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O15270 (SPTC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine palmitoyltransferase 2

EC=2.3.1.50
Alternative name(s):
Long chain base biosynthesis protein 2
Short name=LCB 2
Long chain base biosynthesis protein 2a
Short name=LCB2a
Serine-palmitoyl-CoA transferase 2
Short name=SPT 2
Gene names
Name:SPTLC2
Synonyms:KIAA0526, LCB2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length562 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate. Ref.8 Ref.9

Catalytic activity

Palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2. Ref.8

Cofactor

Pyridoxal phosphate By similarity.

Pathway

Lipid metabolism; sphingolipid metabolism.

Subunit structure

Heterodimer with SPTLC1. Component of the serine palmitoyltransferase (SPT) complex, composed of LCB1/SPTLC1, LCB2 (SPTLC2 or SPTLC3) and ssPT (SPTSSA and SPTSSB). Ref.8

Subcellular location

Endoplasmic reticulum membrane; Single-pass membrane protein By similarity.

Tissue specificity

Widely expressed. Ref.7

Involvement in disease

Neuropathy, hereditary sensory and autonomic, 1C (HSAN1C) [MIM:613640]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by prominent sensory abnormalities with a variable degree of motor and autonomic dysfunction. The neurological phenotype is often complicated by severe infections, osteomyelitis, and amputations. HSAN1C symptoms include loss of touch and vibration in the feet, dysesthesia and severe panmodal sensory loss in the upper and lower limbs, distal lower limb sensory loss with ulceration and osteomyelitis, and distal muscle weakness.
Note: The disease is caused by mutations affecting the gene represented in this entry. SPTLC2 disease mutations cause a shift in the substrate specificity of SPT resulting in the alternative use of L-alanine and L-glycine over its canonical substrate L-serine. This leads to the production of 1-deoxysphingolipids that cannot be correctly metabolized (Ref.11). Ref.9 Ref.11

Sequence similarities

Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.

Sequence caution

The sequence BAA25452.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processLipid metabolism
Sphingolipid metabolism
   Cellular componentEndoplasmic reticulum
Membrane
   DiseaseDisease mutation
Neuropathy
   DomainTransmembrane
Transmembrane helix
   LigandPyridoxal phosphate
   Molecular functionAcyltransferase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processceramide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

sphinganine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

sphingolipid biosynthetic process

Traceable author statement Ref.8. Source: UniProtKB

sphingolipid metabolic process

Traceable author statement. Source: Reactome

sphingomyelin biosynthetic process

Inferred from electronic annotation. Source: Ensembl

sphingosine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrion

Inferred from electronic annotation. Source: Ensembl

serine C-palmitoyltransferase complex

Inferred from direct assay Ref.8. Source: UniProtKB

   Molecular_functionpyridoxal phosphate binding

Inferred from electronic annotation. Source: InterPro

serine C-palmitoyltransferase activity

Inferred from direct assay Ref.8Ref.9. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 562562Serine palmitoyltransferase 2
PRO_0000163858

Regions

Transmembrane67 – 8721Helical; Potential

Amino acid modifications

Modified residue3791N6-(pyridoxal phosphate)lysine By similarity

Natural variations

Natural variant1821A → P in HSAN1C; reduced activity with L-serine as substrate; increased activity toward L-alanine resulting in the accumulation of 1-deoxy-sphinganine. Ref.11
VAR_069525
Natural variant3591V → M in HSAN1C; partial loss of normal activity as measured by reduced formation of sphinganine; affects enzymatic affinity resulting in the accumulation of the alternative metabolite 1-deoxy-sphinganine. Ref.9
VAR_064798
Natural variant3821G → V in HSAN1C; complete loss of normal activity as measured by lack of formation of sphinganine; affects enzymatic affinity resulting in the accumulation of the alternative metabolite 1-deoxy-sphinganine. Ref.9
VAR_064799
Natural variant5041I → F in HSAN1C; partial loss of normal activity as measured by reduced formation of sphinganine; affects enzymatic affinity resulting in the accumulation of the alternative metabolite 1-deoxy-sphinganine. Ref.9
VAR_064800

Experimental info

Sequence conflict61 – 644EAFE → TLAR in AAC50871. Ref.5
Sequence conflict436 – 46934KECVQ…DSPVV → NGITIHEVVQTRNTYHRFSP LSPVFSHQCLWIML Ref.5

Sequences

Sequence LengthMass (Da)Tools
O15270 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 0C1AA1E233DE36F1

FASTA56262,924
        10         20         30         40         50         60 
MRPEPGGCCC RRTVRANGCV ANGEVRNGYV RSSAAAAAAA AAGQIHHVTQ NGGLYKRPFN 

        70         80         90        100        110        120 
EAFEETPMLV AVLTYVGYGV LTLFGYLRDF LRYWRIEKCH HATEREEQKD FVSLYQDFEN 

       130        140        150        160        170        180 
FYTRNLYMRI RDNWNRPICS VPGARVDIME RQSHDYNWSF KYTGNIIKGV INMGSYNYLG 

       190        200        210        220        230        240 
FARNTGSCQE AAAKVLEEYG AGVCSTRQEI GNLDKHEELE ELVARFLGVE AAMAYGMGFA 

       250        260        270        280        290        300 
TNSMNIPALV GKGCLILSDE LNHASLVLGA RLSGATIRIF KHNNMQSLEK LLKDAIVYGQ 

       310        320        330        340        350        360 
PRTRRPWKKI LILVEGIYSM EGSIVRLPEV IALKKKYKAY LYLDEAHSIG ALGPTGRGVV 

       370        380        390        400        410        420 
EYFGLDPEDV DVMMGTFTKS FGASGGYIGG KKELIDYLRT HSHSAVYATS LSPPVVEQII 

       430        440        450        460        470        480 
TSMKCIMGQD GTSLGKECVQ QLAENTRYFR RRLKEMGFII YGNEDSPVVP LMLYMPAKIG 

       490        500        510        520        530        540 
AFGREMLKRN IGVVVVGFPA TPIIESRARF CLSAAHTKEI LDTALKEIDE VGDLLQLKYS 

       550        560 
RHRLVPLLDR PFDETTYEET ED 

« Hide

References

« Hide 'large scale' references
[1]"Human and murine serine-palmitoyl-CoA transferase. Cloning, expression and characterization of the key enzyme in sphingolipid synthesis."
Weiss B., Stoffel W.
Eur. J. Biochem. 249:239-247(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pancreas.
[2]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
Tissue: Lymph.
[5]"Sphingolipid synthesis: identification and characterization of mammalian cDNAs encoding the Lcb2 subunit of serine palmitoyltransferase."
Nagiec M.M., Lester R.L., Dickson R.C.
Gene 177:237-241(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-470.
Tissue: Pancreatic islet.
[6]"A molecular inventory of human pancreatic islets: sequence analysis of 1000 cDNA clones."
Takeda J., Yano H., Eng S., Zeng Y., Bell G.I.
Hum. Mol. Genet. 2:1793-1798(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-144.
Tissue: Pancreatic islet.
[7]"Cloning and initial characterization of a new subunit for mammalian serine-palmitoyltransferase."
Hornemann T., Richard S., Ruetti M.F., Wei Y., von Eckardstein A.
J. Biol. Chem. 281:37275-37281(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities."
Han G., Gupta S.D., Gable K., Niranjanakumari S., Moitra P., Eichler F., Brown R.H. Jr., Harmon J.M., Dunn T.M.
Proc. Natl. Acad. Sci. U.S.A. 106:8186-8191(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE SPT COMPLEX.
[9]"Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I."
Rotthier A., Auer-Grumbach M., Janssens K., Baets J., Penno A., Almeida-Souza L., Van Hoof K., Jacobs A., De Vriendt E., Schlotter-Weigel B., Loscher W., Vondracek P., Seeman P., De Jonghe P., Van Dijck P., Jordanova A., Hornemann T., Timmerman V.
Am. J. Hum. Genet. 87:513-522(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANTS HSAN1C MET-359; VAL-382 AND PHE-504, CHARACTERIZATION OF VARIANTS HSAN1C MET-359; VAL-382 AND PHE-504.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2."
Murphy S.M., Ernst D., Wei Y., Laura M., Liu Y.T., Polke J., Blake J., Winer J., Houlden H., Hornemann T., Reilly M.M.
Neurology 80:2106-2111(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HSAN1C PRO-182, CHARACTERIZATION OF VARIANT HSAN1C PRO-182, PATHOLOGICAL MECHANISM.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y08686 mRNA. Translation: CAA69942.1.
AB011098 mRNA. Translation: BAA25452.2. Different initiation.
AF111168 Genomic DNA. Translation: AAD09621.1.
BC005123 mRNA. Translation: AAH05123.1.
U15555 mRNA. Translation: AAC50871.1.
CCDSCCDS9865.1.
PIRI38873.
RefSeqNP_004854.1. NM_004863.3.
UniGeneHs.435661.

3D structure databases

ProteinModelPortalO15270.
SMRO15270. Positions 170-535.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114894. 2 interactions.
DIPDIP-34604N.
IntActO15270. 4 interactions.
STRING9606.ENSP00000216484.

Chemistry

BindingDBO15270.
ChEMBLCHEMBL1250344.
DrugBankDB00133. L-Serine.
DB00114. Pyridoxal Phosphate.
GuidetoPHARMACOLOGY2510.

PTM databases

PhosphoSiteO15270.

Proteomic databases

MaxQBO15270.
PaxDbO15270.
PeptideAtlasO15270.
PRIDEO15270.

Protocols and materials databases

DNASU9517.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216484; ENSP00000216484; ENSG00000100596.
GeneID9517.
KEGGhsa:9517.
UCSCuc001xub.3. human.

Organism-specific databases

CTD9517.
GeneCardsGC14M077973.
HGNCHGNC:11278. SPTLC2.
HPAHPA027552.
MIM605713. gene.
613640. phenotype.
neXtProtNX_O15270.
Orphanet36386. Hereditary sensory and autonomic neuropathy type 1.
PharmGKBPA36107.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0156.
HOGENOMHOG000206826.
HOVERGENHBG002230.
InParanoidO15270.
KOK00654.
OMAPEPGGCC.
OrthoDBEOG73RBB0.
PhylomeDBO15270.
TreeFamTF300452.

Enzyme and pathway databases

BioCycMetaCyc:HS02117-MONOMER.
BRENDA2.3.1.50. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00222.

Gene expression databases

ArrayExpressO15270.
BgeeO15270.
CleanExHS_SPTLC2.
GenevestigatorO15270.

Family and domain databases

Gene3D3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProIPR001917. Aminotrans_II_pyridoxalP_BS.
IPR004839. Aminotransferase_I/II.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
[Graphical view]
PfamPF00155. Aminotran_1_2. 1 hit.
[Graphical view]
SUPFAMSSF53383. SSF53383. 1 hit.
PROSITEPS00599. AA_TRANSFER_CLASS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSPTLC2. human.
GeneWikiSPTLC2.
GenomeRNAi9517.
NextBio35666.
PROO15270.
SOURCESearch...

Entry information

Entry nameSPTC2_HUMAN
AccessionPrimary (citable) accession number: O15270
Secondary accession number(s): Q16685
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM