BSCL2_HUMAN
ID BSCL2_HUMAN Reviewed; 398 AA.
AC Q96G97; G3XAE4; Q567S1; Q96SV1; Q9BSQ0;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Seipin;
DE AltName: Full=Bernardinelli-Seip congenital lipodystrophy type 2 protein;
GN Name=BSCL2;
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] {ECO:0000305, ECO:0000312|EMBL:BAC11543.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Retinoblastoma {ECO:0000312|EMBL:BAC11543.1}, and
RC Teratocarcinoma {ECO:0000312|EMBL:BAB55175.1};
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 [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Yu W., Sarginson J., Gibbs R.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAH04911.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH12140.1},
RC Lung {ECO:0000312|EMBL:AAH04911.1}, Pancreas {ECO:0000312|EMBL:AAH41640.1},
RC and Pituitary;
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 [6] {ECO:0000305}
RP TISSUE SPECIFICITY, AND VARIANT CGL2 PRO-212.
RX PubMed=11479539; DOI=10.1038/ng585;
RA Magre J., Delepine M., Khallouf E., Gedde-Dahl T. Jr., Van Maldergem L.,
RA Sobel E., Papp J., Meier M., Megarbane A., Bachy A., Verloes A.,
RA d'Abronzo F.H., Seemanova E., Assan R., Baudic N., Bourut C.,
RA Czernichow P., Huet F., Grigorescu F., de Kerdanet M., Lacombe D.,
RA Labrune P., Lanza M., Loret H., Matsuda F., Navarro J.,
RA Nivelon-Chevalier A., Polak M., Robert J.J., Tric P., Tubiana-Rufi N.,
RA Vigouroux C., Weissenbach J., Savasta S., Maassen J.A., Trygstad O.,
RA Bogalho P., Freitas P., Medina J.L., Bonnicci F., Joffe B.I., Loyson G.,
RA Panz V.R., Raal F.J., O'Rahilly S., Stephenson T., Kahn C.R., Lathrop M.,
RA Capeau J.;
RT "Identification of the gene altered in Berardinelli-Seip congenital
RT lipodystrophy on chromosome 11q13.";
RL Nat. Genet. 28:365-370(2001).
RN [7] {ECO:0000305}
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-88, AND VARIANTS SPG17 AND HMN5C
RP SER-88 AND LEU-90.
RX PubMed=14981520; DOI=10.1038/ng1313;
RA Windpassinger C., Auer-Grumbach M., Irobi J., Patel H., Petek E., Hoerl G.,
RA Malli R., Reed J.A., Dierick I., Verpoorten N., Warner T.T., Proukakis C.,
RA Van den Bergh P., Verellen C., Van Maldergem L., Merlini L., De Jonghe P.,
RA Timmerman V., Crosby A.H., Wagner K.;
RT "Heterozygous missense mutations in BSCL2 are associated with distal
RT hereditary motor neuropathy and Silver syndrome.";
RL Nat. Genet. 36:271-276(2004).
RN [8]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=16574104; DOI=10.1016/j.febslet.2006.03.040;
RA Lundin C., Nordstrom R., Wagner K., Windpassinger C., Andersson H.,
RA von Heijne G., Nilsson I.;
RT "Membrane topology of the human seipin protein.";
RL FEBS Lett. 580:2281-2284(2006).
RN [9]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT PRO-212.
RX PubMed=18458148; DOI=10.2337/db08-0184;
RA Payne V.A., Grimsey N., Tuthill A., Virtue S., Gray S.L., Dalla Nora E.,
RA Semple R.K., O'Rahilly S., Rochford J.J.;
RT "The human lipodystrophy gene BSCL2/seipin may be essential for normal
RT adipocyte differentiation.";
RL Diabetes 57:2055-2060(2008).
RN [10]
RP TISSUE SPECIFICITY, AND CHARACTERIZATION OF VARIANT SPG17 SER-88.
RX PubMed=18585921; DOI=10.1016/j.nbd.2008.05.004;
RA Ito D., Fujisawa T., Iida H., Suzuki N.;
RT "Characterization of seipin/BSCL2, a protein associated with spastic
RT paraplegia 17.";
RL Neurobiol. Dis. 31:266-277(2008).
RN [11]
RP FUNCTION.
RX PubMed=19278620; DOI=10.1016/j.biochi.2009.01.011;
RA Boutet E., El Mourabit H., Prot M., Nemani M., Khallouf E., Colard O.,
RA Maurice M., Durand-Schneider A.M., Chretien Y., Gres S., Wolf C.,
RA Saulnier-Blache J.S., Capeau J., Magre J.;
RT "Seipin deficiency alters fatty acid Delta9 desaturation and lipid droplet
RT formation in Berardinelli-Seip congenital lipodystrophy.";
RL Biochimie 91:796-803(2009).
RN [12]
RP FUNCTION, AND VARIANT LEU-90.
RX PubMed=21533227; DOI=10.1371/journal.pgen.1001364;
RA Tian Y., Bi J., Shui G., Liu Z., Xiang Y., Liu Y., Wenk M.R., Yang H.,
RA Huang X.;
RT "Tissue-autonomous function of Drosophila seipin in preventing ectopic
RT lipid droplet formation.";
RL PLoS Genet. 7:E1001364-E1001364(2011).
RN [13]
RP INVOLVEMENT IN PELD.
RX PubMed=23564749; DOI=10.1136/jmedgenet-2013-101525;
RA Guillen-Navarro E., Sanchez-Iglesias S., Domingo-Jimenez R., Victoria B.,
RA Ruiz-Riquelme A., Rabano A., Loidi L., Beiras A., Gonzalez-Mendez B.,
RA Ramos A., Lopez-Gonzalez V., Ballesta-Martinez M.J., Garrido-Pumar M.,
RA Aguiar P., Ruibal A., Requena J.R., Araujo-Vilar D.;
RT "A new seipin-associated neurodegenerative syndrome.";
RL J. Med. Genet. 50:401-409(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289 AND SER-372, AND
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 [15]
RP FUNCTION.
RX PubMed=27564575; DOI=10.7554/elife.16582;
RA Wang H., Becuwe M., Housden B.E., Chitraju C., Porras A.J., Graham M.M.,
RA Liu X.N., Thiam A.R., Savage D.B., Agarwal A.K., Garg A., Olarte M.J.,
RA Lin Q., Froehlich F., Hannibal-Bach H.K., Upadhyayula S., Perrimon N.,
RA Kirchhausen T., Ejsing C.S., Walther T.C., Farese R.V.;
RT "Seipin is required for converting nascent to mature lipid droplets.";
RL Elife 5:0-0(2016).
RN [16]
RP FUNCTION, INTERACTION WITH ZFYVE1 AND RAB18, AND SUBCELLULAR LOCATION.
RX PubMed=30970241; DOI=10.1016/j.celrep.2019.03.025;
RA Li D., Zhao Y.G., Li D., Zhao H., Huang J., Miao G., Feng D., Liu P.,
RA Li D., Zhang H.;
RT "The ER-Localized Protein DFCP1 Modulates ER-Lipid Droplet Contact
RT Formation.";
RL Cell Rep. 27:343-358(2019).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH LDAF1.
RX PubMed=31708432; DOI=10.1016/j.devcel.2019.10.006;
RA Chung J., Wu X., Lambert T.J., Lai Z.W., Walther T.C., Farese R.V. Jr.;
RT "LDAF1 and Seipin Form a Lipid Droplet Assembly Complex.";
RL Dev. Cell 0:0-0(2019).
RN [18]
RP FUNCTION.
RX PubMed=31178403; DOI=10.1016/j.devcel.2019.05.016;
RA Salo V.T., Li S., Vihinen H., Hoelttae-Vuori M., Szkalisity A., Horvath P.,
RA Belevich I., Peraenen J., Thiele C., Somerharju P., Zhao H., Santinho A.,
RA Thiam A.R., Jokitalo E., Ikonen E.;
RT "Seipin Facilitates Triglyceride Flow to Lipid Droplet and Counteracts
RT Droplet Ripening via Endoplasmic Reticulum Contact.";
RL Dev. Cell 50:478-493(2019).
RN [19]
RP VARIANT HMN5C SER-88, AND VARIANT SPG17 LEU-90.
RX PubMed=17663003; DOI=10.1016/j.jns.2007.06.047;
RA Rohkamm B., Reilly M.M., Lochmueller H., Schlotter-Weigel B., Barisic N.,
RA Schoels L., Nicholson G., Pareyson D., Laura M., Janecke A.R.,
RA Miltenberger-Miltenyi G., John E., Fischer C., Grill F., Wakeling W.,
RA Davis M., Pieber T.R., Auer-Grumbach M.;
RT "Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with
RT predominant hand involvement and Silver syndrome.";
RL J. Neurol. Sci. 263:100-106(2007).
RN [20]
RP VARIANT SPG17 LEU-90.
RX PubMed=24604904; DOI=10.1136/jnnp-2013-306740;
RA Klein C.J., Middha S., Duan X., Wu Y., Litchy W.J., Gu W., Dyck P.J.,
RA Gavrilova R.H., Smith D.I., Kocher J.P., Dyck P.J.;
RT "Application of whole exome sequencing in undiagnosed inherited
RT polyneuropathies.";
RL J. Neurol. Neurosurg. Psych. 85:1265-1272(2014).
RN [21]
RP CHARACTERIZATION OF VARIANT CGL2 PRO-212, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=27879284; DOI=10.15252/embj.201695170;
RA Salo V.T., Belevich I., Li S., Karhinen L., Vihinen H., Vigouroux C.,
RA Magre J., Thiele C., Hoelttae-Vuori M., Jokitalo E., Ikonen E.;
RT "Seipin regulates ER-lipid droplet contacts and cargo delivery.";
RL EMBO J. 35:2699-2716(2016).
RN [22]
RP CHARACTERIZATION OF VARIANT CGL2 PRO-212, INTERACTION WITH LDAF1,
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=30901948; DOI=10.3390/cells8030268;
RA Castro I.G., Eisenberg-Bord M., Persiani E., Rochford J.J., Schuldiner M.,
RA Bohnert M.;
RT "Promethin Is a Conserved Seipin Partner Protein.";
RL Cells 8:0-0(2019).
RN [23] {ECO:0007744|PDB:6DS5}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 2-398, FUNCTION,
RP SUBUNIT, AND MUTAGENESIS OF HIS-67; TYR-70; TYR-151; LEU-156; LEU-169 AND
RP GLN-175.
RX PubMed=30293840; DOI=10.1016/j.devcel.2018.09.010;
RA Yan R., Qian H., Lukmantara I., Gao M., Du X., Yan N., Yang H.;
RT "Human SEIPIN Binds Anionic Phospholipids.";
RL Dev. Cell 47:248-256(2018).
CC -!- FUNCTION: Plays a crucial role in the formation of lipid droplets (LDs)
CC which are storage organelles at the center of lipid and energy
CC homeostasis (PubMed:19278620, PubMed:21533227, PubMed:31708432,
CC PubMed:30293840). In association with LDAF1, defines the sites of LD
CC formation in the ER (PubMed:31708432). Also required for growth and
CC maturation of small nascent LDs into larger mature LDs
CC (PubMed:27564575). Mediates the formation and/or stabilization of
CC endoplasmic reticulum-lipid droplets (ER-LD) contacts, facilitating
CC protein and lipid delivery from the ER into growing LDs
CC (PubMed:31178403, PubMed:27879284). Regulates the maturation of ZFYVE1-
CC positive nascent LDs and the function of the RAB18-ZFYVE1 complex in
CC mediating the formation of ER-LD contacts (PubMed:30970241). Binds
CC anionic phospholipids including phosphatidic acid (PubMed:30293840).
CC Plays an important role in the differentiation and development of
CC adipocytes (By similarity). {ECO:0000250|UniProtKB:Q9Z2E9,
CC ECO:0000269|PubMed:19278620, ECO:0000269|PubMed:21533227,
CC ECO:0000269|PubMed:27564575, ECO:0000269|PubMed:27879284,
CC ECO:0000269|PubMed:30293840, ECO:0000269|PubMed:30970241,
CC ECO:0000269|PubMed:31178403, ECO:0000269|PubMed:31708432}.
CC -!- SUBUNIT: [Isoform 1]: Undecamer (an oligomer having eleven subunits)
CC (PubMed:30293840). Oligomerization is important for its function in
CC lipid droplet formation (PubMed:30293840). Interacts with LDAF1 to form
CC an oligomeric complex (PubMed:31708432, PubMed:30901948). Interacts
CC with RAB18 (PubMed:30970241). Interacts with ZFYVE1 in a RAB18-
CC dependent manner (PubMed:30970241). {ECO:0000269|PubMed:30293840,
CC ECO:0000269|PubMed:30901948, ECO:0000269|PubMed:30970241,
CC ECO:0000269|PubMed:31708432}.
CC -!- SUBUNIT: [Isoform 3]: Interacts with LDAF1 to form an oligomeric
CC complex. {ECO:0000269|PubMed:30901948}.
CC -!- INTERACTION:
CC Q96G97; Q9BZL3: SMIM3; NbExp=4; IntAct=EBI-741806, EBI-741850;
CC Q96G97; Q96HH6: TMEM19; NbExp=4; IntAct=EBI-741806, EBI-741829;
CC Q96G97-4; P54252: ATXN3; NbExp=3; IntAct=EBI-10178113, EBI-946046;
CC Q96G97-4; Q9HC96: CAPN10; NbExp=3; IntAct=EBI-10178113, EBI-3915761;
CC Q96G97-4; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-10178113, EBI-350590;
CC Q96G97-4; P42857: NSG1; NbExp=3; IntAct=EBI-10178113, EBI-6380741;
CC Q96G97-4; Q96CV9: OPTN; NbExp=3; IntAct=EBI-10178113, EBI-748974;
CC Q96G97-4; P16284: PECAM1; NbExp=3; IntAct=EBI-10178113, EBI-716404;
CC Q96G97-4; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-10178113, EBI-742388;
CC Q96G97-4; Q9BZL3: SMIM3; NbExp=3; IntAct=EBI-10178113, EBI-741850;
CC Q96G97-4; H3BR10: SMLR1; NbExp=3; IntAct=EBI-10178113, EBI-10178109;
CC Q96G97-4; Q96HH6: TMEM19; NbExp=4; IntAct=EBI-10178113, EBI-741829;
CC Q96G97-4; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-10178113, EBI-358545;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:14981520, ECO:0000269|PubMed:16574104,
CC ECO:0000269|PubMed:18458148, ECO:0000269|PubMed:27879284,
CC ECO:0000269|PubMed:30901948, ECO:0000269|PubMed:31708432}; Multi-pass
CC membrane protein {ECO:0000255}. Lipid droplet
CC {ECO:0000269|PubMed:27879284, ECO:0000269|PubMed:30970241}.
CC Note=Localizes at endoplasmic reticulum-lipid droplets (ER-LD) contact
CC sites. {ECO:0000269|PubMed:27879284}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96G97-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96G97-3; Sequence=VSP_051726, VSP_051727;
CC Name=3;
CC IsoId=Q96G97-4; Sequence=VSP_044545;
CC -!- TISSUE SPECIFICITY: Expressed in motor neurons in the spinal cord and
CC cortical neurons in the frontal lobe (at protein level). Highly
CC expressed in brain, testis and adipose tissue.
CC {ECO:0000269|PubMed:11479539, ECO:0000269|PubMed:18458148,
CC ECO:0000269|PubMed:18585921}.
CC -!- DISEASE: Congenital generalized lipodystrophy 2 (CGL2) [MIM:269700]: An
CC autosomal recessive disorder characterized by a near complete absence
CC of adipose tissue, extreme insulin resistance, hypertriglyceridemia,
CC hepatic steatosis and early onset of diabetes.
CC {ECO:0000269|PubMed:11479539, ECO:0000269|PubMed:27879284,
CC ECO:0000269|PubMed:30901948}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Spastic paraplegia 17, autosomal dominant (SPG17)
CC [MIM:270685]: 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. SPG17 is characterized
CC by prominent amyotrophy of the hand muscles, the presence of mild to
CC severe pyramidal tract signs and spastic paraplegia. SPG17 is a motor
CC neuron disease overlapping with distal spinal muscular atrophy type 5.
CC {ECO:0000269|PubMed:14981520, ECO:0000269|PubMed:17663003,
CC ECO:0000269|PubMed:18585921, ECO:0000269|PubMed:24604904}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Neuronopathy, distal hereditary motor, 5C (HMN5C)
CC [MIM:619112]: A form of distal hereditary motor neuronopathy, a
CC heterogeneous group of neuromuscular diseases caused by selective
CC degeneration of motor neurons in the anterior horn of the spinal cord,
CC without sensory deficit in the posterior horn. HMN5C is characterized
CC by distal muscular atrophy primarily affecting the upper limbs. Lower
CC limb involvement may occur at the same time or later. Clinical features
CC are highly variable even within families, and include poor fine hand
CC motor skills, difficulty walking, foot deformities, spasticity and
CC hyperreflexia. Some HMN5C patients show axonal peripheral neuropathy
CC and distal sensory impairment. HMN5C inheritance is autosomal dominant
CC with incomplete penetrance. {ECO:0000269|PubMed:14981520,
CC ECO:0000269|PubMed:17663003}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Encephalopathy, progressive, with or without lipodystrophy
CC (PELD) [MIM:615924]: A neurodegenerative disease characterized by
CC developmental regression of motor and cognitive skills in the first
CC years of life, often leading to death in the first decade, hyperactive
CC behavior, seizures, tremor and ataxic gait. Patients may show a mild or
CC typical lipodystrophic appearance. {ECO:0000269|PubMed:23564749}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the seipin family. {ECO:0000305}.
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DR EMBL; AK027524; BAB55175.1; -; mRNA.
DR EMBL; AK075317; BAC11543.1; -; mRNA.
DR EMBL; AF052149; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471076; EAW74070.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74074.1; -; Genomic_DNA.
DR EMBL; AP001458; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004911; AAH04911.1; -; mRNA.
DR EMBL; BC012140; AAH12140.1; -; mRNA.
DR EMBL; BC041640; AAH41640.1; -; mRNA.
DR EMBL; BC093048; AAH93048.1; -; mRNA.
DR CCDS; CCDS44627.1; -. [Q96G97-4]
DR CCDS; CCDS55769.1; -. [Q96G97-3]
DR CCDS; CCDS8031.1; -. [Q96G97-2]
DR RefSeq; NP_001116427.1; NM_001122955.3. [Q96G97-4]
DR RefSeq; NP_001124174.2; NM_001130702.2. [Q96G97-3]
DR RefSeq; NP_116056.3; NM_032667.6. [Q96G97-2]
DR PDB; 6DS5; EM; 3.80 A; A/B/C/D/E/F/G/H/I/J/K=2-398.
DR PDBsum; 6DS5; -.
DR AlphaFoldDB; Q96G97; -.
DR SMR; Q96G97; -.
DR BioGRID; 117749; 310.
DR CORUM; Q96G97; -.
DR IntAct; Q96G97; 41.
DR MINT; Q96G97; -.
DR STRING; 9606.ENSP00000354032; -.
DR TCDB; 1.R.1.1.1; the membrane contact site (mcs) family.
DR CarbonylDB; Q96G97; -.
DR GlyConnect; 1728; 7 N-Linked glycans (1 site).
DR GlyGen; Q96G97; 2 sites, 6 N-linked glycans (1 site).
DR iPTMnet; Q96G97; -.
DR PhosphoSitePlus; Q96G97; -.
DR BioMuta; BSCL2; -.
DR DMDM; 269849705; -.
DR EPD; Q96G97; -.
DR jPOST; Q96G97; -.
DR MassIVE; Q96G97; -.
DR MaxQB; Q96G97; -.
DR PaxDb; Q96G97; -.
DR PeptideAtlas; Q96G97; -.
DR PRIDE; Q96G97; -.
DR ProteomicsDB; 33726; -.
DR ProteomicsDB; 76606; -. [Q96G97-2]
DR ProteomicsDB; 76607; -. [Q96G97-3]
DR Antibodypedia; 28672; 172 antibodies from 26 providers.
DR DNASU; 26580; -.
DR Ensembl; ENST00000278893.11; ENSP00000278893.7; ENSG00000168000.16. [Q96G97-3]
DR Ensembl; ENST00000360796.10; ENSP00000354032.5; ENSG00000168000.16. [Q96G97-4]
DR Ensembl; ENST00000403550.5; ENSP00000385561.1; ENSG00000168000.16. [Q96G97-2]
DR Ensembl; ENST00000407022.7; ENSP00000384080.3; ENSG00000168000.16. [Q96G97-2]
DR Ensembl; ENST00000421906.5; ENSP00000413209.1; ENSG00000168000.16. [Q96G97-2]
DR Ensembl; ENST00000524862.6; ENSP00000433888.2; ENSG00000168000.16. [Q96G97-4]
DR Ensembl; ENST00000679883.1; ENSP00000505838.1; ENSG00000168000.16. [Q96G97-4]
DR GeneID; 26580; -.
DR KEGG; hsa:26580; -.
DR MANE-Select; ENST00000360796.10; ENSP00000354032.5; NM_001122955.4; NP_001116427.1. [Q96G97-4]
DR UCSC; uc001nup.4; human. [Q96G97-2]
DR CTD; 26580; -.
DR DisGeNET; 26580; -.
DR GeneCards; BSCL2; -.
DR GeneReviews; BSCL2; -.
DR HGNC; HGNC:15832; BSCL2.
DR HPA; ENSG00000168000; Tissue enhanced (brain, pituitary gland).
DR MalaCards; BSCL2; -.
DR MIM; 269700; phenotype.
DR MIM; 270685; phenotype.
DR MIM; 606158; gene.
DR MIM; 615924; phenotype.
DR MIM; 619112; phenotype.
DR neXtProt; NX_Q96G97; -.
DR OpenTargets; ENSG00000168000; -.
DR Orphanet; 100998; Autosomal dominant spastic paraplegia type 17.
DR Orphanet; 528; Congenital generalized lipodystrophy.
DR Orphanet; 139536; Distal hereditary motor neuropathy type 5.
DR Orphanet; 363400; Severe neurodegenerative syndrome with lipodystrophy.
DR PharmGKB; PA25432; -.
DR VEuPathDB; HostDB:ENSG00000168000; -.
DR eggNOG; KOG4200; Eukaryota.
DR GeneTree; ENSGT00390000011639; -.
DR HOGENOM; CLU_049458_1_1_1; -.
DR InParanoid; Q96G97; -.
DR OMA; WAFEVIF; -.
DR PhylomeDB; Q96G97; -.
DR TreeFam; TF314000; -.
DR PathwayCommons; Q96G97; -.
DR SignaLink; Q96G97; -.
DR BioGRID-ORCS; 26580; 23 hits in 1079 CRISPR screens.
DR ChiTaRS; BSCL2; human.
DR GeneWiki; BSCL2; -.
DR GenomeRNAi; 26580; -.
DR Pharos; Q96G97; Tbio.
DR PRO; PR:Q96G97; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96G97; protein.
DR Bgee; ENSG00000168000; Expressed in superior frontal gyrus and 101 other tissues.
DR ExpressionAtlas; Q96G97; baseline and differential.
DR Genevisible; Q96G97; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0140042; P:lipid droplet formation; IDA:UniProtKB.
DR GO; GO:0034389; P:lipid droplet organization; IMP:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IMP:UniProtKB.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR DisProt; DP02471; -.
DR InterPro; IPR009617; Seipin.
DR PANTHER; PTHR21212; PTHR21212; 1.
DR Pfam; PF06775; Seipin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Congenital generalized lipodystrophy;
KW Diabetes mellitus; Disease variant; Endoplasmic reticulum; Glycoprotein;
KW Hereditary spastic paraplegia; Lipid degradation; Lipid droplet;
KW Lipid metabolism; Membrane; Neurodegeneration; Neuropathy; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..398
FT /note="Seipin"
FT /id="PRO_0000191679"
FT TOPO_DOM 1..26
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 27..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..242
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 281..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..336
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5FVJ6"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5FVJ6"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14981520"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1
FT /note="M -> MSTEKVDQKEEAGEKEVCGDQIKGPDKEEEPPAAASHGQGWRPGGRA
FT ARNARPEPGARHPALPAM (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_044545"
FT VAR_SEQ 225..287
FT /note="YLLYNFPMTCAFIGVASNFTFLSVIVLFSYMQWVWGGIWPRHRFSLQVNIRK
FT RDNSRKEVQRR -> LTSEKETIPGRKSNEGSLLISQGLKARRSQLRNQMLQRMVRALK
FT IPQGQRVSCPRRRNQISSP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_051726"
FT VAR_SEQ 288..398
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_051727"
FT VARIANT 88
FT /note="N -> S (in SPG17 and HMN5C; does not affect protein
FT subcellular location; dbSNP:rs137852972)"
FT /evidence="ECO:0000269|PubMed:14981520,
FT ECO:0000269|PubMed:17663003, ECO:0000269|PubMed:18585921"
FT /id="VAR_022375"
FT VARIANT 90
FT /note="S -> L (in SPG17 and HMN5C; also found in patients
FT with hereditary motor and sensory neuropathy type 2; does
FT not affect the function in lipid storage;
FT dbSNP:rs137852973)"
FT /evidence="ECO:0000269|PubMed:14981520,
FT ECO:0000269|PubMed:17663003, ECO:0000269|PubMed:21533227,
FT ECO:0000269|PubMed:24604904"
FT /id="VAR_022376"
FT VARIANT 212
FT /note="A -> P (in CGL2; increases localization to nuclear
FT envelope; no effect on its interaction with LDAF1; no
FT rescue of aberrant lipid droplet formation in BSCL2-
FT knockdown cells; dbSNP:rs137852971)"
FT /evidence="ECO:0000269|PubMed:11479539,
FT ECO:0000269|PubMed:27879284, ECO:0000269|PubMed:30901948"
FT /id="VAR_022377"
FT MUTAGEN 67
FT /note="H->R: Loss of oligomerization and function in lipid
FT droplet formation; when associated with A-70; A-151; D-156;
FT D-169 and A-175."
FT /evidence="ECO:0000269|PubMed:30293840"
FT MUTAGEN 70
FT /note="Y->A: Loss of oligomerization and function in lipid
FT droplet formation; when associated with R-67; A-151; D-156;
FT D-169 and A-175."
FT /evidence="ECO:0000269|PubMed:30293840"
FT MUTAGEN 151
FT /note="Y->A: Loss of oligomerization and function in lipid
FT droplet biogenesis; when associated with R-67; A-70; D-156;
FT D-169 and A-175."
FT /evidence="ECO:0000269|PubMed:30293840"
FT MUTAGEN 156
FT /note="L->D: Loss of oligomerization and function in lipid
FT droplet formation; when associated with R-67; A-70; A-151;
FT D-169 and A-175."
FT /evidence="ECO:0000269|PubMed:30293840"
FT MUTAGEN 169
FT /note="L->D: Loss of oligomerization and function in lipid
FT droplet formation; when associated with R-67; A-70; A-151;
FT D-156 and A-175."
FT /evidence="ECO:0000269|PubMed:30293840"
FT MUTAGEN 175
FT /note="Q->A: Loss of oligomerization and function in lipid
FT droplet formation; when associated with R-67; A-70; A-151;
FT D-156 and D-169."
FT /evidence="ECO:0000269|PubMed:30293840"
SQ SEQUENCE 398 AA; 44392 MW; 9FB1B37E72493DB9 CRC64;
MVNDPPVPAL LWAQEVGQVL AGRARRLLLQ FGVLFCTILL LLWVSVFLYG SFYYSYMPTV
SHLSPVHFYY RTDCDSSTTS LCSFPVANVS LTKGGRDRVL MYGQPYRVTL ELELPESPVN
QDLGMFLVTI SCYTRGGRII STSSRSVMLH YRSDLLQMLD TLVFSSLLLF GFAEQKQLLE
VELYADYREN SYVPTTGAII EIHSKRIQLY GAYLRIHAHF TGLRYLLYNF PMTCAFIGVA
SNFTFLSVIV LFSYMQWVWG GIWPRHRFSL QVNIRKRDNS RKEVQRRISA HQPGPEGQEE
STPQSDVTED GESPEDPSGT EGQLSEEEKP DQQPLSGEEE LEPEASDGSG SWEDAALLTE
ANLPAPAPAS ASAPVLETLG SSEPAGGALR QRPTCSSS
