UniProtKB - O95470 (SGPL1_HUMAN)
Protein
Sphingosine-1-phosphate lyase 1
Gene
SGPL1
Organism
Homo sapiens (Human)
Status
Functioni
Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis (PubMed:11018465, PubMed:14570870, PubMed:24809814, PubMed:28165339). Required for global lipid homeostasis in liver and cholesterol homeostasis in fibroblasts. Involved in the regulation of pro-inflammatory response and neutrophil trafficking. Modulates neuronal autophagy via phosphoethanolamine production which regulates accumulation of aggregate-prone proteins such as APP (By similarity). Seems to play a role in establishing neuronal contact sites and axonal maintenance (By similarity).By similarity4 Publications
Catalytic activityi
- EC:4.1.2.274 PublicationsThis reaction proceeds in the forward2 Publications direction.
- EC:4.1.2.271 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
pyridoxal 5'-phosphate1 Publication
Kineticsi
- KM=5.2 µM for sphingosine 1-phosphate1 Publication
: sphingolipid metabolism Pathwayi
This protein is involved in the pathway sphingolipid metabolism, which is part of Lipid metabolism.3 PublicationsView all proteins of this organism that are known to be involved in the pathway sphingolipid metabolism and in Lipid metabolism.
GO - Molecular functioni
- carboxy-lyase activity Source: InterPro
- pyridoxal phosphate binding Source: InterPro
- sphinganine-1-phosphate aldolase activity Source: UniProtKB
GO - Biological processi
- ameboidal-type cell migration Source: GO_Central
- androgen metabolic process Source: Ensembl
- apoptotic signaling pathway Source: UniProtKB
- ceramide metabolic process Source: UniProtKB
- estrogen metabolic process Source: Ensembl
- face morphogenesis Source: Ensembl
- fatty acid metabolic process Source: UniProtKB
- fibroblast migration Source: Ensembl
- hemopoiesis Source: Ensembl
- kidney development Source: Ensembl
- Leydig cell differentiation Source: Ensembl
- luteinization Source: Ensembl
- platelet-derived growth factor receptor signaling pathway Source: Ensembl
- post-embryonic development Source: Ensembl
- regulation of multicellular organism growth Source: Ensembl
- roof of mouth development Source: Ensembl
- skeletal system morphogenesis Source: Ensembl
- spermatogenesis Source: Ensembl
- sphingolipid biosynthetic process Source: Reactome
- sphingolipid catabolic process Source: UniProtKB
- vasculogenesis Source: Ensembl
Keywordsi
Molecular function | Lyase |
Biological process | Apoptosis, Lipid metabolism, Sphingolipid metabolism |
Ligand | Pyridoxal phosphate |
Enzyme and pathway databases
BRENDAi | 4.1.2.27, 2681 |
PathwayCommonsi | O95470 |
Reactomei | R-HSA-1660661, Sphingolipid de novo biosynthesis |
UniPathwayi | UPA00222 |
Chemistry databases
SwissLipidsi | SLP:000000107 |
Names & Taxonomyi
Protein namesi | Recommended name: Sphingosine-1-phosphate lyase 1Curated (EC:4.1.2.274 Publications)Short name: S1PLCurated Short name: SP-lyase 1Curated Short name: SPL 1Curated Short name: hSPL Alternative name(s): Sphingosine-1-phosphate aldolase |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10817, SGPL1 |
MIMi | 603729, gene |
neXtProti | NX_O95470 |
VEuPathDBi | HostDB:ENSG00000166224.16 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Single-pass type III membrane protein Sequence analysis; Cytoplasmic side By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: Reactome
- integral component of endoplasmic reticulum membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 40 | LumenalSequence analysisAdd BLAST | 40 | |
Transmembranei | 41 – 61 | Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 62 – 568 | CytoplasmicSequence analysisAdd BLAST | 507 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Involvement in diseasei
Nephrotic syndrome 14 (NPHS14)4 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. NPHS14 is an autosomal recessive syndromic, steroid-resistant form that progresses to end-stage renal failure. Some NPHS14 patients manifest ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079213 | 222 | R → Q in NPHS14; probable disease-associated variant also found in a patient with isolated primary adrenal insufficiency; decreased protein abundance; increased aggregation; decreased sphinganine-1-phosphate aldolase activity. 3 PublicationsCorresponds to variant dbSNP:rs769259446EnsemblClinVar. | 1 | |
Natural variantiVAR_079214 | 222 | R → W in NPHS14. 1 PublicationCorresponds to variant dbSNP:rs1131692255EnsemblClinVar. | 1 | |
Natural variantiVAR_081455 | 340 | R → W in NPHS14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1437439236Ensembl. | 1 | |
Natural variantiVAR_079216 | 416 | Y → C in NPHS14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs779485098Ensembl. | 1 | |
Natural variantiVAR_079217 | 505 – 568 | Missing in NPHS14. 1 PublicationAdd BLAST | 64 | |
Natural variantiVAR_079218 | 545 | Missing in NPHS14; decreased protein abundance. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 132 | E → G: No effect on the sphinganine-1-phosphate aldolase activity; no effect on protein abundance. 1 Publication | 1 | |
Mutagenesisi | 218 | C → G: Loss of sphinganine-1-phosphate aldolase activity. 1 Publication | 1 | |
Mutagenesisi | 317 | C → S: Almost no sphinganine-1-phosphate aldolase activity. 1 Publication | 1 | |
Mutagenesisi | 353 | K → L: Loss of sphinganine-1-phosphate aldolase activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 8879 |
GeneReviewsi | SGPL1 |
MalaCardsi | SGPL1 |
MIMi | 617575, phenotype |
OpenTargetsi | ENSG00000166224 |
Orphaneti | 506334, Familial steroid-resistant nephrotic syndrome with adrenal insufficiency |
PharmGKBi | PA35725 |
Miscellaneous databases
Pharosi | O95470, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3286061 |
DrugBanki | DB00114, Pyridoxal phosphate |
DrugCentrali | O95470 |
GuidetoPHARMACOLOGYi | 2522 |
Genetic variation databases
BioMutai | SGPL1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000147012 | 1 – 568 | Sphingosine-1-phosphate lyase 1Add BLAST | 568 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 353 | N6-(pyridoxal phosphate)lysine; alternate | 1 | |
Modified residuei | 353 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 356 | 3'-nitrotyrosineCombined sources | 1 | |
Modified residuei | 366 | 3'-nitrotyrosineCombined sources | 1 | |
Modified residuei | 564 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, Nitration, PhosphoproteinProteomic databases
EPDi | O95470 |
jPOSTi | O95470 |
MassIVEi | O95470 |
MaxQBi | O95470 |
PaxDbi | O95470 |
PeptideAtlasi | O95470 |
PRIDEi | O95470 |
ProteomicsDBi | 50902 |
PTM databases
iPTMneti | O95470 |
MetOSitei | O95470 |
PhosphoSitePlusi | O95470 |
SwissPalmi | O95470 |
Expressioni
Tissue specificityi
Ubiquitously expressed (PubMed:11018465, PubMed:28165343). Expressed in fetal and adult adrenal gland (at protein level) (PubMed:28165343).2 Publications
Gene expression databases
Bgeei | ENSG00000166224, Expressed in esophagus squamous epithelium and 226 other tissues |
ExpressionAtlasi | O95470, baseline and differential |
Genevisiblei | O95470, HS |
Organism-specific databases
HPAi | ENSG00000166224, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer.
1 PublicationBinary interactionsi
Hide detailsO95470
Protein-protein interaction databases
BioGRIDi | 114398, 126 interactors |
IntActi | O95470, 78 interactors |
MINTi | O95470 |
STRINGi | 9606.ENSP00000362298 |
Chemistry databases
BindingDBi | O95470 |
Miscellaneous databases
RNActi | O95470, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O95470 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1383, Eukaryota |
GeneTreei | ENSGT00390000000046 |
HOGENOMi | CLU_028929_1_1_1 |
InParanoidi | O95470 |
OMAi | DPHKMGL |
OrthoDBi | 517323at2759 |
PhylomeDBi | O95470 |
TreeFami | TF300777 |
Family and domain databases
Gene3Di | 3.40.640.10, 1 hit 3.90.1150.10, 2 hits |
InterProi | View protein in InterPro IPR002129, PyrdxlP-dep_de-COase IPR015424, PyrdxlP-dep_Trfase IPR015422, PyrdxlP-dep_Trfase_dom1 IPR015421, PyrdxlP-dep_Trfase_major |
Pfami | View protein in Pfam PF00282, Pyridoxal_deC, 1 hit |
SUPFAMi | SSF53383, SSF53383, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
O95470-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPSTDLLMLK AFEPYLEILE VYSTKAKNYV NGHCTKYEPW QLIAWSVVWT
60 70 80 90 100
LLIVWGYEFV FQPESLWSRF KKKCFKLTRK MPIIGRKIQD KLNKTKDDIS
110 120 130 140 150
KNMSFLKVDK EYVKALPSQG LSSSAVLEKL KEYSSMDAFW QEGRASGTVY
160 170 180 190 200
SGEEKLTELL VKAYGDFAWS NPLHPDIFPG LRKIEAEIVR IACSLFNGGP
210 220 230 240 250
DSCGCVTSGG TESILMACKA YRDLAFEKGI KTPEIVAPQS AHAAFNKAAS
260 270 280 290 300
YFGMKIVRVP LTKMMEVDVR AMRRAISRNT AMLVCSTPQF PHGVIDPVPE
310 320 330 340 350
VAKLAVKYKI PLHVDACLGG FLIVFMEKAG YPLEHPFDFR VKGVTSISAD
360 370 380 390 400
THKYGYAPKG SSLVLYSDKK YRNYQFFVDT DWQGGIYASP TIAGSRPGGI
410 420 430 440 450
SAACWAALMH FGENGYVEAT KQIIKTARFL KSELENIKGI FVFGNPQLSV
460 470 480 490 500
IALGSRDFDI YRLSNLMTAK GWNLNQLQFP PSIHFCITLL HARKRVAIQF
510 520 530 540 550
LKDIRESVTQ IMKNPKAKTT GMGAIYGMAQ TTVDRNMVAE LSSVFLDSLY
560
STDTVTQGSQ MNGSPKPH
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH7BXL7 | H7BXL7_HUMAN | Sphingosine-1-phosphate lyase 1 | SGPL1 | 202 | Annotation score: | ||
H0Y3V8 | H0Y3V8_HUMAN | Sphingosine-1-phosphate lyase 1 | SGPL1 | 135 | Annotation score: |
Sequence cautioni
The sequence BAA86566 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 404 | C → A in CAA09590 (PubMed:11018465).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048875 | 21 | V → L1 PublicationCorresponds to variant dbSNP:rs12770335Ensembl. | 1 | |
Natural variantiVAR_081454 | 184 | I → T Probable disease-associated variant found in patients with atypical form of axonal peripheral neuropathy, characterized by acute or subacute onset and episodes of recurrent mononeuropathy. 1 PublicationCorresponds to variant dbSNP:rs201533115Ensembl. | 1 | |
Natural variantiVAR_079213 | 222 | R → Q in NPHS14; probable disease-associated variant also found in a patient with isolated primary adrenal insufficiency; decreased protein abundance; increased aggregation; decreased sphinganine-1-phosphate aldolase activity. 3 PublicationsCorresponds to variant dbSNP:rs769259446EnsemblClinVar. | 1 | |
Natural variantiVAR_079214 | 222 | R → W in NPHS14. 1 PublicationCorresponds to variant dbSNP:rs1131692255EnsemblClinVar. | 1 | |
Natural variantiVAR_081455 | 340 | R → W in NPHS14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1437439236Ensembl. | 1 | |
Natural variantiVAR_079215 | 346 | S → I in NPHS1; decreased protein abundance in cells of patients homozygous for the mutation; increased aggregation; decreased sphinganine-1-phosphate aldolase activity. 1 PublicationCorresponds to variant dbSNP:rs1131692256EnsemblClinVar. | 1 | |
Natural variantiVAR_081456 | 361 – 568 | Missing Probable disease-associated variant found in patients with atypical form of axonal peripheral neuropathy, characterized by acute or subacute onset and episodes of recurrent mononeuropathy. 1 PublicationAdd BLAST | 208 | |
Natural variantiVAR_079216 | 416 | Y → C in NPHS14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs779485098Ensembl. | 1 | |
Natural variantiVAR_079217 | 505 – 568 | Missing in NPHS14. 1 PublicationAdd BLAST | 64 | |
Natural variantiVAR_079218 | 545 | Missing in NPHS14; decreased protein abundance. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ011304 mRNA Translation: CAA09590.2 AF144638 mRNA Translation: AAD44755.1 AB033078 mRNA Translation: BAA86566.1 Different initiation. AK314615 mRNA Translation: BAG37181.1 CH471083 Genomic DNA Translation: EAW54414.1 BC052991 mRNA Translation: AAH52991.1 |
CCDSi | CCDS31216.1 |
RefSeqi | NP_003892.2, NM_003901.3 XP_005270320.1, XM_005270263.1 XP_011538618.1, XM_011540316.2 XP_011538619.1, XM_011540317.1 |
Genome annotation databases
Ensembli | ENST00000373202; ENSP00000362298; ENSG00000166224 |
GeneIDi | 8879 |
KEGGi | hsa:8879 |
UCSCi | uc001jrm.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ011304 mRNA Translation: CAA09590.2 AF144638 mRNA Translation: AAD44755.1 AB033078 mRNA Translation: BAA86566.1 Different initiation. AK314615 mRNA Translation: BAG37181.1 CH471083 Genomic DNA Translation: EAW54414.1 BC052991 mRNA Translation: AAH52991.1 |
CCDSi | CCDS31216.1 |
RefSeqi | NP_003892.2, NM_003901.3 XP_005270320.1, XM_005270263.1 XP_011538618.1, XM_011540316.2 XP_011538619.1, XM_011540317.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4Q6R | X-ray | 2.40 | A/B | 62-568 | [»] | |
SMRi | O95470 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114398, 126 interactors |
IntActi | O95470, 78 interactors |
MINTi | O95470 |
STRINGi | 9606.ENSP00000362298 |
Chemistry databases
BindingDBi | O95470 |
ChEMBLi | CHEMBL3286061 |
DrugBanki | DB00114, Pyridoxal phosphate |
DrugCentrali | O95470 |
GuidetoPHARMACOLOGYi | 2522 |
SwissLipidsi | SLP:000000107 |
PTM databases
iPTMneti | O95470 |
MetOSitei | O95470 |
PhosphoSitePlusi | O95470 |
SwissPalmi | O95470 |
Genetic variation databases
BioMutai | SGPL1 |
Proteomic databases
EPDi | O95470 |
jPOSTi | O95470 |
MassIVEi | O95470 |
MaxQBi | O95470 |
PaxDbi | O95470 |
PeptideAtlasi | O95470 |
PRIDEi | O95470 |
ProteomicsDBi | 50902 |
Protocols and materials databases
Antibodypediai | 14941, 175 antibodies |
Genome annotation databases
Ensembli | ENST00000373202; ENSP00000362298; ENSG00000166224 |
GeneIDi | 8879 |
KEGGi | hsa:8879 |
UCSCi | uc001jrm.4, human |
Organism-specific databases
CTDi | 8879 |
DisGeNETi | 8879 |
GeneCardsi | SGPL1 |
GeneReviewsi | SGPL1 |
HGNCi | HGNC:10817, SGPL1 |
HPAi | ENSG00000166224, Low tissue specificity |
MalaCardsi | SGPL1 |
MIMi | 603729, gene 617575, phenotype |
neXtProti | NX_O95470 |
OpenTargetsi | ENSG00000166224 |
Orphaneti | 506334, Familial steroid-resistant nephrotic syndrome with adrenal insufficiency |
PharmGKBi | PA35725 |
VEuPathDBi | HostDB:ENSG00000166224.16 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1383, Eukaryota |
GeneTreei | ENSGT00390000000046 |
HOGENOMi | CLU_028929_1_1_1 |
InParanoidi | O95470 |
OMAi | DPHKMGL |
OrthoDBi | 517323at2759 |
PhylomeDBi | O95470 |
TreeFami | TF300777 |
Enzyme and pathway databases
UniPathwayi | UPA00222 |
BRENDAi | 4.1.2.27, 2681 |
PathwayCommonsi | O95470 |
Reactomei | R-HSA-1660661, Sphingolipid de novo biosynthesis |
Miscellaneous databases
BioGRID-ORCSi | 8879, 7 hits in 994 CRISPR screens |
ChiTaRSi | SGPL1, human |
GeneWikii | SGPL1 |
GenomeRNAii | 8879 |
Pharosi | O95470, Tchem |
PROi | PR:O95470 |
RNActi | O95470, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000166224, Expressed in esophagus squamous epithelium and 226 other tissues |
ExpressionAtlasi | O95470, baseline and differential |
Genevisiblei | O95470, HS |
Family and domain databases
Gene3Di | 3.40.640.10, 1 hit 3.90.1150.10, 2 hits |
InterProi | View protein in InterPro IPR002129, PyrdxlP-dep_de-COase IPR015424, PyrdxlP-dep_Trfase IPR015422, PyrdxlP-dep_Trfase_dom1 IPR015421, PyrdxlP-dep_Trfase_major |
Pfami | View protein in Pfam PF00282, Pyridoxal_deC, 1 hit |
SUPFAMi | SSF53383, SSF53383, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SGPL1_HUMAN | |
Accessioni | O95470Primary (citable) accession number: O95470 Secondary accession number(s): B2RBD4 Q9UN89 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 24, 2003 |
Last sequence update: | October 24, 2003 | |
Last modified: | April 7, 2021 | |
This is version 178 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families