P40015 (ISC1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inositol phosphosphingolipids phospholipase C
Short name=IPS phospholipase C
Short name=IPS-PLC
EC=3.1.4.-

Alternative name(s):
Neutral sphingomyelinase
Short name=N-SMase
Short name=nSMase

Gene names

Name:	ISC1
Ordered Locus Names:	YER019W

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	477 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Responsible for the hydrolysis of the phosphosphingolipids (IPS), inositol phosphorylceramide (IPC), mannosylinositol phosphorylceramide (MIPC), and mannosyldiinositol phosphorylceramide (M(IP)2C). Also active on sphingomyelin, but this activity is probably not physiologically relevant.
Cofactor	Magnesium.
Pathway	Lipid metabolism; sphingolipid metabolism.
Subcellular location	Membrane; Multi-pass membrane protein.
Miscellaneous	Present with 2170 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the neutral sphingomyelinase family.

Ontologies

Keywords
Biological process	Lipid metabolism Sphingolipid metabolism
Cellular component	Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ceramide biosynthetic process Inferred from mutant phenotype PubMed 17880915. Source: SGD response to salt stress Inferred from mutant phenotype PubMed 12180980. Source: SGD sphingolipid catabolic process Inferred from direct assay Ref.3. Source: SGD
Cellular_component	endoplasmic reticulum Inferred from direct assay PubMed 14699160. Source: SGD integral to mitochondrial outer membrane Inferred from direct assay PubMed 17880915. Source: SGD
Molecular_function	inositol phosphosphingolipid phospholipase activity Inferred from direct assay Ref.3. Source: SGD metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AGP1	P25376	1	EBI-9371,EBI-2357
PMP2	P40975	1	EBI-9371,EBI-2043041

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 477	477	Inositol phosphosphingolipids phospholipase C		PRO_0000075695
Regions
	Topological domain	1 – 398	398	Cytoplasmic Potential
	Transmembrane	399 – 417	19	Helical; Potential
	Topological domain	418 – 424	7	Extracellular Potential
	Transmembrane	425 – 449	25	Helical; Potential
	Topological domain	450 – 477	28	Cytoplasmic Potential
Sites
	Active site	334	1	Proton acceptor By similarity
	Metal binding	100	1	Magnesium By similarity
	Site	233	1	Important for substrate recognition By similarity

Sequences

	Sequence		Length	Mass (Da)
	P40015 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 0670FD303FEB8EFF	FASTA	477	53,940
	10 20 30 40 50 60 MYNRKDRDVH ERKEDGQSEF EALNGTNAIM SDNSKAYSIK FLTFNTWGLK YVSKHRKERL 70 80 90 100 110 120 RAIADKLAGH SMLTPISDEL LPNGGDSNEN EDYDVIALQE IWCVEDWKYL ASACASKYPY 130 140 150 160 170 180 QRLFHSGILT GPGLAILSKV PIESTFLYRF PINGRPSAVF RGDWYVGKSI AITVLNTGTR 190 200 210 220 230 240 PIAIMNSHMH APYAKQGDAA YLCHRSCQAW DFSRLIKLYR QAGYAVIVVG DLNSRPGSLP 250 260 270 280 290 300 HKFLTQEAGL VDSWEQLHGK QDLAVIARLS PLQQLLKGCT TCDSLLNTWR AQRQPDEACR 310 320 330 340 350 360 LDYALIDPDF LQTVDAGVRF TERIPHLDCS VSDHFAYSCT LNIVPQGTES RPSTSVKRAK 370 380 390 400 410 420 THDRELILQR YSNYETMIEC IHTYLKTAQR QKFFRGLHFW ASILLLIASL VVTTFTANKA 430 440 450 460 470 GWSSIFWVLF AIAVSISGTI DGAISFLFGR SEIRALIEVE QEVLDAEHHL QTFLSEK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome V." Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E., Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S., Hyman R.W. , Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X., Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y., Botstein D., Davis R.W. Nature 387:78-81(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[3]	"Identification of ISC1 (YER019w) as inositol phosphosphingolipid phospholipase C in Saccharomyces cerevisiae." Sawai H., Okamoto Y., Luberto C., Mao C., Bielawska A., Domae N., Hannun Y.A. J. Biol. Chem. 275:39793-39798(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[4]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[5]	"A global topology map of the Saccharomyces cerevisiae membrane proteome." Kim H., Melen K., Oesterberg M., von Heijne G. Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY [LARGE SCALE ANALYSIS]. Strain: ATCC 208353 / W303-1A.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U18778 Genomic DNA. Translation: AAB64552.1. BK006939 Genomic DNA. Translation: DAA07671.1.
PIR	S50477.
RefSeq	NP_010935.1. NM_001178910.1.
3D structure databases
ProteinModelPortal	P40015.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-5002N.
IntAct	P40015. 3 interactions.
MINT	MINT-486977.
STRING	4932.YER019W.
Proteomic databases
PaxDb	P40015.
PeptideAtlas	P40015.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YER019W; YER019W; YER019W.
GeneID	856739.
KEGG	sce:YER019W.
Organism-specific databases
CYGD	YER019w.
SGD	S000000821. ISC1.
Phylogenomic databases
eggNOG	NOG269293.
GeneTree	ENSGT00390000009166.
HOGENOM	HOG000215232.
KO	K01128.
OMA	NSHMHAP.
OrthoDB	EOG44XNRN.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-17704.
UniPathway	UPA00222.
Gene expression databases
Genevestigator	P40015.
GermOnline	YER019W. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR005135. Endo/exonuclease/phosphatase. [Graphical view]
Pfam	PF03372. Exo_endo_phos. 1 hit. [Graphical view]
SUPFAM	SSF56219. Exo_endo_phos. 1 hit.
ProtoNet	Search...
Other
NextBio	982867.

Entry information

Entry name

ISC1_YEAST

Accession

Primary (citable) accession number: P40015
Secondary accession number(s): D3DLR7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	April 3, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program