ID   ERLN2_MOUSE             Reviewed;         340 AA.
AC   Q8BFZ9; Q8BML8;
DT   07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 148.
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=Spfh2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Pituitary;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
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   [3]
RP   INTERACTION WITH ITPR1.
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   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
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   [6]
RP   INTERACTION WITH TMEM259.
RX   PubMed=25977983; DOI=10.7554/elife.06500;
RA   Yang B., Qu M., Wang R., Chatterton J.E., Liu X.B., Zhu B., Narisawa S.,
RA   Millan J.L., Nakanishi N., Swoboda K., Lipton S.A., Zhang D.;
RT   "The critical role of membralin in postnatal motor neuron survival and
RT   disease.";
RL   Elife 4:0-0(2015).
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. Promotes sterol-
CC       accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing
CC       ubiquitin ligase complex. Involved in regulation of cellular
CC       cholesterol homeostasis by regulation the SREBP signaling pathway. May
CC       promote ER retention of the SCAP-SREBF complex (By similarity).
CC       {ECO:0000250|UniProtKB:O94905}.
CC   -!- SUBUNIT: Forms a heteromeric complex with ERLIN1 (By similarity). In
CC       complex with ERLIN1, interacts with RNF170 (PubMed:21610068). Interacts
CC       with activated ITPR1, independently of the degree of ITPR1
CC       polyubiquitination (PubMed:17502376). Interacts with SCAP, INSIG1,
CC       SREBF1 and SREBF2 under cholesterol sufficiency conditions; indicative
CC       for an association with the SCAP-SREBP-INSIG complex (By similarity).
CC       Probably part of an AMFR/gp78 and INSIG1-containing ubiquitin ligase
CC       complex involved in ERAD of HMGCR (By similarity). Interacts with
CC       TMUB1; TMUB1 bridges the association with AMFR (By similarity).
CC       Interacts with SYVN1 and RNF139 (By similarity). Interacts with TMEM259
CC       (PubMed:25977983). Interacts with TMEM41B (By similarity).
CC       {ECO:0000250|UniProtKB:O94905, ECO:0000269|PubMed:17502376,
CC       ECO:0000269|PubMed:21610068, ECO:0000269|PubMed:25977983}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC       Single-pass type II membrane protein {ECO:0000250}. Note=Associated
CC       with lipid raft-like domains of the endoplasmic reticulum membrane.
CC       {ECO:0000250}.
CC   -!- PTM: Deubiquitinated by USP25; leading to stabilization.
CC       {ECO:0000250|UniProtKB:O75477}.
CC   -!- SIMILARITY: Belongs to the band 7/mec-2 family. {ECO:0000305}.
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DR   EMBL; AK030557; BAC27019.1; -; mRNA.
DR   EMBL; BC036333; AAH36333.1; -; mRNA.
DR   EMBL; BC038374; AAH38374.1; -; mRNA.
DR   CCDS; CCDS22209.1; -.
DR   RefSeq; NP_705820.1; NM_153592.2.
DR   RefSeq; XP_006509179.1; XM_006509116.2.
DR   RefSeq; XP_006509180.1; XM_006509117.1.
DR   AlphaFoldDB; Q8BFZ9; -.
DR   SMR; Q8BFZ9; -.
DR   BioGRID; 232642; 13.
DR   IntAct; Q8BFZ9; 7.
DR   MINT; Q8BFZ9; -.
DR   STRING; 10090.ENSMUSP00000033873; -.
DR   GlyConnect; 2301; 2 N-Linked glycans (1 site).
DR   GlyCosmos; Q8BFZ9; 1 site, 2 glycans.
DR   GlyGen; Q8BFZ9; 2 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; Q8BFZ9; -.
DR   PhosphoSitePlus; Q8BFZ9; -.
DR   SwissPalm; Q8BFZ9; -.
DR   EPD; Q8BFZ9; -.
DR   jPOST; Q8BFZ9; -.
DR   MaxQB; Q8BFZ9; -.
DR   PaxDb; 10090-ENSMUSP00000033873; -.
DR   PeptideAtlas; Q8BFZ9; -.
DR   ProteomicsDB; 275538; -.
DR   Pumba; Q8BFZ9; -.
DR   Antibodypedia; 719; 296 antibodies from 33 providers.
DR   DNASU; 244373; -.
DR   Ensembl; ENSMUST00000033873.9; ENSMUSP00000033873.8; ENSMUSG00000031483.9.
DR   GeneID; 244373; -.
DR   KEGG; mmu:244373; -.
DR   UCSC; uc009lhr.2; mouse.
DR   AGR; MGI:2387215; -.
DR   CTD; 11160; -.
DR   MGI; MGI:2387215; Erlin2.
DR   VEuPathDB; HostDB:ENSMUSG00000031483; -.
DR   eggNOG; KOG2962; Eukaryota.
DR   GeneTree; ENSGT00390000014666; -.
DR   HOGENOM; CLU_058701_0_0_1; -.
DR   InParanoid; Q8BFZ9; -.
DR   OMA; MFMDHAG; -.
DR   OrthoDB; 3129813at2759; -.
DR   PhylomeDB; Q8BFZ9; -.
DR   TreeFam; TF313059; -.
DR   Reactome; R-MMU-382556; ABC-family proteins mediated transport.
DR   BioGRID-ORCS; 244373; 5 hits in 82 CRISPR screens.
DR   ChiTaRS; Erlin2; mouse.
DR   PRO; PR:Q8BFZ9; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; Q8BFZ9; Protein.
DR   Bgee; ENSMUSG00000031483; Expressed in spermatocyte and 220 other cell types or tissues.
DR   ExpressionAtlas; Q8BFZ9; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0045121; C:membrane raft; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0015485; F:cholesterol binding; IBA:GO_Central.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; ISO:MGI.
DR   GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISO:MGI.
DR   GO; GO:0045540; P:regulation of cholesterol biosynthetic process; ISO:MGI.
DR   GO; GO:0032933; P:SREBP signaling pathway; ISO:MGI.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISO:MGI.
DR   CDD; cd03406; SPFH_like_u3; 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.
DR   Genevisible; Q8BFZ9; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cholesterol metabolism; Endoplasmic reticulum; Glycoprotein;
KW   Lipid metabolism; Membrane; Reference proteome; Signal-anchor;
KW   Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix.
FT   CHAIN           1..340
FT                   /note="Erlin-2"
FT                   /id="PRO_0000002788"
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..340
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   REGION          177..309
FT                   /note="Interaction with ERLIN1"
FT                   /evidence="ECO:0000250"
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:0000255"
FT   CONFLICT        281
FT                   /note="L -> Q (in Ref. 1; BAC27019)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        304
FT                   /note="M -> I (in Ref. 1; BAC27019)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   340 AA;  37873 MW;  DA76718E5DCB7664 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 ECYTALKIAE ANKLKLTPEY LQLMKYKAIA SNSKIYFGKD
     IPNMFMDSAG GLGKQFEGLS DDKLGFGLED EPLEAPTKEN
//