GREM1_RAT
ID GREM1_RAT Reviewed; 184 AA.
AC O35793;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Gremlin-1;
DE AltName: Full=Cysteine knot superfamily 1, BMP antagonist 1;
DE AltName: Full=Down-regulated in Mos-transformed cells protein;
DE Flags: Precursor;
GN Name=Grem1; Synonyms=Cktsf1b1, Drm;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=9234736; DOI=10.1128/mcb.17.8.4801;
RA Topol L.Z., Marx M., Laugier D., Bogdanova N.N., Boubnov N.V.,
RA Clausen P.A., Calothy G., Blair D.G.;
RT "Identification of drm, a novel gene whose expression is suppressed in
RT transformed cells and which can inhibit growth of normal but not
RT transformed cells in culture.";
RL Mol. Cell. Biol. 17:4801-4810(1997).
RN [2]
RP INTERACTION WITH SLIT1 AND SLIT2, FUNCTION, AND MUTAGENESIS OF
RP 42-ASN--SER-44.
RX PubMed=15528323; DOI=10.4049/jimmunol.173.10.5914;
RA Chen B., Blair D.G., Plisov S., Vasiliev G., Perantoni A.O., Chen Q.,
RA Athanasiou M., Wu J.Y., Oppenheim J.J., Yang D.;
RT "Bone morphogenetic protein antagonists Drm/Gremlin and Dan interact with
RT Slits and act as negative regulators of monocyte chemotaxis.";
RL J. Immunol. 173:5914-5917(2004).
CC -!- FUNCTION: Cytokine that may play an important role during
CC carcinogenesis and metanephric kidney organogenesis, as a BMP
CC antagonist required for early limb outgrowth and patterning in
CC maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4
CC signaling in a dose-dependent manner (By similarity). Antagonist of
CC BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro)
CC (By similarity). Acts as inhibitor of monocyte chemotaxis
CC (PubMed:15528323). Can inhibit the growth or viability of normal cells
CC but not transformed cells when is overexpressed.
CC {ECO:0000250|UniProtKB:O60565, ECO:0000250|UniProtKB:O70326,
CC ECO:0000269|PubMed:15528323, ECO:0000269|PubMed:9234736}.
CC -!- SUBUNIT: Homodimer; can also form homooligomers. Interacts with BMP2;
CC can form higher oligomers with BMP2 (By similarity). Interacts with
CC SLIT1 and SLIT2 in a glycosylation-dependent manner (PubMed:15528323).
CC {ECO:0000250|UniProtKB:O60565, ECO:0000269|PubMed:15528323}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, kidney, spleen, and
CC testis and weakly expressed in the lung and liver. Predominantly
CC expressed in differentiated cells as neurons in brain, type I cells in
CC lung and globlet cells in intestine. {ECO:0000269|PubMed:9234736}.
CC -!- INDUCTION: Down-regulated in cells transformed by oncogenes.
CC {ECO:0000269|PubMed:9234736}.
CC -!- SIMILARITY: Belongs to the DAN family. {ECO:0000305}.
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DR EMBL; Y10019; CAA71126.1; -; mRNA.
DR RefSeq; NP_062155.1; NM_019282.3.
DR AlphaFoldDB; O35793; -.
DR SMR; O35793; -.
DR BioGRID; 248391; 1.
DR IntAct; O35793; 1.
DR STRING; 10116.ENSRNOP00000035888; -.
DR GlyGen; O35793; 2 sites.
DR PaxDb; O35793; -.
DR Ensembl; ENSRNOT00000037895; ENSRNOP00000035888; ENSRNOG00000026053.
DR Ensembl; ENSRNOT00000104302; ENSRNOP00000084612; ENSRNOG00000026053.
DR GeneID; 50566; -.
DR KEGG; rno:50566; -.
DR UCSC; RGD:2359; rat.
DR CTD; 26585; -.
DR RGD; 2359; Grem1.
DR eggNOG; ENOG502QQ5X; Eukaryota.
DR GeneTree; ENSGT00940000154209; -.
DR HOGENOM; CLU_101024_0_0_1; -.
DR InParanoid; O35793; -.
DR OMA; MPRTRCA; -.
DR OrthoDB; 1270652at2759; -.
DR PhylomeDB; O35793; -.
DR TreeFam; TF106445; -.
DR PRO; PR:O35793; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000026053; Expressed in colon and 12 other tissues.
DR Genevisible; O35793; RN.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0036122; F:BMP binding; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0048018; F:receptor ligand activity; ISO:RGD.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; ISO:RGD.
DR GO; GO:0043184; F:vascular endothelial growth factor receptor 2 binding; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEP:RGD.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; IEA:Ensembl.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:RGD.
DR GO; GO:0000902; P:cell morphogenesis; ISO:RGD.
DR GO; GO:0007267; P:cell-cell signaling; ISO:RGD.
DR GO; GO:0030199; P:collagen fibril organization; ISO:RGD.
DR GO; GO:0048263; P:determination of dorsal identity; ISO:RGD.
DR GO; GO:0030326; P:embryonic limb morphogenesis; ISO:RGD.
DR GO; GO:0043542; P:endothelial cell migration; ISO:RGD.
DR GO; GO:0060173; P:limb development; ISO:RGD.
DR GO; GO:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0030502; P:negative regulation of bone mineralization; ISO:RGD.
DR GO; GO:1900158; P:negative regulation of bone mineralization involved in bone maturation; ISO:RGD.
DR GO; GO:0046851; P:negative regulation of bone remodeling; ISO:RGD.
DR GO; GO:1900155; P:negative regulation of bone trabecula formation; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:RGD.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISO:RGD.
DR GO; GO:0002689; P:negative regulation of leukocyte chemotaxis; IDA:RGD.
DR GO; GO:0090027; P:negative regulation of monocyte chemotaxis; IDA:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:ARUK-UCL.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; ISO:RGD.
DR GO; GO:0090291; P:negative regulation of osteoclast proliferation; ISO:RGD.
DR GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISO:RGD.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; ISO:RGD.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:RGD.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISO:RGD.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0009954; P:proximal/distal pattern formation; ISO:RGD.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; ISO:RGD.
DR GO; GO:0038098; P:sequestering of BMP from receptor via BMP binding; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR GO; GO:0060676; P:ureteric bud formation; ISO:RGD.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR004133; DAN.
DR InterPro; IPR017159; Gremlin-1/2.
DR Pfam; PF03045; DAN; 1.
DR PIRSF; PIRSF037254; Gremlin_precursor; 1.
DR SMART; SM00041; CT; 1.
PE 1: Evidence at protein level;
KW Cytokine; Disulfide bond; Glycoprotein; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000250"
FT CHAIN 25..184
FT /note="Gremlin-1"
FT /id="PRO_0000006717"
FT DOMAIN 94..184
FT /note="CTCK"
FT REGION 24..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 94..144
FT /evidence="ECO:0000250|UniProtKB:O60565"
FT DISULFID 108..158
FT /evidence="ECO:0000250|UniProtKB:O60565"
FT DISULFID 118..176
FT /evidence="ECO:0000250|UniProtKB:O60565"
FT DISULFID 122..178
FT /evidence="ECO:0000250|UniProtKB:O60565"
FT MUTAGEN 42..44
FT /note="NDS->IEA: No interaction with SLIT1."
FT /evidence="ECO:0000269|PubMed:15528323"
SQ SEQUENCE 184 AA; 20680 MW; 90AC99749B1AD8F6 CRC64;
MNRTAYTVGA LLLLLGTLLP AAEGKKKGSQ GAIPPPDKAQ HNDSEQTQSP PQPGSRTRGR
GQGRGTAMPG EEVLESSQEA LHVTERKYLK RDWCKTQPLK QTIHEEGCNS RTIINRFCYG
QCNSFYIPRH IRKEEGSFQS CSFCKPKKFT TMMVTLNCPE LQPPTKKKRV TRVKQCRCIS
IDLD
