ID ERLN2_HUMAN Reviewed; 339 AA. AC O94905; A0JLQ1; A8K5S9; B4DM38; D3DSW0; Q6NW21; Q86VS6; Q86W49; DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 05-FEB-2025, entry version 188. DE RecName: Full=Erlin-2; DE AltName: Full=Endoplasmic reticulum lipid raft-associated protein 2; DE AltName: Full=Stomatin-prohibitin-flotillin-HflC/K domain-containing protein 2; DE Short=SPFH domain-containing protein 2; GN Name=ERLIN2; Synonyms=C8orf2, SPFH2; ORFNames=UNQ2441/PRO5003/PRO9924; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND TISSUE RP SPECIFICITY. RX PubMed=10449903; DOI=10.1159/000015298; RA Ikegawa S., Isomura M., Koshizuka Y., Nakamura Y.; RT "Cloning and characterization of a novel gene (C8orf2), a human RT representative of a novel gene family with homology to C. elegans RT C42.C1.9."; RL Cytogenet. Cell Genet. 85:227-231(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph node; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain, and Fetal brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 1-338 (ISOFORM 1). RC TISSUE=Duodenum, Prostate, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION, RP AND INTERACTION WITH ERLIN1. RX PubMed=19240031; DOI=10.1074/jbc.m809801200; RA Pearce M.M.P., Wormer D.B., Wilkens S., Wojcikiewicz R.J.H.; RT "An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2 RT mediates the ER-associated degradation of inositol 1,4,5-trisphosphate RT receptors."; RL J. Biol. Chem. 284:10433-10445(2009). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=16835267; DOI=10.1242/jcs.03060; RA Browman D.T., Resek M.E., Zajchowski L.D., Robbins S.M.; RT "Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins RT that define lipid-raft-like domains of the ER."; RL J. Cell Sci. 119:3149-3160(2006). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-106, AND MUTAGENESIS RP OF ASN-106. RX PubMed=17502376; DOI=10.1074/jbc.m701862200; RA Pearce M.M., Wang Y., Kelley G.G., Wojcikiewicz R.J.H.; RT "SPFH2 mediates the endoplasmic reticulum-associated degradation of RT inositol 1,4,5-trisphosphate receptors and other substrates in mammalian RT cells."; RL J. Biol. Chem. 282:20104-20115(2007). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP INVOLVEMENT IN SPG18B. RX PubMed=21330303; DOI=10.1093/hmg/ddr070; RA Yildirim Y., Orhan E.K., Iseri S.A., Serdaroglu-Oflazer P., Kara B., RA Solakoglu S., Tolun A.; RT "A frameshift mutation of ERLIN2 in recessive intellectual disability, RT motor dysfunction and multiple joint contractures."; RL Hum. Mol. Genet. 20:1886-1892(2011). RN [12] RP FUNCTION, INTERACTION WITH AMFR; SYVN1; RNF139 AND TMUB1, AND SUBUNIT. RX PubMed=21343306; DOI=10.1074/jbc.m110.211326; RA Jo Y., Sguigna P.V., DeBose-Boyd R.A.; RT "Membrane-associated ubiquitin ligase complex containing gp78 mediates RT sterol-accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A RT reductase."; RL J. Biol. Chem. 286:15022-15031(2011). RN [13] RP INTERACTION WITH RNF170. RX PubMed=21610068; DOI=10.1074/jbc.m111.251983; RA Lu J.P., Wang Y., Sliter D.A., Pearce M.M., Wojcikiewicz R.J.; RT "RNF170 protein, an endoplasmic reticulum membrane ubiquitin ligase, RT mediates inositol 1,4,5-trisphosphate receptor ubiquitination and RT degradation."; RL J. Biol. Chem. 286:24426-24433(2011). RN [14] RP FUNCTION, AND INTERACTION WITH SCAP; INSIG1; SREBF1 AND SREBF2. RX PubMed=24217618; DOI=10.1083/jcb.201305076; RA Huber M.D., Vesely P.W., Datta K., Gerace L.; RT "Erlins restrict SREBP activation in the ER and regulate cellular RT cholesterol homeostasis."; RL J. Cell Biol. 203:427-436(2013). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP INTERACTION WITH TMEM41B. RX PubMed=30352685; DOI=10.1016/j.bbrc.2018.10.073; RA Van Alstyne M., Lotti F., Dal Mas A., Area-Gomez E., Pellizzoni L.; RT "Stasimon/Tmem41b localizes to mitochondria-associated ER membranes and is RT essential for mouse embryonic development."; RL Biochem. Biophys. Res. Commun. 506:463-470(2018). RN [18] RP VARIANT SPG18B CYS-180. RX PubMed=27824013; DOI=10.4103/0366-6999.193444; RA Tian W.T., Shen J.Y., Liu X.L., Wang T., Luan X.H., Zhou H.Y., Chen S.D., RA Huang X.J., Cao L.; RT "Novel Mutations in Endoplasmic Reticulum Lipid Raft-associated Protein 2 RT Gene Cause Pure Hereditary Spastic Paraplegia Type 18."; RL Chin. Med. J. 129:2759-2761(2016). RN [19] RP VARIANT SPG18B VAL-300. RX PubMed=28832565; DOI=10.1038/ejhg.2017.124; RA Morais S., Raymond L., Mairey M., Coutinho P., Brandao E., Ribeiro P., RA Loureiro J.L., Sequeiros J., Brice A., Alonso I., Stevanin G.; RT "Massive sequencing of 70 genes reveals a myriad of missing genes or RT mechanisms to be uncovered in hereditary spastic paraplegias."; RL Eur. J. Hum. Genet. 25:1217-1228(2017). RN [20] RP VARIANT SPG18A THR-129, AND INVOLVEMENT IN SPG18A. RX PubMed=29528531; DOI=10.1111/ene.13625; RA Rydning S.L., Dudesek A., Rimmele F., Funke C., Krueger S., Biskup S., RA Vigeland M.D., Hjorthaug H.S., Sejersted Y., Tallaksen C., Selmer K.K., RA Kamm C.; RT "A novel heterozygous variant in ERLIN2 causes autosomal dominant pure RT hereditary spastic paraplegia."; RL Eur. J. Neurol. 25:943e71-943e71(2018). RN [21] RP VARIANT SPG18A VAL-151. RX PubMed=32094424; DOI=10.1038/s41598-020-60374-y; RA Park J.M., Lee B., Kim J.H., Park S.Y., Yu J., Kim U.K., Park J.S.; RT "An autosomal dominant ERLIN2 mutation leads to a pure HSP phenotype RT distinct from the autosomal recessive ERLIN2 mutations (SPG18)."; RL Sci. Rep. 10:3295-3295(2020). CC -!- FUNCTION: Component of the ERLIN1/ERLIN2 complex which mediates the CC endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5- CC trisphosphate receptors (IP3Rs) such as ITPR1 (PubMed:17502376, CC PubMed:19240031). Promotes sterol-accelerated ERAD of HMGCR probably CC implicating an AMFR/gp78-containing ubiquitin ligase complex CC (PubMed:21343306). Involved in regulation of cellular cholesterol CC homeostasis by regulation the SREBP signaling pathway. May promote ER CC retention of the SCAP-SREBF complex (PubMed:24217618). CC {ECO:0000269|PubMed:17502376, ECO:0000269|PubMed:19240031, CC ECO:0000269|PubMed:21343306, ECO:0000269|PubMed:24217618}. CC -!- SUBUNIT: Forms a heteromeric complex with ERLIN1. In complex with CC ERLIN1, interacts with RNF170 (PubMed:19240031, PubMed:21610068). CC Interacts with activated ITPR1, independently of the degree of ITPR1 CC polyubiquitination (By similarity). Interacts with SCAP, INSIG1, SREBF1 CC and SREBF2 under cholesterol sufficiency conditions; indicative for an CC association with the SCAP-SREBP-INSIG complex (PubMed:24217618). CC Probably part of an AMFR/gp78 and INSIG1-containing ubiquitin ligase CC complex involved in ERAD of HMGCR. Interacts with TMUB1; TMUB1 bridges CC the association with AMFR. Interacts with SYVN1 and RNF139 CC (PubMed:21343306). Interacts with TMEM259 (By similarity). Interacts CC with TMEM41B (PubMed:30352685). {ECO:0000250|UniProtKB:Q8BFZ9, CC ECO:0000269|PubMed:19240031, ECO:0000269|PubMed:21343306, CC ECO:0000269|PubMed:21610068, ECO:0000269|PubMed:24217618, CC ECO:0000269|PubMed:30352685, ECO:0000305|PubMed:21343306}. CC -!- INTERACTION: CC O94905; Q9UKV5: AMFR; NbExp=10; IntAct=EBI-4400770, EBI-1046367; CC O94905; O75477: ERLIN1; NbExp=5; IntAct=EBI-4400770, EBI-359299; CC O94905; Q86TM6: SYVN1; NbExp=2; IntAct=EBI-4400770, EBI-947849; CC O94905; Q9BVT8: TMUB1; NbExp=6; IntAct=EBI-4400770, EBI-11425701; CC O94905; P00347: HMGCR; Xeno; NbExp=2; IntAct=EBI-4400770, EBI-11426687; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:16835267, ECO:0000269|PubMed:17502376, CC ECO:0000269|PubMed:19240031}; Single-pass type II membrane protein CC {ECO:0000269|PubMed:16835267, ECO:0000269|PubMed:17502376, CC ECO:0000269|PubMed:19240031}. Note=Associated with lipid raft-like CC domains of the endoplasmic reticulum membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O94905-1; Sequence=Displayed; CC Name=2; CC IsoId=O94905-2; Sequence=VSP_008713, VSP_008714; CC Name=3; CC IsoId=O94905-3; Sequence=VSP_013940, VSP_013941; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10449903}. CC -!- PTM: Deubiquitinated by USP25; leading to stabilization. CC {ECO:0000250|UniProtKB:O75477}. CC -!- DISEASE: Spastic paraplegia 18B, autosomal recessive (SPG18B) CC [MIM:611225]: A form of spastic paraplegia, a neurodegenerative CC disorder characterized by a slow, gradual, progressive weakness and CC spasticity of the lower limbs. Rate of progression and the severity of CC symptoms are quite variable. Initial symptoms may include difficulty CC with balance, weakness and stiffness in the legs, muscle spasms, and CC dragging the toes when walking. In some forms of the disorder, bladder CC symptoms (such as incontinence) may appear, or the weakness and CC stiffness may spread to other parts of the body. SPG18B is a severe CC form with onset in early childhood. Most affected individuals have CC severe psychomotor retardation. Some may develop significant joint CC contractures. {ECO:0000269|PubMed:21330303, CC ECO:0000269|PubMed:27824013, ECO:0000269|PubMed:28832565}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Spastic paraplegia 18A, autosomal dominant (SPG18A) CC [MIM:620512]: A form of spastic paraplegia, a neurodegenerative CC disorder characterized by a slow, gradual, progressive weakness and CC spasticity of the lower limbs. Rate of progression and the severity of CC symptoms are quite variable. Initial symptoms may include difficulty CC with balance, weakness and stiffness in the legs, muscle spasms, and CC dragging the toes when walking. In some forms of the disorder, bladder CC symptoms (such as incontinence) may appear, or the weakness and CC stiffness may spread to other parts of the body. SPG18A is a pure form. CC Age at onset of symptoms varies considerably from childhood to CC adulthood. {ECO:0000269|PubMed:29528531, ECO:0000269|PubMed:32094424}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the band 7/mec-2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH50611.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB018790; BAA36845.1; -; Genomic_DNA. DR EMBL; AL442077; CAC09443.1; -; mRNA. DR EMBL; AY358108; AAQ88475.1; -; mRNA. DR EMBL; AY358851; AAQ89210.1; -; mRNA. DR EMBL; AK291394; BAF84083.1; -; mRNA. DR EMBL; AK297279; BAG59750.1; -; mRNA. DR EMBL; CH471080; EAW63365.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63366.1; -; Genomic_DNA. DR EMBL; BC005950; AAH05950.1; ALT_TERM; mRNA. DR EMBL; BC048308; AAH48308.1; -; mRNA. DR EMBL; BC050611; AAH50611.1; ALT_INIT; mRNA. DR EMBL; BC067765; AAH67765.1; -; mRNA. DR CCDS; CCDS34879.1; -. [O94905-2] DR CCDS; CCDS6095.1; -. [O94905-1] DR RefSeq; NP_001003790.1; NM_001003790.3. [O94905-2] DR RefSeq; NP_001003791.1; NM_001003791.2. [O94905-2] DR RefSeq; NP_009106.1; NM_007175.6. [O94905-1] DR RefSeq; XP_005273449.1; XM_005273392.2. DR RefSeq; XP_016868489.1; XM_017013000.1. DR AlphaFoldDB; O94905; -. DR SMR; O94905; -. DR BioGRID; 116331; 316. DR ComplexPortal; CPX-7121; ERLIN1-ERLIN2 complex. DR CORUM; O94905; -. DR IntAct; O94905; 138. DR MINT; O94905; -. DR STRING; 9606.ENSP00000428112; -. DR ChEMBL; CHEMBL4739672; -. DR TCDB; 1.P.1.1.1; the polyoma virus sv40 er penetration channel (vpec) family. DR TCDB; 8.A.195.1.1; the erlin1/2 complex (erlin) family. DR GlyConnect; 1222; 10 N-Linked glycans (1 site). DR GlyCosmos; O94905; 1 site, 10 glycans. DR GlyGen; O94905; 5 sites, 11 N-linked glycans (1 site), 2 O-linked glycans (4 sites). DR iPTMnet; O94905; -. DR PhosphoSitePlus; O94905; -. DR SwissPalm; O94905; -. DR BioMuta; ERLIN2; -. DR CPTAC; CPTAC-361; -. DR CPTAC; CPTAC-362; -. DR jPOST; O94905; -. DR MassIVE; O94905; -. DR PaxDb; 9606-ENSP00000276461; -. DR PeptideAtlas; O94905; -. DR PRIDE; O94905; -. DR ProteomicsDB; 50538; -. [O94905-1] DR ProteomicsDB; 50539; -. [O94905-2] DR ProteomicsDB; 50540; -. [O94905-3] DR Pumba; O94905; -. DR Antibodypedia; 719; 314 antibodies from 33 providers. DR DNASU; 11160; -. DR Ensembl; ENST00000335171.10; ENSP00000335220.6; ENSG00000147475.17. [O94905-2] DR Ensembl; ENST00000518586.5; ENSP00000427847.1; ENSG00000147475.17. [O94905-3] DR Ensembl; ENST00000519638.3; ENSP00000428112.1; ENSG00000147475.17. [O94905-1] DR Ensembl; ENST00000523107.5; ENSP00000473292.1; ENSG00000147475.17. [O94905-3] DR Ensembl; ENST00000523887.5; ENSP00000429903.1; ENSG00000147475.17. [O94905-3] DR Ensembl; ENST00000648919.1; ENSP00000497100.1; ENSG00000147475.17. [O94905-2] DR GeneID; 11160; -. DR KEGG; hsa:11160; -. DR MANE-Select; ENST00000519638.3; ENSP00000428112.1; NM_007175.8; NP_009106.1. DR UCSC; uc003xkc.5; human. [O94905-1] DR AGR; HGNC:1356; -. DR CTD; 11160; -. DR DisGeNET; 11160; -. DR GeneCards; ERLIN2; -. DR HGNC; HGNC:1356; ERLIN2. DR HPA; ENSG00000147475; Low tissue specificity. DR MalaCards; ERLIN2; -. DR MIM; 611225; phenotype. DR MIM; 611605; gene. DR MIM; 620512; phenotype. DR neXtProt; NX_O94905; -. DR OpenTargets; ENSG00000147475; -. DR Orphanet; 209951; Autosomal spastic paraplegia type 18. DR Orphanet; 247604; Juvenile primary lateral sclerosis. DR Orphanet; 280384; Recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome. DR PharmGKB; PA25961; -. DR VEuPathDB; HostDB:ENSG00000147475; -. DR eggNOG; KOG2962; Eukaryota. DR GeneTree; ENSGT00390000014666; -. DR HOGENOM; CLU_1643079_0_0_1; -. DR InParanoid; O94905; -. DR OMA; YNMVRNF; -. DR OrthoDB; 77368at2759; -. DR PhylomeDB; O94905; -. DR TreeFam; TF313059; -. DR PathwayCommons; O94905; -. DR Reactome; R-HSA-382556; ABC-family proteins mediated transport. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-5678895; Defective CFTR causes cystic fibrosis. DR Reactome; R-HSA-8853336; Signaling by plasma membrane FGFR1 fusions. DR SignaLink; O94905; -. DR SIGNOR; O94905; -. DR BioGRID-ORCS; 11160; 14 hits in 1156 CRISPR screens. DR ChiTaRS; ERLIN2; human. DR GeneWiki; ERLIN2; -. DR GenomeRNAi; 11160; -. DR Pharos; O94905; Tbio. DR PRO; PR:O94905; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; O94905; protein. DR Bgee; ENSG00000147475; Expressed in choroid plexus epithelium and 199 other cell types or tissues. DR ExpressionAtlas; O94905; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0015485; F:cholesterol binding; IBA:GO_Central. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW. DR GO; GO:0036503; P:ERAD pathway; IDA:UniProtKB. DR GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; IMP:UniProtKB. DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IMP:UniProtKB. DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; IDA:ComplexPortal. DR GO; GO:0032933; P:SREBP signaling pathway; IMP:UniProtKB. DR CDD; cd03406; SPFH_like_u3; 1. DR FunFam; 3.30.479.30:FF:000009; Erlin-2 isoform 1; 1. DR Gene3D; 3.30.479.30; Band 7 domain; 1. DR InterPro; IPR001107; Band_7. DR InterPro; IPR036013; Band_7/SPFH_dom_sf. DR InterPro; IPR033294; Erlin1/2. DR PANTHER; PTHR15351; ERLIN (ER LIPID RAFT ASSOCIATED PROTEIN) HOMOLOG; 1. DR PANTHER; PTHR15351:SF4; ERLIN-2; 1. DR Pfam; PF01145; Band_7; 1. DR SMART; SM00244; PHB; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cholesterol metabolism; KW Direct protein sequencing; Disease variant; Endoplasmic reticulum; KW Glycoprotein; Hereditary spastic paraplegia; Lipid metabolism; Membrane; KW Neurodegeneration; Proteomics identification; Reference proteome; KW Signal-anchor; Steroid metabolism; Sterol metabolism; Transmembrane; KW Transmembrane helix. FT CHAIN 1..339 FT /note="Erlin-2" FT /id="PRO_0000002787" FT TOPO_DOM 1..3 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 4..24 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 25..339 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REGION 177..309 FT /note="Interaction with ERLIN1" FT /evidence="ECO:0000269|PubMed:19240031" FT MOD_RES 267 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:O75477" FT CARBOHYD 106 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17502376" FT VAR_SEQ 142..206 FT /note="DQIDENLKLALQQDLTSMAPGLVIQAVRVTKPNIPEAIRRNYELMESEKTKL FT LIAAQKQKVVEKE -> GKKVSPEHAVLKQGSWNPASLHCLKPGCLQGVMVTYGQEMLK FT NLVLRSWSQRSSWRMLIAMQQDP (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_013940" FT VAR_SEQ 142..152 FT /note="DQIDENLKLAL -> GLENDFSQESS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:15489334" FT /id="VSP_008713" FT VAR_SEQ 153..339 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:15489334" FT /id="VSP_008714" FT VAR_SEQ 207..339 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_013941" FT VARIANT 71 FT /note="V -> A (in dbSNP:rs2032066)" FT /id="VAR_059140" FT VARIANT 129 FT /note="S -> T (in SPG18A; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:29528531" FT /id="VAR_089040" FT VARIANT 151 FT /note="A -> V (in SPG18A; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32094424" FT /id="VAR_089041" FT VARIANT 180 FT /note="R -> C (in SPG18B; uncertain significance)" FT /evidence="ECO:0000269|PubMed:27824013" FT /id="VAR_089042" FT VARIANT 300 FT /note="D -> V (in SPG18B; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28832565" FT /id="VAR_089043" FT MUTAGEN 106 FT /note="N->Q: Loss of glycosylation." FT /evidence="ECO:0000269|PubMed:17502376" FT CONFLICT 61 FT /note="S -> P (in Ref. 6; AAH05950)" FT /evidence="ECO:0000305" SQ SEQUENCE 339 AA; 37840 MW; 3CF322548FD58DB0 CRC64; MAQLGAVVAV ASSFFCASLF SAVHKIEEGH IGVYYRGGAL LTSTSGPGFH LMLPFITSYK SVQTTLQTDE VKNVPCGTSG GVMIYFDRIE VVNFLVPNAV YDIVKNYTAD YDKALIFNKI HHELNQFCSV HTLQEVYIEL FDQIDENLKL ALQQDLTSMA PGLVIQAVRV TKPNIPEAIR RNYELMESEK TKLLIAAQKQ KVVEKEAETE RKKALIEAEK VAQVAEITYG QKVMEKETEK KISEIEDAAF LAREKAKADA ECYTAMKIAE ANKLKLTPEY LQLMKYKAIA SNSKIYFGKD IPNMFMDSAG SVSKQFEGLA DKLSFGLEDE PLETATKEN //