D4AB34 · ERFE_RAT
- ProteinErythroferrone
- GeneErfe
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids341 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
function
Iron-regulatory hormone that acts as an erythroid regulator after hemorrhage: produced by erythroblasts following blood loss and mediates suppression of hepcidin (HAMP) expression in the liver, thereby promoting increased iron absorption and mobilization from stores (By similarity).
Promotes lipid uptake into adipocytes and hepatocytes via transcriptional up-regulation of genes involved in fatty acid uptake (PubMed:22351773).
Inhibits apoptosis and inflammatory response in cardiomyocytes via promotion of sphingosine-1-phosphate (S1P) and cAMP-dependent activation of AKT signaling (PubMed:30566056).
Inhibits autophagy induced by nutrient deficiency in hepatocytes via promoting the phosphorylation of IRS1, AKT, and MTOR, and thereby subsequent activation of the AKT-MTOR signaling pathway (PubMed:24187137).
Negatively regulates the differentiation of osteoblasts, potentially via sequestering BMP2, and thereby inhibits the activation of SMAD signaling (By similarity).
The reduction in BMP2 signaling in osteoblasts also results in an increase in expression of the osteoclastogenesis-promoting factors TNFSF11/RANKL and SOST, thereby indirectly promotes bone resorption (By similarity).
Promotes lipid uptake into adipocytes and hepatocytes via transcriptional up-regulation of genes involved in fatty acid uptake (PubMed:22351773).
Inhibits apoptosis and inflammatory response in cardiomyocytes via promotion of sphingosine-1-phosphate (S1P) and cAMP-dependent activation of AKT signaling (PubMed:30566056).
Inhibits autophagy induced by nutrient deficiency in hepatocytes via promoting the phosphorylation of IRS1, AKT, and MTOR, and thereby subsequent activation of the AKT-MTOR signaling pathway (PubMed:24187137).
Negatively regulates the differentiation of osteoblasts, potentially via sequestering BMP2, and thereby inhibits the activation of SMAD signaling (By similarity).
The reduction in BMP2 signaling in osteoblasts also results in an increase in expression of the osteoclastogenesis-promoting factors TNFSF11/RANKL and SOST, thereby indirectly promotes bone resorption (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 320 | Required for correct protein folding in the endoplasmic reticulum | ||||
Sequence: N |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | extracellular space | |
Molecular Function | hormone activity | |
Molecular Function | identical protein binding | |
Biological Process | establishment of localization in cell | |
Biological Process | fatty acid transport | |
Biological Process | intracellular iron ion homeostasis | |
Biological Process | negative regulation of apoptotic process | |
Biological Process | negative regulation of autophagy | |
Biological Process | negative regulation of gluconeogenesis | |
Biological Process | negative regulation of osteoblast differentiation | |
Biological Process | negative regulation of osteoclast differentiation | |
Biological Process | positive regulation of fatty acid transport | |
Biological Process | positive regulation of glucose import | |
Biological Process | positive regulation of insulin receptor signaling pathway | |
Biological Process | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | |
Biological Process | regulation of fatty acid metabolic process |
Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameErythroferrone
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionD4AB34
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Secreted when glycosylated at Asn-230 and Asn-282 (By similarity).
Hydroxylation promotes secretion (By similarity).
Hydroxylation promotes secretion (By similarity).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, modified residue, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-24 | |||||
Sequence: MASTRSPGGARTLLACASLLAAMG | ||||||
Chain | PRO_0000422122 | 25-341 | Erythroferrone | |||
Sequence: LGVPESAEPVGTQARPQPPGTELPAPPAHSPPEPTIAHAHSVDPRDAWMLFVKQSDKGINSKKRSRTKARRLKLGLPGPPGPPGPQGPPGPFIPSEVLLKEFQLLLKGAVRQRESTEHCTRDLTTPASGGPSRDPVTQELESQDQGAVLALLAATLAQSPRAPRVEAAFHCRLRRDVQVERRALHELGVYYLPEVEGAFRRGPGLNLTSGQYTAPVAGFYALAATLHVALTKQPRKGPPQPRDRLRLLICIQSLCQHNASLETVMGLENSSELFTISVNGVLYLQTGHYTSVFLDNASGSSLTVRGGSHFSAILLGL | ||||||
Modified residue | 101 | Hydroxyproline | ||||
Sequence: P | ||||||
Modified residue | 103 | Hydroxyproline | ||||
Sequence: P | ||||||
Modified residue | 104 | Hydroxyproline | ||||
Sequence: P | ||||||
Modified residue | 106 | Hydroxyproline | ||||
Sequence: P | ||||||
Modified residue | 107 | Hydroxyproline | ||||
Sequence: P | ||||||
Modified residue | 109 | Hydroxyproline | ||||
Sequence: P | ||||||
Glycosylation | 230 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 282 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 293 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 320 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
N-glycosylated; required for secretion of the mature protein.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Homodimer; disulfide-linked (By similarity).
Forms trimer, hexamers and higher molecular weight oligomers (By similarity).
May form heteromeric complexes with C1QTNF2 and C1QTNF12 and, to a lesser extent, with C1QTNF5 and C1QTNF10 (By similarity).
Interacts with BMP5 and BMP7; the interaction inhibits BMP-induced transcription of HAMP (By similarity).
Interacts with BMP6; the interaction inhibits BMP-induced transcription of HAMP (By similarity).
Interacts with BMP2 (By similarity).
Interacts with heterodimers composed of BMP2 and BMP6 in vitro, the interaction inhibits the heterodimer binding to its receptor BMPR1A/ALK3 and thereby suppresses expression of HAMP (By similarity).
Forms trimer, hexamers and higher molecular weight oligomers (By similarity).
May form heteromeric complexes with C1QTNF2 and C1QTNF12 and, to a lesser extent, with C1QTNF5 and C1QTNF10 (By similarity).
Interacts with BMP5 and BMP7; the interaction inhibits BMP-induced transcription of HAMP (By similarity).
Interacts with BMP6; the interaction inhibits BMP-induced transcription of HAMP (By similarity).
Interacts with BMP2 (By similarity).
Interacts with heterodimers composed of BMP2 and BMP6 in vitro, the interaction inhibits the heterodimer binding to its receptor BMPR1A/ALK3 and thereby suppresses expression of HAMP (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 30-65 | Disordered | ||||
Sequence: SAEPVGTQARPQPPGTELPAPPAHSPPEPTIAHAHS | ||||||
Compositional bias | 43-57 | Pro residues | ||||
Sequence: PGTELPAPPAHSPPE | ||||||
Region | 78-115 | Disordered | ||||
Sequence: QSDKGINSKKRSRTKARRLKLGLPGPPGPPGPQGPPGP | ||||||
Compositional bias | 100-115 | Pro residues | ||||
Sequence: LPGPPGPPGPQGPPGP | ||||||
Region | 137-165 | Disordered | ||||
Sequence: RESTEHCTRDLTTPASGGPSRDPVTQELE | ||||||
Compositional bias | 145-165 | Polar residues | ||||
Sequence: RDLTTPASGGPSRDPVTQELE | ||||||
Domain | 186-341 | C1q | ||||
Sequence: APRVEAAFHCRLRRDVQVERRALHELGVYYLPEVEGAFRRGPGLNLTSGQYTAPVAGFYALAATLHVALTKQPRKGPPQPRDRLRLLICIQSLCQHNASLETVMGLENSSELFTISVNGVLYLQTGHYTSVFLDNASGSSLTVRGGSHFSAILLGL |
Sequence similarities
Belongs to the adipolin/erythroferrone family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length341
- Mass (Da)36,369
- Last updated2010-04-20 v1
- Checksum9467635C8DEFDBBD
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 43-57 | Pro residues | ||||
Sequence: PGTELPAPPAHSPPE | ||||||
Compositional bias | 100-115 | Pro residues | ||||
Sequence: LPGPPGPPGPQGPPGP | ||||||
Compositional bias | 145-165 | Polar residues | ||||
Sequence: RDLTTPASGGPSRDPVTQELE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
CH473997 EMBL· GenBank· DDBJ | EDL92028.1 EMBL· GenBank· DDBJ | Genomic DNA |