GREM2

Protein identityUniProt · HPA

UniProt accession

Q9H772

Gene

GREM2

Ensembl

ENSG00000180875

Chromosome

1

Canonical length

168 aa

Protein class

Disease related genes, Human disease related genes, Predicted secreted proteins

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

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. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

168 residues, UniProt reviewed canonical sequence.

>Q9H772|GREM2
     1  MFWKLSLSLF LVAVLVKVAE ARKNRPAGAI PSPYKDGSSN NSERWQHQIK EVLASSQEAL
    61  VVTERKYLKS DWCKTQPLRQ TVSEEGCRSR TILNRFCYGQ CNSFYIPRHV KKEEESFQSC
   121  AFCKPQRVTS VLVELECPGL DPPFRLKKIQ KVKQCRCMSV NLSDSDKQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GREM2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.48

Highest tissue expression

29 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GREM2.

Disease | AllUniProt

Conditions GREM2 is implicated in, by any mechanism.

• Tooth agenesis, selective, 9 (STHAG9) MIM:617275

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 25 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Tooth agenesis, selective, 9

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.27

gnomAD pLI

0.03

gnomAD missense Z

1.23

DepMap mean gene effect

0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cytokine-mediated signaling pathway
• determination of dorsal identity
• embryonic body morphogenesis
• sequestering of BMP from receptor via BMP binding
• regulation of cytokine activity

Molecular functions

• BMP binding
• cytokine activity
• heparin binding
• identical protein binding
• receptor ligand activity

Cellular components

• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• DAN
• Cystine knot, C-terminal
• Gremlin-1/2
• Cystine-knot cytokine
• DAN domain

KeywordsUniProt

• Cytokine
• Developmental protein
• Disulfide bond
• Glycoprotein
• Heparin-binding
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of GREM2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BMP2
• BMP4
• BMP7