FLRG (follistatin-related gene, follistatin-like-3 or FSTL3) is a member of the follistatin-module protein family, which is composed of extracellular matrix-associated glycoproteins thought to act in a paracrine manner to bind morphogens or growth/differen-tiation factors and regulate their activity during development. The FSTL3 protein contains 2 potential N-glycosylation sites and the predicted mass of the unmodified core protein is 27 kDa. FLRG is expressed in a wide range of human and murine adult tissues and its expression seems to be tightly regulated during murine embryogenesis. Immunohistochemistry reveals the presence of FLRG in the basement membrane between the dermis and the epidermis and around blood vessels.
Function:
Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such us activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiationc. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. Isoform 2 or the nuclear form is probably involved in transcriptional regulation via interaction with MLLT10.
Subcellular Location:
Secreted and Nucleus. Although alternative initiation has been demonstrated and resulted in different localization, the major source of nuclear FSTL3 appears not to depend on translation initiation at Met-27 according to.
Tissue Specificity:
Expressed in a wide range of tissues.
DISEASE:
Note=A chromosomal aberration involving FSTL3 is found in a case of B-cell chronic lymphocytic leukemia. Translocation t(11;19)(q13;p13) with CCDN1.
Similarity:
Contains 2 follistatin-like domains.
Contains 2 Kazal-like domains.
Contains 1 TB (TGF-beta binding) domain.
SWISS:
O95633
Gene ID:
10272
Database links:
Entrez Gene: 10272 Human
SwissProt: O95633 Human
Unigene: 529038 Human
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