfactory epithelium (at protein level) . Expressed in fibroblasts (at protein level) . Expressed by the blood vessels of different tissues. In the developing embryo it is found predominantly in the nervous system. In adult tissues, it is highly expressed in heart and placenta; moderately in lung, liver, skeletal muscle, kidney and pancreas; and low in adult brain (, ). Expressed in the central nervous system, including olfactory related regions such as the olfactory tubercles and paraolfactory gyri .
The expression of isoforms 1 and 2 does not seem to overlap. Found in liver hepatocytes, kidney distal and proximal tubules.