UniProtKB - O60565 (GREM1_HUMAN)
Gremlin-1
GREM1
Functioni
Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP 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 (By similarity).
Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (PubMed:27036124).
Acts as inhibitor of monocyte chemotaxis. Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed (By similarity).
By similarity1 PublicationGO - Molecular functioni
- BMP binding Source: UniProtKB
- cytokine activity Source: UniProtKB-KW
- morphogen activity Source: BHF-UCL
- protein homodimerization activity Source: UniProtKB
- receptor ligand 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
- animal organ morphogenesis Source: GO_Central
- apoptotic process Source: Ensembl
- cell-cell signaling Source: Ensembl
- cell migration involved in sprouting angiogenesis Source: BHF-UCL
- cell morphogenesis Source: BHF-UCL
- collagen fibril organization Source: BHF-UCL
- determination of dorsal identity Source: BHF-UCL
- embryonic limb morphogenesis Source: Ensembl
- limb development Source: AgBase
- mesenchymal to epithelial transition involved in metanephros morphogenesis Source: Ensembl
- negative regulation of apoptotic process Source: AgBase
- negative regulation of BMP signaling pathway Source: BHF-UCL
- negative regulation of bone mineralization Source: BHF-UCL
- negative regulation of bone mineralization involved in bone maturation Source: BHF-UCL
- negative regulation of bone remodeling Source: BHF-UCL
- negative regulation of bone trabecula formation Source: BHF-UCL
- negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
- negative regulation of cell growth Source: Ensembl
- negative regulation of chondrocyte differentiation Source: AgBase
- negative regulation of monocyte chemotaxis Source: BHF-UCL
- negative regulation of osteoblast differentiation Source: UniProtKB
- negative regulation of osteoblast proliferation Source: BHF-UCL
- negative regulation of osteoclast proliferation Source: BHF-UCL
- negative regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
- negative regulation of transcription, DNA-templated Source: Ensembl
- positive regulation of angiogenesis Source: Ensembl
- positive regulation of branching involved in ureteric bud morphogenesis Source: Ensembl
- positive regulation of cardiac muscle cell differentiation Source: BHF-UCL
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of NF-kappaB transcription factor activity Source: Ensembl
- positive regulation of NIK/NF-kappaB signaling Source: Ensembl
- positive regulation of peptidyl-tyrosine autophosphorylation Source: BHF-UCL
- positive regulation of receptor internalization Source: BHF-UCL
- positive regulation of signaling receptor activity Source: BHF-UCL
- positive regulation of telomerase activity Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II 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: Ensembl
- regulation of epithelial to mesenchymal transition Source: UniProtKB
- regulation of focal adhesion assembly Source: Ensembl
- sequestering of BMP from receptor via BMP binding Source: GO_Central
- signal transduction Source: BHF-UCL
- ureteric bud formation Source: Ensembl
Keywordsi
Molecular function | Cytokine |
Enzyme and pathway databases
PathwayCommonsi | O60565 |
SignaLinki | O60565 |
Names & Taxonomyi
Protein namesi | Recommended name: Gremlin-1Alternative name(s): 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 21 Publication Short name: IHG-21 Publication |
Gene namesi | Name:GREM1 Synonyms:CKTSF1B1, DAND2, DRM ORF Names:PIG2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2001, GREM1 |
MIMi | 603054, gene |
neXtProti | NX_O60565 |
VEuPathDBi | HostDB:ENSG00000166923 |
Subcellular locationi
Extracellular region or secreted
- Secreted Curated
Extracellular region or secreted
- extracellular space Source: GO_Central
Other locations
- cell surface Source: Ensembl
- collagen-containing extracellular matrix Source: BHF-UCL
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Polyposis syndrome, mixed hereditary 1 (HMPS1)1 Publication
Organism-specific databases
DisGeNETi | 26585 |
MalaCardsi | GREM1 |
MIMi | 601228, phenotype |
OpenTargetsi | ENSG00000166923 |
Orphaneti | 157794, Hereditary mixed polyposis syndrome |
PharmGKBi | PA26537 |
Miscellaneous databases
Pharosi | O60565, Tbio |
Genetic variation databases
BioMutai | GREM1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | 1 PublicationAdd BLAST | 24 | |
ChainiPRO_0000006714 | 25 – 184 | Gremlin-1Add BLAST | 160 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 42 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 94 ↔ 144 | Combined sources1 Publication | ||
Disulfide bondi | 108 ↔ 158 | Combined sources1 Publication | ||
Disulfide bondi | 118 ↔ 176 | Combined sources1 Publication | ||
Disulfide bondi | 122 ↔ 178 | Combined sources1 Publication |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | O60565 |
MassIVEi | O60565 |
MaxQBi | O60565 |
PaxDbi | O60565 |
PeptideAtlasi | O60565 |
PRIDEi | O60565 |
ProteomicsDBi | 49469 [O60565-1] 49470 [O60565-2] |
PTM databases
GlyGeni | O60565, 2 sites, 1 O-linked glycan (1 site) |
iPTMneti | O60565 |
PhosphoSitePlusi | O60565 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000166923, Expressed in stromal cell of endometrium and 187 other tissues |
ExpressionAtlasi | O60565, baseline and differential |
Genevisiblei | O60565, HS |
Organism-specific databases
HPAi | ENSG00000166923, Tissue enhanced (gallbladder, smooth muscle) |
Interactioni
Subunit structurei
Binary interactionsi
O60565
With | #Exp. | IntAct |
---|---|---|
KDR [P35968] | 4 | EBI-944395,EBI-1005487 |
KRTAP12-2 [P59991] | 3 | EBI-944395,EBI-10176379 |
MDFI [Q99750] | 3 | EBI-944395,EBI-724076 |
YWHAH [Q04917] | 5 | EBI-944395,EBI-306940 |
GO - Molecular functioni
- BMP binding Source: UniProtKB
- cytokine activity Source: UniProtKB-KW
- morphogen activity Source: BHF-UCL
- protein homodimerization activity Source: UniProtKB
- receptor ligand activity Source: BHF-UCL
- vascular endothelial growth factor receptor 2 binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 117754, 4 interactors |
IntActi | O60565, 8 interactors |
MINTi | O60565 |
STRINGi | 9606.ENSP00000478319 |
Miscellaneous databases
RNActi | O60565, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O60565 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 94 – 184 | CTCKAdd BLAST | 91 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 24 – 77 | DisorderedSequence analysisAdd BLAST | 54 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 40 – 59 | Polar residuesSequence analysisAdd BLAST | 20 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502QQ5X, Eukaryota |
GeneTreei | ENSGT00940000154209 |
HOGENOMi | CLU_101024_0_0_1 |
InParanoidi | O60565 |
OMAi | PDKDQPN |
PhylomeDBi | O60565 |
TreeFami | TF106445 |
Family and domain databases
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View protein in InterPro IPR006207, Cys_knot_C IPR029034, Cystine-knot_cytokine IPR004133, DAN IPR017159, Gremlin-1/2 |
Pfami | View protein in Pfam PF03045, DAN, 1 hit |
PIRSFi | PIRSF037254, Gremlin_precursor, 1 hit |
SMARTi | View protein in SMART SM00041, CT, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSRTAYTVGA LLLLLGTLLP AAEGKKKGSQ GAIPPPDKAQ HNDSEQTQSP
60 70 80 90 100
QQPGSRNRGR GQGRGTAMPG EEVLESSQEA LHVTERKYLK RDWCKTQPLK
110 120 130 140 150
QTIHEEGCNS RTIINRFCYG QCNSFYIPRH IRKEEGSFQS CSFCKPKKFT
160 170 180
TMMVTLNCPE LQPPTKKKRV TRVKQCRCIS IDLD
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH0YLY2 | H0YLY2_HUMAN | Gremlin-1 | GREM1 | 42 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_013321 | 39 – 79 | Missing in isoform 2. 1 PublicationAdd BLAST | 41 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF045800 mRNA Translation: AAC39725.1 AF110137 mRNA Translation: AAF06677.1 AF154054 mRNA Translation: AAG23891.1 AB032372 Genomic DNA Translation: BAA84462.1 AY232290 mRNA Translation: AAP69985.1 AK095890 mRNA Translation: BAC04643.1 BC069525 mRNA Translation: AAH69525.1 BC093778 mRNA Translation: AAH93778.1 BC101611 mRNA Translation: AAI01612.1 |
CCDSi | CCDS10029.1 [O60565-1] CCDS53927.1 [O60565-2] |
RefSeqi | NP_001178252.1, NM_001191323.1 [O60565-2] NP_037504.1, NM_013372.6 [O60565-1] |
Genome annotation databases
Ensembli | ENST00000300177; ENSP00000300177; ENSG00000276886 ENST00000322805; ENSP00000323101; ENSG00000276886 [O60565-2] ENST00000560830; ENSP00000453141; ENSG00000166923 [O60565-2] ENST00000632478; ENSP00000488158; ENSG00000282046 [O60565-2] ENST00000651081; ENSP00000498897; ENSG00000282046 ENST00000651154; ENSP00000498748; ENSG00000166923 ENST00000651986; ENSP00000498605; ENSG00000282046 ENST00000652365; ENSP00000498763; ENSG00000166923 |
GeneIDi | 26585 |
KEGGi | hsa:26585 |
MANE-Selecti | ENST00000651154.1; ENSP00000498748.1; NM_013372.7; NP_037504.1 |
UCSCi | uc001zhe.3, human [O60565-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF045800 mRNA Translation: AAC39725.1 AF110137 mRNA Translation: AAF06677.1 AF154054 mRNA Translation: AAG23891.1 AB032372 Genomic DNA Translation: BAA84462.1 AY232290 mRNA Translation: AAP69985.1 AK095890 mRNA Translation: BAC04643.1 BC069525 mRNA Translation: AAH69525.1 BC093778 mRNA Translation: AAH93778.1 BC101611 mRNA Translation: AAI01612.1 |
CCDSi | CCDS10029.1 [O60565-1] CCDS53927.1 [O60565-2] |
RefSeqi | NP_001178252.1, NM_001191323.1 [O60565-2] NP_037504.1, NM_013372.6 [O60565-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5AEJ | X-ray | 1.90 | A/B/C/D | 72-184 | [»] | |
SMRi | O60565 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 117754, 4 interactors |
IntActi | O60565, 8 interactors |
MINTi | O60565 |
STRINGi | 9606.ENSP00000478319 |
PTM databases
GlyGeni | O60565, 2 sites, 1 O-linked glycan (1 site) |
iPTMneti | O60565 |
PhosphoSitePlusi | O60565 |
Genetic variation databases
BioMutai | GREM1 |
Proteomic databases
jPOSTi | O60565 |
MassIVEi | O60565 |
MaxQBi | O60565 |
PaxDbi | O60565 |
PeptideAtlasi | O60565 |
PRIDEi | O60565 |
ProteomicsDBi | 49469 [O60565-1] 49470 [O60565-2] |
Protocols and materials databases
Antibodypediai | 2030, 567 antibodies from 33 providers |
DNASUi | 26585 |
Genome annotation databases
Organism-specific databases
CTDi | 26585 |
DisGeNETi | 26585 |
GeneCardsi | GREM1 |
HGNCi | HGNC:2001, GREM1 |
HPAi | ENSG00000166923, Tissue enhanced (gallbladder, smooth muscle) |
MalaCardsi | GREM1 |
MIMi | 601228, phenotype 603054, gene |
neXtProti | NX_O60565 |
OpenTargetsi | ENSG00000166923 |
Orphaneti | 157794, Hereditary mixed polyposis syndrome |
PharmGKBi | PA26537 |
VEuPathDBi | HostDB:ENSG00000166923 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QQ5X, Eukaryota |
GeneTreei | ENSGT00940000154209 |
HOGENOMi | CLU_101024_0_0_1 |
InParanoidi | O60565 |
OMAi | PDKDQPN |
PhylomeDBi | O60565 |
TreeFami | TF106445 |
Enzyme and pathway databases
PathwayCommonsi | O60565 |
SignaLinki | O60565 |
Miscellaneous databases
BioGRID-ORCSi | 26585, 7 hits in 1032 CRISPR screens |
ChiTaRSi | GREM1, human |
GenomeRNAii | 26585 |
Pharosi | O60565, Tbio |
PROi | PR:O60565 |
RNActi | O60565, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000166923, Expressed in stromal cell of endometrium and 187 other tissues |
ExpressionAtlasi | O60565, baseline and differential |
Genevisiblei | O60565, HS |
Family and domain databases
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View protein in InterPro IPR006207, Cys_knot_C IPR029034, Cystine-knot_cytokine IPR004133, DAN IPR017159, Gremlin-1/2 |
Pfami | View protein in Pfam PF03045, DAN, 1 hit |
PIRSFi | PIRSF037254, Gremlin_precursor, 1 hit |
SMARTi | View protein in SMART SM00041, CT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | GREM1_HUMAN | |
Accessioni | O60565Primary (citable) accession number: O60565 Secondary accession number(s): Q52LV3, Q8N914, Q8N936 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 12, 2005 |
Last sequence update: | August 1, 1998 | |
Last modified: | February 23, 2022 | |
This is version 167 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families