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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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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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