Gene: Grem1

Basic information

Tag Content
Uniprot ID O70326
Entrez ID 23892
Genbank protein ID AAH15293.1; AAC40111.1; AAD54056.1;
Genbank nucleotide ID NM_011824.4
Ensembl protein ID ENSMUSP00000097170
Ensembl nucleotide ID ENSMUSG00000074934
Gene name Gremlin-1
Gene symbol Grem1
Organism Mus musculus
NCBI taxa ID 10090
Cleft type
Developmental stage
Data sources Homology search
Reference
Functional description Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as BMP a antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop (PubMed:12808456, PubMed:15201225). Down-regulates the BMP4 signaling in a dose-dependent manner (PubMed:15133038). Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (By similarity). Acts as inhibitor of monocyte chemotaxis (By similarity).
Sequence
MNRTAYTVGA LLLLLGTLLP TAEGKKKGSQ GAIPPPDKAQ HNDSEQTQSP PQPGSRTRGR 60
GQGRGTAMPG EEVLESSQEA LHVTERKYLK RDWCKTQPLK QTIHEEGCNS RTIINRFCYG 120
QCNSFYIPRH IRKEEGSFQS CSFCKPKKFT TMMVTLNCPE LQPPTKKKRV TRVKQCRCIS 180
IDLD 184

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Protein structural annotations

3D structure in PDB database

There is no related protein structure for this gene.

Protein disorder information

Orthologous information

Relation Gene symbol Entrez ID UniProt ID Cleft type Developmental stage Species Evidence Details
1:1 orthologGREM1539079A2VE87Bos taurusPredictionMore>>
1:1 orthologGREM1A0A452E4N7Capra hircusPredictionMore>>
1:1 orthologGREM126585O60565CL/PHomo sapiensPublicationMore>>
1:1 orthologGrem123892O70326Mus musculusPredictionMore>>
1:1 orthologGREM1A0A287ABW3Sus scrofaPredictionMore>>
1:1 orthologGREM1100342066G1TUM4Oryctolagus cuniculusPredictionMore>>
1:1 orthologGrem150566O35793Rattus norvegicusPredictionMore>>
1:1 orthologgrem1bA0A0R4IYE7Danio rerioPredictionMore>>

Identified variants/mutations related to cleft phenotype

Gene symbol Significant Variants/SNPS Methods PubMed ID
GREM1rs16969681Genotyping26043427
GREM1rs1258763Genotyping26043427
GREM1rs16969816Genotyping26043427
GREM1rs2280738Sanger sequencing32687624
GREM1rs12915554 (Heterozygous; increase risk)PCR-RFLP or T-ARMS-PCR31650875
GREM1rs3743105 (Heterozygous and dominant; reduce risk)PCR-RFLP or T-ARMS-PCR31650875
GREM1rs1129456 (Heterozygous; positively associate risk)PCR-RFLP or T-ARMS-PCR31650875
GREM1rs10318 (Homozygous; dominant andrecessive; reduce risk)PCR-RFLP or T-ARMS-PCR31650875
GREM1c.4900C>T< p.Pro164SerSanger sequencing29489415
GREM1c.182G>A; p.Gly61AspSanger sequencing29489415

Other genetic variants/mutations

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Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID GO Term Evidence
GO:0005125 cytokine activityIEA
GO:0030297 transmembrane receptor protein tyrosine kinase activator activityIDA
GO:0036122 BMP bindingISS
GO:0036122 BMP bindingISO
GO:0042803 protein homodimerization activityISO
GO:0043184 vascular endothelial growth factor receptor 2 bindingIPI
GO:0043395 heparan sulfate proteoglycan bindingTAS
GO:0048018 receptor ligand activityIPI

GO:Biological Process

GO ID GO Term Evidence
GO:0000902 cell morphogenesisISO
GO:0001525 angiogenesisIDA
GO:0002042 cell migration involved in sprouting angiogenesisIDA
GO:0002092 positive regulation of receptor internalizationIDA
GO:0002689 negative regulation of leukocyte chemotaxisISO
GO:0003257 positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiationIDA
GO:0003337 mesenchymal to epithelial transition involved in metanephros morphogenesisIDA
GO:0006915 apoptotic processIEA
GO:0007165 signal transductionIDA
GO:0007171 activation of transmembrane receptor protein tyrosine kinase activityIEA
GO:0007267 cell-cell signalingIMP
GO:0008284 positive regulation of cell population proliferationISO
GO:0009887 animal organ morphogenesisIMP
GO:0009954 proximal/distal pattern formationIMP
GO:0010717 regulation of epithelial to mesenchymal transitionISO
GO:0030199 collagen fibril organizationISO
GO:0030308 negative regulation of cell growthISO
GO:0030326 embryonic limb morphogenesisIMP
GO:0030502 negative regulation of bone mineralizationISO
GO:0030514 negative regulation of BMP signaling pathwayISS
GO:0030514 negative regulation of BMP signaling pathwayISO
GO:0030514 negative regulation of BMP signaling pathwayIMP
GO:0032331 negative regulation of chondrocyte differentiationISO
GO:0033689 negative regulation of osteoblast proliferationISO
GO:0043066 negative regulation of apoptotic processISO
GO:0043542 endothelial cell migrationIDA
GO:0045668 negative regulation of osteoblast differentiationISS
GO:0045668 negative regulation of osteoblast differentiationISO
GO:0045766 positive regulation of angiogenesisISO
GO:0045766 positive regulation of angiogenesisIMP
GO:0045892 negative regulation of transcription, DNA-templatedIMP
GO:0045893 positive regulation of transcription, DNA-templatedIDA
GO:0045944 positive regulation of transcription by RNA polymerase IIIDA
GO:0046851 negative regulation of bone remodelingISO
GO:0048263 determination of dorsal identityISO
GO:0051092 positive regulation of NF-kappaB transcription factor activityIDA
GO:0051893 regulation of focal adhesion assemblyIDA
GO:0051973 positive regulation of telomerase activityISO
GO:0060173 limb developmentISO
GO:0060394 negative regulation of pathway-restricted SMAD protein phosphorylationISO
GO:0060676 ureteric bud formationIDA
GO:0061098 positive regulation of protein tyrosine kinase activityIDA
GO:0090027 negative regulation of monocyte chemotaxisISO
GO:0090090 negative regulation of canonical Wnt signaling pathwayISO
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesisIDA
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesisIGI
GO:0090291 negative regulation of osteoclast proliferationISO
GO:1900086 positive regulation of peptidyl-tyrosine autophosphorylationIDA
GO:1900155 negative regulation of bone trabecula formationISO
GO:1900158 negative regulation of bone mineralization involved in bone maturationISO
GO:1901224 positive regulation of NIK/NF-kappaB signalingIDA
GO:2000273 positive regulation of signaling receptor activityIDA
GO:2000727 positive regulation of cardiac muscle cell differentiationIDA
GO:0032872 regulation of stress-activated MAPK cascadeIDA
GO:0072331 signal transduction by p53 class mediatorIGI

GO:Cellular Component

GO ID GO Term Evidence
GO:0005615 extracellular spaceISO
GO:0005615 extracellular spaceIDA
GO:0009986 cell surfaceISO
GO:0009986 cell surfaceIDA

Reactome Pathway

Reactome ID Reactome Term Evidence

Functional annotations

Keywords

Keyword ID Keyword Term
KW-0202 Cytokine
KW-1015 Disulfide bond
KW-0325 Glycoprotein
KW-1185 Reference proteome
KW-0964 Secreted
KW-0732 Signal

Interpro

InterPro ID InterPro Term
IPR006207 Cys_knot_C
IPR029034 Cystine-knot_cytokine
IPR004133 DAN
IPR017159 Gremlin-1/2

PROSITE

PROSITE ID PROSITE Term

Pfam

Pfam ID Pfam Term
PF03045 DAN