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Protein

Erlin-2

Gene

ERLIN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 (PubMed:19240031, PubMed:17502376). 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).4 Publications

GO - Molecular functioni

  • cholesterol binding Source: GO_Central
  • protein tyrosine kinase activity Source: Reactome
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

GO - Biological processi

Keywordsi

Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

ReactomeiR-HSA-382556 ABC-family proteins mediated transport
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-8853336 Signaling by plasma membrane FGFR1 fusions

Protein family/group databases

TCDBi1.P.1.1.1 the polyoma virus sv40 er penitration channel (vpec) family

Names & Taxonomyi

Protein namesi
Recommended name:
Erlin-2
Alternative name(s):
Endoplasmic reticulum lipid raft-associated protein 2
Stomatin-prohibitin-flotillin-HflC/K domain-containing protein 2
Short name:
SPFH domain-containing protein 2
Gene namesi
Name:ERLIN2
Synonyms:C8orf2, SPFH2
ORF Names:UNQ2441/PRO5003/PRO9924
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000147475.14
HGNCiHGNC:1356 ERLIN2
MIMi611605 gene
neXtProtiNX_O94905

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 3CytoplasmicSequence analysis3
Transmembranei4 – 24HelicalSequence analysisAdd BLAST21
Topological domaini25 – 339LumenalSequence analysisAdd BLAST315

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 18, autosomal recessive (SPG18)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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. SPG18 is a severe form with onset in early childhood. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures.
See also OMIM:611225

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi106N → Q: Loss of glycosylation. 1 Publication1

Keywords - Diseasei

Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

DisGeNETi11160
MalaCardsiERLIN2
MIMi611225 phenotype
OpenTargetsiENSG00000147475
Orphaneti209951 Autosomal recessive spastic paraplegia type 18
247604 Juvenile primary lateral sclerosis
280384 Recessive intellectual disability - motor dysfunction - multiple joint contractures
PharmGKBiPA25961

Polymorphism and mutation databases

BioMutaiERLIN2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000027871 – 339Erlin-2Add BLAST339

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi106N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei267N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Glycoprotein

Proteomic databases

EPDiO94905
MaxQBiO94905
PaxDbiO94905
PeptideAtlasiO94905
PRIDEiO94905
ProteomicsDBi50538
50539 [O94905-2]
50540 [O94905-3]

PTM databases

GlyConnecti1222
iPTMnetiO94905
PhosphoSitePlusiO94905
SwissPalmiO94905

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSG00000147475 Expressed in 219 organ(s), highest expression level in choroid plexus epithelium
CleanExiHS_ERLIN2
ExpressionAtlasiO94905 baseline and differential
GenevisibleiO94905 HS

Organism-specific databases

HPAiCAB014894
HPA002025

Interactioni

Subunit structurei

Forms a heteromeric complex with ERLIN1. In complex with ERLIN1, interacts with RNF170 (PubMed:19240031, PubMed:21610068). 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).By similarity1 Publication4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116331, 111 interactors
CORUMiO94905
IntActiO94905, 69 interactors
MINTiO94905
STRINGi9606.ENSP00000276461

Structurei

3D structure databases

ProteinModelPortaliO94905
SMRiO94905
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni177 – 309Interaction with ERLIN11 PublicationAdd BLAST133

Sequence similaritiesi

Belongs to the band 7/mec-2 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2962 Eukaryota
ENOG410XQSH LUCA
GeneTreeiENSGT00390000014666
HOVERGENiHBG050934
InParanoidiO94905
OMAiEGHTGVY
OrthoDBiEOG091G037D
PhylomeDBiO94905
TreeFamiTF313059

Family and domain databases

CDDicd03406 SPFH_like_u3, 1 hit
InterProiView protein in InterPro
IPR001107 Band_7
IPR033294 Erlin1/2
PANTHERiPTHR15351 PTHR15351, 1 hit
PfamiView protein in Pfam
PF01145 Band_7, 1 hit
SMARTiView protein in SMART
SM00244 PHB, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O94905-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAQLGAVVAV ASSFFCASLF SAVHKIEEGH IGVYYRGGAL LTSTSGPGFH
60 70 80 90 100
LMLPFITSYK SVQTTLQTDE VKNVPCGTSG GVMIYFDRIE VVNFLVPNAV
110 120 130 140 150
YDIVKNYTAD YDKALIFNKI HHELNQFCSV HTLQEVYIEL FDQIDENLKL
160 170 180 190 200
ALQQDLTSMA PGLVIQAVRV TKPNIPEAIR RNYELMESEK TKLLIAAQKQ
210 220 230 240 250
KVVEKEAETE RKKALIEAEK VAQVAEITYG QKVMEKETEK KISEIEDAAF
260 270 280 290 300
LAREKAKADA ECYTAMKIAE ANKLKLTPEY LQLMKYKAIA SNSKIYFGKD
310 320 330
IPNMFMDSAG SVSKQFEGLA DKLSFGLEDE PLETATKEN
Length:339
Mass (Da):37,840
Last modified:May 1, 1999 - v1
Checksum:i3CF322548FD58DB0
GO
Isoform 2 (identifier: O94905-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     142-152: DQIDENLKLAL → GLENDFSQESS
     153-339: Missing.

Show »
Length:152
Mass (Da):16,814
Checksum:i13EE2B91F5293642
GO
Isoform 3 (identifier: O94905-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     142-206: DQIDENLKLA...AQKQKVVEKE → GKKVSPEHAV...RMLIAMQQDP
     207-339: Missing.

Show »
Length:206
Mass (Da):22,939
Checksum:iC585C9F7DB01A671
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RHW4E5RHW4_HUMAN
Erlin-2
ERLIN2
338Annotation score:
E5RJ09E5RJ09_HUMAN
Erlin-2
ERLIN2
197Annotation score:

Sequence cautioni

The sequence AAH50611 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61S → P in AAH05950 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05914071V → A. Corresponds to variant dbSNP:rs2032066Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013940142 – 206DQIDE…VVEKE → GKKVSPEHAVLKQGSWNPAS LHCLKPGCLQGVMVTYGQEM LKNLVLRSWSQRSSWRMLIA MQQDP in isoform 3. 2 PublicationsAdd BLAST65
Alternative sequenceiVSP_008713142 – 152DQIDENLKLAL → GLENDFSQESS in isoform 2. 2 PublicationsAdd BLAST11
Alternative sequenceiVSP_008714153 – 339Missing in isoform 2. 2 PublicationsAdd BLAST187
Alternative sequenceiVSP_013941207 – 339Missing in isoform 3. 2 PublicationsAdd BLAST133

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018790 Genomic DNA Translation: BAA36845.1
AL442077 mRNA Translation: CAC09443.1
AY358108 mRNA Translation: AAQ88475.1
AY358851 mRNA Translation: AAQ89210.1
AK291394 mRNA Translation: BAF84083.1
AK297279 mRNA Translation: BAG59750.1
CH471080 Genomic DNA Translation: EAW63365.1
CH471080 Genomic DNA Translation: EAW63366.1
BC005950 mRNA Translation: AAH05950.1 Different termination.
BC048308 mRNA Translation: AAH48308.1
BC050611 mRNA Translation: AAH50611.1 Different initiation.
BC067765 mRNA Translation: AAH67765.1
CCDSiCCDS34879.1 [O94905-2]
CCDS6095.1 [O94905-1]
RefSeqiNP_001003790.1, NM_001003790.3 [O94905-2]
NP_001003791.1, NM_001003791.2 [O94905-2]
NP_009106.1, NM_007175.6 [O94905-1]
XP_005273449.1, XM_005273392.2 [O94905-1]
XP_016868489.1, XM_017013000.1 [O94905-2]
UniGeneiHs.669261
Hs.705490

Genome annotation databases

EnsembliENST00000276461; ENSP00000276461; ENSG00000147475 [O94905-1]
ENST00000335171; ENSP00000335220; ENSG00000147475 [O94905-2]
ENST00000397228; ENSP00000380405; ENSG00000147475 [O94905-2]
ENST00000518586; ENSP00000427847; ENSG00000147475 [O94905-3]
ENST00000519638; ENSP00000428112; ENSG00000147475 [O94905-1]
ENST00000523107; ENSP00000473292; ENSG00000147475 [O94905-3]
ENST00000523887; ENSP00000429903; ENSG00000147475 [O94905-3]
GeneIDi11160
KEGGihsa:11160
UCSCiuc003xkc.5 human [O94905-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018790 Genomic DNA Translation: BAA36845.1
AL442077 mRNA Translation: CAC09443.1
AY358108 mRNA Translation: AAQ88475.1
AY358851 mRNA Translation: AAQ89210.1
AK291394 mRNA Translation: BAF84083.1
AK297279 mRNA Translation: BAG59750.1
CH471080 Genomic DNA Translation: EAW63365.1
CH471080 Genomic DNA Translation: EAW63366.1
BC005950 mRNA Translation: AAH05950.1 Different termination.
BC048308 mRNA Translation: AAH48308.1
BC050611 mRNA Translation: AAH50611.1 Different initiation.
BC067765 mRNA Translation: AAH67765.1
CCDSiCCDS34879.1 [O94905-2]
CCDS6095.1 [O94905-1]
RefSeqiNP_001003790.1, NM_001003790.3 [O94905-2]
NP_001003791.1, NM_001003791.2 [O94905-2]
NP_009106.1, NM_007175.6 [O94905-1]
XP_005273449.1, XM_005273392.2 [O94905-1]
XP_016868489.1, XM_017013000.1 [O94905-2]
UniGeneiHs.669261
Hs.705490

3D structure databases

ProteinModelPortaliO94905
SMRiO94905
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116331, 111 interactors
CORUMiO94905
IntActiO94905, 69 interactors
MINTiO94905
STRINGi9606.ENSP00000276461

Protein family/group databases

TCDBi1.P.1.1.1 the polyoma virus sv40 er penitration channel (vpec) family

PTM databases

GlyConnecti1222
iPTMnetiO94905
PhosphoSitePlusiO94905
SwissPalmiO94905

Polymorphism and mutation databases

BioMutaiERLIN2

Proteomic databases

EPDiO94905
MaxQBiO94905
PaxDbiO94905
PeptideAtlasiO94905
PRIDEiO94905
ProteomicsDBi50538
50539 [O94905-2]
50540 [O94905-3]

Protocols and materials databases

DNASUi11160
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000276461; ENSP00000276461; ENSG00000147475 [O94905-1]
ENST00000335171; ENSP00000335220; ENSG00000147475 [O94905-2]
ENST00000397228; ENSP00000380405; ENSG00000147475 [O94905-2]
ENST00000518586; ENSP00000427847; ENSG00000147475 [O94905-3]
ENST00000519638; ENSP00000428112; ENSG00000147475 [O94905-1]
ENST00000523107; ENSP00000473292; ENSG00000147475 [O94905-3]
ENST00000523887; ENSP00000429903; ENSG00000147475 [O94905-3]
GeneIDi11160
KEGGihsa:11160
UCSCiuc003xkc.5 human [O94905-1]

Organism-specific databases

CTDi11160
DisGeNETi11160
EuPathDBiHostDB:ENSG00000147475.14
GeneCardsiERLIN2
HGNCiHGNC:1356 ERLIN2
HPAiCAB014894
HPA002025
MalaCardsiERLIN2
MIMi611225 phenotype
611605 gene
neXtProtiNX_O94905
OpenTargetsiENSG00000147475
Orphaneti209951 Autosomal recessive spastic paraplegia type 18
247604 Juvenile primary lateral sclerosis
280384 Recessive intellectual disability - motor dysfunction - multiple joint contractures
PharmGKBiPA25961
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2962 Eukaryota
ENOG410XQSH LUCA
GeneTreeiENSGT00390000014666
HOVERGENiHBG050934
InParanoidiO94905
OMAiEGHTGVY
OrthoDBiEOG091G037D
PhylomeDBiO94905
TreeFamiTF313059

Enzyme and pathway databases

ReactomeiR-HSA-382556 ABC-family proteins mediated transport
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-8853336 Signaling by plasma membrane FGFR1 fusions

Miscellaneous databases

GeneWikiiERLIN2
GenomeRNAii11160
PROiPR:O94905
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147475 Expressed in 219 organ(s), highest expression level in choroid plexus epithelium
CleanExiHS_ERLIN2
ExpressionAtlasiO94905 baseline and differential
GenevisibleiO94905 HS

Family and domain databases

CDDicd03406 SPFH_like_u3, 1 hit
InterProiView protein in InterPro
IPR001107 Band_7
IPR033294 Erlin1/2
PANTHERiPTHR15351 PTHR15351, 1 hit
PfamiView protein in Pfam
PF01145 Band_7, 1 hit
SMARTiView protein in SMART
SM00244 PHB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiERLN2_HUMAN
AccessioniPrimary (citable) accession number: O94905
Secondary accession number(s): A0JLQ1
, A8K5S9, B4DM38, D3DSW0, Q6NW21, Q86VS6, Q86W49
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: May 1, 1999
Last modified: October 10, 2018
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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