Reviewed, UniProtKB/Swiss-Prot O15269 (SPTC1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine palmitoyltransferase 1
    EC=2.3.1.50
Alternative name(s):
    Serine-palmitoyl-CoA transferase 1
      Short name=SPT 1
      Short name=SPT1
    Long chain base biosynthesis protein 1
      Short name=LCB 1

Gene names

Name:	SPTLC1
Synonyms:	LCB1

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

General annotation (Comments)

Function	Serine palmitoyltransferase (SPT). The heterodimer formed with LCB2 (SPTLC2 or SPTLC3) constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SSSPTA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SSSPTA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. The SPTLC1-SPTLC2-SSSPTB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SSSPTB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference. Ref.8
Catalytic activity	Palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2. Ref.8
Cofactor	Pyridoxal phosphate By similarity.
Pathway	Lipid metabolism; sphingolipid metabolism.
Subunit structure	Heterodimer; with SPTLC2 or SPTLC3. Component of the serine palmitoyltransferase (SPT) complex, composed of LCB1/SPTLC1, LCB2 (SPTLC2 or SPTLC3) and ssPT (SSSPTA or SSSPTB). Interacts with C14orf147/SSSPTA and C3orf57/SSSPTB; the interaction is direct. Ref.8
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein By similarity.
Tissue specificity	Widely expressed. Not detected in small intestine. Ref.6
Involvement in disease	Defects in SPTLC1 are the cause of hereditary sensory and autonomic neuropathy type 1 (HSAN1) [MIM:162400]. The hereditary sensory and autonomic neuropathies are a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN1 is an autosomal dominant axonal neuropathy 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. Ref.2 Ref.9
Sequence similarities	Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neuropathy
Domain	Transmembrane
Ligand	Pyridoxal phosphate
Molecular function	Acyltransferase Transferase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	sphingolipid biosynthetic process Ref.8 Traceable author statement. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell serine C-palmitoyltransferase complex Ref.8 Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro serine C-palmitoyltransferase activity Ref.1 Ref.8 Inferred from direct assay. Source: UniProtKB transferase activity, transferring nitrogenous groups Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
C20orf24	Q9BUV8	1	EBI-1044323,EBI-1050079
MAGED1	Q9Y5V3	1	EBI-1044323,EBI-716006
RGS20	O76081	1	EBI-1044323,EBI-1052678

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 473	473	Serine palmitoyltransferase 1		PRO_0000163853
Regions
	Transmembrane	16 – 36	21	Potential
Natural variations
	Natural variant	133	1	C → W in HSAN1. Ref.2		VAR_011392
	Natural variant	133	1	C → Y in HSAN1. Ref.2		VAR_011393
	Natural variant	144	1	V → D in HSAN1. Ref.2		VAR_011394
	Natural variant	151	1	R → L: dbSNP rs45461899. Ref.10		VAR_037889
	Natural variant	239	1	R → W in a breast cancer sample; somatic mutation. Ref.11		VAR_036610
	Natural variant	387	1	G → A in HSAN1. Ref.9		VAR_037890

Sequences

	Sequence		Length	Mass (Da)
	O15269-1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: BA9E056A869D2EA2	FASTA	473	52,744
	10 20 30 40 50 60 MATATEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLLF SKTYKLQERS DLTVKEKEEL 70 80 90 100 110 120 IEEWQPEPLV PPVPKDHPAL NYNIVSGPPS HKTVVNGKEC INFASFNFLG LLDNPRVKAA 130 140 150 160 170 180 ALASLKKYGV GTCGPRGFYG TFDVHLDLED RLAKFMKTEE AIIYSYGFAT IASAIPAYSK 190 200 210 220 230 240 RGDIVFVDRA ACFAIQKGLQ ASRSDIKLFK HNDMADLERL LKEQEIEDQK NPRKARVTRR 250 260 270 280 290 300 FIVVEGLYMN TGTICPLPEL VKLKYKYKAR IFLEESLSFG VLGEHGRGVT EHYGINIDDI 310 320 330 340 350 360 DLISANMENA LASIGGFCCG RSFVIDHQRL SGQGYCFSAS LPPLLAAAAI EALNIMEENP 370 380 390 400 410 420 GIFAVLKEKC GQIHKALQGI SGLKVVGESL SPAFHLQLEE STGSREQDVR LLQEIVDQCM 430 440 450 460 470 NRSIALTQAR YLEKEEKCLP PPSIRVVVTV EQTEEELERA ASTIKEVAQA VLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human and murine serine-palmitoyl-CoA transferase. Cloning, expression and characterization of the key enzyme in sphingolipid synthesis." Weiss B., Stoffel W. Eur. J. Biochem. 249:239-247(1997) [PubMed: 9363775] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I." Dawkins J.L., Hulme D.J., Brahmbhatt S.B., Auer-Grumbach M., Nicholson G.A. Nat. Genet. 27:309-312(2001) [PubMed: 11242114] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS HSAN1 TRP-133; TYR-133 AND ASP-144.
[3]	"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: Placenta.
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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]	"Cloning and initial characterization of a new subunit for mammalian serine-palmitoyltransferase." Hornemann T., Richard S., Ruetti M.F., Wei Y., von Eckardstein A. J. Biol. Chem. 281:37275-37281(2006) [PubMed: 17023427] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities." Han G., Gupta S.D., Gable K., Niranjanakumari S., Moitra P., Eichler F., Brown R.H. Jr., Harmon J.M., Dunn T.M. Proc. Natl. Acad. Sci. U.S.A. 106:8186-8191(2009) [PubMed: 19416851] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE SPT COMPLEX, INTERACTION WITH C3ORF57 AND C14ORF147.
[9]	"SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I." Verhoeven K., Coen K., De Vriendt E., Jacobs A., Van Gerwen V., Smouts I., Pou-Serradell A., Martin J.-J., Timmerman V., De Jonghe P. Neurology 62:1001-1002(2004) [PubMed: 15037712] [Abstract] Cited for: VARIANT HSAN1 ALA-387.
[10]	"Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene." Meggouh F., Bienfait H.M.E., Weterman M.A.J., de Visser M., Baas F. Neurology 67:1476-1478(2006) [PubMed: 17060578] [Abstract] Cited for: VARIANT LEU-151.
[11]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] TRP-239.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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, AL391219 Genomic DNA. Translation: CAH69924.1. CH471089 Genomic DNA. Translation: EAW62804.1.
IPI	IPI00005745.
RefSeq	NP_006406.1.
UniGene	Hs.90458
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O15269. 5 interactions.
STRING	O15269.
PTM databases
PhosphoSite	O15269.
Proteomic databases
PeptideAtlas	O15269.
PRIDE	O15269.
Genome annotation databases
Ensembl	ENST00000262554; ENSP00000262554; ENSG00000090054; Homo sapiens. [Genome view]
GeneID	10558.
KEGG	hsa:10558.
UCSC	uc004arl.1. human.
Organism-specific databases
CTD	10558.
GeneCards	GC09M093833.
H-InvDB	HIX0008162.
HGNC	HGNC:11277. SPTLC1.
HPA	CAB018747. HPA010860.
MIM	162400. phenotype. 605712. gene.
Orphanet	36386. Hereditary sensory and autonomic neuropathy, type 1.
PharmGKB	PA36106.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O15269.
OrthoDB	EOG9S1WTB
Enzyme and pathway databases
BRENDA	2.3.1.50. 247.
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	O15269.
Bgee	O15269.
CleanEx	HS_SPTLC1.
Genevestigator	O15269.
GermOnline	ENSG00000090054. Homo sapiens.
Family and domain databases
InterPro	IPR004839. Aminotransferase_I/II. IPR015424. PyrdxlP-dep_Trfase_major. IPR015421. PyrdxlP-dep_Trfase_major_sub1. [Graphical view]
Gene3D	G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 1 hit.
Pfam	PF00155. Aminotran_1_2. 1 hit. [Graphical view]
PROSITE	PS00599. AA_TRANSFER_CLASS_2. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00133. L-Serine. DB00114. Pyridoxal Phosphate.
NextBio	40067.
SOURCE	Search...

Entry information

Entry name

SPTC1_HUMAN

Accession

Primary (citable) accession number: O15269
Secondary accession number(s): A8K681, Q5VWB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 1, 1998
Last modified:	November 24, 2009
This is version 90 of the entry and version 1 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.