Protein: Bone morphogenetic protein 6 (P22004)
Organism: Homo sapiens (Human)
Function: Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation. Also plays an important role in the regulation of HAMP/hepcidin expression and iron metabolism by acting as a ligand for hemojuvelin/HJV. Also acts to promote expression of HAMP, potentially via the interaction with its receptor BMPR1A/ALK3. Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2B. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target. Can also signal through non-canonical pathway such as TAZ-Hippo signaling cascade to modulate VEGF signaling by regulating VEGFR2 expression
Subcellular location: Secreted
Sequence: MPGLGRRAQWLCWWWGLLCSCCGPPPLRPPLPAAAAAAAGGQLLGDGGSPGRTEQPPPSPQSSSGFLYRRLKTQEKREMQKEILSVLGLPHRPRPLHGLQQPQPPALRQQEEQQQQQQLPRGEPPPGRLKSAPLFMLDLYNALSADNDEDGASEGERQQSWPHEAASSSQRRQPPPGAAHPLNRKSLLAPGSGSGGASPLTSAQDSAFLNDADMVMSFVNLVEYDKEFSPRQRHHKEFKFNLSQIPEGEVVTAAEFRIYKDCVMGSFKNQTFLISIYQVLQEHQHRDSDLFLLDTRVVWASEEGWLEFDITATSNLWVVTPQHNMGLQLSVVTRDGVHVHPRAAGLVGRDGPYDKQPFMVAFFKVSEVHVRTTRSASSRRRQQSRNRSTQSQDVARVSSASDYNSSELKTACRKHELYVSFQDLGWQDWIIAPKGYAANYCDGECSFPLNAHMNATNHAIVQTLVHLMNPEYVPKPCCAPTKLNAISVLYFDDNSNVILKKYRNMVVRACGCH
InterPro domains: - IPR017948: Transforming growth factor beta, conserved site (conserved_site) [430-445]
- IPR001111: TGF-beta, propeptide (domain) [63-362]
- IPR029034: Cystine-knot cytokine (homologous_superfamily) [400-513]
- IPR015615: Transforming growth factor-beta-related (family) [32-513]
- IPR001839: Transforming growth factor-beta, C-terminal (domain) [394-513]
Interaction partners: - Bone morphogenetic protein receptor type-1A
- Activin receptor type-1
- Bone morphogenetic protein receptor type-1B
- Activin receptor type-2A
- Bone morphogenetic protein receptor type-2
- Hemojuvelin
- Activin receptor type-2B
- Noggin
- Chordin
- Bone morphogenetic protein 4
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0005102 (signaling receptor binding), GO:0033612 (receptor serine/threonine kinase binding), GO:0070696 (transmembrane receptor protein serine/threonine kinase binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0023056 (positive regulation of signaling), GO:0007275 (multicellular organism development), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0065008 (regulation of biological quality), GO:0050794 (regulation of cellular process), GO:0023051 (regulation of signaling), GO:0051094 (positive regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0045597 (positive regulation of cell differentiation), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1903530 (regulation of secretion by cell), GO:0051049 (regulation of transport), GO:0060548 (negative regulation of cell death), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0031018 (endocrine pancreas development), GO:0060255 (regulation of macromolecule metabolic process), GO:0010817 (regulation of hormone levels), GO:0031324 (negative regulation of cellular metabolic process), GO:0046883 (regulation of hormone secretion), GO:0045165 (cell fate commitment), GO:0010941 (regulation of cell death), GO:0009888 (tissue development), GO:0010646 (regulation of cell communication), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0045595 (regulation of cell differentiation), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0010647 (positive regulation of cell communication), GO:0080090 (regulation of primary metabolic process), GO:0035270 (endocrine system development), GO:0045664 (regulation of neuron differentiation), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0009914 (hormone transport), GO:0010468 (regulation of gene expression), GO:0030855 (epithelial cell differentiation), GO:0003309 (type B pancreatic cell differentiation), GO:0022008 (neurogenesis), GO:0003309 (type B pancreatic cell differentiation), GO:0007399 (nervous system development), GO:0090087 (regulation of peptide transport), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051046 (regulation of secretion), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0060429 (epithelium development), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0030182 (neuron differentiation), GO:0031016 (pancreas development), GO:0042981 (regulation of apoptotic process), GO:0002066 (columnar/cuboidal epithelial cell development), GO:0043066 (negative regulation of apoptotic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0002065 (columnar/cuboidal epithelial cell differentiation), GO:0002791 (regulation of peptide secretion), GO:0048699 (generation of neurons), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045892 (negative regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0002067 (glandular epithelial cell differentiation), GO:0035883 (enteroendocrine cell differentiation), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)