UniProt UniProt http://www.uniprot.org Mock publication and experiment for abstract interactions that are not interaction evidences. Mock publication and experiment for abstract interactions that are not interaction evidences. unspecified method Structural insights into the regulation of human serine palmitoyltransferase complexes. Structural insights into the regulation of human serine palmitoyltransferase complexes. Nature structural & molecular biology 2021 imex curation Wang Y., Niu Y., Zhang Z., Gable K., Gupta SD., Somashekarappa N., Han G., Zhao H., Myasnikov AG., Kalathur RC., Dunn TM., Lee CH. ChiaHsueh.Lee@stjude.org Only protein-protein interactions imex curation in vitro In vitro enzymatic study enzymatic study predetermined predetermined participant predetermined Wang Y., Niu Y., Zhang Z., Gable K., Gupta SD., Somashekarappa N., Han G., Zhao H., Myasnikov AG., Kalathur RC., Dunn TM., Lee CH. ChiaHsueh.Lee@stjude.org Accepted 2021-JUN-01 AT 17:18 BST AT 17:18 BST by KALPANAP Nature structural & molecular biology 2021 Only protein-protein interactions imex curation imex curation Structural insights into the regulation of human serine palmitoyltransferase complexes. Structural insights into the regulation of human serine palmitoyltransferase complexes. Nature structural & molecular biology 2021 imex curation Wang Y., Niu Y., Zhang Z., Gable K., Gupta SD., Somashekarappa N., Han G., Zhao H., Myasnikov AG., Kalathur RC., Dunn TM., Lee CH. ChiaHsueh.Lee@stjude.org Only protein-protein interactions imex curation human-293s_gnti HEK293S GnTI -adenovirus 5 transformed, glycosylation deficient Human 293s_gnti HEK293S GnTI -adenovirus 5 transformed, glycosylation deficient ATCC® CRL-3022 3d-em 3D electron microscopy 3D-EM electron tomog structure determination identification by structure determination identification by structure determination structure determination Wang Y., Niu Y., Zhang Z., Gable K., Gupta SD., Somashekarappa N., Han G., Zhao H., Myasnikov AG., Kalathur RC., Dunn TM., Lee CH. ChiaHsueh.Lee@stjude.org Accepted 2021-JUN-01 AT 17:18 BST AT 17:18 BST by KALPANAP Nature structural & molecular biology 2021 Only protein-protein interactions imex curation imex curation sptc1_human Serine palmitoyltransferase 1 Serine-palmitoyl-CoA transferase 1 Long chain base biosynthesis protein 1 SPTLC1 LCB1 protein protein human Homo sapiens Human MATATEQWVLVEMVQALYEAPAYHLILEGILILWIIRLLFSKTYKLQERSDLTVKEKEELIEEWQPEPLVPPVPKDHPALNYNIVSGPPSHKTVVNGKECINFASFNFLGLLDNPRVKAAALASLKKYGVGTCGPRGFYGTFDVHLDLEDRLAKFMKTEEAIIYSYGFATIASAIPAYSKRGDIVFVDRAACFAIQKGLQASRSDIKLFKHNDMADLERLLKEQEIEDQKNPRKARVTRRFIVVEGLYMNTGTICPLPELVKLKYKYKARIFLEESLSFGVLGEHGRGVTEHYGINIDDIDLISANMENALASIGGFCCGRSFVIDHQRLSGQGYCFSASLPPLLAAAAIEALNIMEENPGIFAVLKEKCGQIHKALQGISGLKVVGESLSPAFHLQLEESTGSREQDVRLLQEIVDQCMNRSIALTQARYLEKEEKCLPPPSIRVVVTVEQTEEELERAASTIKEVAQAVLL DIP protein O15269 original sequence version: 130 DIP protein O15269 original sequence version: 92 DIP protein O15269 original sequence version: 146 BA9E056A869D2EA2 myriocin myriocin antibiotic ISP-I Thermozymocidin (2S,3R,4R,6E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoicos-6-enoic acid small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) l-serine L-serine (2S)-2-amino-3-hydroxypropanoic acid (S)-(-)-serine (S)-2-amino-3-hydroxypropanoic acid (S)-alpha-Amino-beta-hydroxypropionic acid (S)-serine beta-Hydroxy-L-alanine beta-Hydroxyalanine L-(-)-serine L-2-Amino-3-hydroxypropionic acid L-3-Hydroxy-2-aminopropionic acid L-3-Hydroxy-alanine L-Ser L-Serin L-Serine S Ser SERINE Serine L-serine small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) palmitoyl-coa palmitoyl-CoA small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) sptsa_human Serine palmitoyltransferase small subunit A SPTSSA C14orf147 SSSPTA Small subunit of serine palmitoyltransferase A protein protein human Homo sapiens Human MAGMALARAWKQMSWFYYQYLLVTALYMLEPWERTVFNSMLVSIVGMALYTGYVFMPQHIMAILHYFEIVQ DIP protein Q969W0 original sequence version: 82 ED4F188040EE703C sptc2_human Serine palmitoyltransferase 2 Serine-palmitoyl-CoA transferase 2 Long chain base biosynthesis protein 2 SPTLC2 KIAA0526 LCB2 Long chain base biosynthesis protein 2a protein protein human Homo sapiens Human MRPEPGGCCCRRTVRANGCVANGEVRNGYVRSSAAAAAAAAAGQIHHVTQNGGLYKRPFNEAFEETPMLVAVLTYVGYGVLTLFGYLRDFLRYWRIEKCHHATEREEQKDFVSLYQDFENFYTRNLYMRIRDNWNRPICSVPGARVDIMERQSHDYNWSFKYTGNIIKGVINMGSYNYLGFARNTGSCQEAAAKVLEEYGAGVCSTRQEIGNLDKHEELEELVARFLGVEAAMAYGMGFATNSMNIPALVGKGCLILSDELNHASLVLGARLSGATIRIFKHNNMQSLEKLLKDAIVYGQPRTRRPWKKILILVEGIYSMEGSIVRLPEVIALKKKYKAYLYLDEAHSIGALGPTGRGVVEYFGLDPEDVDVMMGTFTKSFGASGGYIGGKKELIDYLRTHSHSAVYATSLSPPVVEQIITSMKCIMGQDGTSLGKECVQQLAENTRYFRRRLKEMGFIIYGNEDSPVVPLMLYMPAKIGAFGREMLKRNIGVVVVGFPATPIIESRARFCLSAAHTKEILDTALKEIDEVGDLLQLKYSRHRLVPLLDRPFDETTYEETED DIP protein O15270 original sequence version: 130 0C1AA1E233DE36F1 orml3_human ORM1-like protein 3 ORMDL3 protein protein human Homo sapiens Human MNVGTAHSEVNPNTRVMNSRGIWLSYVLAIGLLHIVLLSIPFVSVPVVWTLTNLIHNMGMYIFLHTVKGTPFETPDQGKARLLTHWEQMDYGVQFTASRKFLTITPIVLYFLTSFYTKYDQIHFVLNTVSLMSVLIPKLPQLHGVRIFGINKY DIP protein Q8N138 original sequence version: 56 3EF483CA5C03EC2E pyridoxal 5'-phosphate(2-) pyridoxal 5'-phosphate(2-) 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphate dianion 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphate(2-) pyridoxal 5'-phosphate pyridoxal 5'-phosphate dianion (4-formyl-5-hydroxy-6-methylpyridin-3-yl)methyl phosphate small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) NGVDGCNFYWLIFO-UHFFFAOYSA-L NGVDGCNFYWLIFO-UHFFFAOYSA-L sptlc1-sptlc2-4 3 11 cofactor cofactor coenzyme unspecified role unspecified role 8 unspecified role unspecified role neutral component neutral component purified purified 9 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain 4 unspecified role unspecified role neutral component neutral component purified purified physical association physical association Table 1 sptlc1-sptlc2-3 3 11 cofactor cofactor coenzyme unspecified role unspecified role 8 unspecified role unspecified role neutral component neutral component purified purified 9 unspecified role unspecified role neutral component neutral component purified purified 4 unspecified role unspecified role neutral component neutral component purified purified physical association physical association Table 1 ormdl3-pyridoxal 5'_phosphate(2_)-1 3 10 unspecified role unspecified role neutral component neutral component purified purified 11 cofactor cofactor coenzyme neutral component neutral component 8 unspecified role unspecified role neutral component neutral component purified purified 9 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain 4 unspecified role unspecified role neutral component neutral component purified purified physical association physical association Table 1 sptlc1_sptlc2_2-1 2 32 enzyme enzyme unspecified role unspecified role purified purified 6 enzyme target enzyme target substrate substrate unspecified role unspecified role 7 enzyme target enzyme target substrate substrate unspecified role unspecified role enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction Fig. 1B Km for serine l_serine-myriocin-1 2 32 enzyme enzyme unspecified role unspecified role purified purified 5 inhibitor inhibitor unspecified role unspecified role 6 enzyme target enzyme target substrate substrate unspecified role unspecified role 7 enzyme target enzyme target substrate substrate unspecified role unspecified role enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction Fig. 1B Km for serine spt-c2-sa_human Serine palmitoyltransferase complex, SPTLC1-SPTLC2-SPTSSA variant SPT complex Serine C-palmitoyltransferase complex 2xSPTLC1:2xSPTLC2:2xSPTSSA 8 unspecified role unspecified role sptlc2 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 9 enzyme enzyme sptssa binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined pyridoxal 5'-phosphate(2-) binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain sptlc1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined sptlc1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 4 unspecified role unspecified role sptlc2 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined sptlc2 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 11 cofactor cofactor coenzyme sptlc2 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 11 cofactor cofactor coenzyme sptlc2 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 8 unspecified role unspecified role sptlc2 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 9 enzyme enzyme sptssa binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined pyridoxal 5'-phosphate(2-) binding region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain sptlc1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined sptlc1 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 4 unspecified role unspecified role sptlc2 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined sptlc2 binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 41 43 51 44 45 48 46 63 49 59 53 58 57 55 60 62 physical association physical association human Homo sapiens Human stable complex stable complex physical interaction evidence used in manual assertion physical interaction evidence used in manual assertion IPI inferred from physical interaction Catalyzes the first, rate-limiting step of the sphingolipid synthesis pathway, driving the condensation of L-serine and acyl-CoA thioester substrates to form 3-dehydrosphinganinium (CHEBI:58299). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for a C16-CoA substrate, typically palmitoyl-CoA. The cytosolic regions of SPTLC1 and SPTLC2 interact to form a heterodimer which further assembles into a dimer-of-dimers. SPTSSA then interacts with SPTLC2 via its cytosolic interfacial helix and appears to promote the catalytic activity of the complex by stabilizing SPTLC2. The side chain of SPTSSA Met-28 protrudes into and seals the substrate-binding tunnel formed mainly by SPTLC2. Binding of any substrates longer than a C16-CoA would be energetically disfavoured due to steric clashes with Met-28. The pyridoxal 5'-phosphate (PLP) molecules bind primarily to SPTLC2 residues, where the amine group of L-serine attacks and displaces the lysine bound to PLP indicating that SPTLC2 is the catalytic subunit of the enzyme complex. Hereditary sensory neuropathy type I (HSN I) [Orphanet:36386]: a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. Heterohexamer Accepted 2021-JUN-22 by BMELDAL