Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine palmitoyltransferase 1

Gene

SPTLC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

  • ceramide biosynthetic process Source: MGI
  • positive regulation of lipophagy Source: MGI
  • sphinganine biosynthetic process Source: Ensembl
  • sphingolipid biosynthetic process Source: UniProtKB
  • sphingolipid metabolic process Source: ProtInc
  • sphingomyelin biosynthetic process Source: Ensembl
  • sphingosine biosynthetic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Lipid metabolism, Sphingolipid metabolism

Keywords - Ligandi

Pyridoxal phosphate

Enzyme and pathway databases

BioCyciMetaCyc:HS01673-MONOMER.
ZFISH:HS01673-MONOMER.
BRENDAi2.3.1.50. 2681.
ReactomeiR-HSA-1660661. Sphingolipid de novo biosynthesis.
SIGNORiO15269.
UniPathwayiUPA00222.

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

HGNCiHGNC:11277. SPTLC1.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: Reactome
  • integral component of membrane Source: UniProtKB-KW
  • serine C-palmitoyltransferase complex Source: UniProtKB
  • SPOTS complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Neuropathy, hereditary sensory and autonomic, 1A (HSAN1A)5 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 rs119482082dbSNPEnsembl.1
Natural variantiVAR_011393133C → Y in HSAN1A; reduced activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant rs119482081dbSNPEnsembl.1
Natural variantiVAR_011394144V → D in HSAN1A; reduced activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant rs119482083dbSNPEnsembl.1
Natural variantiVAR_068476310A → G Found in a patient with HSAN1A; uncertain pathological significance. 1 PublicationCorresponds to variant rs768841574dbSNPEnsembl.1
Natural variantiVAR_066245331S → F in HSAN1A; severe form with early onset; reduced activity. 3 PublicationsCorresponds to variant rs267607087dbSNPEnsembl.1
Natural variantiVAR_066246352A → V in HSAN1A; reduced activity. 2 PublicationsCorresponds to variant rs267607088dbSNPEnsembl.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.

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

Chemistry databases

ChEMBLiCHEMBL1250343.
DrugBankiDB00133. L-Serine.

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.

PTM databases

iPTMnetiO15269.
PhosphoSitePlusiO15269.
SwissPalmiO15269.

Expressioni

Tissue specificityi

Widely expressed. Not detected in small intestine.1 Publication

Gene expression databases

BgeeiENSG00000090054.
CleanExiHS_SPTLC1.
ExpressionAtlasiO15269. baseline and differential.
GenevisibleiO15269. HS.

Organism-specific databases

HPAiCAB018747.
HPA010860.

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

Protein-protein interaction databases

BioGridi115809. 28 interactors.
DIPiDIP-45626N.
IntActiO15269. 33 interactors.
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.
HOVERGENiHBG003992.
InParanoidiO15269.
KOiK00654.
OMAiQKYKLRL.
OrthoDBiEOG091G0DOG.
PhylomeDBiO15269.
TreeFamiTF314877.

Family and domain databases

Gene3Di3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProiIPR004839. 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.

Sequences (2)i

Sequence statusi: Complete.

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

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

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 rs119482082dbSNPEnsembl.1
Natural variantiVAR_011393133C → Y in HSAN1A; reduced activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant rs119482081dbSNPEnsembl.1
Natural variantiVAR_011394144V → D in HSAN1A; reduced activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant rs119482083dbSNPEnsembl.1
Natural variantiVAR_037889151R → L.1 PublicationCorresponds to variant rs45461899dbSNPEnsembl.1
Natural variantiVAR_036610239R → W in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs542876370dbSNPEnsembl.1
Natural variantiVAR_068476310A → G Found in a patient with HSAN1A; uncertain pathological significance. 1 PublicationCorresponds to variant rs768841574dbSNPEnsembl.1
Natural variantiVAR_066245331S → F in HSAN1A; severe form with early onset; reduced activity. 3 PublicationsCorresponds to variant rs267607087dbSNPEnsembl.1
Natural variantiVAR_073294331S → Y Probable disease-associated mutation found in severe HMSN; reduced activity. 1 Publication1
Natural variantiVAR_066246352A → V in HSAN1A; reduced activity. 2 PublicationsCorresponds to variant rs267607088dbSNPEnsembl.1
Natural variantiVAR_037890387G → A Rare polymorphism; does not affect activity; does not interfere with SPT complex formation. 2 PublicationsCorresponds to variant rs119482084dbSNPEnsembl.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, AL354751 Genomic DNA. Translation: CAH70209.1.
AL354751 Genomic DNA. Translation: CAH69923.1.
AL354751, AL391219 Genomic DNA. Translation: CAH69924.1.
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

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, AL354751 Genomic DNA. Translation: CAH70209.1.
AL354751 Genomic DNA. Translation: CAH69923.1.
AL354751, AL391219 Genomic DNA. Translation: CAH69924.1.
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. 28 interactors.
DIPiDIP-45626N.
IntActiO15269. 33 interactors.
STRINGi9606.ENSP00000262554.

Chemistry databases

BindingDBiO15269.
ChEMBLiCHEMBL1250343.
DrugBankiDB00133. L-Serine.

PTM databases

iPTMnetiO15269.
PhosphoSitePlusiO15269.
SwissPalmiO15269.

Proteomic databases

EPDiO15269.
MaxQBiO15269.
PaxDbiO15269.
PeptideAtlasiO15269.
PRIDEiO15269.

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.
GeneCardsiSPTLC1.
GeneReviewsiSPTLC1.
H-InvDBHIX0034871.
HGNCiHGNC:11277. SPTLC1.
HPAiCAB018747.
HPA010860.
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.
HOVERGENiHBG003992.
InParanoidiO15269.
KOiK00654.
OMAiQKYKLRL.
OrthoDBiEOG091G0DOG.
PhylomeDBiO15269.
TreeFamiTF314877.

Enzyme and pathway databases

UniPathwayiUPA00222.
BioCyciMetaCyc:HS01673-MONOMER.
ZFISH:HS01673-MONOMER.
BRENDAi2.3.1.50. 2681.
ReactomeiR-HSA-1660661. Sphingolipid de novo biosynthesis.
SIGNORiO15269.

Miscellaneous databases

ChiTaRSiSPTLC1. human.
GeneWikiiSPTLC1.
GenomeRNAii10558.
PROiO15269.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000090054.
CleanExiHS_SPTLC1.
ExpressionAtlasiO15269. baseline and differential.
GenevisibleiO15269. HS.

Family and domain databases

Gene3Di3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProiIPR004839. 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.
ProtoNetiSearch...

Entry informationi

Entry nameiSPTC1_HUMAN
AccessioniPrimary (citable) accession number: O15269
Secondary accession number(s): A8K681, Q5VWB4, Q96IX6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 160 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

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.