O94905 · ERLN2_HUMAN
- ProteinErlin-2
- GeneERLIN2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids339 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Promotes sterol-accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing ubiquitin ligase complex (PubMed:21343306).
Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. May promote ER retention of the SCAP-SREBF complex (PubMed:24217618).
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 | cytosol | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | membrane raft | |
Cellular Component | plasma membrane | |
Cellular Component | protein-containing complex | |
Molecular Function | cholesterol binding | |
Molecular Function | ubiquitin protein ligase binding | |
Biological Process | cholesterol metabolic process | |
Biological Process | ERAD pathway | |
Biological Process | negative regulation of cholesterol biosynthetic process | |
Biological Process | negative regulation of fatty acid biosynthetic process | |
Biological Process | regulation of cholesterol biosynthetic process | |
Biological Process | SREBP signaling pathway |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameErlin-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 accessionO94905
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-3 | Cytoplasmic | ||||
Sequence: MAQ | ||||||
Transmembrane | 4-24 | Helical | ||||
Sequence: LGAVVAVASSFFCASLFSAVH | ||||||
Topological domain | 25-339 | Lumenal | ||||
Sequence: KIEEGHIGVYYRGGALLTSTSGPGFHLMLPFITSYKSVQTTLQTDEVKNVPCGTSGGVMIYFDRIEVVNFLVPNAVYDIVKNYTADYDKALIFNKIHHELNQFCSVHTLQEVYIELFDQIDENLKLALQQDLTSMAPGLVIQAVRVTKPNIPEAIRRNYELMESEKTKLLIAAQKQKVVEKEAETERKKALIEAEKVAQVAEITYGQKVMEKETEKKISEIEDAAFLAREKAKADAECYTAMKIAEANKLKLTPEYLQLMKYKAIASNSKIYFGKDIPNMFMDSAGSVSKQFEGLADKLSFGLEDEPLETATKEN |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Spastic paraplegia 18B, autosomal recessive (SPG18B)
- Note
- DescriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG18B is a severe form with onset in early childhood. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures.
- See alsoMIM:611225
Natural variants in SPG18B
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_089042 | 180 | R>C | in SPG18B; uncertain significance | |
VAR_089043 | 300 | D>V | in SPG18B; uncertain significance |
Spastic paraplegia 18A, autosomal dominant (SPG18A)
- Note
- DescriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG18A is a pure form. Age at onset of symptoms varies considerably from childhood to adulthood.
- See alsoMIM:620512
Natural variants in SPG18A
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_089040 | 129 | S>T | in SPG18A; likely pathogenic | |
VAR_089041 | 151 | A>V | in SPG18A; uncertain significance |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_059140 | 71 | in dbSNP:rs2032066 | |||
Sequence: V → A | ||||||
Mutagenesis | 106 | Loss of glycosylation. | ||||
Sequence: N → Q | ||||||
Natural variant | VAR_089040 | 129 | in SPG18A; likely pathogenic | |||
Sequence: S → T | ||||||
Natural variant | VAR_089041 | 151 | in SPG18A; uncertain significance | |||
Sequence: A → V | ||||||
Natural variant | VAR_089042 | 180 | in SPG18B; uncertain significance | |||
Sequence: R → C | ||||||
Natural variant | VAR_089043 | 300 | in SPG18B; uncertain significance | |||
Sequence: D → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 309 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), glycosylation, modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000002787 | 1-339 | UniProt | Erlin-2 | |||
Sequence: MAQLGAVVAVASSFFCASLFSAVHKIEEGHIGVYYRGGALLTSTSGPGFHLMLPFITSYKSVQTTLQTDEVKNVPCGTSGGVMIYFDRIEVVNFLVPNAVYDIVKNYTADYDKALIFNKIHHELNQFCSVHTLQEVYIELFDQIDENLKLALQQDLTSMAPGLVIQAVRVTKPNIPEAIRRNYELMESEKTKLLIAAQKQKVVEKEAETERKKALIEAEKVAQVAEITYGQKVMEKETEKKISEIEDAAFLAREKAKADAECYTAMKIAEANKLKLTPEYLQLMKYKAIASNSKIYFGKDIPNMFMDSAGSVSKQFEGLADKLSFGLEDEPLETATKEN | |||||||
Modified residue (large scale data) | 61 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Glycosylation | 106 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 267 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with activated ITPR1, independently of the degree of ITPR1 polyubiquitination (By similarity).
Interacts with SCAP, INSIG1, SREBF1 and SREBF2 under cholesterol sufficiency conditions; indicative for an association with the SCAP-SREBP-INSIG complex (PubMed:24217618).
Probably part of an AMFR/gp78 and INSIG1-containing ubiquitin ligase complex involved in ERAD of HMGCR. Interacts with TMUB1; TMUB1 bridges the association with AMFR. Interacts with SYVN1 and RNF139 (PubMed:21343306).
Interacts with TMEM259 (By similarity).
Interacts with TMEM41B (PubMed:30352685).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O94905 | AMFR Q9UKV5 | 10 | EBI-4400770, EBI-1046367 | |
BINARY | O94905 | ERLIN1 O75477 | 5 | EBI-4400770, EBI-359299 | |
XENO | O94905 | HMGCR P00347 | 2 | EBI-4400770, EBI-11426687 | |
BINARY | O94905 | SYVN1 Q86TM6 | 2 | EBI-4400770, EBI-947849 | |
BINARY | O94905 | TMUB1 Q9BVT8 | 6 | EBI-4400770, EBI-11425701 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 177-309 | Interaction with ERLIN1 | ||||
Sequence: EAIRRNYELMESEKTKLLIAAQKQKVVEKEAETERKKALIEAEKVAQVAEITYGQKVMEKETEKKISEIEDAAFLAREKAKADAECYTAMKIAEANKLKLTPEYLQLMKYKAIASNSKIYFGKDIPNMFMDSA |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
O94905-1
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
- Length339
- Mass (Da)37,840
- Last updated1999-05-01 v1
- Checksum3CF322548FD58DB0
O94905-2
- Name2
O94905-3
- Name3
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 61 | in Ref. 6; AAH05950 | ||||
Sequence: S → P | ||||||
Alternative sequence | VSP_008713 | 142-152 | in isoform 2 | |||
Sequence: DQIDENLKLAL → GLENDFSQESS | ||||||
Alternative sequence | VSP_013940 | 142-206 | in isoform 3 | |||
Sequence: DQIDENLKLALQQDLTSMAPGLVIQAVRVTKPNIPEAIRRNYELMESEKTKLLIAAQKQKVVEKE → GKKVSPEHAVLKQGSWNPASLHCLKPGCLQGVMVTYGQEMLKNLVLRSWSQRSSWRMLIAMQQDP | ||||||
Alternative sequence | VSP_008714 | 153-339 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_013941 | 207-339 | in isoform 3 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB018790 EMBL· GenBank· DDBJ | BAA36845.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL442077 EMBL· GenBank· DDBJ | CAC09443.1 EMBL· GenBank· DDBJ | mRNA | ||
AY358108 EMBL· GenBank· DDBJ | AAQ88475.1 EMBL· GenBank· DDBJ | mRNA | ||
AY358851 EMBL· GenBank· DDBJ | AAQ89210.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291394 EMBL· GenBank· DDBJ | BAF84083.1 EMBL· GenBank· DDBJ | mRNA | ||
AK297279 EMBL· GenBank· DDBJ | BAG59750.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471080 EMBL· GenBank· DDBJ | EAW63365.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471080 EMBL· GenBank· DDBJ | EAW63366.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005950 EMBL· GenBank· DDBJ | AAH05950.1 EMBL· GenBank· DDBJ | mRNA | Different termination. | |
BC048308 EMBL· GenBank· DDBJ | AAH48308.1 EMBL· GenBank· DDBJ | mRNA | ||
BC050611 EMBL· GenBank· DDBJ | AAH50611.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC067765 EMBL· GenBank· DDBJ | AAH67765.1 EMBL· GenBank· DDBJ | mRNA |