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    Grem2 gremlin 2, DAN family BMP antagonist [ Mus musculus (house mouse) ]

    Gene ID: 23893, updated on 5-Mar-2024

    Summary

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    Official Symbol
    Grem2provided by MGI
    Official Full Name
    gremlin 2, DAN family BMP antagonistprovided by MGI
    Primary source
    MGI:MGI:1344367
    See related
    Ensembl:ENSMUSG00000050069 AllianceGenome:MGI:1344367
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Prdc; Gremlin2
    Summary
    Enables BMP binding activity; heparin binding activity; and identical protein binding activity. Involved in several processes, including determination of dorsal identity; embryonic body morphogenesis; and regulation of signal transduction. Located in extracellular space. Is expressed in several structures, including chondrocranium; integument; intestine smooth muscle circular layer; lung; and neural tube. Human ortholog(s) of this gene implicated in tooth agenesis. Orthologous to human GREM2 (gremlin 2, DAN family BMP antagonist). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Broad expression in ovary adult (RPKM 15.0), lung adult (RPKM 14.2) and 20 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Grem2 in Genome Data Viewer
    Location:
    1 H3; 1 81.08 cM
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 1 NC_000067.7 (174661352..174749386, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 1 NC_000067.6 (174833785..174921911, complement)

    Chromosome 1 - NC_000067.7Genomic Context describing neighboring genes Neighboring gene formin 2 Neighboring gene STARR-seq mESC enhancer starr_03094 Neighboring gene lines homolog 2 pseudogene Neighboring gene predicted gene, 51689 Neighboring gene STARR-seq mESC enhancer starr_03095 Neighboring gene STARR-seq mESC enhancer starr_03096 Neighboring gene STARR-seq mESC enhancer starr_03097 Neighboring gene STARR-seq mESC enhancer starr_03098 Neighboring gene STARR-seq mESC enhancer starr_03100 Neighboring gene regulator of G protein signaling 7 Neighboring gene predicted gene, 53483 Neighboring gene STARR-seq mESC enhancer starr_03101 Neighboring gene STARR-positive B cell enhancer ABC_E5859 Neighboring gene STARR-seq mESC enhancer starr_03102 Neighboring gene predicted gene, 36307

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Deletion of Gremlin-2 alters estrous cyclicity and disrupts female fertility in mice†. Rydze RT, et al. Biol Reprod, 2021 Nov 15. PMID 34333627, Free PMC Article
    2. Gremlin2 Regulates the Differentiation and Function of Cardiac Progenitor Cells via the Notch Signaling Pathway. Li W, et al. Cell Physiol Biochem, 2018. PMID 29794428
    3. Malformation of incisor teeth in Grem2⁻/⁻ mice. Vogel P, et al. Vet Pathol, 2015 Jan. PMID 24686385
    4. BMP Antagonist Gremlin 2 Limits Inflammation After Myocardial Infarction. Sanders LN, et al. Circ Res, 2016 Jul 22. PMID 27283840, Free PMC Article
    5. The onset of heat-induced testicular calcification in mice: involvement of the telomeric locus on chromosome 1. Chihara M, et al. Am J Pathol, 2014 Sep. PMID 25041854

    See all (36) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The inhibitory effect of Gremlin-2 on adipogenesis suppresses breast cancer cell growth and metastasis.
      Title: The inhibitory effect of Gremlin-2 on adipogenesis suppresses breast cancer cell growth and metastasis.
    2. Deletion of Gremlin-2 alters estrous cyclicity and disrupts female fertility in micedagger.
      Title: Deletion of Gremlin-2 alters estrous cyclicity and disrupts female fertility in mice†.
    3. Grem2 knockdown inhibited cardiomyocyte differentiation, and this effect was similar to that of Notch1 pathway inhibition in vitro. Grem2 enhances the protective effect of cardiac progenitor cells on heart function in a mouse model of myocardial infarction.
      Title: Gremlin2 Regulates the Differentiation and Function of Cardiac Progenitor Cells via the Notch Signaling Pathway.
    4. Grem2 provides a molecular barrier that controls the extent of inflammatory cell infiltration by suppressing BMP2 after myocardial infarction.
      Title: BMP Antagonist Gremlin 2 Limits Inflammation After Myocardial Infarction.
    5. Grem2 expression is regulated during development and embryonic stem cell differentiation.
      Title: Gremlin 2 promotes differentiation of embryonic stem cells to atrial fate by activation of the JNK signaling pathway.
    6. PRDC binds heparin with high affinity and that heparin binding to PRDC interferes with BMP antagonism.
      Title: Structure of protein related to Dan and Cerberus: insights into the mechanism of bone morphogenetic protein antagonism.
    7. We show that Tbx2 directly represses Grem1 in distal regions of the posterior limb mesenchyme allowing Bone morphogenetic protein (Bmp) signaling to abrogate Fgf4/9/17 expression in the overlying epithelium.
      Title: Tbx2 terminates shh/fgf signaling in the developing mouse limb bud by direct repression of gremlin1.
    8. Through a combination of biophysical and biochemical studies, the authors determined that PRDC forms biologically active dimers that potently inhibit BMP ligands.
      Title: Members of the DAN family are BMP antagonists that form highly stable noncovalent dimers.
    9. The differential regulation of Gremlin2 gene expressions by BMP2 may explain the critical function of these genes during osteoblast differentiation.
      Title: BMP2 differentially regulates the expression of Gremlin1 and Gremlin2, the negative regulators of BMP function, during osteoblast differentiation.
    10. PRDC expression in osteoblasts suppresses differentiation and that reduction of PRDC expression promotes osteogenesis in vitro. PRDC is accordingly identified as a potential novel therapeutic target for the regulation of bone formation.
      Title: Protein related to DAN and cerberus (PRDC) inhibits osteoblastic differentiation and its suppression promotes osteogenesis in vitro.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    General gene information

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    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables BMP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables BMP binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables cytokine activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables heparin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables receptor ligand activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in animal organ morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cytokine-mediated signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in determination of dorsal identity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in embryonic body morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within multicellular organism development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of BMP signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of cytokine activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in sequestering of BMP from receptor via BMP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sequestering of BMP from receptor via BMP binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    gremlin-2
    Names
    Gremlin1
    cysteine knot superfamily 1, BMP antagonist 2
    gremlin 2 homolog, cysteine knot superfamily
    protein related to DAN and cerberus

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001421483.1 → NP_001408412.1  gremlin-2 precursor

      Status: VALIDATED

      Source sequence(s)
      AC117627
      UniProtKB/Swiss-Prot
      O88273
      UniProtKB/TrEMBL
      Q3TST1

    2. NM_001421484.1 → NP_001408413.1  gremlin-2 precursor

      Status: VALIDATED

      Source sequence(s)
      AC117627
      UniProtKB/Swiss-Prot
      O88273
      UniProtKB/TrEMBL
      Q3TST1

    3. NM_001421485.1 → NP_001408414.1  gremlin-2 precursor

      Status: VALIDATED

      Source sequence(s)
      AC117627
      UniProtKB/Swiss-Prot
      O88273
      UniProtKB/TrEMBL
      Q3TST1

    4. NM_001421486.1 → NP_001408415.1  gremlin-2 precursor

      Status: VALIDATED

      Source sequence(s)
      AC117627
      UniProtKB/Swiss-Prot
      O88273
      UniProtKB/TrEMBL
      Q3TST1

    5. NM_011825.2 → NP_035955.1  gremlin-2 precursor

      See identical proteins and their annotated locations for NP_035955.1

      Status: VALIDATED

      Source sequence(s)
      AC117627
      Consensus CDS
      CCDS15545.1
      UniProtKB/Swiss-Prot
      O88273
      UniProtKB/TrEMBL
      Q3TST1
      Related
      ENSMUSP00000049640.4, ENSMUST00000055294.4
      Conserved Domains (1) summary
      pfam03045
      Location:51 → 158
      DAN; DAN domain

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000067.7 Reference GRCm39 C57BL/6J

      Range
      174661352..174749386 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O88273.1 GenPept UniProtKB/Swiss-Prot:O88273

    Gene LinkOut

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