O15270 (SPTC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine palmitoyltransferase 2
EC=2.3.1.50

Alternative name(s):
Long chain base biosynthesis protein 2
Short name=LCB 2
Long chain base biosynthesis protein 2a
Short name=LCB2a
Serine-palmitoyl-CoA transferase 2
Short name=SPT 2

Gene names

Name:	SPTLC2
Synonyms:	KIAA0526, LCB2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	562 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 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-SPTLC2-SSSPTB complex displays a preference for C18-CoA substrate. Ref.9 Ref.10
Catalytic activity	Palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2. Ref.9
Cofactor	Pyridoxal phosphate By similarity.
Pathway	Lipid metabolism; sphingolipid metabolism.
Subunit structure	Heterodimer with SPTLC1. Component of the serine palmitoyltransferase (SPT) complex, composed of LCB1/SPTLC1, LCB2 (SPTLC2 or SPTLC3) and ssPT (C14orf147/SSSPTA and C3orf57/SSSPTB).
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein By similarity.
Tissue specificity	Widely expressed. Ref.7
Involvement in disease	Defects in SPTLC2 are the cause of hereditary sensory and autonomic neuropathy type 1C (HSAN1C) [MIM:613640]. It is a form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by prominent sensory abnormalities with a variable degree of motor and autonomic dysfunction. The neurological phenotype is often complicated by severe infections, osteomyelitis, and amputations. HSAN1C symptoms include loss of touch and vibration in the feet, dysesthesia and severe panmodal sensory loss in the upper and lower limbs, distal lower limb sensory loss with ulceration and osteomyelitis, and distal muscle weakness. Ref.10
Sequence similarities	Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
Sequence caution	The sequence BAA25452.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Disease	Disease mutation Neuropathy
Domain	Transmembrane Transmembrane helix
Ligand	Pyridoxal phosphate
Molecular function	Acyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW serine C-palmitoyltransferase complex Inferred from direct assay Ref.9. Source: UniProtKB
Molecular function	pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro serine C-palmitoyltransferase activity Inferred from direct assay Ref.9Ref.10. Source: UniProtKB transferase activity, transferring nitrogenous groups Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 562	562	Serine palmitoyltransferase 2		PRO_0000163858
Regions
	Transmembrane	67 – 87	21	Helical; Potential
Amino acid modifications
	Modified residue	379	1	N6-(pyridoxal phosphate)lysine By similarity
	Modified residue	384	1	Phosphoserine Ref.8
	Modified residue	387	1	Phosphotyrosine Ref.8
Natural variations
	Natural variant	359	1	V → M in HSAN1C; partial loss of normal activity as measured by reduced formation of sphinganine; affects enzymatic affinity resulting in the accumulation of the alternative metabolite 1-deoxy-sphinganine. Ref.10		VAR_064798
	Natural variant	382	1	G → V in HSAN1C; complete loss of normal activity as measured by lack of formation of sphinganine; affects enzymatic affinity resulting in the accumulation of the alternative metabolite 1-deoxy-sphinganine. Ref.10		VAR_064799
	Natural variant	504	1	I → F in HSAN1C; partial loss of normal activity as measured by reduced formation of sphinganine; affects enzymatic affinity resulting in the accumulation of the alternative metabolite 1-deoxy-sphinganine. Ref.10		VAR_064800
Experimental info
	Sequence conflict	61 – 64	4	EAFE → TLAR in AAC50871. Ref.5
	Sequence conflict	436 – 469	34	KECVQ…DSPVV → NGITIHEVVQTRNTYHRFSP LSPVFSHQCLWIML Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O15270 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 0C1AA1E233DE36F1	FASTA	562	62,924
	10 20 30 40 50 60 MRPEPGGCCC RRTVRANGCV ANGEVRNGYV RSSAAAAAAA AAGQIHHVTQ NGGLYKRPFN 70 80 90 100 110 120 EAFEETPMLV AVLTYVGYGV LTLFGYLRDF LRYWRIEKCH HATEREEQKD FVSLYQDFEN 130 140 150 160 170 180 FYTRNLYMRI RDNWNRPICS VPGARVDIME RQSHDYNWSF KYTGNIIKGV INMGSYNYLG 190 200 210 220 230 240 FARNTGSCQE AAAKVLEEYG AGVCSTRQEI GNLDKHEELE ELVARFLGVE AAMAYGMGFA 250 260 270 280 290 300 TNSMNIPALV GKGCLILSDE LNHASLVLGA RLSGATIRIF KHNNMQSLEK LLKDAIVYGQ 310 320 330 340 350 360 PRTRRPWKKI LILVEGIYSM EGSIVRLPEV IALKKKYKAY LYLDEAHSIG ALGPTGRGVV 370 380 390 400 410 420 EYFGLDPEDV DVMMGTFTKS FGASGGYIGG KKELIDYLRT HSHSAVYATS LSPPVVEQII 430 440 450 460 470 480 TSMKCIMGQD GTSLGKECVQ QLAENTRYFR RRLKEMGFII YGNEDSPVVP LMLYMPAKIG 490 500 510 520 530 540 AFGREMLKRN IGVVVVGFPA TPIIESRARF CLSAAHTKEI LDTALKEIDE VGDLLQLKYS 550 560 RHRLVPLLDR PFDETTYEET ED

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: Pancreas.
[2]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed: 9628581] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Lymph.
[5]	"Sphingolipid synthesis: identification and characterization of mammalian cDNAs encoding the Lcb2 subunit of serine palmitoyltransferase." Nagiec M.M., Lester R.L., Dickson R.C. Gene 177:237-241(1996) [PubMed: 8921873] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-470. Tissue: Pancreatic islet.
[6]	"A molecular inventory of human pancreatic islets: sequence analysis of 1000 cDNA clones." Takeda J., Yano H., Eng S., Zeng Y., Bell G.I. Hum. Mol. Genet. 2:1793-1798(1993) [PubMed: 7506601] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-144. Tissue: Pancreatic islet.
[7]	"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.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-384 AND TYR-387, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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.
[10]	"Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I." Rotthier A., Auer-Grumbach M., Janssens K., Baets J., Penno A., Almeida-Souza L., Van Hoof K., Jacobs A., De Vriendt E., Schlotter-Weigel B., Loscher W., Vondracek P., Seeman P., De Jonghe P., Van Dijck P., Jordanova A., Hornemann T., Timmerman V. Am. J. Hum. Genet. 87:513-522(2010) [PubMed: 20920666] [Abstract] Cited for: FUNCTION, VARIANTS HSAN1C MET-359; VAL-382 AND PHE-504, CHARACTERIZATION OF VARIANTS HSAN1C MET-359; VAL-382 AND PHE-504.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y08686 mRNA. Translation: CAA69942.1. AB011098 mRNA. Translation: BAA25452.2. Different initiation. AF111168 Genomic DNA. Translation: AAD09621.1. BC005123 mRNA. Translation: AAH05123.1. U15555 mRNA. Translation: AAC50871.1.
IPI	IPI00005751.
PIR	I38873.
RefSeq	NP_004854.1. NM_004863.3.
UniGene	Hs.435661.
3D structure databases
ProteinModelPortal	O15270.
SMR	O15270. Positions 136-537.
ModBase	Search...
Protein-protein interaction databases
IntAct	O15270. 3 interactions.
STRING	O15270.
PTM databases
PhosphoSite	O15270.
Proteomic databases
PeptideAtlas	O15270.
PRIDE	O15270.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216484; ENSP00000216484; ENSG00000100596.
GeneID	9517.
KEGG	hsa:9517.
NMPDR	fig|9606.3.peg.9944.
UCSC	uc001xub.1. human.
Organism-specific databases
CTD	9517.
GeneCards	GC14M077973.
H-InvDB	HIX0202041.
HGNC	HGNC:11278. SPTLC2.
HPA	HPA027552.
MIM	605713. gene. 613640. phenotype.
neXtProt	NX_O15270.
Orphanet	36386. Hereditary sensory and autonomic neuropathy type 1.
PharmGKB	PA36107.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04428.
GeneTree	ENSGT00550000074678.
HOGENOM	HBG591819.
HOVERGEN	HBG002230.
InParanoid	O15270.
OMA	TGACQEA.
OrthoDB	EOG4WM4TJ.
PhylomeDB	O15270.
Enzyme and pathway databases
BRENDA	2.3.1.50. 2681.
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	O15270.
Bgee	O15270.
CleanEx	HS_SPTLC2.
Genevestigator	O15270.
GermOnline	ENSG00000100596. Homo sapiens.
Family and domain databases
InterPro	IPR001917. Aminotrans_II_pyridoxalP_BS. IPR004839. Aminotransferase_I/II. IPR015424. PyrdxlP-dep_Trfase_major_dom. IPR015421. PyrdxlP-dep_Trfase_major_sub1. IPR015422. PyrdxlP-dep_Trfase_major_sub2. [Graphical view]
Gene3D	G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 1 hit. G3DSA:3.90.1150.10. PyrdxlP-dep_Trfase_major_sub2. 1 hit.
KO	K00654.
Pfam	PF00155. Aminotran_1_2. 1 hit. [Graphical view]
SUPFAM	SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.
PROSITE	PS00599. AA_TRANSFER_CLASS_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00133. L-Serine. DB00114. Pyridoxal Phosphate.
NextBio	35666.
SOURCE	Search...

Entry information

Entry name

SPTC2_HUMAN

Accession

Primary (citable) accession number: O15270
Secondary accession number(s): Q16685

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 1, 1998
Last modified:	January 25, 2012
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.