SCGF is a novel innate immune protector against infection.
SARS-CoV-2-infected patients with higher serum SCGF level are asymptomatic (632). The finding indicates
that serum SCGF level determines onset of SARS-CoV-2 infection, and more importantly, SCGF could 
control a novel protective innate immune mechanisms against infection, for example by binding to SARS-CoV-2
spike protein to protect ACE2+ cells from viral invasion. Alternatively SCGF competes with SARS-CoV-2
spike protein through RGD peptide for binding to integrinα5β1 of target cells and resultantly inhibits viral
invasion into cells (
667,668). As for 2018-2019 outbreak of Andes orthohantavirus pulmonary syndrome in
Argentina, reduced serum SCGF level is associated with hantavirus spreaders compared to non-spreaders, and
among spreaders, notably with superspreaders compared to non-superspreaders (
636). Like SARS-CoV-2
infection SCGF could be a critical player of innate immunity against hantavirus infection.

Scgf gene expression is up-regulatedin vitro in rainbow trout head kidney cells in response to fungal PAMPs
including  β-glucan peptide and furfurman (
663). SCGF could exhibit innate immunity against fungus infection,
e.g. Malassezia furfur, like same C-type lectin dectin-2 that is a receptor for furfurman.

NF-κB regulates  scgf positively or negatively?
   Gene network plays a key role in cell proliferation. As forscgf, an interaction with NF-κB is important but
results in diverse and complex effects depending on cell types and experimental design. Overexpression and/or
knockdown of each or both of  scgf and NF-κB clarify the interaction-induced effects in a variety of cells.

SCGF interactome: Sav1, Cep85, Traf2/7, XIAP
   Protein-protein interaction database  BioGRID3.5presents a list of SCGF-interacting proteins. They are
demonstrated using affinity purification mass spectrometry of HA-tagged SCGF expressed in HEK293T cells.
In particular, several proteins below play a crucial role in malignancy, cell proliferation and apoptosis.
   Sav1 (Salvador homolog 1) interacts with Mst1/2 to activate LATS1/2 and inhibits YAP/TAZ-TEAD1-4
pathway in Hippo signal transduction to suppress cell proliferation. Liver-specific  sav1knockout induces
hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis
(NASH) model mice (591). SCGF binds to SAV1 to unleash the SAV1-induced inhibition in Hippo pathway
resulting in HCC progression. SCGF-SAV1 mediated mechanism in HCC promotion is consistent with the
clinical finding that  scgf is a poor prognostic signature gene in HCC (587). Anti-scgf therapy is rational for
anti-HCC therapy.
   Cep85 is located in centrosome but little characterized. SCGF is immunohistochemically detected in
centrosome (The Human Protein Atlas), indicating that SCGF-Cep85 interaction in centrosome fulfills some
function in cell division.
   Traf2/7 and XIAP are major apoptotic proteins. SCGF is predicted to block apoptosis by an interaction
with them. SCGF-induced inhibition of apoptosis favorably accelerates malignant cell growth.
   Anti-scgf  therapy contributes to eradicate  scgf-upregulated malignancies, and SCGF is reasonably
administered to treat  scgf-downregulated diseases, e.g. aplastic anemia.

SCGF Receptor (SCGFR)
  SCGFR is unidentified yet. SCGFR is predictedly expressed on stem cells themselves, and minority  of  stem
cell population in the normal tissues makes it difficult to recover SCGFR+cells enough to analyze  SCGF-
SCGFR interaction and identify SCGFR gene. A possible candidate for identifying SCGFR seems to  be
malignant cell lines of leukemia or cancer origin, particularly their Hoechst 33342-excluding side population can
be promising.
  Identification of SCGFR is a prerequisite for analyzing proliferation mechanisms of stem cells, even if SCGF
takes a part in making physiologically quiescent stem cells enter into the cell cycle in response to  certain
stimuli. SCGFR, if identified, could provide more important proliferation mechanisms of normal and  cancer
stem cells and further enable regulating an SCGF-SCGFR interaction to treat cancer.

What function does exosomal SCGF carry out?
Is SCGF a transcriptokine bifunctioning as cytokine and intracellular regulator?
   SCGF is extracellularly secreted or released into exosomes/microvesicles from a variety of cells including
MSCs, normal and cancer cells, and acts on the ambient and remote cells. SCGF also possibly remains
intracellularly. SCGF binds to SCGFR and/or integrin, is incorporated along microtubules by the guidance of
elevator proteins or through exosomes, and carries out some function in the cytoplasm and intracellular
organelles, e.g. centrosome. SCGF can be a protein bifunctioning as cytokine (SCGFR- and/or integrin-
mediated signal transduction) and intracellular regulator (transcription factor and protein-protein interaction)
for cell division and proliferation

SCGF, a therapeutic target for cancer and leukemia cells
   Apoptosis is induced in cancer cells through SCGF exhaustion using anti-SCGF antibody or  scgf siRNA.
SCGF is a potential therapeutic target for cancer and leukemia cells including their stem cells.

What type of sugar does SCGF bind?
Sugar target for SCGF has not yet been identified. Tetranectin, C-type lectin roughly akin to SCGF, does not
bind to sugar, implicating that SCGF does not bind to any specific sugar although it has a C-type lectin