P33947 · ERD22_HUMAN
- ProteinER lumen protein-retaining receptor 2
- GeneKDELR2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids212 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Membrane receptor that binds the K-D-E-L sequence motif in the C-terminal part of endoplasmic reticulum resident proteins and maintains their localization in that compartment by participating to their vesicle-mediated recycling back from the Golgi (PubMed:1325562, PubMed:18086916, PubMed:33053334).
Binding is pH dependent, and is optimal at pH 5-5.4 (By similarity).
Binding is pH dependent, and is optimal at pH 5-5.4 (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 5 | Interaction with the K-D-E-L motif on target proteins | ||||
Sequence: R | ||||||
Site | 54 | Interaction with the K-D-E-L motif on target proteins | ||||
Sequence: S | ||||||
Site | 117 | Interaction with the K-D-E-L motif on target proteins | ||||
Sequence: E | ||||||
Site | 193 | Important for recycling of cargo proteins with the sequence motif K-D-E-L from the Golgi to the endoplasmic reticulum | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cis-Golgi network | |
Cellular Component | COPI-coated vesicle membrane | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | Golgi membrane | |
Cellular Component | membrane | |
Cellular Component | transport vesicle | |
Molecular Function | ER retention sequence binding | |
Molecular Function | KDEL sequence binding | |
Biological Process | endoplasmic reticulum to Golgi vesicle-mediated transport | |
Biological Process | maintenance of protein localization in endoplasmic reticulum | |
Biological Process | protein retention in ER lumen | |
Biological Process | protein transport | |
Biological Process | retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameER lumen protein-retaining receptor 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP33947
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Golgi apparatus membrane ; Multi-pass membrane protein
Cytoplasmic vesicle, COPI-coated vesicle membrane ; Multi-pass membrane protein
Note: Localized in the Golgi in the absence of bound proteins with the sequence motif K-D-E-L. Trafficks back to the endoplasmic reticulum together with cargo proteins containing the sequence motif K-D-E-L.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-4 | Lumenal | ||||
Sequence: MNIF | ||||||
Transmembrane | 5-24 | Helical | ||||
Sequence: RLTGDLSHLAAIVILLLKIW | ||||||
Topological domain | 25-32 | Cytoplasmic | ||||
Sequence: KTRSCAGI | ||||||
Transmembrane | 33-52 | Helical | ||||
Sequence: SGKSQLLFALVFTTRYLDLF | ||||||
Topological domain | 53-58 | Lumenal | ||||
Sequence: TSFISL | ||||||
Transmembrane | 59-79 | Helical | ||||
Sequence: YNTSMKVIYLACSYATVYLIY | ||||||
Topological domain | 80-92 | Cytoplasmic | ||||
Sequence: LKFKATYDGNHDT | ||||||
Transmembrane | 93-110 | Helical | ||||
Sequence: FRVEFLVVPVGGLSFLVN | ||||||
Topological domain | 111-116 | Lumenal | ||||
Sequence: HDFSPL | ||||||
Transmembrane | 117-135 | Helical | ||||
Sequence: EILWTFSIYLESVAILPQL | ||||||
Topological domain | 136-149 | Cytoplasmic | ||||
Sequence: FMISKTGEAETITT | ||||||
Transmembrane | 150-168 | Helical | ||||
Sequence: HYLFFLGLYRALYLVNWIW | ||||||
Topological domain | 169-178 | Lumenal | ||||
Sequence: RFYFEGFFDL | ||||||
Transmembrane | 179-199 | Helical | ||||
Sequence: IAVVAGVVQTILYCDFFYLYI | ||||||
Topological domain | 200-212 | Cytoplasmic | ||||
Sequence: TKVLKGKKLSLPA |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Osteogenesis imperfecta 21 (OI21)
- Note
- DescriptionAn autosomal recessive form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI21 is a progressively deforming form characterized by multiple fractures appearing at birth or early childhood.
- See alsoMIM:619131
Natural variants in OI21
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_085601 | 5 | R>W | in OI21; uncertain significance; dbSNP:rs1265005474 | |
VAR_085602 | 12 | H>D | in OI21; changed maintenance of protein localization in endoplasmic reticulum; SERPINH1 is not retained in the endoplasmic reticulum and secreted; leads to a loss of fiber formation of the bones connective tissue; no effect on protein abundance; dbSNP:rs1785976222 | |
VAR_085603 | 120-212 | missing | in OI21; loss of protein expression; changed maintenance of protein localization in endoplasmic reticulum; SERPINH1 is not retained in the endoplasmic reticulum and secreted; leads to a loss of fiber formation of the bones connective tissue | |
VAR_085604 | 133 | P>L | in OI21; uncertain significance; dbSNP:rs1785501859 | |
VAR_085605 | 162 | Y>C | in OI21; uncertain significance; dbSNP:rs1785499146 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_085601 | 5 | in OI21; uncertain significance; dbSNP:rs1265005474 | |||
Sequence: R → W | ||||||
Natural variant | VAR_085602 | 12 | in OI21; changed maintenance of protein localization in endoplasmic reticulum; SERPINH1 is not retained in the endoplasmic reticulum and secreted; leads to a loss of fiber formation of the bones connective tissue; no effect on protein abundance; dbSNP:rs1785976222 | |||
Sequence: H → D | ||||||
Natural variant | VAR_085603 | 120-212 | in OI21; loss of protein expression; changed maintenance of protein localization in endoplasmic reticulum; SERPINH1 is not retained in the endoplasmic reticulum and secreted; leads to a loss of fiber formation of the bones connective tissue | |||
Sequence: Missing | ||||||
Natural variant | VAR_085604 | 133 | in OI21; uncertain significance; dbSNP:rs1785501859 | |||
Sequence: P → L | ||||||
Natural variant | VAR_085605 | 162 | in OI21; uncertain significance; dbSNP:rs1785499146 | |||
Sequence: Y → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 229 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000194155 | 1-212 | ER lumen protein-retaining receptor 2 | |||
Sequence: MNIFRLTGDLSHLAAIVILLLKIWKTRSCAGISGKSQLLFALVFTTRYLDLFTSFISLYNTSMKVIYLACSYATVYLIYLKFKATYDGNHDTFRVEFLVVPVGGLSFLVNHDFSPLEILWTFSIYLESVAILPQLFMISKTGEAETITTHYLFFLGLYRALYLVNWIWRFYFEGFFDLIAVVAGVVQTILYCDFFYLYITKVLKGKKLSLPA |
Proteomic databases
PTM databases
Expression
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 47-48 | Interaction with the K-D-E-L motif on target proteins | ||||
Sequence: RY | ||||||
Region | 159-169 | Interaction with the K-D-E-L motif on target proteins | ||||
Sequence: RALYLVNWIWR | ||||||
Region | 204-207 | Important for recycling of cargo proteins with the sequence motif K-D-E-L from the Golgi to the endoplasmic reticulum | ||||
Sequence: KGKK |
Domain
Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein (By similarity).
This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity).
This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity).
Sequence similarities
Belongs to the ERD2 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P33947-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length212
- Mass (Da)24,422
- Last updated1994-02-01 v1
- Checksum81BECB983E503142
P33947-2
- Name2
- Differences from canonical
- 118-212: ILWTFSIYLESVAILPQLFMISKTGEAETITTHYLFFLGLYRALYLVNWIWRFYFEGFFDLIAVVAGVVQTILYCDFFYLYITKVLKGKKLSLPA → YSRERSSVCQHKCQRPSPASVLQGARTEFLPQQRHKMLDTENQKLNSFVADSHQWLCKNAEEKSQKVSV
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H7BYF7 | H7BYF7_HUMAN | KDELR2 | 38 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_036712 | 118-212 | in isoform 2 | |||
Sequence: ILWTFSIYLESVAILPQLFMISKTGEAETITTHYLFFLGLYRALYLVNWIWRFYFEGFFDLIAVVAGVVQTILYCDFFYLYITKVLKGKKLSLPA → YSRERSSVCQHKCQRPSPASVLQGARTEFLPQQRHKMLDTENQKLNSFVADSHQWLCKNAEEKSQKVSV | ||||||
Sequence conflict | 137 | in Ref. 6; AAH12994 | ||||
Sequence: M → V |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X63745 EMBL· GenBank· DDBJ | CAA45277.1 EMBL· GenBank· DDBJ | mRNA | ||
M88458 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AC072052 EMBL· GenBank· DDBJ | AAS02002.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK315702 EMBL· GenBank· DDBJ | BAG38064.1 EMBL· GenBank· DDBJ | mRNA | ||
CH236963 EMBL· GenBank· DDBJ | EAL23722.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH878731 EMBL· GenBank· DDBJ | EAW55030.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC008081 EMBL· GenBank· DDBJ | AAH08081.1 EMBL· GenBank· DDBJ | mRNA | ||
BC012994 EMBL· GenBank· DDBJ | AAH12994.1 EMBL· GenBank· DDBJ | mRNA | ||
BC071982 EMBL· GenBank· DDBJ | AAH71982.1 EMBL· GenBank· DDBJ | mRNA |