Human Gene ERLIN2 (uc003xke.4)
  Description: Homo sapiens ER lipid raft associated 2 (ERLIN2), transcript variant 1, mRNA.
RefSeq Summary (NM_007175): This gene encodes a member of the SPFH domain-containing family of lipid raft-associated proteins. The encoded protein is localized to lipid rafts of the endoplasmic reticulum and plays a critical role in inositol 1,4,5-trisphosphate (IP3) signaling by mediating ER-associated degradation of activated IP3 receptors. Mutations in this gene are a cause of spastic paraplegia-18 (SPG18). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012].
Transcript (Including UTRs)
   Position: hg19 chr8:37,594,097-37,615,319 Size: 21,223 Total Exon Count: 12 Strand: +
Coding Region
   Position: hg19 chr8:37,595,441-37,611,633 Size: 16,193 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr8:37,594,097-37,615,319)mRNA (may differ from genome)Protein (339 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Erlin-2; AltName: Full=Endoplasmic reticulum lipid raft-associated protein 2; AltName: Full=Stomatin-prohibitin-flotillin-HflC/K domain-containing protein 2; Short=SPFH domain-containing protein 2;
FUNCTION: Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Also involved in ITPR1 degradation by the ERAD pathway.
SUBUNIT: Interacts with activated ITPR1, independently of the degree of ITPR1 polyubiquitination (By similarity). Forms a heteromeric complex with ERLIN1. In complex with ERLIN1, interacts with RNF170.
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type II membrane protein. Note=Associated with lipid raft-like domains of the endoplasmic reticulum membrane.
DISEASE: Defects in ERLIN2 are the cause of spastic paraplegia autosomal recessive type 18 (SPG18) [MIM:611225]. A 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.
SIMILARITY: Belongs to the band 7/mec-2 family.
SEQUENCE CAUTION: Sequence=AAH50611.1; Type=Erroneous initiation;

-  MalaCards Disease Associations
  MalaCards Gene Search: ERLIN2
Diseases sorted by gene-association score: spastic paraplegia 18, autosomal recessive* (1277), spastic paraplegia 18* (540), recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome* (350), primary lateral sclerosis, juvenile* (247), spastic paraplegia 47, autosomal recessive (10), spastic paraplegia 48, autosomal recessive (10), spastic paraplegia 39, autosomal recessive (10), spastic paraplegia 30, autosomal recessive (8), spastic paraplegia 42, autosomal dominant (8), spastic paraplegia 13, autosomal dominant (8), spastic paraplegia 8, autosomal dominant (7), spastic paraplegia 44, autosomal recessive (7), spastic paraplegia 12, autosomal dominant (7), spastic paraplegia 35, autosomal recessive (7), spastic paraplegia 6, autosomal dominant (6), spastic paraplegia 2, x-linked (6), masa syndrome (5), cystic fibrosis (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 10.04 RPKM in Cells - Cultured fibroblasts
Total median expression: 292.43 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -42.90115-0.373 Picture PostScript Text
3' UTR -1128.323686-0.306 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001107 - Band_7

Pfam Domains:
PF01145 - SPFH domain / Band 7 family

ModBase Predicted Comparative 3D Structure on O94905
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologGenome BrowserNo ortholog
Gene DetailsGene Details  Gene Details 
Gene SorterGene Sorter  Gene Sorter 
 RGDEnsembl WormBase 
 Protein SequenceProtein Sequence Protein Sequence 
 AlignmentAlignment Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0015485 cholesterol binding
GO:0031625 ubiquitin protein ligase binding

Biological Process:
GO:0006629 lipid metabolic process
GO:0008202 steroid metabolic process
GO:0008203 cholesterol metabolic process
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0030433 ER-associated ubiquitin-dependent protein catabolic process
GO:0032933 SREBP signaling pathway
GO:0045541 negative regulation of cholesterol biosynthetic process
GO:0045717 negative regulation of fatty acid biosynthetic process
GO:0055085 transmembrane transport

Cellular Component:
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0032991 macromolecular complex
GO:0045121 membrane raft

-  Descriptions from all associated GenBank mRNAs
  KJ902213 - Synthetic construct Homo sapiens clone ccsbBroadEn_11607 ERLIN2 gene, encodes complete protein.
KJ893241 - Synthetic construct Homo sapiens clone ccsbBroadEn_02635 ERLIN2 gene, encodes complete protein.
LF208067 - JP 2014500723-A/15570: Polycomb-Associated Non-Coding RNAs.
AL442077 - Homo sapiens mRNA; cDNA DKFZp667H242 (from clone DKFZp667H242).
BC050611 - Homo sapiens ER lipid raft associated 2, mRNA (cDNA clone IMAGE:5202154), partial cds.
AK297279 - Homo sapiens cDNA FLJ53807 complete cds, highly similar to Homo sapiens SPFH domain family, member 2 (SPFH2), transcript variant 3, mRNA.
AK291394 - Homo sapiens cDNA FLJ76849 complete cds, highly similar to Homo sapiens SPFH domain family, member 2 (SPFH2), transcript variant 1, mRNA.
AY358108 - Homo sapiens clone DNA125201 C8orf2 (UNQ2441) mRNA, complete cds.
AY358851 - Homo sapiens clone DNA92284 C8orf2 (UNQ2441) mRNA, complete cds.
BC005950 - Homo sapiens ER lipid raft associated 2, mRNA (cDNA clone IMAGE:4248728), partial cds.
BC067765 - Homo sapiens ER lipid raft associated 2, mRNA (cDNA clone MGC:87072 IMAGE:5296776), complete cds.
BC048308 - Homo sapiens ER lipid raft associated 2, mRNA (cDNA clone IMAGE:5550432), complete cds.
CU690572 - Synthetic construct Homo sapiens gateway clone IMAGE:100022721 5' read ERLIN2 mRNA.
AB463029 - Synthetic construct DNA, clone: pF1KB8575, Homo sapiens ERLIN2 gene for ER lipid raft associated 2, without stop codon, in Flexi system.
AM393041 - Synthetic construct Homo sapiens clone IMAGE:100001861 for hypothetical protein (SPFH2 gene).
AM393068 - Synthetic construct Homo sapiens clone IMAGE:100001855 for hypothetical protein (SPFH2 gene).
GQ891347 - Homo sapiens clone HEL-S-118d epididymis secretory sperm binding protein mRNA, complete cds.
LF371844 - JP 2014500723-A/179347: Polycomb-Associated Non-Coding RNAs.
LF371845 - JP 2014500723-A/179348: Polycomb-Associated Non-Coding RNAs.
DQ581063 - Homo sapiens piRNA piR-49175, complete sequence.
LF371848 - JP 2014500723-A/179351: Polycomb-Associated Non-Coding RNAs.
LF371849 - JP 2014500723-A/179352: Polycomb-Associated Non-Coding RNAs.
LF371850 - JP 2014500723-A/179353: Polycomb-Associated Non-Coding RNAs.
LF371851 - JP 2014500723-A/179354: Polycomb-Associated Non-Coding RNAs.
LF371852 - JP 2014500723-A/179355: Polycomb-Associated Non-Coding RNAs.
JD272760 - Sequence 253784 from Patent EP1572962.
Z36802 - H.sapiens (xs150) mRNA, 260bp.
JD452955 - Sequence 433979 from Patent EP1572962.
JD348137 - Sequence 329161 from Patent EP1572962.
BC035980 - Homo sapiens ER lipid raft associated 2, mRNA (cDNA clone IMAGE:4133024), with apparent retained intron.
AY358205 - Homo sapiens clone DNA139652 C8orf2 (UNQ2441) mRNA, complete cds.
JD315276 - Sequence 296300 from Patent EP1572962.
JD523885 - Sequence 504909 from Patent EP1572962.
AK057557 - Homo sapiens cDNA FLJ32995 fis, clone THYMU1000136.
LF371853 - JP 2014500723-A/179356: Polycomb-Associated Non-Coding RNAs.
LF371854 - JP 2014500723-A/179357: Polycomb-Associated Non-Coding RNAs.
LF371855 - JP 2014500723-A/179358: Polycomb-Associated Non-Coding RNAs.
MA607421 - JP 2018138019-A/179347: Polycomb-Associated Non-Coding RNAs.
MA607422 - JP 2018138019-A/179348: Polycomb-Associated Non-Coding RNAs.
MA607425 - JP 2018138019-A/179351: Polycomb-Associated Non-Coding RNAs.
MA607426 - JP 2018138019-A/179352: Polycomb-Associated Non-Coding RNAs.
MA607427 - JP 2018138019-A/179353: Polycomb-Associated Non-Coding RNAs.
MA607428 - JP 2018138019-A/179354: Polycomb-Associated Non-Coding RNAs.
MA607429 - JP 2018138019-A/179355: Polycomb-Associated Non-Coding RNAs.
MA607430 - JP 2018138019-A/179356: Polycomb-Associated Non-Coding RNAs.
MA607431 - JP 2018138019-A/179357: Polycomb-Associated Non-Coding RNAs.
MA607432 - JP 2018138019-A/179358: Polycomb-Associated Non-Coding RNAs.
MA443644 - JP 2018138019-A/15570: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O94905 (Reactome details) participates in the following event(s):

R-HSA-8853322 Plasma membrane FGFR1 fusions dimerize
R-HSA-8853325 Plasma membrane FGFR1 fusions autophosphorylate
R-HSA-8866551 CFTR binds components of the ERAD machinery for ubiquitination and degradation
R-HSA-8866857 CFTR F508del binds components of the ERAD machinery for ubiquitination and degradation
R-HSA-8866542 VCP-catalyzed ATP hydrolysis promotes the translocation of misfolded CFTR into the cytosol
R-HSA-8866854 VCP-catalyzed ATP hydrolysis promotes the translocation of CFTR F508del into the cytosol
R-HSA-5655269 Activated FGFR1 mutants bind FRS2
R-HSA-8866546 RNF5 and RNF185 ubiquitinate misfolded CFTR
R-HSA-8866856 RNF5 and RNF185 ubiquitinate CFTR F508del
R-HSA-5655240 Activated FGFR1 mutants:p-FRS2 binds GRB2:GAB1:PIK3R1
R-HSA-5655266 Activated FGFR1 mutants:p-FRS2 binds GRB2-SOS1
R-HSA-5655278 Activated FGFR1 mutants phosphorylate FRS2
R-HSA-1839094 Activated FGFR1 mutants and fusions bind PLCG1
R-HSA-1839100 p-4Y- PLCG1 dissociates from activated FGFR1 mutants and fusions
R-HSA-5655263 Activated FGFR1 mutants:p-FRS2:GRB2:GAB1:PIK3R1 binds PIK3CA
R-HSA-1839098 Activated FGFR1 mutants and fusions phosphorylate PLCG1
R-HSA-5655326 Activated FGFR1 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
R-HSA-5655290 Activated FGFR1 mutant-associated PI3K phosphorylates PIP2 to PIP3
R-HSA-8853336 Signaling by plasma membrane FGFR1 fusions
R-HSA-1839124 FGFR1 mutant receptor activation
R-HSA-382556 ABC-family proteins mediated transport
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-5655302 Signaling by FGFR1 in disease
R-HSA-382551 Transport of small molecules
R-HSA-5619084 ABC transporter disorders
R-HSA-1226099 Signaling by FGFR in disease
R-HSA-5619115 Disorders of transmembrane transporters
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: A0JLQ1, A8K5S9, B4DM38, C8orf2, D3DSW0, ERLN2_HUMAN, NM_007175, NP_009106, O94905, Q6NW21, Q86VS6, Q86W49, SPFH2, UNQ2441/PRO5003/PRO9924
UCSC ID: uc003xke.4
RefSeq Accession: NM_007175
Protein: O94905 (aka ERLN2_HUMAN)
CCDS: CCDS6095.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ERLIN2:
hsp (Hereditary Spastic Paraplegia Overview)

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_007175.6
exon count: 12CDS single in 3' UTR: no RNA size: 4836
ORF size: 1020CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2240.00frame shift in genome: no % Coverage: 99.69
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.