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Protein

Gremlin-2

Gene

Grem2

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

Functioni

Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells.3 Publications

GO - Molecular functioni

  • BMP binding Source: UniProtKB
  • heparin binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • cytokine-mediated signaling pathway Source: UniProtKB
  • determination of dorsal identity Source: UniProtKB
  • embryonic body morphogenesis Source: UniProtKB
  • negative regulation of BMP signaling pathway Source: UniProtKB
  • regulation of cytokine activity Source: UniProtKB
  • sequestering of BMP from receptor via BMP binding Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Developmental protein

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiR-MMU-201451. Signaling by BMP.

Names & Taxonomyi

Protein namesi
Recommended name:
Gremlin-2
Alternative name(s):
Cysteine knot superfamily 1, BMP antagonist 2
Protein related to DAN and cerberus
Short name:
PRDC
Gene namesi
Name:Grem2
Synonyms:Cktsf1b2, Prdc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1344367. Grem2.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi68 – 681L → A: Slightly reduces affinity for BMP2 and BMP4. No effect on inhibition of BMP2 signaling. 1 Publication
Mutagenesisi72 – 721W → A: Strongly reduces affinity for BMP2 and BMP4. Reduces inhibition of BMP2 signaling. 1 Publication
Mutagenesisi96 – 961F → A: Reduces affinity for BMP2 and BMP4. Reduces inhibition of BMP2 signaling. 1 Publication
Mutagenesisi98 – 981Y → A: Strongly reduces affinity for BMP2 and BMP4. Strongly reduces inhibition of BMP2 signaling. 1 Publication
Mutagenesisi104 – 1041F → A: Reduces affinity for BMP2 and BMP4. Strongly reduces inhibition of BMP2 signaling. 1 Publication
Mutagenesisi105 – 1051Y → A: Strongly reduces affinity for BMP2 and BMP4. Strongly reduces inhibition of BMP2 signaling. 1 Publication
Mutagenesisi117 – 1171F → A: Strongly reduces affinity for BMP2 and BMP4. Strongly reduces inhibition of BMP2 signaling. 1 Publication
Mutagenesisi120 – 1201C → S: No effect on dimerization. No effect on inhibition of BMP signaling. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 168147Gremlin-2PRO_0000006721Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi40 – 401N-linked (GlcNAc...)Sequence analysis
Disulfide bondi73 ↔ 123PROSITE-ProRule annotation1 Publication
Disulfide bondi87 ↔ 137PROSITE-ProRule annotation1 Publication
Disulfide bondi97 ↔ 155PROSITE-ProRule annotation1 Publication
Disulfide bondi101 ↔ 157PROSITE-ProRule annotation1 Publication
Glycosylationi161 – 1611N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO88273.
PRIDEiO88273.

PTM databases

PhosphoSiteiO88273.

Expressioni

Tissue specificityi

Highly expressed in the ovary, followed by brain, spleen, colon, kidney and uterus. In ovary expressed in granulosa cells of selective early antral follicles.1 Publication

Developmental stagei

Expressed in commissural neurons in the developing spinal cord.1 Publication

Inductioni

Up-regulated by gonadotropin treatment.1 Publication

Gene expression databases

BgeeiO88273.
ExpressionAtlasiO88273. baseline and differential.
GenevisibleiO88273. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with BMP2, BMP4 and BMP7, but has lower affinity for BMP7 than for BMP2 and BMP4. Binds heparin; this impairs the interaction with BMP2.3 Publications

GO - Molecular functioni

  • BMP binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

DIPiDIP-60475N.
STRINGi10090.ENSMUSP00000049640.

Structurei

Secondary structure

1
168
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi49 – 535Combined sources
Helixi57 – 626Combined sources
Helixi65 – 684Combined sources
Beta strandi72 – 8211Combined sources
Beta strandi90 – 10718Combined sources
Beta strandi110 – 1134Combined sources
Beta strandi116 – 1205Combined sources
Beta strandi122 – 13615Combined sources
Beta strandi140 – 15819Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4JPHX-ray2.25A/B/C/D22-168[»]
ProteinModelPortaliO88273.
SMRiO88273. Positions 46-160.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini73 – 16391CTCKPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the DAN family.Curated
Contains 1 CTCK (C-terminal cystine knot-like) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IG3Z. Eukaryota.
ENOG4111HEF. LUCA.
HOGENOMiHOG000237358.
HOVERGENiHBG051837.
InParanoidiO88273.
OMAiCAFCKPH.
OrthoDBiEOG7Q2N7B.
PhylomeDBiO88273.
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]
PROSITEiPS01225. CTCK_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O88273-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFWKLSLTLL LVAVLVKVAE TRKNRPAGAI PSPYKDGSSN NSERWHHQIK
60 70 80 90 100
EVLASSQEAL VVTERKYLKS DWCKTQPLRQ TVSEEGCRSR TILNRFCYGQ
110 120 130 140 150
CNSFYIPRHV KKEEDSFQSC AFCKPQRVTS VIVELECPGL DPPFRIKKIQ
160
KVKHCRCMSV NLSDSDKQ
Length:168
Mass (Da):19,334
Last modified:November 1, 1998 - v1
Checksum:i6361C1581D49C281
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011030 mRNA. Translation: BAA29038.1.
BC079905 mRNA. Translation: AAH79905.1.
CCDSiCCDS15545.1.
RefSeqiNP_035955.1. NM_011825.1.
XP_006496889.1. XM_006496826.2.
XP_011237109.1. XM_011238807.1.
UniGeneiMm.25760.

Genome annotation databases

EnsembliENSMUST00000055294; ENSMUSP00000049640; ENSMUSG00000050069.
GeneIDi23893.
KEGGimmu:23893.
UCSCiuc007dtf.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011030 mRNA. Translation: BAA29038.1.
BC079905 mRNA. Translation: AAH79905.1.
CCDSiCCDS15545.1.
RefSeqiNP_035955.1. NM_011825.1.
XP_006496889.1. XM_006496826.2.
XP_011237109.1. XM_011238807.1.
UniGeneiMm.25760.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4JPHX-ray2.25A/B/C/D22-168[»]
ProteinModelPortaliO88273.
SMRiO88273. Positions 46-160.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60475N.
STRINGi10090.ENSMUSP00000049640.

PTM databases

PhosphoSiteiO88273.

Proteomic databases

PaxDbiO88273.
PRIDEiO88273.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000055294; ENSMUSP00000049640; ENSMUSG00000050069.
GeneIDi23893.
KEGGimmu:23893.
UCSCiuc007dtf.1. mouse.

Organism-specific databases

CTDi64388.
MGIiMGI:1344367. Grem2.

Phylogenomic databases

eggNOGiENOG410IG3Z. Eukaryota.
ENOG4111HEF. LUCA.
HOGENOMiHOG000237358.
HOVERGENiHBG051837.
InParanoidiO88273.
OMAiCAFCKPH.
OrthoDBiEOG7Q2N7B.
PhylomeDBiO88273.
TreeFamiTF106445.

Enzyme and pathway databases

ReactomeiR-MMU-201451. Signaling by BMP.

Miscellaneous databases

NextBioi303653.
PROiO88273.
SOURCEiSearch...

Gene expression databases

BgeeiO88273.
ExpressionAtlasiO88273. baseline and differential.
GenevisibleiO88273. 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]
PROSITEiPS01225. CTCK_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence and expression of a novel mouse gene PRDC (protein related to DAN and cerberus) identified by a gene trap approach."
    Minabe-Saegusa C., Saegusa H., Tsukahara M., Noguchi S.
    Dev. Growth Differ. 40:343-353(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
    Strain: C57BL/6J.
    Tissue: CNS.
  2. "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: C57BL/6J.
    Tissue: Head.
  3. "Protein related to DAN and cerberus is a bone morphogenetic protein antagonist that participates in ovarian paracrine regulation."
    Sudo S., Avsian-Kretchmer O., Wang L.S., Hsueh A.J.
    J. Biol. Chem. 279:23134-23141(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH BMP2 AND BMP4, TISSUE SPECIFICITY, INDUCTION.
  4. "Members of the DAN family are BMP antagonists that form highly stable noncovalent dimers."
    Kattamuri C., Luedeke D.M., Nolan K., Rankin S.A., Greis K.D., Zorn A.M., Thompson T.B.
    J. Mol. Biol. 424:313-327(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH BMP2; BMP4 AND BMP7, MUTAGENESIS OF CYS-120, SUBUNIT, GLYCOSYLATION, IDENTIFICATION BY MASS SPECTROMETRY.
  5. "Structure of protein related to Dan and Cerberus: insights into the mechanism of bone morphogenetic protein antagonism."
    Nolan K., Kattamuri C., Luedeke D.M., Deng X., Jagpal A., Zhang F., Linhardt R.J., Kenny A.P., Zorn A.M., Thompson T.B.
    Structure 21:1417-1429(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 22-168, FUNCTION, SUBUNIT, INTERACTION WITH BMP2 AND BMP4, HEPARIN-BINDING, MUTAGENESIS OF LEU-68; TRP-72; PHE-96; TYR-98; PHE-104; TYR-105 AND PHE-117, DISULFIDE BONDS.

Entry informationi

Entry nameiGREM2_MOUSE
AccessioniPrimary (citable) accession number: O88273
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: November 1, 1998
Last modified: March 16, 2016
This is version 95 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.