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Protein

Serine palmitoyltransferase 1

Gene

SPTLC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine palmitoyltransferase (SPT). The heterodimer formed with SPTLC2 or SPTLC3 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-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference.1 Publication

Caution

Variant Ala-387 has been originally thought to cause HSAN1A (PubMed:15037712). Subsequently, it has been shown to be a rare, benign polymorphism found in homozygous state in a healthy individual (PubMed:19132419).2 Publications

Catalytic activityi

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

Cofactori

Kineticsi

  1. KM=0.75 mM for serine1 Publication
  1. Vmax=1350 pmol/min/mg enzyme1 Publication

Pathwayi: sphingolipid metabolism

This protein is involved in the pathway sphingolipid metabolism, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway sphingolipid metabolism and in Lipid metabolism.

GO - Molecular functioni

  • pyridoxal phosphate binding Source: InterPro
  • serine C-palmitoyltransferase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionAcyltransferase, Transferase
Biological processLipid metabolism, Sphingolipid metabolism
LigandPyridoxal phosphate

Enzyme and pathway databases

BioCyciMetaCyc:HS01673-MONOMER
BRENDAi2.3.1.50 2681
ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis
SIGNORiO15269
UniPathwayi
UPA00222

Names & Taxonomyi

Protein namesi
Recommended name:
Serine palmitoyltransferase 1 (EC:2.3.1.50)
Alternative name(s):
Long chain base biosynthesis protein 1
Short name:
LCB 1
Serine-palmitoyl-CoA transferase 1
Short name:
SPT 1
Short name:
SPT1
Gene namesi
Name:SPTLC1
Synonyms:LCB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000090054.13
HGNCiHGNC:11277 SPTLC1
MIMi605712 gene
neXtProtiNX_O15269

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 15LumenalSequence analysisAdd BLAST15
Transmembranei16 – 36HelicalSequence analysisAdd BLAST21
Topological domaini37 – 473CytoplasmicSequence analysisAdd BLAST437

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Neuropathy, hereditary sensory and autonomic, 1A (HSAN1A)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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. HSAN1A is an autosomal dominant axonal form with onset in the second or third decades. Initial symptoms are loss of pain, touch, heat, and cold sensation over the feet, followed by distal muscle wasting and weakness. Loss of pain sensation leads to chronic skin ulcers and distal amputations.
See also OMIM:162400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011392133C → W in HSAN1A; inactive in the heterodimeric SPT complex; largely reduced activity with serine as substrate, but nearly no effect on serine affinity in the heterotrimeric SPT complex; in contrast to wild-type is able to use alanine as substrate leading to the formation of 1-deoxysphinganine (1-deoxySa); does not interfere with SPT complex formation. 4 PublicationsCorresponds to variant dbSNP:rs119482082EnsemblClinVar.1
Natural variantiVAR_011393133C → Y in HSAN1A; reduced activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant dbSNP:rs119482081EnsemblClinVar.1
Natural variantiVAR_011394144V → D in HSAN1A; reduced activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant dbSNP:rs119482083EnsemblClinVar.1
Natural variantiVAR_066245331S → F in HSAN1A; severe form with early onset; reduced activity. 3 PublicationsCorresponds to variant dbSNP:rs267607087EnsemblClinVar.1
Natural variantiVAR_066246352A → V in HSAN1A; reduced activity. 2 PublicationsCorresponds to variant dbSNP:rs267607088EnsemblClinVar.1
SPTLC1 mutations at Ser-331 are responsible for severe hereditary motor and sensory neuropathy (HMSN) forms, whose core features are severe, diffuse muscle wasting and hypotonia, motor and sensory disturbances, foot ulcers, amputations and/or burns, joint hypermobility, cataracts and considerable growth retardation.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi164Y → F: Increased serine palmitoyltransferase activity and sphingolipid content. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi10558
GeneReviewsiSPTLC1
MalaCardsiSPTLC1
MIMi162400 phenotype
OpenTargetsiENSG00000090054
Orphaneti36386 Hereditary sensory and autonomic neuropathy type 1
PharmGKBiPA36106

Chemistry databases

ChEMBLiCHEMBL1250343
DrugBankiDB00133 L-Serine
DB00114 Pyridoxal Phosphate

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001638531 – 473Serine palmitoyltransferase 1Add BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei164Phosphotyrosine; by ABL1 Publication1

Post-translational modificationi

Phosphorylation at Tyr-164 inhibits activity and promotes cell survival.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO15269
MaxQBiO15269
PaxDbiO15269
PeptideAtlasiO15269
PRIDEiO15269
ProteomicsDBi48557
48558 [O15269-2]

PTM databases

iPTMnetiO15269
PhosphoSitePlusiO15269
SwissPalmiO15269

Expressioni

Tissue specificityi

Widely expressed. Not detected in small intestine.1 Publication

Gene expression databases

BgeeiENSG00000090054 Expressed in 240 organ(s), highest expression level in sigmoid colon
CleanExiHS_SPTLC1
ExpressionAtlasiO15269 baseline and differential
GenevisibleiO15269 HS

Organism-specific databases

HPAiCAB018747
HPA010860
HPA063907

Interactioni

Subunit structurei

Heterodimer with SPTLC2 or SPTLC3. Component of the serine palmitoyltransferase (SPT) complex, composed of SPTLC1, either SPTLC2 or SPTLC3, and either SPTSSA or SPTSSB. Interacts with SPTSSA and SPTSSB; the interaction is direct. Interacts with ORMDL3.2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi115809, 31 interactors
CORUMiO15269
DIPiDIP-45626N
IntActiO15269, 51 interactors
MINTiO15269
STRINGi9606.ENSP00000262554

Chemistry databases

BindingDBiO15269

Structurei

3D structure databases

ProteinModelPortaliO15269
SMRiO15269
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1358 Eukaryota
COG0156 LUCA
GeneTreeiENSGT00550000074872
HOGENOMiHOG000216602
HOVERGENiHBG074776
InParanoidiO15269
KOiK00654
OMAiCVGSHFI
OrthoDBiEOG091G0DOG
PhylomeDBiO15269
TreeFamiTF314877

Family and domain databases

Gene3Di3.40.640.10, 1 hit
3.90.1150.10, 1 hit
InterProiView protein in InterPro
IPR004839 Aminotransferase_I/II
IPR015424 PyrdxlP-dep_Trfase
IPR015422 PyrdxlP-dep_Trfase_dom1
IPR015421 PyrdxlP-dep_Trfase_major
PfamiView protein in Pfam
PF00155 Aminotran_1_2, 1 hit
SUPFAMiSSF53383 SSF53383, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O15269-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MATATEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLLF SKTYKLQERS
60 70 80 90 100
DLTVKEKEEL IEEWQPEPLV PPVPKDHPAL NYNIVSGPPS HKTVVNGKEC
110 120 130 140 150
INFASFNFLG LLDNPRVKAA ALASLKKYGV GTCGPRGFYG TFDVHLDLED
160 170 180 190 200
RLAKFMKTEE AIIYSYGFAT IASAIPAYSK RGDIVFVDRA ACFAIQKGLQ
210 220 230 240 250
ASRSDIKLFK HNDMADLERL LKEQEIEDQK NPRKARVTRR FIVVEGLYMN
260 270 280 290 300
TGTICPLPEL VKLKYKYKAR IFLEESLSFG VLGEHGRGVT EHYGINIDDI
310 320 330 340 350
DLISANMENA LASIGGFCCG RSFVIDHQRL SGQGYCFSAS LPPLLAAAAI
360 370 380 390 400
EALNIMEENP GIFAVLKEKC GQIHKALQGI SGLKVVGESL SPAFHLQLEE
410 420 430 440 450
STGSREQDVR LLQEIVDQCM NRSIALTQAR YLEKEEKCLP PPSIRVVVTV
460 470
EQTEEELERA ASTIKEVAQA VLL
Length:473
Mass (Da):52,744
Last modified:January 1, 1998 - v1
Checksum:iBA9E056A869D2EA2
GO
Isoform 2 (identifier: O15269-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     143-143: D → E
     144-473: Missing.

Note: No experimental confirmation available.
Show »
Length:143
Mass (Da):16,073
Checksum:iED13F62F871136BF
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8Y6A2A0A2R8Y6A2_HUMAN
Serine palmitoyltransferase 1
SPTLC1
144Annotation score:
A0A2R8Y4S0A0A2R8Y4S0_HUMAN
Serine palmitoyltransferase 1
SPTLC1
143Annotation score:
A0A2R8Y763A0A2R8Y763_HUMAN
Serine palmitoyltransferase 1
SPTLC1
22Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011392133C → W in HSAN1A; inactive in the heterodimeric SPT complex; largely reduced activity with serine as substrate, but nearly no effect on serine affinity in the heterotrimeric SPT complex; in contrast to wild-type is able to use alanine as substrate leading to the formation of 1-deoxysphinganine (1-deoxySa); does not interfere with SPT complex formation. 4 PublicationsCorresponds to variant dbSNP:rs119482082EnsemblClinVar.1
Natural variantiVAR_011393133C → Y in HSAN1A; reduced activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant dbSNP:rs119482081EnsemblClinVar.1
Natural variantiVAR_011394144V → D in HSAN1A; reduced activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant dbSNP:rs119482083EnsemblClinVar.1
Natural variantiVAR_037889151R → L1 PublicationCorresponds to variant dbSNP:rs45461899EnsemblClinVar.1
Natural variantiVAR_036610239R → W in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs542876370Ensembl.1
Natural variantiVAR_068476310A → G Found in a patient with HSAN1A; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs768841574EnsemblClinVar.1
Natural variantiVAR_066245331S → F in HSAN1A; severe form with early onset; reduced activity. 3 PublicationsCorresponds to variant dbSNP:rs267607087EnsemblClinVar.1
Natural variantiVAR_073294331S → Y Probable disease-associated mutation found in severe HMSN; reduced activity. 1 PublicationCorresponds to variant dbSNP:rs267607087EnsemblClinVar.1
Natural variantiVAR_066246352A → V in HSAN1A; reduced activity. 2 PublicationsCorresponds to variant dbSNP:rs267607088EnsemblClinVar.1
Natural variantiVAR_037890387G → A Rare polymorphism; does not affect activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant dbSNP:rs119482084EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043127143D → E in isoform 2. 1 Publication1
Alternative sequenceiVSP_043128144 – 473Missing in isoform 2. 1 PublicationAdd BLAST330

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08685 mRNA Translation: CAA69941.1
AF286717
, AF286703, AF286704, AF286705, AF286706, AF286707, AF286708, AF286709, AF286710, AF286711, AF286712, AF286713, AF286714, AF286715, AF286716 Genomic DNA Translation: AAK29328.1
AK291546 mRNA Translation: BAF84235.1
AL391219 Genomic DNA No translation available.
AL354751 Genomic DNA No translation available.
CH471089 Genomic DNA Translation: EAW62804.1
BC007085 mRNA Translation: AAH07085.1
CCDSiCCDS6692.1 [O15269-1]
CCDS6693.1 [O15269-2]
RefSeqiNP_001268232.1, NM_001281303.1
NP_006406.1, NM_006415.3 [O15269-1]
NP_847894.1, NM_178324.2 [O15269-2]
UniGeneiHs.90458

Genome annotation databases

EnsembliENST00000262554; ENSP00000262554; ENSG00000090054 [O15269-1]
ENST00000337841; ENSP00000337635; ENSG00000090054 [O15269-2]
GeneIDi10558
KEGGihsa:10558
UCSCiuc004arl.3 human [O15269-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08685 mRNA Translation: CAA69941.1
AF286717
, AF286703, AF286704, AF286705, AF286706, AF286707, AF286708, AF286709, AF286710, AF286711, AF286712, AF286713, AF286714, AF286715, AF286716 Genomic DNA Translation: AAK29328.1
AK291546 mRNA Translation: BAF84235.1
AL391219 Genomic DNA No translation available.
AL354751 Genomic DNA No translation available.
CH471089 Genomic DNA Translation: EAW62804.1
BC007085 mRNA Translation: AAH07085.1
CCDSiCCDS6692.1 [O15269-1]
CCDS6693.1 [O15269-2]
RefSeqiNP_001268232.1, NM_001281303.1
NP_006406.1, NM_006415.3 [O15269-1]
NP_847894.1, NM_178324.2 [O15269-2]
UniGeneiHs.90458

3D structure databases

ProteinModelPortaliO15269
SMRiO15269
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115809, 31 interactors
CORUMiO15269
DIPiDIP-45626N
IntActiO15269, 51 interactors
MINTiO15269
STRINGi9606.ENSP00000262554

Chemistry databases

BindingDBiO15269
ChEMBLiCHEMBL1250343
DrugBankiDB00133 L-Serine
DB00114 Pyridoxal Phosphate

PTM databases

iPTMnetiO15269
PhosphoSitePlusiO15269
SwissPalmiO15269

Proteomic databases

EPDiO15269
MaxQBiO15269
PaxDbiO15269
PeptideAtlasiO15269
PRIDEiO15269
ProteomicsDBi48557
48558 [O15269-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262554; ENSP00000262554; ENSG00000090054 [O15269-1]
ENST00000337841; ENSP00000337635; ENSG00000090054 [O15269-2]
GeneIDi10558
KEGGihsa:10558
UCSCiuc004arl.3 human [O15269-1]

Organism-specific databases

CTDi10558
DisGeNETi10558
EuPathDBiHostDB:ENSG00000090054.13
GeneCardsiSPTLC1
GeneReviewsiSPTLC1
H-InvDBiHIX0034871
HGNCiHGNC:11277 SPTLC1
HPAiCAB018747
HPA010860
HPA063907
MalaCardsiSPTLC1
MIMi162400 phenotype
605712 gene
neXtProtiNX_O15269
OpenTargetsiENSG00000090054
Orphaneti36386 Hereditary sensory and autonomic neuropathy type 1
PharmGKBiPA36106
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1358 Eukaryota
COG0156 LUCA
GeneTreeiENSGT00550000074872
HOGENOMiHOG000216602
HOVERGENiHBG074776
InParanoidiO15269
KOiK00654
OMAiCVGSHFI
OrthoDBiEOG091G0DOG
PhylomeDBiO15269
TreeFamiTF314877

Enzyme and pathway databases

UniPathwayi
UPA00222

BioCyciMetaCyc:HS01673-MONOMER
BRENDAi2.3.1.50 2681
ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis
SIGNORiO15269

Miscellaneous databases

ChiTaRSiSPTLC1 human
GeneWikiiSPTLC1
GenomeRNAii10558
PROiPR:O15269
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000090054 Expressed in 240 organ(s), highest expression level in sigmoid colon
CleanExiHS_SPTLC1
ExpressionAtlasiO15269 baseline and differential
GenevisibleiO15269 HS

Family and domain databases

Gene3Di3.40.640.10, 1 hit
3.90.1150.10, 1 hit
InterProiView protein in InterPro
IPR004839 Aminotransferase_I/II
IPR015424 PyrdxlP-dep_Trfase
IPR015422 PyrdxlP-dep_Trfase_dom1
IPR015421 PyrdxlP-dep_Trfase_major
PfamiView protein in Pfam
PF00155 Aminotran_1_2, 1 hit
SUPFAMiSSF53383 SSF53383, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSPTC1_HUMAN
AccessioniPrimary (citable) accession number: O15269
Secondary accession number(s): A8K681, Q5VWB4, Q96IX6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 178 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
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