Q96G97 (BSCL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Seipin

Alternative name(s):
Bernardinelli-Seip congenital lipodystrophy type 2 protein

Gene names

Name:

BSCL2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	398 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Is a regulator of lipid catabolism essential for adipocyte differentiation. May also be involved in the central regulation of energy homeostasis By similarity. Necessary for correct lipid storage and lipid droplets maintenance; may play a tissue-autonomous role in controlling lipid storage in adipocytes and in preventing ectopic lipid droplet formation in non-adipose tissues. Ref.11 Ref.12
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.7 Ref.8 Ref.9.
Tissue specificity	Expressed in motor neurons in the spinal cord and cortical neurons in the frontal lobe (at protein level). Highly expressed in brain, testis and adipose tissue. Ref.6 Ref.9 Ref.10
Involvement in disease	Congenital generalized lipodystrophy 2 (CGL2) [MIM:269700]: An autosomal recessive disorder characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Spastic paraplegia 17 (SPG17) [MIM:270685]: 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. SPG17 is characterized by prominent amyotrophy of the hand muscles, the presence of mild to severe pyramidal tract signs and spastic paraplegia. SPG17 is a motor neuron disease overlapping with distal spinal muscular atrophy type 5. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.10 Distal hereditary motor neuronopathy 5A (HMN5A) [MIM:600794]: A disorder characterized by distal muscular atrophy mainly affecting the upper extremities, in contrast to other distal motor neuronopathies. These constitute a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the seipin family.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Disease	Congenital generalized lipodystrophy Diabetes mellitus Disease mutation Hereditary spastic paraplegia Neurodegeneration
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW fat cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW lipid particle organization Inferred from mutant phenotype Ref.11. Source: UniProtKB lipid storage Inferred from mutant phenotype Ref.11. Source: UniProtKB negative regulation of lipid catabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	integral to endoplasmic reticulum membrane Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96G97-2)

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.

Isoform 2 (identifier: Q96G97-3)

The sequence of this isoform differs from the canonical sequence as follows:
     225-287: YLLYNFPMTC...DNSRKEVQRR → LTSEKETIPG...PRRRNQISSP
     288-398: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q96G97-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSTEKVDQKEEAGEKEVCGDQIKGPDKEEEPPAAASHGQGWRPGGRAARNARPEPGARHPALPAM

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 398	398	Seipin		PRO_0000191679
Regions
	Topological domain	1 – 26	26	Cytoplasmic Potential
	Transmembrane	27 – 47	21	Helical; Potential
	Topological domain	48 – 242	195	Lumenal Potential
	Transmembrane	243 – 263	21	Helical; Potential
	Topological domain	264 – 398	135	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	88	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	242	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1	1	M → MSTEKVDQKEEAGEKEVCGD QIKGPDKEEEPPAAASHGQG WRPGGRAARNARPEPGARHP ALPAM in isoform 3.		VSP_044545
	Alternative sequence	225 – 287	63	YLLYN…EVQRR → LTSEKETIPGRKSNEGSLLI SQGLKARRSQLRNQMLQRMV RALKIPQGQRVSCPRRRNQI SSP in isoform 2.		VSP_051726
	Alternative sequence	288 – 398	111	Missing in isoform 2.		VSP_051727
	Natural variant	88	1	N → S in SPG17 and HMN5A; does not affect protein subcellular location. Ref.7 Ref.10		VAR_022375
	Natural variant	90	1	S → L in SPG17 and HMN5A; does not affect the function in lipid storage. Ref.7 Ref.12		VAR_022376
	Natural variant	212	1	A → P in CGL2; increases localization to nuclear envelope. Ref.6 Ref.9		VAR_022377

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 3. Checksum: 9FB1B37E72493DB9	FASTA	398	44,392
	10 20 30 40 50 60 MVNDPPVPAL LWAQEVGQVL AGRARRLLLQ FGVLFCTILL LLWVSVFLYG SFYYSYMPTV 70 80 90 100 110 120 SHLSPVHFYY RTDCDSSTTS LCSFPVANVS LTKGGRDRVL MYGQPYRVTL ELELPESPVN 130 140 150 160 170 180 QDLGMFLVTI SCYTRGGRII STSSRSVMLH YRSDLLQMLD TLVFSSLLLF GFAEQKQLLE 190 200 210 220 230 240 VELYADYREN SYVPTTGAII EIHSKRIQLY GAYLRIHAHF TGLRYLLYNF PMTCAFIGVA 250 260 270 280 290 300 SNFTFLSVIV LFSYMQWVWG GIWPRHRFSL QVNIRKRDNS RKEVQRRISA HQPGPEGQEE 310 320 330 340 350 360 STPQSDVTED GESPEDPSGT EGQLSEEEKP DQQPLSGEEE LEPEASDGSG SWEDAALLTE 370 380 390 ANLPAPAPAS ASAPVLETLG SSEPAGGALR QRPTCSSS
	Isoform 2 [UniParc]. Checksum: 674512CF110B8382	FASTA	287	32,654
	10 20 30 40 50 60 MVNDPPVPAL LWAQEVGQVL AGRARRLLLQ FGVLFCTILL LLWVSVFLYG SFYYSYMPTV 70 80 90 100 110 120 SHLSPVHFYY RTDCDSSTTS LCSFPVANVS LTKGGRDRVL MYGQPYRVTL ELELPESPVN 130 140 150 160 170 180 QDLGMFLVTI SCYTRGGRII STSSRSVMLH YRSDLLQMLD TLVFSSLLLF GFAEQKQLLE 190 200 210 220 230 240 VELYADYREN SYVPTTGAII EIHSKRIQLY GAYLRIHAHF TGLRLTSEKE TIPGRKSNEG 250 260 270 280 SLLISQGLKA RRSQLRNQML QRMVRALKIP QGQRVSCPRR RNQISSP
	Isoform 3 [UniParc]. Checksum: 2DBDD5A48366AF48	FASTA	462	51,159
	10 20 30 40 50 60 MSTEKVDQKE EAGEKEVCGD QIKGPDKEEE PPAAASHGQG WRPGGRAARN ARPEPGARHP 70 80 90 100 110 120 ALPAMVNDPP VPALLWAQEV GQVLAGRARR LLLQFGVLFC TILLLLWVSV FLYGSFYYSY 130 140 150 160 170 180 MPTVSHLSPV HFYYRTDCDS STTSLCSFPV ANVSLTKGGR DRVLMYGQPY RVTLELELPE 190 200 210 220 230 240 SPVNQDLGMF LVTISCYTRG GRIISTSSRS VMLHYRSDLL QMLDTLVFSS LLLFGFAEQK 250 260 270 280 290 300 QLLEVELYAD YRENSYVPTT GAIIEIHSKR IQLYGAYLRI HAHFTGLRYL LYNFPMTCAF 310 320 330 340 350 360 IGVASNFTFL SVIVLFSYMQ WVWGGIWPRH RFSLQVNIRK RDNSRKEVQR RISAHQPGPE 370 380 390 400 410 420 GQEESTPQSD VTEDGESPED PSGTEGQLSE EEKPDQQPLS GEEELEPEAS DGSGSWEDAA 430 440 450 460 LLTEANLPAP APASASAPVL ETLGSSEPAG GALRQRPTCS SS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Retinoblastoma and Teratocarcinoma.
[2]	Yu W., Sarginson J., Gibbs R.A. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney, Lung, Pancreas and Pituitary.
[6]	"Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13." Magre J., Delepine M., Khallouf E., Gedde-Dahl T. Jr., Van Maldergem L., Sobel E., Papp J., Meier M., Megarbane A., Bachy A., Verloes A., d'Abronzo F.H., Seemanova E., Assan R., Baudic N., Bourut C., Czernichow P., Huet F. , Grigorescu F., de Kerdanet M., Lacombe D., Labrune P., Lanza M., Loret H., Matsuda F., Navarro J., Nivelon-Chevalier A., Polak M., Robert J.J., Tric P., Tubiana-Rufi N., Vigouroux C., Weissenbach J., Savasta S., Maassen J.A., Trygstad O., Bogalho P., Freitas P., Medina J.L., Bonnicci F., Joffe B.I., Loyson G., Panz V.R., Raal F.J., O'Rahilly S., Stephenson T., Kahn C.R., Lathrop M., Capeau J. Nat. Genet. 28:365-370(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, VARIANT CGL2 PRO-212.
[7]	"Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome." Windpassinger C., Auer-Grumbach M., Irobi J., Patel H., Petek E., Hoerl G., Malli R., Reed J.A., Dierick I., Verpoorten N., Warner T.T., Proukakis C., Van den Bergh P., Verellen C., Van Maldergem L., Merlini L., De Jonghe P., Timmerman V., Crosby A.H., Wagner K. Nat. Genet. 36:271-276(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-88, VARIANTS SPG17 AND HMN5A SER-88 AND LEU-90.
[8]	"Membrane topology of the human seipin protein." Lundin C., Nordstrom R., Wagner K., Windpassinger C., Andersson H., von Heijne G., Nilsson I. FEBS Lett. 580:2281-2284(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TOPOLOGY.
[9]	"The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiation." Payne V.A., Grimsey N., Tuthill A., Virtue S., Gray S.L., Dalla Nora E., Semple R.K., O'Rahilly S., Rochford J.J. Diabetes 57:2055-2060(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT PRO-212.
[10]	"Characterization of seipin/BSCL2, a protein associated with spastic paraplegia 17." Ito D., Fujisawa T., Iida H., Suzuki N. Neurobiol. Dis. 31:266-277(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT SPG17 SER-88.
[11]	"Seipin deficiency alters fatty acid Delta9 desaturation and lipid droplet formation in Berardinelli-Seip congenital lipodystrophy." Boutet E., El Mourabit H., Prot M., Nemani M., Khallouf E., Colard O., Maurice M., Durand-Schneider A.M., Chretien Y., Gres S., Wolf C., Saulnier-Blache J.S., Capeau J., Magre J. Biochimie 91:796-803(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Tissue-autonomous function of Drosophila seipin in preventing ectopic lipid droplet formation." Tian Y., Bi J., Shui G., Liu Z., Xiang Y., Liu Y., Wenk M.R., Yang H., Huang X. PLoS Genet. 7:E1001364-E1001364(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, VARIANT LEU-90.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK027524 mRNA. Translation: BAB55175.1. AK075317 mRNA. Translation: BAC11543.1. AF052149 mRNA. No translation available. CH471076 Genomic DNA. Translation: EAW74070.1. CH471076 Genomic DNA. Translation: EAW74074.1. AP001458 Genomic DNA. No translation available. BC004911 mRNA. Translation: AAH04911.1. BC012140 mRNA. Translation: AAH12140.1. BC041640 mRNA. Translation: AAH41640.1. BC093048 mRNA. Translation: AAH93048.1.
IPI	IPI00045906. IPI00783278.
RefSeq	NP_001116427.1. NM_001122955.3. NP_001124174.2. NM_001130702.2. NP_116056.3. NM_032667.6.
UniGene	Hs.533709.
3D structure databases
ProteinModelPortal	Q96G97.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96G97. 5 interactions.
MINT	MINT-1452482.
STRING	9606.ENSP00000354032.
PTM databases
PhosphoSite	Q96G97.
Polymorphism databases
DMDM	269849705.
Proteomic databases
PaxDb	Q96G97.
PRIDE	Q96G97.
Protocols and materials databases
DNASU	26580.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000278893; ENSP00000278893; ENSG00000168000. ENST00000360796; ENSP00000354032; ENSG00000168000. ENST00000403550; ENSP00000385561; ENSG00000168000. ENST00000407022; ENSP00000384080; ENSG00000168000. ENST00000421906; ENSP00000413209; ENSG00000168000. ENST00000433053; ENSP00000414002; ENSG00000168000.
GeneID	26580.
KEGG	hsa:26580.
UCSC	uc001nup.3. human. uc009yoc.2. human.
Organism-specific databases
CTD	26580.
GeneCards	GC11M062457.
HGNC	HGNC:15832. BSCL2.
HPA	HPA042394.
MIM	269700. phenotype. 270685. phenotype. 600794. phenotype. 606158. gene.
neXtProt	NX_Q96G97.
Orphanet	100998. Autosomal dominant spastic paraplegia type 17. 528. Berardinelli-Seip congenital lipodystrophy. 139536. Distal hereditary motor neuropathy type 5.
PharmGKB	PA25432.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG316839.
HOGENOM	HOG000220875.
HOVERGEN	HBG050736.
OrthoDB	EOG40CHHQ.
Gene expression databases
ArrayExpress	Q96G97.
Bgee	Q96G97.
CleanEx	HS_BSCL2.
Genevestigator	Q96G97.
GermOnline	ENSG00000168000. Homo sapiens.
Family and domain databases
InterPro	IPR009617. Adipose-reg_protein_Seipin. [Graphical view]
Pfam	PF06775. Seipin. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	BSCL2. human.
GenomeRNAi	26580.
NextBio	48934.
SOURCE	Search...

Entry information

Entry name

BSCL2_HUMAN

Accession

Primary (citable) accession number: Q96G97
Secondary accession number(s): G3XAE4 , Q567S1, Q96SV1, Q9BSQ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	November 24, 2009
Last modified:	May 1, 2013
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.