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O15270

- SPTC2_HUMAN

UniProt

O15270 - SPTC2_HUMAN

Protein

Serine palmitoyltransferase 2

Gene

SPTLC2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    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.2 Publications

    Catalytic activityi

    Palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2.1 Publication

    Cofactori

    Pyridoxal phosphate.By similarity

    Pathwayi

    GO - Molecular functioni

    1. pyridoxal phosphate binding Source: InterPro
    2. serine C-palmitoyltransferase activity Source: UniProtKB

    GO - Biological processi

    1. ceramide biosynthetic process Source: Ensembl
    2. small molecule metabolic process Source: Reactome
    3. sphinganine biosynthetic process Source: Ensembl
    4. sphingolipid biosynthetic process Source: UniProtKB
    5. sphingolipid metabolic process Source: Reactome
    6. sphingomyelin biosynthetic process Source: Ensembl
    7. sphingosine biosynthetic process Source: Ensembl

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Lipid metabolism, Sphingolipid metabolism

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:HS02117-MONOMER.
    BRENDAi2.3.1.50. 2681.
    ReactomeiREACT_115810. Sphingolipid de novo biosynthesis.
    UniPathwayiUPA00222.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:SPTLC2
    Synonyms:KIAA0526, LCB2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:11278. SPTLC2.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome
    2. integral component of membrane Source: UniProtKB-KW
    3. mitochondrion Source: Ensembl
    4. serine C-palmitoyltransferase complex Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    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 (PubMed:23658386).1 Publication
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti182 – 1821A → P in HSAN1C; reduced activity with L-serine as substrate; increased activity toward L-alanine resulting in the accumulation of 1-deoxy-sphinganine. 1 Publication
    VAR_069525
    Natural varianti359 – 3591V → 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. 1 Publication
    VAR_064798
    Natural varianti382 – 3821G → 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. 1 Publication
    VAR_064799
    Natural varianti504 – 5041I → 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. 1 Publication
    VAR_064800

    Keywords - Diseasei

    Disease mutation, Neuropathy

    Organism-specific databases

    MIMi613640. phenotype.
    Orphaneti36386. Hereditary sensory and autonomic neuropathy type 1.
    PharmGKBiPA36107.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 562562Serine palmitoyltransferase 2PRO_0000163858Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei379 – 3791N6-(pyridoxal phosphate)lysineBy similarity

    Proteomic databases

    MaxQBiO15270.
    PaxDbiO15270.
    PeptideAtlasiO15270.
    PRIDEiO15270.

    PTM databases

    PhosphoSiteiO15270.

    Expressioni

    Tissue specificityi

    Widely expressed.1 Publication

    Gene expression databases

    ArrayExpressiO15270.
    BgeeiO15270.
    CleanExiHS_SPTLC2.
    GenevestigatoriO15270.

    Organism-specific databases

    HPAiHPA027552.

    Interactioni

    Subunit structurei

    Heterodimer with SPTLC1. Component of the serine palmitoyltransferase (SPT) complex, composed of LCB1/SPTLC1, LCB2 (SPTLC2 or SPTLC3) and ssPT (SPTSSA and SPTSSB).1 Publication

    Protein-protein interaction databases

    BioGridi114894. 2 interactions.
    DIPiDIP-34604N.
    IntActiO15270. 4 interactions.
    STRINGi9606.ENSP00000216484.

    Structurei

    3D structure databases

    ProteinModelPortaliO15270.
    SMRiO15270. Positions 170-535.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei67 – 8721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0156.
    HOGENOMiHOG000206826.
    HOVERGENiHBG002230.
    InParanoidiO15270.
    KOiK00654.
    OMAiPEPGGCC.
    OrthoDBiEOG73RBB0.
    PhylomeDBiO15270.
    TreeFamiTF300452.

    Family and domain databases

    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProiIPR001917. 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]
    PfamiPF00155. Aminotran_1_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF53383. SSF53383. 1 hit.
    PROSITEiPS00599. AA_TRANSFER_CLASS_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O15270-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRPEPGGCCC RRTVRANGCV ANGEVRNGYV RSSAAAAAAA AAGQIHHVTQ    50
    NGGLYKRPFN EAFEETPMLV AVLTYVGYGV LTLFGYLRDF LRYWRIEKCH 100
    HATEREEQKD FVSLYQDFEN FYTRNLYMRI RDNWNRPICS VPGARVDIME 150
    RQSHDYNWSF KYTGNIIKGV INMGSYNYLG FARNTGSCQE AAAKVLEEYG 200
    AGVCSTRQEI GNLDKHEELE ELVARFLGVE AAMAYGMGFA TNSMNIPALV 250
    GKGCLILSDE LNHASLVLGA RLSGATIRIF KHNNMQSLEK LLKDAIVYGQ 300
    PRTRRPWKKI LILVEGIYSM EGSIVRLPEV IALKKKYKAY LYLDEAHSIG 350
    ALGPTGRGVV EYFGLDPEDV DVMMGTFTKS FGASGGYIGG KKELIDYLRT 400
    HSHSAVYATS LSPPVVEQII TSMKCIMGQD GTSLGKECVQ QLAENTRYFR 450
    RRLKEMGFII YGNEDSPVVP LMLYMPAKIG AFGREMLKRN IGVVVVGFPA 500
    TPIIESRARF CLSAAHTKEI LDTALKEIDE VGDLLQLKYS RHRLVPLLDR 550
    PFDETTYEET ED 562
    Length:562
    Mass (Da):62,924
    Last modified:January 1, 1998 - v1
    Checksum:i0C1AA1E233DE36F1
    GO

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti61 – 644EAFE → TLAR in AAC50871. (PubMed:8921873)Curated
    Sequence conflicti436 – 46934KECVQ…DSPVV → NGITIHEVVQTRNTYHRFSP LSPVFSHQCLWIML(PubMed:8921873)CuratedAdd
    BLAST

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti182 – 1821A → P in HSAN1C; reduced activity with L-serine as substrate; increased activity toward L-alanine resulting in the accumulation of 1-deoxy-sphinganine. 1 Publication
    VAR_069525
    Natural varianti359 – 3591V → 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. 1 Publication
    VAR_064798
    Natural varianti382 – 3821G → 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. 1 Publication
    VAR_064799
    Natural varianti504 – 5041I → 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. 1 Publication
    VAR_064800

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS9865.1.
    PIRiI38873.
    RefSeqiNP_004854.1. NM_004863.3.
    UniGeneiHs.435661.

    Genome annotation databases

    EnsembliENST00000216484; ENSP00000216484; ENSG00000100596.
    GeneIDi9517.
    KEGGihsa:9517.
    UCSCiuc001xub.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS9865.1.
    PIRi I38873.
    RefSeqi NP_004854.1. NM_004863.3.
    UniGenei Hs.435661.

    3D structure databases

    ProteinModelPortali O15270.
    SMRi O15270. Positions 170-535.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114894. 2 interactions.
    DIPi DIP-34604N.
    IntActi O15270. 4 interactions.
    STRINGi 9606.ENSP00000216484.

    Chemistry

    BindingDBi O15270.
    ChEMBLi CHEMBL1250344.
    DrugBanki DB00133. L-Serine.
    GuidetoPHARMACOLOGYi 2510.

    PTM databases

    PhosphoSitei O15270.

    Proteomic databases

    MaxQBi O15270.
    PaxDbi O15270.
    PeptideAtlasi O15270.
    PRIDEi O15270.

    Protocols and materials databases

    DNASUi 9517.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000216484 ; ENSP00000216484 ; ENSG00000100596 .
    GeneIDi 9517.
    KEGGi hsa:9517.
    UCSCi uc001xub.3. human.

    Organism-specific databases

    CTDi 9517.
    GeneCardsi GC14M077973.
    HGNCi HGNC:11278. SPTLC2.
    HPAi HPA027552.
    MIMi 605713. gene.
    613640. phenotype.
    neXtProti NX_O15270.
    Orphaneti 36386. Hereditary sensory and autonomic neuropathy type 1.
    PharmGKBi PA36107.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0156.
    HOGENOMi HOG000206826.
    HOVERGENi HBG002230.
    InParanoidi O15270.
    KOi K00654.
    OMAi PEPGGCC.
    OrthoDBi EOG73RBB0.
    PhylomeDBi O15270.
    TreeFami TF300452.

    Enzyme and pathway databases

    UniPathwayi UPA00222 .
    BioCyci MetaCyc:HS02117-MONOMER.
    BRENDAi 2.3.1.50. 2681.
    Reactomei REACT_115810. Sphingolipid de novo biosynthesis.

    Miscellaneous databases

    ChiTaRSi SPTLC2. human.
    GeneWikii SPTLC2.
    GenomeRNAii 9517.
    NextBioi 35666.
    PROi O15270.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15270.
    Bgeei O15270.
    CleanExi HS_SPTLC2.
    Genevestigatori O15270.

    Family and domain databases

    Gene3Di 3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProi IPR001917. 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 ]
    Pfami PF00155. Aminotran_1_2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53383. SSF53383. 1 hit.
    PROSITEi PS00599. AA_TRANSFER_CLASS_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. Cited for: FUNCTION, VARIANTS HSAN1C MET-359; VAL-382 AND PHE-504, CHARACTERIZATION OF VARIANTS HSAN1C MET-359; VAL-382 AND PHE-504.
    10. 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.

    Entry informationi

    Entry nameiSPTC2_HUMAN
    AccessioniPrimary (citable) accession number: O15270
    Secondary accession number(s): Q16685
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 136 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3