Src is the human homolog of the v-Src gene of the rous sarcoma virus, also designated avian sarcoma virus or ASV. Src was the first proto-oncogenic non-receptor tyrosine kinase characterized in human. The Src family, which has common structural motifs, is composed of nine members in vertebrates, including Src, Yes, Fgr, Frk, Fyn, Lyn, Hck, Lck and Blk. Src-family kinases transduce signals that are involved in the control of a variety of cellular processes, including proliferation, differentiation, motility and adhesion. Src-family ki-nases contain an amino-terminal cell membrane anchor followed by an SH3 domain and an SH2 domain, which are involved in modular association and activation, respectively. Src-family kinases, which are normally maintained in an inactive state and can be activated transiently during cellular events such as mitosis. Different subcellular localizations of Src-family kinases may be important for the regulation of specific cellular processes such as mitogenesis, cytoskeletal organization and membrane trafficking. c-Fgr is a human non-receptor tyrosine kinase family member that was discovered by using a probe toward the v-Fgr portion of the cell-derived domain of Gardner-Rasheed feline sarcoma virus. The human c-Fgr gene encodes a 529 amino acid protein.
Function:
Fgr is a member of the Src family of non-receptor tyrosine kinases. It is expressed in neutrophils, monocytes, macrophages and natural killer cells. Expression of Fgr is developmentally regulated and required in normal myelomonocytic differentiation in vivo. HL-60 cells induced to differentiate with retinoic acid express high levels of Fgr.
Subunit:
Interacts with ITGB1, ITGB2, MS4A2/FCER1B, FCER1G, FCGR2A and/or FCGR2B. Interacts (via SH2 domain) with SYK (tyrosine phosphorylated). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with PTK2/FAK1. Interacts (via SH2 domain) with HCLS1 (tyrosine phosphorylated by SYK). Interacts with SIRPA and PTPNS1. Interacts (not phosphorylated on tyrosine residues) with CBL; FGR tyrosine phosphorylation promotes dissociation. Interacts with PIK3R1 and FASLG (By similarity).
Subcellular Location:
Cell membrane; Lipid-anchor; Cytoplasmic side Probable. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection ?ruffle membrane. Cytoplasm ?cytosol. Cytoplasm ?cytoskeleton. Mitochondrion inner membrane. Mitochondrion intermembrane space. Note: Detected in mitochondrial intermembrane space and at inner membranes. Colocalizes with actin fibers at membrane ruffles. Detected at plasma membrane lipid rafts.
Tissue Specificity:
Detected in neutrophils, monocytes and natural killer cells (at protein level). Detected in monocytes and large lymphocytes.
Post-translational modifications:
Ubiquitinated. Becomes ubiquitinated in response to ITGB2 signaling; this does not lead to degradation.
Phosphorylated. Autophosphorylated on tyrosine residues. Becomes phosphorylated in response to FCGR2A and/or FCGR2B engagement, cell adhesion and signaling by ITGB2. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412.
DISEASE:
Note=Mutations that cause aberrant kinase activation can confer oncogene activity and promote aberrant cell proliferation.
Similarity:
Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
Contains 1 protein kinase domain.
Contains 1 SH2 domain.
Contains 1 SH3 domain.
SWISS:
P09769
Gene ID:
2268
Database links:
Entrez Gene: 2268 Human
Entrez Gene: 14191 Mouse
NCBI: 4885235 Human
Omim: 164940 Human
SwissProt: P09769 Human
SwissProt: P14234 Mouse
Unigene: 1422 Human
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