Endometriosis Knowledgebase

Search Result

Gene id

26585

Gene Summary Protein Summary Gene ontology KEGG pathways Diseases PubMed references

Gene Summary

Gene Symbol

GREM1 Gene UCSC Ensembl

Aliases

C15DUPq, CKTSF1B1, CRAC1, CRCS4, DAND2, DRM, DUP15q, GREMLIN, HMPS, HMPS1, IHG-2, MPSH, PIG2

Gene name

gremlin 1, DAN family BMP antagonist

Alternate names

gremlin-1, DAN domain family member 2, cell proliferation-inducing gene 2 protein, colorectal adenoma and carcinoma 1, cysteine knot superfamily 1, BMP antagonist 1, down-regulated in Mos-transformed cells protein, gremlin 1, cysteine knot superfamily, homolog, ,

Gene location

15q13.3 (32717939: 32734668) Exons: 3 NC_000015.10

Gene summary(Entrez)

This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. In mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

OMIM

603054

Protein Summary

Protein general information

O60565

Name: Gremlin 1 (Cell proliferation inducing gene 2 protein) (Cysteine knot superfamily 1, BMP antagonist 1) (DAN domain family member 2) (Down regulated in Mos transformed cells protein) (Increased in high glucose protein 2) (IHG 2)

Length: 184 Mass: 20,697

Tissue specificity: Highly expressed in small intestine, fetal brain and colon. Expression is restricted to intestinal subepithelial myofibroblasts (ISEMFs) at the crypt base. In subjects with HMPS1, by contrast, GREM1 is expressed, not only in basal ISEM

Sequence

MSRTAYTVGALLLLLGTLLPAAEGKKKGSQGAIPPPDKAQHNDSEQTQSPQQPGSRNRGRGQGRGTAMPGEEVLE
SSQEALHVTERKYLKRDWCKTQPLKQTIHEEGCNSRTIINRFCYGQCNSFYIPRHIRKEEGSFQSCSFCKPKKFT
TMMVTLNCPELQPPTKKKRVTRVKQCRCISIDLD

Structural information

Protein Domains	CTCK. (94-184)
Interpro:	IPR006207 IPR029034 IPR004133 IPR017159
Pfam:	PF03045
PDB:	5AEJ
PDBsum:	5AEJ
MINT:	7997222
STRING:	ENSP00000300177;

Other Databases

GeneCards: GREM1; Malacards: GREM1

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0000902	cell morphogenesis	IDA	biological_process
GO:0001658	branching involved in ure teric bud morphogenesis	IEA	biological_process
GO:0002042	cell migration involved i n sprouting angiogenesis	ISS	biological_process
GO:0002092	positive regulation of re ceptor internalization	ISS	biological_process
GO:0003257	positive regulation of tr anscription from RNA poly merase II promoter involv ed in myocardial precurso r cell differentiation	ISS	biological_process
GO:0003337	mesenchymal to epithelial transition involved in m etanephros morphogenesis	IEA	biological_process
GO:0005125	cytokine activity	IEA	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005615	extracellular space	NAS	cellular_component
GO:0006915	apoptotic process	IEA	biological_process
GO:0007165	signal transduction	ISS	biological_process
GO:0007171	activation of transmembra ne receptor protein tyros ine kinase activity	IEA	biological_process
GO:0007267	cell-cell signaling	IEA	biological_process
GO:0008284	positive regulation of ce ll proliferation	IDA	biological_process
GO:0009954	proximal/distal pattern f ormation	IEA	biological_process
GO:0009986	cell surface	IEA	cellular_component
GO:0010717	regulation of epithelial to mesenchymal transition	IMP	biological_process
GO:0016015	morphogen activity	ISS	molecular_function
GO:0030199	collagen fibril organizat ion	IMP	biological_process
GO:0030297	transmembrane receptor pr otein tyrosine kinase act ivator activity	ISS	molecular_function
GO:0030308	negative regulation of ce ll growth	IEA	biological_process
GO:0030326	embryonic limb morphogene sis	IEA	biological_process
GO:0030502	negative regulation of bo ne mineralization	IMP	biological_process
GO:0030514	negative regulation of BM P signaling pathway	IDA	biological_process
GO:0030514	negative regulation of BM P signaling pathway	IMP	biological_process
GO:0032331	negative regulation of ch ondrocyte differentiation	IMP	biological_process
GO:0033689	negative regulation of os teoblast proliferation	IMP	biological_process
GO:0036122	BMP binding	ISS	molecular_function
GO:0042346	positive regulation of NF -kappaB import into nucle us	IEA	biological_process
GO:0043066	negative regulation of ap optotic process	IMP	biological_process
GO:0043184	vascular endothelial grow th factor receptor 2 bind ing	ISS	molecular_function
GO:0045766	positive regulation of an giogenesis	IEA	biological_process
GO:0045892	negative regulation of tr anscription, DNA-template d	IEA	biological_process
GO:0045944	positive regulation of tr anscription from RNA poly merase II promoter	ISS	biological_process
GO:0046851	negative regulation of bo ne remodeling	IMP	biological_process
GO:0048018	receptor agonist activity	ISS	molecular_function
GO:0048263	determination of dorsal i dentity	IMP	biological_process
GO:0051092	positive regulation of NF -kappaB transcription fac tor activity	IEA	biological_process
GO:0051893	regulation of focal adhes ion assembly	IEA	biological_process
GO:0051973	positive regulation of te lomerase activity	IDA	biological_process
GO:0060173	limb development	IMP	biological_process
GO:0060394	negative regulation of pa thway-restricted SMAD pro tein phosphorylation	IDA	biological_process
GO:0060676	ureteric bud formation	IEA	biological_process
GO:0061098	positive regulation of pr otein tyrosine kinase act ivity	IEA	biological_process
GO:0090027	negative regulation of mo nocyte chemotaxis	ISS	biological_process
GO:0090090	negative regulation of ca nonical Wnt signaling pat hway	IDA	biological_process
GO:0090190	positive regulation of br anching involved in urete ric bud morphogenesis	IEA	biological_process
GO:0090191	negative regulation of br anching involved in urete ric bud morphogenesis	IEA	biological_process
GO:0090291	negative regulation of os teoclast proliferation	IMP	biological_process
GO:1900086	positive regulation of pe ptidyl-tyrosine autophosp horylation	ISS	biological_process
GO:1900155	negative regulation of bo ne trabecula formation	IMP	biological_process
GO:1900158	negative regulation of bo ne mineralization involve d in bone maturation	IMP	biological_process
GO:2000273	positive regulation of re ceptor activity	ISS	biological_process
GO:2000727	positive regulation of ca rdiac muscle cell differe ntiation	ISS	biological_process
GO:0032872	regulation of stress-acti vated MAPK cascade	ISS	biological_process
GO:0072331	signal transduction by p5 3 class mediator	ISS	biological_process
GO:0000902	cell morphogenesis	IDA	biological_process
GO:0001525	angiogenesis	IEA	biological_process
GO:0001658	branching involved in ure teric bud morphogenesis	IEA	biological_process
GO:0002042	cell migration involved i n sprouting angiogenesis	IEA	biological_process
GO:0002042	cell migration involved i n sprouting angiogenesis	ISS	biological_process
GO:0002092	positive regulation of re ceptor internalization	IEA	biological_process
GO:0002092	positive regulation of re ceptor internalization	ISS	biological_process
GO:0002689	negative regulation of le ukocyte chemotaxis	IEA	biological_process
GO:0003257	positive regulation of tr anscription from RNA poly merase II promoter involv ed in myocardial precurso r cell differentiation	IEA	biological_process
GO:0003257	positive regulation of tr anscription from RNA poly merase II promoter involv ed in myocardial precurso r cell differentiation	ISS	biological_process
GO:0003337	mesenchymal to epithelial transition involved in m etanephros morphogenesis	IEA	biological_process
GO:0005125	cytokine activity	IEA	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005576	extracellular region	IEA	cellular_component
GO:0005576	extracellular region	IEA	cellular_component
GO:0005615	extracellular space	IEA	cellular_component
GO:0005615	extracellular space	IEA	cellular_component
GO:0005615	extracellular space	NAS	cellular_component
GO:0006915	apoptotic process	IEA	biological_process
GO:0007165	signal transduction	IEA	biological_process
GO:0007165	signal transduction	ISS	biological_process
GO:0007171	activation of transmembra ne receptor protein tyros ine kinase activity	IEA	biological_process
GO:0007267	cell-cell signaling	IEA	biological_process
GO:0008284	positive regulation of ce ll proliferation	IDA	biological_process
GO:0009887	animal organ morphogenesi s	IEA	biological_process
GO:0009954	proximal/distal pattern f ormation	IEA	biological_process
GO:0009986	cell surface	IEA	cellular_component
GO:0010717	regulation of epithelial to mesenchymal transition	IMP	biological_process
GO:0016015	morphogen activity	ISS	molecular_function
GO:0030199	collagen fibril organizat ion	IMP	biological_process
GO:0030297	transmembrane receptor pr otein tyrosine kinase act ivator activity	IEA	molecular_function
GO:0030297	transmembrane receptor pr otein tyrosine kinase act ivator activity	ISS	molecular_function
GO:0030308	negative regulation of ce ll growth	IEA	biological_process
GO:0030326	embryonic limb morphogene sis	IEA	biological_process
GO:0030502	negative regulation of bo ne mineralization	IMP	biological_process
GO:0030514	negative regulation of BM P signaling pathway	IEA	biological_process
GO:0030514	negative regulation of BM P signaling pathway	IDA	biological_process
GO:0030514	negative regulation of BM P signaling pathway	IMP	biological_process
GO:0032331	negative regulation of ch ondrocyte differentiation	IMP	biological_process
GO:0033689	negative regulation of os teoblast proliferation	IMP	biological_process
GO:0036122	BMP binding	ISS	molecular_function
GO:0042346	positive regulation of NF -kappaB import into nucle us	IEA	biological_process
GO:0043066	negative regulation of ap optotic process	IMP	biological_process
GO:0043184	vascular endothelial grow th factor receptor 2 bind ing	IEA	molecular_function
GO:0043184	vascular endothelial grow th factor receptor 2 bind ing	ISS	molecular_function
GO:0043542	endothelial cell migratio n	IEA	biological_process
GO:0045766	positive regulation of an giogenesis	IEA	biological_process
GO:0045892	negative regulation of tr anscription, DNA-template d	IEA	biological_process
GO:0045893	positive regulation of tr anscription, DNA-template d	IEA	biological_process
GO:0045944	positive regulation of tr anscription from RNA poly merase II promoter	IEA	biological_process
GO:0045944	positive regulation of tr anscription from RNA poly merase II promoter	ISS	biological_process
GO:0046851	negative regulation of bo ne remodeling	IMP	biological_process
GO:0048018	receptor agonist activity	IEA	molecular_function
GO:0048018	receptor agonist activity	ISS	molecular_function
GO:0048263	determination of dorsal i dentity	IMP	biological_process
GO:0051092	positive regulation of NF -kappaB transcription fac tor activity	IEA	biological_process
GO:0051893	regulation of focal adhes ion assembly	IEA	biological_process
GO:0051973	positive regulation of te lomerase activity	IDA	biological_process
GO:0060173	limb development	IMP	biological_process
GO:0060394	negative regulation of pa thway-restricted SMAD pro tein phosphorylation	IDA	biological_process
GO:0060676	ureteric bud formation	IEA	biological_process
GO:0061098	positive regulation of pr otein tyrosine kinase act ivity	IEA	biological_process
GO:0090027	negative regulation of mo nocyte chemotaxis	IEA	biological_process
GO:0090027	negative regulation of mo nocyte chemotaxis	ISS	biological_process
GO:0090090	negative regulation of ca nonical Wnt signaling pat hway	IDA	biological_process
GO:0090190	positive regulation of br anching involved in urete ric bud morphogenesis	IEA	biological_process
GO:0090191	negative regulation of br anching involved in urete ric bud morphogenesis	IEA	biological_process
GO:0090291	negative regulation of os teoclast proliferation	IMP	biological_process
GO:1900086	positive regulation of pe ptidyl-tyrosine autophosp horylation	IEA	biological_process
GO:1900086	positive regulation of pe ptidyl-tyrosine autophosp horylation	ISS	biological_process
GO:1900155	negative regulation of bo ne trabecula formation	IMP	biological_process
GO:1900158	negative regulation of bo ne mineralization involve d in bone maturation	IMP	biological_process
GO:2000273	positive regulation of re ceptor activity	IEA	biological_process
GO:2000273	positive regulation of re ceptor activity	ISS	biological_process
GO:2000727	positive regulation of ca rdiac muscle cell differe ntiation	IEA	biological_process
GO:2000727	positive regulation of ca rdiac muscle cell differe ntiation	ISS	biological_process
GO:0032872	regulation of stress-acti vated MAPK cascade	ISS	biological_process
GO:0072331	signal transduction by p5 3 class mediator	ISS	biological_process
GO:0000902	cell morphogenesis	IDA	biological_process
GO:0002042	cell migration involved i n sprouting angiogenesis	ISS	biological_process
GO:0002092	positive regulation of re ceptor internalization	ISS	biological_process
GO:0003257	positive regulation of tr anscription from RNA poly merase II promoter involv ed in myocardial precurso r cell differentiation	ISS	biological_process
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005615	extracellular space	NAS	cellular_component
GO:0007165	signal transduction	ISS	biological_process
GO:0008284	positive regulation of ce ll proliferation	IDA	biological_process
GO:0010717	regulation of epithelial to mesenchymal transition	IMP	biological_process
GO:0016015	morphogen activity	ISS	molecular_function
GO:0030199	collagen fibril organizat ion	IMP	biological_process
GO:0030297	transmembrane receptor pr otein tyrosine kinase act ivator activity	ISS	molecular_function
GO:0030502	negative regulation of bo ne mineralization	IMP	biological_process
GO:0030514	negative regulation of BM P signaling pathway	IDA	biological_process
GO:0030514	negative regulation of BM P signaling pathway	IMP	biological_process
GO:0032331	negative regulation of ch ondrocyte differentiation	IMP	biological_process
GO:0033689	negative regulation of os teoblast proliferation	IMP	biological_process
GO:0036122	BMP binding	ISS	molecular_function
GO:0043066	negative regulation of ap optotic process	IMP	biological_process
GO:0043184	vascular endothelial grow th factor receptor 2 bind ing	ISS	molecular_function
GO:0045944	positive regulation of tr anscription from RNA poly merase II promoter	ISS	biological_process
GO:0046851	negative regulation of bo ne remodeling	IMP	biological_process
GO:0048018	receptor agonist activity	ISS	molecular_function
GO:0048263	determination of dorsal i dentity	IMP	biological_process
GO:0051973	positive regulation of te lomerase activity	IDA	biological_process
GO:0060173	limb development	IMP	biological_process
GO:0060394	negative regulation of pa thway-restricted SMAD pro tein phosphorylation	IDA	biological_process
GO:0090027	negative regulation of mo nocyte chemotaxis	ISS	biological_process
GO:0090090	negative regulation of ca nonical Wnt signaling pat hway	IDA	biological_process
GO:0090291	negative regulation of os teoclast proliferation	IMP	biological_process
GO:1900086	positive regulation of pe ptidyl-tyrosine autophosp horylation	ISS	biological_process
GO:1900155	negative regulation of bo ne trabecula formation	IMP	biological_process
GO:1900158	negative regulation of bo ne mineralization involve d in bone maturation	IMP	biological_process
GO:2000273	positive regulation of re ceptor activity	ISS	biological_process
GO:2000727	positive regulation of ca rdiac muscle cell differe ntiation	ISS	biological_process
GO:0032872	regulation of stress-acti vated MAPK cascade	ISS	biological_process
GO:0072331	signal transduction by p5 3 class mediator	ISS	biological_process

Diseases

Associated diseases	References
Cancer	PMID: 19505925
Cleft lip	PMID: 20023658
Diminished ovarian reserve (DOR)	PMID: 22160428
Endometriosis	PMID: 23460397
Fertilization rate	PMID: 19602522
M�llerian duct differentiation	INFBASE23460397
Endometriosis	INFBASE23460397

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes	Abstract
18314105	Endometrio sis			58 (35 patients with endometri osis, 23 health y control women )		GREM1	Show abstract
23460397	Endometrio sis					BMP4 GREM1	Show abstract