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Protein

Gremlin-1

Gene

Grem1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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. Down-regulates the BMP4 signaling in a dose-dependent manner. Acts as inhibitor of monocyte chemotaxis.3 Publications

GO - Molecular functioni

  • heparan sulfate proteoglycan binding Source: BHF-UCL
  • receptor agonist activity Source: BHF-UCL
  • transmembrane receptor protein tyrosine kinase activator activity Source: BHF-UCL
  • vascular endothelial growth factor receptor 2 binding Source: BHF-UCL

GO - Biological processi

  • angiogenesis Source: MGI
  • apoptotic process Source: Ensembl
  • branching involved in ureteric bud morphogenesis Source: MGI
  • cell-cell signaling Source: MGI
  • cell migration involved in sprouting angiogenesis Source: BHF-UCL
  • cell morphogenesis Source: MGI
  • collagen fibril organization Source: MGI
  • determination of dorsal identity Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • endothelial cell migration Source: BHF-UCL
  • limb development Source: MGI
  • mesenchymal to epithelial transition involved in metanephros morphogenesis Source: UniProtKB
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of BMP signaling pathway Source: MGI
  • negative regulation of bone mineralization Source: MGI
  • negative regulation of bone mineralization involved in bone maturation Source: MGI
  • negative regulation of bone remodeling Source: MGI
  • negative regulation of bone trabecula formation Source: MGI
  • negative regulation of branching involved in ureteric bud morphogenesis Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of cell growth Source: Ensembl
  • negative regulation of chondrocyte differentiation Source: MGI
  • negative regulation of monocyte chemotaxis Source: Ensembl
  • negative regulation of osteoblast proliferation Source: MGI
  • negative regulation of osteoclast proliferation Source: MGI
  • negative regulation of pathway-restricted SMAD protein phosphorylation Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • organ morphogenesis Source: MGI
  • positive regulation of angiogenesis Source: BHF-UCL
  • positive regulation of branching involved in ureteric bud morphogenesis Source: UniProtKB
  • positive regulation of cardiac muscle cell differentiation Source: BHF-UCL
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of NF-kappaB import into nucleus Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: MGI
  • positive regulation of peptidyl-tyrosine autophosphorylation Source: BHF-UCL
  • positive regulation of protein tyrosine kinase activity Source: BHF-UCL
  • positive regulation of receptor activity Source: BHF-UCL
  • positive regulation of receptor internalization Source: BHF-UCL
  • positive regulation of telomerase activity Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation Source: BHF-UCL
  • proximal/distal pattern formation Source: MGI
  • regulation of epithelial to mesenchymal transition Source: MGI
  • regulation of focal adhesion assembly Source: BHF-UCL
  • signal transduction Source: BHF-UCL
  • ureteric bud formation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Names & Taxonomyi

Protein namesi
Recommended name:
Gremlin-1
Alternative name(s):
Cysteine knot superfamily 1, BMP antagonist 1
Down-regulated in Mos-transformed cells protein
Gene namesi
Name:Grem1
Synonyms:Cktsf1b1, Drm
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1344337. Grem1.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: Ensembl
  • extracellular space Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424By similarityAdd
BLAST
Chaini25 – 184160Gremlin-1PRO_0000006716Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi42 – 421N-linked (GlcNAc...)Sequence analysis
Disulfide bondi94 ↔ 144By similarity
Disulfide bondi108 ↔ 158By similarity
Disulfide bondi118 ↔ 176By similarity
Disulfide bondi122 ↔ 178By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO70326.
PeptideAtlasiO70326.
PRIDEiO70326.

PTM databases

iPTMnetiO70326.
PhosphoSiteiO70326.

Expressioni

Tissue specificityi

Highly expressed in spleen and to a lesser extent in lung, skeletal muscle and kidney. Expressed only in non-transformed cells or primary fibroblasts in culture but not in established transformed or tumor derived cell lines. Broadly expressed in limb bud mesenchyme but restricted to the distal limb bud mesenchyme and concentrated posteriorly. Expressed in ovary especially in granulosa cells of follicles of type 4.3 Publications

Inductioni

Up-regulated by GDF9 dose-dependent manner and BMP4 in granulosa cells. Highly regulated during folliculogenesis.1 Publication

Gene expression databases

BgeeiO70326.
CleanExiMM_GREM1.
ExpressionAtlasiO70326. baseline and differential.
GenevisibleiO70326. MM.

Interactioni

Subunit structurei

Interacts with SLIT1 and SLIT2 in a glycosylation-dependent manner.By similarity

GO - Molecular functioni

  • heparan sulfate proteoglycan binding Source: BHF-UCL
  • receptor agonist activity Source: BHF-UCL
  • vascular endothelial growth factor receptor 2 binding Source: BHF-UCL

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000097170.

Structurei

3D structure databases

ProteinModelPortaliO70326.
SMRiO70326. Positions 71-181.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini94 – 18491CTCKAdd
BLAST

Sequence similaritiesi

Belongs to the DAN family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IG3Z. Eukaryota.
ENOG4111HEF. LUCA.
HOVERGENiHBG051837.
InParanoidiO70326.
OMAiRVKECRC.
OrthoDBiEOG7Q2N7B.
TreeFamiTF106445.

Family and domain databases

InterProiIPR006207. Cys_knot_C.
IPR004133. DAN.
IPR017159. Gremlin-1/2.
[Graphical view]
PfamiPF03045. DAN. 1 hit.
[Graphical view]
PIRSFiPIRSF037254. Gremlin_precursor. 1 hit.
SMARTiSM00041. CT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O70326-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNRTAYTVGA LLLLLGTLLP TAEGKKKGSQ GAIPPPDKAQ HNDSEQTQSP
60 70 80 90 100
PQPGSRTRGR GQGRGTAMPG EEVLESSQEA LHVTERKYLK RDWCKTQPLK
110 120 130 140 150
QTIHEEGCNS RTIINRFCYG QCNSFYIPRH IRKEEGSFQS CSFCKPKKFT
160 170 180
TMMVTLNCPE LQPPTKKKRV TRVKQCRCIS IDLD
Length:184
Mass (Da):20,710
Last modified:August 1, 1998 - v1
Checksum:iD1BD99783CDC0F2D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045801 mRNA. Translation: AAC40111.1.
AF108189 mRNA. Translation: AAD54056.1.
BC015293 mRNA. Translation: AAH15293.1.
CCDSiCCDS16560.1.
RefSeqiNP_035954.1. NM_011824.4.
UniGeneiMm.166318.

Genome annotation databases

EnsembliENSMUST00000099575; ENSMUSP00000097170; ENSMUSG00000074934.
GeneIDi23892.
KEGGimmu:23892.
UCSCiuc008lpp.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045801 mRNA. Translation: AAC40111.1.
AF108189 mRNA. Translation: AAD54056.1.
BC015293 mRNA. Translation: AAH15293.1.
CCDSiCCDS16560.1.
RefSeqiNP_035954.1. NM_011824.4.
UniGeneiMm.166318.

3D structure databases

ProteinModelPortaliO70326.
SMRiO70326. Positions 71-181.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000097170.

PTM databases

iPTMnetiO70326.
PhosphoSiteiO70326.

Proteomic databases

PaxDbiO70326.
PeptideAtlasiO70326.
PRIDEiO70326.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000099575; ENSMUSP00000097170; ENSMUSG00000074934.
GeneIDi23892.
KEGGimmu:23892.
UCSCiuc008lpp.2. mouse.

Organism-specific databases

CTDi26585.
MGIiMGI:1344337. Grem1.

Phylogenomic databases

eggNOGiENOG410IG3Z. Eukaryota.
ENOG4111HEF. LUCA.
HOVERGENiHBG051837.
InParanoidiO70326.
OMAiRVKECRC.
OrthoDBiEOG7Q2N7B.
TreeFamiTF106445.

Miscellaneous databases

PROiO70326.
SOURCEiSearch...

Gene expression databases

BgeeiO70326.
CleanExiMM_GREM1.
ExpressionAtlasiO70326. baseline and differential.
GenevisibleiO70326. MM.

Family and domain databases

InterProiIPR006207. Cys_knot_C.
IPR004133. DAN.
IPR017159. Gremlin-1/2.
[Graphical view]
PfamiPF03045. DAN. 1 hit.
[Graphical view]
PIRSFiPIRSF037254. Gremlin_precursor. 1 hit.
SMARTiSM00041. CT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities."
    Hsu D.R., Economides A.N., Wang X., Eimon P.M., Harland R.M.
    Mol. Cell 1:673-683(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Cloning of the murine Drm gene (Cktsf1b1) and characterization of its oncogene suppressible promoter."
    Zhang Q., Topol L.Z., Athanasiou M., Copeland N.G., Gilbert D.J., Jenkins N.A., Blair D.G.
    Cytogenet. Cell Genet. 89:242-251(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Spleen.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Colon.
  4. "Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning."
    Khokha M.K., Hsu D., Brunet L.J., Dionne M.S., Harland R.M.
    Nat. Genet. 34:303-307(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  5. "Growth differentiation factor 9 regulates expression of the bone morphogenetic protein antagonist gremlin."
    Pangas S.A., Jorgez C.J., Matzuk M.M.
    J. Biol. Chem. 279:32281-32286(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
  6. "Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis."
    Michos O., Panman L., Vintersten K., Beier K., Zeller R., Zuniga A.
    Development 131:3401-3410(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiGREM1_MOUSE
AccessioniPrimary (citable) accession number: O70326
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: August 1, 1998
Last modified: July 6, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.