id: O15269
gene_symbol: SPTLC1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  SPTLC1 (serine palmitoyltransferase long chain base subunit 1; LCB1) is a
  membrane subunit of the serine palmitoyltransferase (SPT) holoenzyme, which
  catalyzes the first, committed and rate-limiting step of de novo sphingolipid
  biosynthesis, namely the pyridoxal-5'-phosphate (PLP)-dependent condensation of
  L-serine with palmitoyl-CoA to form 3-ketodihydrosphingosine (3-oxosphinganine),
  releasing CO2 and CoA (EC 2.3.1.50). SPTLC1 is a single-pass endoplasmic reticulum
  membrane protein whose catalytic domain faces the cytoplasm. The catalytic core is
  a heterodimer of SPTLC1 with SPTLC2 (or SPTLC3) that assembles as a dimer of
  heterodimers; SPTLC1 forms part of the active-site environment, while the
  PLP-binding catalytic lysine resides on SPTLC2. Small subunits SPTSSA/SPTSSB confer
  full activity and tune acyl-CoA substrate specificity, and ORMDL proteins (notably
  ORMDL3) negatively regulate the complex in a ceramide-dependent manner to maintain
  sphingolipid homeostasis. Dominant SPTLC1 missense variants cause hereditary
  sensory and autonomic neuropathy type 1 (HSAN1A) by shifting the enzyme toward
  alanine/glycine to produce toxic 1-deoxysphingolipids, while other variants that
  escape ORMDL-mediated inhibition cause juvenile amyotrophic lateral sclerosis
  (ALS27) through excess canonical sphingolipid synthesis.
alternative_products:
- name: '1'
  id: O15269-1
- name: '2'
  id: O15269-2
  sequence_note: VSP_043127, VSP_043128
existing_annotations:
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetically inferred ER localization for the SPT catalytic subunit.
      SPTLC1 is a single-pass ER membrane protein, so ER localization is correct,
      though the more specific term (ER membrane) is also annotated separately.
    action: ACCEPT
    reason: SPTLC1 is an integral ER membrane protein and the SPT complex acts at the
      ER; the IBA is consistent with experimental and IEA annotations.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0046512
    label: sphingosine biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference that SPTLC1 is involved in sphingosine (long-chain
      base) biosynthesis, the initial de novo sphingolipid step catalyzed by SPT.
    action: ACCEPT
    reason: SPT produces the long-chain base precursor of sphingosine; this represents
      the committed step of the pathway and is well supported.
    supported_by:
    - reference_id: PMID:9363775
      supporting_text: is the key enzyme in sphingolipid
- term:
    id: GO:0046513
    label: ceramide biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference that SPTLC1 participates in ceramide biosynthesis.
      The SPT-catalyzed step is the entry point of the de novo pathway that produces
      long-chain bases, which are N-acylated to ceramide.
    action: ACCEPT
    reason: SPT initiates the de novo pathway whose downstream product is ceramide;
      the involved_in relationship for the pathway entry enzyme is appropriate.
    supported_by:
    - reference_id: PMID:9363775
      supporting_text: is the key enzyme in sphingolipid
- term:
    id: GO:0004758
    label: serine C-palmitoyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assignment of the core serine C-palmitoyltransferase molecular
      function (EC 2.3.1.50 / RHEA:14761) to SPTLC1. This is the defining catalytic
      activity of the SPT complex and matches experimental annotations.
    action: ACCEPT
    reason: The IEA correctly captures the core molecular function; it is supported by
      the mapped RHEA/EC and by direct experimental annotations from the same term.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: catalyzes the initial and rate-limiting step in
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic assignment of ER membrane localization, consistent with the
      single-pass ER membrane topology of SPTLC1.
    action: ACCEPT
    reason: Matches the experimentally supported subcellular location; ER membrane is
      the core CC for this subunit.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based assignment of PLP binding from the class-II PLP-dependent
      aminotransferase signature. SPT is a PLP-dependent enzyme, but the PLP-binding
      catalytic lysine resides on SPTLC2, not SPTLC1; SPTLC1 retains the fold but
      lacks the catalytic lysine.
    action: MARK_AS_OVER_ANNOTATED
    reason: The PLP cofactor is bound at the SPTLC2 active-site lysine within the
      heterodimer; the InterPro signature is over-propagated from the family fold to
      the non-catalytic SPTLC1 subunit. Retained but flagged as over-annotation, since
      PLP is not directly coordinated by SPTLC1.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: Belongs to the class-II pyridoxal-phosphate-dependent
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19416851
  qualifier: enables
  review:
    summary: IntAct-curated physical interactions of SPTLC1 with SPT complex partners
      (SPTLC2, SPTLC3, SPTSSA). The informative content (SPT complex membership and
      small-subunit interactions) is captured by GO:0017059.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' is uninformative; the specific and biologically
      meaningful assemblies are already represented by the serine palmitoyltransferase
      complex annotations.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: each interacts with both hLCB1 and
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20182505
  qualifier: enables
  review:
    summary: IntAct-curated interaction of SPTLC1 with ORMDL3 (the negative regulator
      of SPT). Informative regulatory context is better captured by complex membership
      and activity-regulation terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' adds no functional detail beyond the ORMDL-SPT
      interaction already documented; retained but flagged as over-annotation.
    supported_by:
    - reference_id: PMID:20182505
      supporting_text: complex with serine palmitoyltransferase, the first and
        rate-limiting enzyme in
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33558761
  qualifier: enables
  review:
    summary: Cryo-EM/interaction evidence for SPTLC1 within the human SPT holocomplex
      (with SPTLC2, ssSPTa/SPTSSA, ORMDL3). The specific assembly is represented by
      GO:0017059.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' is uninformative relative to the structurally
      defined SPT holocomplex membership already annotated.
    supported_by:
    - reference_id: PMID:33558761
      supporting_text: palmitoyltransferase holocomplex, which consists of catalytic
        components (SPTLC1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33558762
  qualifier: enables
  review:
    summary: Structural/interaction evidence for SPTLC1 within the SPT-ORMDL3 complex
      (SPTLC1-SPTLC2-SPTssa dimer of heterodimers). Captured by complex membership.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' adds nothing beyond the structurally defined SPT
      complex annotation; retained but flagged.
    supported_by:
    - reference_id: PMID:33558762
      supporting_text: SPTLC1 and SPTLC2 form a dimer of heterodimers as the catalytic
        core.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome detecting SPTLC1-SPTLC2 physical
      association at scale. Uninformative bare term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare protein binding is uninformative; the SPTLC1-SPTLC2 interaction is
      already represented by serine palmitoyltransferase complex membership.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: 'O15269; O15270: SPTLC2'
- term:
    id: GO:0006665
    label: sphingolipid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic assignment of the broad sphingolipid metabolic process. SPT
      catalyzes the entry reaction of sphingolipid metabolism.
    action: ACCEPT
    reason: Correct but general; the more specific biosynthetic terms (GO:0030148,
      GO:0046512, GO:0046513) are also annotated and are the core BP terms.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: 'PATHWAY: Lipid metabolism; sphingolipid metabolism.'
- term:
    id: GO:0006686
    label: sphingomyelin biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic (ARBA/ortholog) assignment of sphingomyelin biosynthesis.
      Sphingomyelin synthesis (headgroup transfer onto ceramide by sphingomyelin
      synthases in the Golgi) is several steps downstream of the SPT-catalyzed entry
      reaction and is not a direct SPTLC1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: This is a downstream pathway terminus, not the reaction SPTLC1 participates
      in; over-broad electronic mapping. The core biosynthetic role is captured by the
      LCB/ceramide biosynthesis terms.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: catalyzes the initial and rate-limiting step in
- term:
    id: GO:1904649
    label: regulation of fat cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl orthology transfer from mouse Sptlc1 (O35704) of a role in
      regulating adipocyte apoptosis, reflecting the requirement of de novo
      sphingolipid synthesis for adipocyte viability.
    action: KEEP_AS_NON_CORE
    reason: Peripheral, physiology-level phenotype transferred by orthology; not the
      core molecular/biosynthetic function of the enzyme, but plausible given
      sphingolipid requirements for adipocyte homeostasis.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: Required for adipocyte cell
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: NAS
  original_reference_id: PMID:33558761
  qualifier: located_in
  review:
    summary: ComplexPortal non-traceable assertion of ER membrane localization for the
      SPT complex, consistent with all other localization evidence.
    action: ACCEPT
    reason: ER membrane is the well-established core location; corroborated by EXP, IEA
      and TAS annotations.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0017059
    label: serine palmitoyltransferase complex
  evidence_type: IPI
  original_reference_id: PMID:19416851
  qualifier: part_of
  review:
    summary: SPTLC1 is a subunit of the serine palmitoyltransferase complex, shown by
      identification of SPTLC1 in the SPT complex and its interaction with the small
      subunits SPTSSA/SPTSSB.
    action: ACCEPT
    reason: Core cellular-component annotation; SPTLC1 is a defining, obligate subunit
      of the SPT enzyme complex.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: each interacts with both hLCB1 and
- term:
    id: GO:0017059
    label: serine palmitoyltransferase complex
  evidence_type: IPI
  original_reference_id: PMID:33558761
  qualifier: part_of
  review:
    summary: Cryo-EM of the human SPT holocomplex confirms SPTLC1 as a catalytic-core
      subunit of the serine palmitoyltransferase complex.
    action: ACCEPT
    reason: Structurally validated core CC annotation for the SPT complex.
    supported_by:
    - reference_id: PMID:33558761
      supporting_text: palmitoyltransferase holocomplex, which consists of catalytic
        components (SPTLC1
- term:
    id: GO:0046512
    label: sphingosine biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:19416851
  qualifier: involved_in
  review:
    summary: Direct assay of SPT isozymes containing SPTLC1 shows production of
      long-chain (sphingoid) bases with distinct acyl-CoA preferences, supporting a
      role in sphingosine/long-chain-base biosynthesis.
    action: ACCEPT
    reason: Experimentally supported involvement in the LCB-producing entry step of the
      de novo pathway.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: differences in acyl-CoA preference that offer a potential
        explanation for the
- term:
    id: GO:0046512
    label: sphingosine biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:33558761
  qualifier: involved_in
  review:
    summary: Structural and biochemical characterization of the SPT holocomplex
      containing SPTLC1 supports its role in long-chain base (sphingosine precursor)
      biosynthesis.
    action: ACCEPT
    reason: Consistent with the enzyme's defined catalytic role at the pathway entry.
    supported_by:
    - reference_id: PMID:33558761
      supporting_text: palmitoyltransferase holocomplex, which consists of catalytic
        components (SPTLC1
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence localizing SPTLC1 to the endoplasmic reticulum.
    action: ACCEPT
    reason: Direct localization evidence consistent with the ER membrane topology; the
      more specific ER membrane term is also annotated.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: EXP
  original_reference_id: PMID:21618344
  qualifier: located_in
  review:
    summary: Experimental characterization of HSAN1-associated SPTLC1 mutants included
      determination of subcellular location at the ER membrane.
    action: ACCEPT
    reason: Core CC annotation; SPTLC1 is a single-pass ER membrane protein. The
      curator read the full text; the UniProt record cites this paper for the ER
      membrane subcellular location.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: Endoplasmic reticulum membrane
- term:
    id: GO:0004758
    label: serine C-palmitoyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:19416851
  qualifier: contributes_to
  review:
    summary: SPTLC1-containing SPT isozymes were directly assayed for serine
      C-palmitoyltransferase activity. The contributes_to qualifier reflects that
      catalysis requires the SPTLC1-SPTLC2/3 heterodimer.
    action: ACCEPT
    reason: Direct experimental support for the core molecular function; contributes_to
      is appropriate because SPTLC1 provides part of the active-site environment within
      the obligate heterodimer.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: Serine palmitoyltransferase (SPT) catalyzes the first committed
        step in
- term:
    id: GO:0006686
    label: sphingomyelin biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:30242129
  qualifier: involved_in
  review:
    summary: This annotation attributes sphingomyelin biosynthesis to SPTLC1 via a
      paper (PMID:30242129) that studies the SMS1 (SGMS1)-GCS (UGCG) Golgi complex.
      The cached full text does not mention SPTLC1 or serine palmitoyltransferase at
      all, and sphingomyelin synthesis (phosphocholine transfer onto ceramide) is
      several steps downstream of the SPT-catalyzed entry reaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: The reference does not assay SPTLC1 and sphingomyelin biosynthesis is not a
      direct SPTLC1 function; it is a downstream terminus of the broader pathway. Per
      curation policy for experimental annotations this is flagged as over-annotation
      rather than removed.
    supported_by:
    - reference_id: PMID:30242129
      supporting_text: initiated by the condensation of serine and palmitoyl-CoA
- term:
    id: GO:0046513
    label: ceramide biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:19416851
  qualifier: involved_in
  review:
    summary: Direct characterization of SPTLC1-containing SPT isozymes and their
      long-chain base output supports involvement in the de novo pathway that yields
      ceramide.
    action: ACCEPT
    reason: SPT initiates the pathway whose downstream product is ceramide;
      experimentally supported involvement.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: Serine palmitoyltransferase (SPT) catalyzes the first committed
        step in
- term:
    id: GO:0006688
    label: glycosphingolipid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:19416851
  qualifier: involved_in
  review:
    summary: SPT activity produces long-chain bases that feed the wider sphingolipid
      network, including glycosphingolipids. The direct enzymatic product is a
      3-ketosphingoid, and glycosphingolipid formation is many steps downstream.
    action: KEEP_AS_NON_CORE
    reason: Correct as a pathway-level involvement but distal to the SPTLC1-catalyzed
      step; retained as non-core rather than a defining function.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: differences in acyl-CoA preference that offer a potential
        explanation for the
- term:
    id: GO:0017059
    label: serine palmitoyltransferase complex
  evidence_type: IDA
  original_reference_id: PMID:19416851
  qualifier: part_of
  review:
    summary: Identification of SPTLC1 in the SPT complex, including its association with
      SPTLC2/3 and the small subunits.
    action: ACCEPT
    reason: Core CC annotation; SPTLC1 is an obligate subunit of the SPT complex.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: each interacts with both hLCB1 and
- term:
    id: GO:0098554
    label: cytoplasmic side of endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:19416851
  qualifier: is_active_in
  review:
    summary: The catalytic domain of SPTLC1 (residues 37-473) is cytoplasmic, so the
      SPT active site faces the cytoplasmic side of the ER membrane, where long-chain
      base synthesis occurs.
    action: ACCEPT
    reason: Consistent with the single-pass topology (lumenal N-terminus, TM 16-36,
      cytoplasmic catalytic domain); de novo LCB synthesis is known to occur on the
      cytosolic ER leaflet.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: 'TOPO_DOM        37..473'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-428127
  qualifier: located_in
  review:
    summary: Reactome traceable assertion placing the SPTLC complexes at the ER
      membrane where they transfer acyl-CoA onto serine.
    action: ACCEPT
    reason: Consistent with all other localization evidence; ER membrane is the core CC.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:1904649
    label: regulation of fat cell apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse Sptlc1 of a role in regulating
      adipocyte apoptosis, mirroring the requirement of de novo sphingolipid synthesis
      for adipocyte viability.
    action: KEEP_AS_NON_CORE
    reason: Peripheral orthology-based phenotype; not the core catalytic/biosynthetic
      function but biologically plausible.
    supported_by:
    - reference_id: file:human/SPTLC1/SPTLC1-uniprot.txt
      supporting_text: Required for adipocyte cell
- term:
    id: GO:0004758
    label: serine C-palmitoyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:25691431
  qualifier: contributes_to
  review:
    summary: SPTLC1-containing SPT complexes were assayed for de novo sphingolipid
      biosynthetic (serine C-palmitoyltransferase) activity in the context of ORMDL/SPT
      stoichiometry experiments.
    action: ACCEPT
    reason: Direct support for the core molecular function; contributes_to reflects the
      obligate heterodimeric catalytic core.
    supported_by:
    - reference_id: PMID:25691431
      supporting_text: enzyme in sphingolipid biosynthesis, serine palmitoyltransferase
        (SPT).
- term:
    id: GO:0017059
    label: serine palmitoyltransferase complex
  evidence_type: IDA
  original_reference_id: PMID:25691431
  qualifier: part_of
  review:
    summary: SPTLC1 shown to form stable complexes with ORMDL and the SPT machinery,
      confirming its membership in the serine palmitoyltransferase complex.
    action: ACCEPT
    reason: Core CC annotation supported by direct assay of SPT/ORMDL complexes.
    supported_by:
    - reference_id: PMID:25691431
      supporting_text: ORMDLs and SPT form stable
- term:
    id: GO:0046513
    label: ceramide biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:25691431
  qualifier: acts_upstream_of_or_within
  review:
    summary: SPTLC1/SPT activity controls flux into the de novo pathway that produces
      ceramide; manipulating ORMDL/SPT levels alters cellular ceramide/sphingolipid
      levels.
    action: ACCEPT
    reason: Appropriate acts_upstream_of_or_within relationship for the pathway-entry
      enzyme whose activity determines ceramide output.
    supported_by:
    - reference_id: PMID:25691431
      supporting_text: enzyme in sphingolipid biosynthesis, serine palmitoyltransferase
        (SPT).
- term:
    id: GO:0004758
    label: serine C-palmitoyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:25332431
  qualifier: contributes_to
  review:
    summary: Overexpression of serine palmitoyltransferase (elevating de novo
      sphingolipid biosynthesis) was used to assay SPT-dependent flux, supporting the
      core serine C-palmitoyltransferase activity contributed by SPTLC1.
    action: ACCEPT
    reason: Direct support for the core molecular function within the obligate SPT
      heterodimer (contributes_to).
    supported_by:
    - reference_id: PMID:25332431
      supporting_text: overexpression of serine palmitoyltransferase to elevate de novo
        sphingolipid
- term:
    id: GO:0030148
    label: sphingolipid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:25332431
  qualifier: acts_upstream_of_or_within
  review:
    summary: Elevating SPT activity increases de novo sphingolipid biosynthesis in the
      liver, placing SPTLC1 upstream of/within the sphingolipid biosynthetic process.
    action: ACCEPT
    reason: Core biosynthetic-process annotation; the SPT-catalyzed step is the
      committed entry into de novo sphingolipid synthesis.
    supported_by:
    - reference_id: PMID:25332431
      supporting_text: overexpression of serine palmitoyltransferase to elevate de novo
        sphingolipid
- term:
    id: GO:1904504
    label: positive regulation of lipophagy
  evidence_type: IDA
  original_reference_id: PMID:25332431
  qualifier: acts_upstream_of_or_within
  review:
    summary: In mouse liver, elevating de novo sphingolipid synthesis by SPT
      overexpression induces autophagy, linking SPT activity to lipophagy/autophagy
      induction. This is an indirect, physiology-level consequence of elevated flux.
    action: KEEP_AS_NON_CORE
    reason: A downstream, indirect regulatory effect of excess sphingolipid synthesis
      rather than a direct molecular function of SPTLC1; retained as non-core.
    supported_by:
    - reference_id: PMID:25332431
      supporting_text: overexpression of serine palmitoyltransferase to elevate de novo
        sphingolipid
- term:
    id: GO:0017059
    label: serine palmitoyltransferase complex
  evidence_type: IDA
  original_reference_id: PMID:20182505
  qualifier: part_of
  review:
    summary: SPTLC1 was shown to form a conserved complex with the Orm/ORMDL proteins
      and serine palmitoyltransferase, confirming SPT complex membership.
    action: ACCEPT
    reason: Core CC annotation; SPTLC1 is an obligate subunit of the SPT complex.
    supported_by:
    - reference_id: PMID:20182505
      supporting_text: complex with serine palmitoyltransferase, the first and
        rate-limiting enzyme in
- term:
    id: GO:0004758
    label: serine C-palmitoyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:19416851
  qualifier: enables
  review:
    summary: Direct assay of SPTLC1-containing SPT isozymes demonstrates serine
      C-palmitoyltransferase (EC 2.3.1.50) activity; this UniProt annotation uses the
      enables qualifier for the enzymatic activity of the complex containing SPTLC1.
    action: ACCEPT
    reason: This is the defining, experimentally demonstrated core molecular function of
      the SPT enzyme that SPTLC1 is part of.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: Serine palmitoyltransferase (SPT) catalyzes the first committed
        step in
- term:
    id: GO:0030148
    label: sphingolipid biosynthetic process
  evidence_type: TAS
  original_reference_id: PMID:19416851
  qualifier: involved_in
  review:
    summary: Traceable assertion that SPTLC1/SPT is involved in sphingolipid
      biosynthesis, the pathway whose committed first step it catalyzes.
    action: ACCEPT
    reason: Core biological-process annotation, directly reflecting the enzyme's role.
    supported_by:
    - reference_id: PMID:19416851
      supporting_text: Serine palmitoyltransferase (SPT) catalyzes the first committed
        step in
- term:
    id: GO:0004758
    label: serine C-palmitoyltransferase activity
  evidence_type: TAS
  original_reference_id: PMID:9363775
  qualifier: enables
  review:
    summary: The founding cloning/characterization paper establishes SPT (EC 2.3.1.50)
      as the key enzyme in sphingolipid biosynthesis, catalyzing the PLP-dependent
      condensation of L-serine and palmitoyl-CoA to 3-oxosphinganine.
    action: ACCEPT
    reason: Core molecular-function annotation with an authoritative traceable source.
    supported_by:
    - reference_id: PMID:9363775
      supporting_text: It catalyzes the pyridoxal-5'-phosphate-dependent condensation of
- term:
    id: GO:0006665
    label: sphingolipid metabolic process
  evidence_type: TAS
  original_reference_id: PMID:9363775
  qualifier: involved_in
  review:
    summary: Traceable assertion that SPT is the key enzyme in sphingolipid metabolism.
    action: ACCEPT
    reason: Correct but broad; the specific biosynthetic-process terms are the core BP
      annotations. Retained as supporting general context.
    supported_by:
    - reference_id: PMID:9363775
      supporting_text: is the key enzyme in sphingolipid
core_functions:
- description: Serine C-palmitoyltransferase activity as the catalytic core subunit of
    the serine palmitoyltransferase (SPT) complex, catalyzing the PLP-dependent
    condensation of L-serine and palmitoyl-CoA to 3-ketodihydrosphingosine, the first
    and committed step of de novo sphingolipid biosynthesis.
  supported_by:
  - reference_id: PMID:9363775
    supporting_text: It catalyzes the pyridoxal-5'-phosphate-dependent condensation of
  - reference_id: PMID:19416851
    supporting_text: Serine palmitoyltransferase (SPT) catalyzes the first committed
      step in
  molecular_function:
    id: GO:0004758
    label: serine C-palmitoyltransferase activity
  directly_involved_in:
  - id: GO:0030148
    label: sphingolipid biosynthetic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  in_complex:
    id: GO:0017059
    label: serine palmitoyltransferase complex
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:19416851
  title: Identification of small subunits of mammalian serine palmitoyltransferase
    that confer distinct acyl-CoA substrate specificities.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary experimental identification of the human SPT complex and its
      small subunits; supports the core catalytic-activity and complex annotations for
      SPTLC1.
- id: PMID:20182505
  title: Orm family proteins mediate sphingolipid homeostasis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the Orm/ORMDL-SPT (SPOTS) complex; supports SPTLC1 complex
      membership and ORMDL interaction.
- id: PMID:21618344
  title: Characterization of two mutations in the SPTLC1 subunit of serine palmitoyltransferase
    associated with hereditary sensory and autonomic neuropathy type I.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: HSAN1 SPTLC1 mutant characterization; cited by UniProt for the ER
      membrane subcellular location.
- id: PMID:25332431
  title: Autophagy regulates sphingolipid levels in the liver.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Mouse-liver study; SPT overexpression elevates de novo sphingolipids
      and induces autophagy. Supports flux/biosynthetic-process annotations; the
      lipophagy link is indirect.
- id: PMID:25691431
  title: ORMDL/serine palmitoyltransferase stoichiometry determines effects of ORMDL3
    expression on sphingolipid biosynthesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: SPT/ORMDL stoichiometry and complex formation; supports complex
      membership and serine C-palmitoyltransferase activity annotations.
- id: PMID:30242129
  title: Complex formation of sphingomyelin synthase 1 with glucosylceramide synthase
    increases sphingomyelin and decreases glucosylceramide levels.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: Full text is about SMS1 (SGMS1) and GCS (UGCG); it does not mention
      SPTLC1 or serine palmitoyltransferase. Used to annotate SPTLC1 to sphingomyelin
      biosynthetic process, a downstream terminus not assayed here; the SPTLC1
      annotation is over-annotated/miscited.
- id: PMID:33558761
  title: Structural insights into the regulation of human serine palmitoyltransferase
    complexes.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cryo-EM of the human SPT holocomplex (SPTLC1/SPTLC2/ssSPTa/ORMDL3);
      supports complex membership and catalytic-core role.
- id: PMID:33558762
  title: Structural insights into the assembly and substrate selectivity of human
    SPT-ORMDL3 complex.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cryo-EM showing SPTLC1-SPTLC2 form a dimer of heterodimers as the
      catalytic core; supports complex and MF annotations.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Large-scale endogenous-tagging interactome; detects SPTLC1-SPTLC2
      association. Supports only a bare protein-binding annotation (over-annotated).
- id: PMID:9363775
  title: Human and murine serine-palmitoyl-CoA transferase--cloning, expression and
    characterization of the key enzyme in sphingolipid synthesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Founding cloning/characterization of human/murine SPT (LCB1/LCB2);
      defines the PLP-dependent serine + palmitoyl-CoA condensation reaction.
- id: Reactome:R-HSA-428127
  title: SPTLC complexes transfer acyl-CoA onto serine
  findings: []
- id: file:human/SPTLC1/SPTLC1-uniprot.txt
  title: UniProtKB entry O15269 (SPTC1_HUMAN), Serine palmitoyltransferase 1
  findings: []