O70326 (GREM1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gremlin-1

Alternative name(s):
Cysteine knot superfamily 1, BMP antagonist 1
Down-regulated in Mos-transformed cells protein

Gene names

Name:	Grem1
Synonyms:	Cktsf1b1, Drm

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	184 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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. Ref.4 Ref.5 Ref.6
Subunit structure	Interacts with SLIT1 and SLIT2 in a glycosylation-dependent manner By similarity.
Subcellular location	Secreted Probable.
Tissue specificity	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. Ref.2 Ref.4 Ref.5
Induction	Up-regulated by GDF9 dose-dependent manner and BMP4 in granulosa cells. Highly regulated during folliculogenesis. Ref.5
Sequence similarities	Belongs to the DAN family. Contains 1 CTCK (C-terminal cystine knot-like) domain.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	angiogenesis Inferred from direct assay. Source: MGI branching involved in ureteric bud morphogenesis Inferred from genetic interaction. Source: MGI cell-cell signaling Inferred from mutant phenotype Ref.6. Source: MGI embryonic limb morphogenesis Inferred from mutant phenotype Ref.4. Source: MGI mesenchymal to epithelial transition involved in metanephros morphogenesis Inferred from direct assay. Source: UniProtKB negative regulation of BMP signaling pathway Inferred from mutant phenotype. Source: MGI negative regulation of branching involved in ureteric bud morphogenesis Inferred from direct assay. Source: MGI negative regulation of transcription, DNA-dependent Inferred from mutant phenotype. Source: UniProtKB positive regulation of NF-kappaB import into nucleus Inferred from direct assay. Source: MGI positive regulation of NF-kappaB transcription factor activity Inferred from direct assay. Source: MGI positive regulation of branching involved in ureteric bud morphogenesis Inferred from direct assay. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: UniProtKB proximal/distal pattern formation Inferred from mutant phenotype Ref.4. Source: MGI ureteric bud formation Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	By similarity
	Chain	25 – 184	160	Gremlin-1		PRO_0000006716
Regions
	Domain	94 – 184	91	CTCK
Amino acid modifications
	Glycosylation	42	1	N-linked (GlcNAc...) Potential
	Disulfide bond	94 ↔ 144		By similarity
	Disulfide bond	108 ↔ 158		By similarity
	Disulfide bond	118 ↔ 176		By similarity
	Disulfide bond	122 ↔ 178		By similarity

Sequences

	Sequence		Length	Mass (Da)
	O70326 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: D1BD99783CDC0F2D	FASTA	184	20,710
	10 20 30 40 50 60 MNRTAYTVGA LLLLLGTLLP TAEGKKKGSQ GAIPPPDKAQ HNDSEQTQSP PQPGSRTRGR 70 80 90 100 110 120 GQGRGTAMPG EEVLESSQEA LHVTERKYLK RDWCKTQPLK QTIHEEGCNS RTIINRFCYG 130 140 150 160 170 180 QCNSFYIPRH IRKEEGSFQS CSFCKPKKFT TMMVTLNCPE LQPPTKKKRV TRVKQCRCIS IDLD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 9660951] [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: 10965135] [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: 15489334] [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: 12808456] [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: 15133038] [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: 15201225] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF045801 mRNA. Translation: AAC40111.1. AF108189 mRNA. Translation: AAD54056.1. BC015293 mRNA. Translation: AAH15293.1.
IPI	IPI00280124.
RefSeq	NP_035954.1. NM_011824.4.
UniGene	Mm.166318.
3D structure databases
ProteinModelPortal	O70326.
ModBase	Search...
Protein-protein interaction databases
STRING	O70326.
Proteomic databases
PRIDE	O70326.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000099575; ENSMUSP00000097170; ENSMUSG00000074934.
GeneID	23892.
KEGG	mmu:23892.
Organism-specific databases
CTD	26585.
MGI	MGI:1344337. Grem1.
Phylogenomic databases
eggNOG	roNOG14590.
HOVERGEN	HBG051837.
InParanoid	O70326.
OMA	NDSEQTE.
OrthoDB	EOG4K9BDB.
PhylomeDB	O70326.
Gene expression databases
ArrayExpress	O70326.
Bgee	O70326.
CleanEx	MM_GREM1.
Genevestigator	O70326.
GermOnline	ENSMUSG00000074934. Mus musculus.
Family and domain databases
InterPro	IPR006207. Cys_knot_C. IPR004133. DAN. IPR017159. Gremlin_precursor. [Graphical view]
Pfam	PF03045. DAN. 1 hit. [Graphical view]
PIRSF	PIRSF037254. Gremlin_precursor. 1 hit.
SMART	SM00041. CT. 1 hit. [Graphical view]
PROSITE	PS01225. CTCK_2. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	303649.
SOURCE	Search...

Entry information

Entry name

GREM1_MOUSE

Accession

Primary (citable) accession number: O70326

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	August 1, 1998
Last modified:	January 25, 2012
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program