From NCBI Gene: Hemochromatosis type 1Brachydactyly type A2

     From NCBI Gene: This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Duplication of a regulatory region downstream of this gene causes a form of brachydactyly characterized by a malformed index finger and second toe in human patients. [provided by RefSeq, Jul 2016] From UniProt: Induces cartilage and bone formation (PubMed:3201241). Stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A- ATF4 pathway. BMP2 activation of EIF2AK3 stimulates phosphorylation of EIF2A which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation. In addition stimulates TMEM119, which upregulates the expression of ATF4 (PubMed:24362451).

The following transcription factors affect gene expression:

• NF-kappaB
• NF-kappaB1
• Nkx2-5
• MEF-2A
• Sox9
• Sox5

Tissue specificity:

Particularly abundant in lung, spleen and colon and in low but significant levels in heart, brain, placenta, liver, skeletal muscle, kidney, pancreas, prostate, ovary and small intestine.

Molecular Function:

• Retinol Dehydrogenase Activity
• Receptor Binding
• Cytokine Activity
• Transforming Growth Factor Beta Receptor Binding
• Phosphatase Activator Activity
• Co-Receptor Binding
• Smad Binding
• Protein Heterodimerization Activity
• Bmp Receptor Binding

Biological Processes:

• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Activation Of Mapk Activity
• Skeletal System Development
• Osteoblast Differentiation
• Branching Involved In Ureteric Bud Morphogenesis
• Response To Hypoxia
• In Utero Embryonic Development
• Epithelial To Mesenchymal Transition
• Positive Regulation Of Protein Phosphorylation
• Positive Regulation Of Endothelial Cell Proliferation
• Chondrocyte Differentiation
• Bmp Signaling Pathway Involved In Heart Induction
• Atrioventricular Valve Morphogenesis
• Endocardial Cushion Morphogenesis
• Negative Regulation Of Wnt Signaling Pathway Involved In Heart Development
• Proteoglycan Metabolic Process
• Regulation Of Transcription, Dna-Templated
• Protein Phosphorylation
• Inflammatory Response
• Notch Signaling Pathway
• Cell-Cell Signaling
• Heart Development
• Negative Regulation Of Cell Proliferation
• Embryo Development
• Animal Organ Morphogenesis
• Positive Regulation Of Gene Expression
• Positive Regulation Of Epithelial To Mesenchymal Transition
• Positive Regulation Of Pathway-Restricted Smad Protein Phosphorylation
• Negative Regulation Of Steroid Biosynthetic Process
• Positive Regulation Of Phosphatase Activity
• Telencephalon Development
• Telencephalon Regionalization
• Positive Regulation Of Wnt Signaling Pathway
• Bone Mineralization
• Positive Regulation Of Cell Migration
• Positive Regulation Of Bone Mineralization
• Bmp Signaling Pathway
• Protein Destabilization
• Negative Regulation Of Aldosterone Biosynthetic Process
• Positive Regulation Of Osteoblast Proliferation
• Cardiocyte Differentiation
• Embryonic Heart Tube Anterior/Posterior Pattern Specification
• Bone Mineralization Involved In Bone Maturation
• Growth
• Odontogenesis Of Dentin-Containing Tooth
• Positive Regulation Of Odontogenesis
• Regulation Of Odontogenesis Of Dentin-Containing Tooth
• Positive Regulation Of Apoptotic Process
• Positive Regulation Of Mapk Cascade
• Negative Regulation Of Insulin-Like Growth Factor Receptor Signaling Pathway
• Cell Fate Commitment
• Positive Regulation Of Fat Cell Differentiation
• Positive Regulation Of Neuron Differentiation
• Positive Regulation Of Osteoblast Differentiation
• Positive Regulation Of Ossification
• Negative Regulation Of Cell Cycle
• Negative Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Positive Regulation Of Astrocyte Differentiation
• Mesenchymal Cell Differentiation
• Inner Ear Development
• Negative Regulation Of Calcium-Independent Cell-Cell Adhesion
• Cardiac Muscle Cell Differentiation
• Cardiac Muscle Tissue Morphogenesis
• Pericardium Development
• Corticotropin Hormone Secreting Cell Differentiation
• Thyroid-Stimulating Hormone-Secreting Cell Differentiation
• Cardiac Epithelial To Mesenchymal Transition
• Pathway-Restricted Smad Protein Phosphorylation
• Smad Protein Signal Transduction
• Mesenchyme Development
• Positive Regulation Of Wnt Signaling Pathway By Bmp Signaling Pathway
• Positive Regulation Of Cartilage Development
• Positive Regulation Of Erk1 And Erk2 Cascade
• Cellular Response To Organic Cyclic Compound
• Cellular Response To Bmp Stimulus
• Mesenchymal Cell Proliferation Involved In Ureteric Bud Development
• Negative Regulation Of Canonical Wnt Signaling Pathway
• Positive Regulation Of P38mapk Cascade
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter Involved In Cellular Response To Chemical Stimulus
• Positive Regulation Of Pri-Mirna Transcription From Rna Polymerase Ii Promoter
• Negative Regulation Of Cortisol Biosynthetic Process
• Negative Regulation Of Cardiac Muscle Cell Differentiation