Biomarker: BMP

Histology type: endometrial carcinoma

Country: Sweden

Followed up time :

Conclusion: Our results suggest that BMP signaling promotes EC tumorigenesis, and that TWSG1 antagonizes BMP7 in EC. BMP signaling inhibitors, in combination with chemotherapy, might be useful in the treatment of EC patients.

Funtion description: Ishikawa cells secreted higher amounts of BMP2 compared with ovarian cancer cell lines. Exogenous BMP2 stimulation enhanced EC cell sphere formation via c-KIT induction. BMP2 also induced EMT of EC cells, and promoted migration by induction of SLUG. The BMP receptor kinase inhibitor LDN193189 augmented the growth inhibitory effects of carboplatin. Analyses of mRNAs of several BMP antagonists revealed that TWSG1 mRNA was abundantly expressed in Ishikawa cells. TWSG1 suppressed BMP7-induced, but not BMP2-induced, EC cell sphere formation and migration.

Funtion Uniprot: Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis (PubMed:18436533, PubMed:31019025, PubMed:24362451). Induces cartilage and bone formation (PubMed:3201241). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2 (PubMed:15064755, PubMed:17295905, PubMed:18436533). Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A (PubMed:7791754). In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Can also signal through non-canonical pathways such as ERK/MAP kinase signaling cascade that regulates osteoblast differentiation (PubMed:20851880, PubMed:16771708). Stimulates also the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A phosphorylation which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation (PubMed:24362451).

UniProt ID: P12643

UniProt Link: https://www.uniprot.org/uniprotkb/P12643/entry

Biological function from UniProt: #Chondrogenesis #Differentiation #Osteogenesis

Molecular function from UniProt:

Tissue specificity from UniProt: 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.

Subcellular UniProt: #Secreted

Alternative name from UniProt:

Recommended name: Bone morphogenetic protein 2

Gene name from HGNC: BMP2 (BMP2A)

HPA class: Cancer-related genes Disease related genes Human disease related genes

AlphaFold DB: P12643

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P12643

HPA link: https://www.proteinatlas.org/ENSG00000125845-BMP2

Tissue specificity RNA from HPA: Low tissue specificity

Single cell type specificity Cell type enhanced (Basal keratinocytes, Alveolar cells type 2, Distal enterocytes, Suprabasal keratinocytes)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Vesicles

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000125845-BMP2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000125845-BMP2/pathology/endometrial+cancer

Survival figure legend: Overall survival was analyzed using RNA-Seq data of KM plotter, which contained 542 EC patients

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346149/figure/ijms-22-07882-f001/

Phenotype ID: 112600$ 617877

Disease: Brachydactyly A2 (BDA2)$ The disease is caused by variants affecting the gene represented in this entry

Note1: The gene represented in this entry is involved in disease pathogenesis. Duplications of a cis-regulatory element located approximately 110 kb downstream of BMP2 have been found in BDA2 families. They likely cause altered BMP2 expression with pathological consequences $ The disease is caused by variants affecting the gene represented in this entry

OMIM: 112261

OMIM link1: https://www.omim.org/entry/112600 $https://www.omim.org/entry/617877

OMIM link2: https://www.omim.org/entry/112261

HGNC ID: HGNC:1069

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1069