Reviewed, UniProtKB/Swiss-Prot O95470 (SGPL1_HUMAN)

Names and origin

Protein names

Recommended name:
    Sphingosine-1-phosphate lyase 1
      Short name=SP-lyase
      Short name=hSPL
    EC=4.1.2.27
Alternative name(s):
    Sphingosine-1-phosphate aldolase

Gene names

Name:	SGPL1
Synonyms:	KIAA1252

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	568 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis. Ref.2
Catalytic activity	Sphinganine 1-phosphate = phosphoethanolamine + palmitaldehyde.
Cofactor	Pyridoxal phosphate By similarity.
Pathway	Lipid metabolism; sphingolipid metabolism.
Subcellular location	Endoplasmic reticulum membrane; Single-pass type III membrane protein.
Tissue specificity	Found in liver and kidney.
Sequence similarities	Belongs to the group II decarboxylase family. Sphingosine-1-phosphate lyase subfamily.

Ontologies

Keywords
Biological process	Apoptosis Lipid metabolism
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane
Ligand	Pyridoxal phosphate
Molecular function	Lyase
PTM	Acetylation Nitration Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Ref.2 Inferred from direct assay. Source: UniProtKB carboxylic acid metabolic process Inferred from electronic annotation. Source: InterPro ceramide metabolic process Ref.2 Inferred from direct assay. Source: UniProtKB sphingolipid catabolic process Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	integral to endoplasmic reticulum membrane Ref.1 Non-traceable author statement. Source: UniProtKB
Molecular function	carboxy-lyase activity Inferred from electronic annotation. Source: InterPro pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro sphinganine-1-phosphate aldolase activity Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 568	568	Sphingosine-1-phosphate lyase 1		PRO_0000147012
Regions
	Topological domain	1 – 40	40	Lumenal Potential
	Transmembrane	41 – 61	21	Signal-anchor for type III membrane protein Potential
	Topological domain	62 – 568	507	Cytoplasmic Potential
Amino acid modifications
	Modified residue	353	1	N6-(pyridoxal phosphate)lysine By similarity
	Modified residue	353	1	N6-acetyllysine Ref.10
	Modified residue	356	1	Nitrated tyrosine
	Modified residue	366	1	Nitrated tyrosine
	Modified residue	468	1	Phosphothreonine Ref.8
Natural variations
	Natural variant	21	1	V → L: dbSNP rs12770335.		VAR_048875
Experimental info
	Mutagenesis	218	1	C → G: Loss of activity. Ref.1
	Mutagenesis	317	1	C → S: Almost no activity. Ref.1
	Mutagenesis	353	1	K → L: Loss of activity. Ref.2
	Sequence conflict	404	1	C → A in CAA09590. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O95470-1 [UniParc]. Last modified October 24, 2003. Version 3. Checksum: 3B16FDEFC4B2FDB6	FASTA	568	63,524
	10 20 30 40 50 60 MPSTDLLMLK AFEPYLEILE VYSTKAKNYV NGHCTKYEPW QLIAWSVVWT LLIVWGYEFV 70 80 90 100 110 120 FQPESLWSRF KKKCFKLTRK MPIIGRKIQD KLNKTKDDIS KNMSFLKVDK EYVKALPSQG 130 140 150 160 170 180 LSSSAVLEKL KEYSSMDAFW QEGRASGTVY SGEEKLTELL VKAYGDFAWS NPLHPDIFPG 190 200 210 220 230 240 LRKIEAEIVR IACSLFNGGP DSCGCVTSGG TESILMACKA YRDLAFEKGI KTPEIVAPQS 250 260 270 280 290 300 AHAAFNKAAS YFGMKIVRVP LTKMMEVDVR AMRRAISRNT AMLVCSTPQF PHGVIDPVPE 310 320 330 340 350 360 VAKLAVKYKI PLHVDACLGG FLIVFMEKAG YPLEHPFDFR VKGVTSISAD THKYGYAPKG 370 380 390 400 410 420 SSLVLYSDKK YRNYQFFVDT DWQGGIYASP TIAGSRPGGI SAACWAALMH FGENGYVEAT 430 440 450 460 470 480 KQIIKTARFL KSELENIKGI FVFGNPQLSV IALGSRDFDI YRLSNLMTAK GWNLNQLQFP 490 500 510 520 530 540 PSIHFCITLL HARKRVAIQF LKDIRESVTQ IMKNPKAKTT GMGAIYGMAQ TTVDRNMVAE 550 560 LSSVFLDSLY STDTVTQGSQ MNGSPKPH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human sphingosine-1-phosphate lyase: cDNA cloning, functional expression studies and mapping to chromosome 10q22." Van Veldhoven P.P., Gijsbers S., Mannaerts G.P., Vermeesch J.R., Brys V. Biochim. Biophys. Acta 1487:128-134(2000) [PubMed: 11018465] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, MUTAGENESIS OF CYS-218 AND CYS-317.
[2]	"Sphingosine-phosphate lyase enhances stress-induced ceramide generation and apoptosis." Reiss U., Oskouian B., Zhou J., Gupta V., Sooriyakumaran P., Kelly S., Wang E., Merrill A.H. Jr., Saba J.D. J. Biol. Chem. 279:1281-1290(2004) [PubMed: 14570870] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF LYS-353.
[3]	"Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O. DNA Res. 6:337-345(1999) [PubMed: 10574462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[7]	"Nitroproteins from a human pituitary adenoma tissue discovered with a nitrotyrosine affinity column and tandem mass spectrometry." Zhan X., Desiderio D.M. Anal. Biochem. 354:279-289(2006) [PubMed: 16777052] [Abstract] Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-356 AND TYR-366, MASS SPECTROMETRY. Tissue: Pituitary adenoma.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-468, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-353, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00099463.
RefSeq	NP_003892.2.
UniGene	Hs.499984
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O95470. 1 interaction.
STRING	O95470.
Proteomic databases
PeptideAtlas	O95470.
PRIDE	O95470.
Genome annotation databases
Ensembl	ENST00000299297; ENSP00000299297; ENSG00000166224; Homo sapiens. [Genome view] ENST00000373202; ENSP00000362298; ENSG00000166224; Homo sapiens. [Genome view] ENST00000409118; ENSP00000386549; ENSG00000166224; Homo sapiens. [Genome view] ENST00000419379; ENSP00000403911; ENSG00000166224; Homo sapiens. [Genome view]
GeneID	8879.
KEGG	hsa:8879.
UCSC	uc001jrm.1. human.
Organism-specific databases
CTD	8879.
GeneCards	GC10P072245.
H-InvDB	HIX0018350.
HGNC	HGNC:10817. SGPL1.
HPA	HPA021125. HPA023086.
MIM	603729. gene.
PharmGKB	PA35725.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95470.
HOVERGEN	O95470.
OMA	IIAACWA.
Enzyme and pathway databases
BRENDA	4.1.2.27. 247.
Pathway_Interaction_DB	s1p_meta_pathway. Sphingosine 1-phosphate (S1P) pathway.
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	O95470.
Bgee	O95470.
CleanEx	HS_SGPL1.
Genevestigator	O95470.
GermOnline	ENSG00000166224. Homo sapiens.
Family and domain databases
InterPro	IPR002129. PyrdxlP-dep_de-COase. IPR015421. PyrdxlP-dep_Trfase_major_sub1. [Graphical view]
Gene3D	G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 1 hit.
PANTHER	PTHR11999. Pyridoxal_deC. 1 hit.
Pfam	PF00282. Pyridoxal_deC. 1 hit. [Graphical view]
PROSITE	PS00392. DDC_GAD_HDC_YDC. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00114. Pyridoxal Phosphate.
NextBio	33339.
SOURCE	Search...

Entry information

Entry name

SGPL1_HUMAN

Accession

Primary (citable) accession number: O95470
Secondary accession number(s): B2RBD4 , Q7Z732, Q9ULG8, Q9UN89

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2003
Last sequence update:	October 24, 2003
Last modified:	November 3, 2009
This is version 75 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.