SMS2_HUMAN
ID SMS2_HUMAN Reviewed; 365 AA.
AC Q8NHU3; A8K2S9; B2RA61;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Phosphatidylcholine:ceramide cholinephosphotransferase 2;
DE EC=2.7.8.27 {ECO:0000269|PubMed:14685263, ECO:0000269|PubMed:17449912, ECO:0000269|PubMed:17982138};
DE AltName: Full=Sphingomyelin synthase 2 {ECO:0000303|PubMed:19233134};
GN Name=SGMS2 {ECO:0000303|PubMed:30779713, ECO:0000312|HGNC:HGNC:28395};
GN Synonyms=SMS2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAH28705.1};
RN [1] {ECO:0000312|EMBL:AAP13352.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kim N.-S., Shon H.-Y., Oh J.-H., Lee J.-Y., Kim J.-M., Hahn Y., Park H.-S.,
RA Kim S., Kim Y.S.;
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4] {ECO:0000312|EMBL:AAP13352.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis {ECO:0000312|EMBL:AAH28705.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP ACTIVITY REGULATION, AND TOPOLOGY OF C-TERMINUS.
RX PubMed=14685263; DOI=10.1038/sj.emboj.7600034;
RA Huitema K., Van Den Dikkenberg J., Brouwers J.F.H.M., Holthuis J.C.;
RT "Identification of a family of animal sphingomyelin synthases.";
RL EMBO J. 23:33-44(2004).
RN [7]
RP OVEREXPRESSION IN MOUSE.
RX PubMed=16508036; DOI=10.1194/jlr.m600040-jlr200;
RA Dong J., Liu J., Lou B., Li Z., Ye X., Wu M., Jiang X.-C.;
RT "Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2
RT increases the atherogenic potential in mice.";
RL J. Lipid Res. 47:1307-1314(2006).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17449912; DOI=10.1074/jbc.m702423200;
RA Tafesse F.G., Huitema K., Hermansson M., van der Poel S.,
RA van den Dikkenberg J., Uphoff A., Somerharju P., Holthuis J.C.M.;
RT "Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin
RT homeostasis and growth in human HeLa cells.";
RL J. Biol. Chem. 282:17537-17547(2007).
RN [9]
RP ACTIVE SITES, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-227; HIS-229;
RP HIS-272 AND ASP-276.
RX PubMed=18694848; DOI=10.1016/j.bbalip.2008.07.002;
RA Yeang C., Varshney S., Wang R., Zhang Y., Ye D., Jiang X.C.;
RT "The domain responsible for sphingomyelin synthase (SMS) activity.";
RL Biochim. Biophys. Acta 1781:610-617(2008).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=18370930; DOI=10.1042/bj20071240;
RA Villani M., Subathra M., Im Y.B., Choi Y., Signorelli P., Del Poeta M.,
RA Luberto C.;
RT "Sphingomyelin synthases regulate production of diacylglycerol at the
RT Golgi.";
RL Biochem. J. 414:31-41(2008).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=17982138; DOI=10.1194/jlr.m700401-jlr200;
RA Ding T., Li Z., Hailemariam T., Mukherjee S., Maxfield F.R., Wu M.P.,
RA Jiang X.C.;
RT "SMS overexpression and knockdown: impact on cellular sphingomyelin and
RT diacylglycerol metabolism, and cell apoptosis.";
RL J. Lipid Res. 49:376-385(2008).
RN [12]
RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-331; CYS-332; CYS-343 AND
RP CYS-348, AND MUTAGENESIS OF 331-CYS-CYS-332; CYS-343 AND CYS-348.
RX PubMed=19233134; DOI=10.1016/j.bbrc.2009.02.063;
RA Tani M., Kuge O.;
RT "Sphingomyelin synthase 2 is palmitoylated at the COOH-terminal tail, which
RT is involved in its localization in plasma membranes.";
RL Biochem. Biophys. Res. Commun. 381:328-332(2009).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19454763; DOI=10.1194/jlr.m900230-jlr200;
RA Ternes P., Brouwers J.F., van den Dikkenberg J., Holthuis J.C.;
RT "Sphingomyelin synthase SMS2 displays dual activity as ceramide
RT phosphoethanolamine synthase.";
RL J. Lipid Res. 50:2270-2277(2009).
RN [14]
RP FUNCTION.
RX PubMed=21980337; DOI=10.1371/journal.pone.0023644;
RA Subathra M., Qureshi A., Luberto C.;
RT "Sphingomyelin synthases regulate protein trafficking and secretion.";
RL PLoS ONE 6:e23644-e23644(2011).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN CDL, INVOLVEMENT IN CDLSMD,
RP VARIANT CDL 50-ARG--THR-365 DEL, VARIANTS CDLSMD SER-62 AND ARG-64,
RP CHARACTERIZATION OF VARIANT CDL 50-ARG--THR-365 DEL, CHARACTERIZATION OF
RP VARIANTS CDLSMD SER-62 AND ARG-64, AND MUTAGENESIS OF ASP-276.
RX PubMed=30779713; DOI=10.1172/jci.insight.126180;
RA Pekkinen M., Terhal P.A., Botto L.D., Henning P., Maekitie R.E.,
RA Roschger P., Jain A., Kol M., Kjellberg M.A., Paschalis E.P.,
RA van Gassen K., Murray M., Bayrak-Toydemir P., Magnusson M.K., Jans J.,
RA Kausar M., Carey J.C., Somerharju P., Lerner U.H., Olkkonen V.M.,
RA Klaushofer K., Holthuis J.C., Maekitie O.;
RT "Osteoporosis and skeletal dysplasia caused by pathogenic variants in
RT SGMS2.";
RL JCI Insight 4:0-0(2019).
CC -!- FUNCTION: Sphingomyelin synthase that primarily contributes to
CC sphingomyelin synthesis and homeostasis at the plasma membrane.
CC Catalyzes the reversible transfer of phosphocholine moiety in
CC sphingomyelin biosynthesis: in the forward reaction transfers
CC phosphocholine head group of phosphatidylcholine (PC) on to ceramide
CC (CER) to form ceramide phosphocholine (sphingomyelin, SM) and
CC diacylglycerol (DAG) as by-product, and in the reverse reaction
CC transfers phosphocholine from SM to DAG to form PC and CER. The
CC direction of the reaction appears to depend on the levels of CER and
CC DAG in the plasma membrane (PubMed:14685263, PubMed:17449912,
CC PubMed:17982138, PubMed:18370930). Does not use free phosphorylcholine
CC or CDP-choline as donors (PubMed:14685263). Can also transfer
CC phosphoethanolamine head group of phosphatidylethanolamine (PE) on to
CC ceramide (CER) to form ceramide phosphoethanolamine (CPE)
CC (PubMed:19454763). Regulates receptor-mediated signal transduction via
CC mitogenic DAG and proapoptotic CER, as well as via SM, a structural
CC component of membrane rafts that serve as platforms for signal
CC transduction and protein sorting (PubMed:17449912, PubMed:17982138). To
CC a lesser extent, plays a role in secretory transport via regulation of
CC DAG pool at the Golgi apparatus and its downstream effects on PRKD1
CC (PubMed:18370930, PubMed:21980337). Required for normal bone matrix
CC mineralization (PubMed:30779713). {ECO:0000269|PubMed:14685263,
CC ECO:0000269|PubMed:17449912, ECO:0000269|PubMed:17982138,
CC ECO:0000269|PubMed:18370930, ECO:0000269|PubMed:19454763,
CC ECO:0000269|PubMed:21980337, ECO:0000269|PubMed:30779713}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-
CC enine = a 1,2-diacyl-sn-glycerol + a sphingomyelin;
CC Xref=Rhea:RHEA:18765, ChEBI:CHEBI:17636, ChEBI:CHEBI:17815,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:57643; EC=2.7.8.27;
CC Evidence={ECO:0000269|PubMed:14685263, ECO:0000269|PubMed:17449912,
CC ECO:0000269|PubMed:17982138, ECO:0000269|PubMed:18370930};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18766;
CC Evidence={ECO:0000305|PubMed:14685263};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18767;
CC Evidence={ECO:0000305|PubMed:14685263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + an N-
CC acylsphing-4-enine = 1,2-dihexadecanoyl-sn-glycerol + a
CC sphingomyelin; Xref=Rhea:RHEA:43324, ChEBI:CHEBI:17636,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:72999, ChEBI:CHEBI:82929;
CC Evidence={ECO:0000269|PubMed:14685263};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43325;
CC Evidence={ECO:0000305|PubMed:14685263};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:43326;
CC Evidence={ECO:0000305|PubMed:14685263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-2-acyl-sn-3-glycerol + a sphingomyelin = a
CC 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + an N-
CC acylsphing-4-enine; Xref=Rhea:RHEA:43320, ChEBI:CHEBI:17636,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:78421, ChEBI:CHEBI:82983;
CC Evidence={ECO:0000269|PubMed:14685263};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43321;
CC Evidence={ECO:0000305|PubMed:14685263};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:43322;
CC Evidence={ECO:0000305|PubMed:14685263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + N-
CC hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-
CC sphinganine-1-phosphocholine; Xref=Rhea:RHEA:41796,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:57643, ChEBI:CHEBI:67042,
CC ChEBI:CHEBI:78647; Evidence={ECO:0000269|PubMed:19454763};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41797;
CC Evidence={ECO:0000305|PubMed:14685263, ECO:0000305|PubMed:19454763};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41798;
CC Evidence={ECO:0000305|PubMed:14685263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + N-hexadecanoyl-
CC (4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-
CC (4R)-hydroxysphinganine-phosphocholine; Xref=Rhea:RHEA:42140,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:57643, ChEBI:CHEBI:65107,
CC ChEBI:CHEBI:78650; Evidence={ECO:0000269|PubMed:19454763};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42141;
CC Evidence={ECO:0000305|PubMed:14685263, ECO:0000305|PubMed:19454763};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42142;
CC Evidence={ECO:0000305|PubMed:14685263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + N-
CC hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-
CC sphinganine-1-phosphoethanolamine; Xref=Rhea:RHEA:42128,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:64612, ChEBI:CHEBI:67042,
CC ChEBI:CHEBI:78654; Evidence={ECO:0000269|PubMed:19454763};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42129;
CC Evidence={ECO:0000305|PubMed:19454763};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + N-
CC hexadecanoyl-(4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-
CC hexadecanoyl-(4R)-hydroxysphinganine-1-phosphoethanolamine;
CC Xref=Rhea:RHEA:42144, ChEBI:CHEBI:17815, ChEBI:CHEBI:64612,
CC ChEBI:CHEBI:65107, ChEBI:CHEBI:78656;
CC Evidence={ECO:0000269|PubMed:19454763};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42145;
CC Evidence={ECO:0000305|PubMed:19454763};
CC -!- ACTIVITY REGULATION: Inhibited by bacterial PC-phospholipase C
CC inhibitor D609. {ECO:0000269|PubMed:14685263}.
CC -!- PATHWAY: Sphingolipid metabolism. {ECO:0000269|PubMed:17982138}.
CC -!- INTERACTION:
CC Q8NHU3; Q8TED1: GPX8; NbExp=3; IntAct=EBI-10977284, EBI-11721746;
CC Q8NHU3; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-10977284, EBI-12033434;
CC Q8NHU3; Q59EV6: PPGB; NbExp=3; IntAct=EBI-10977284, EBI-14210385;
CC Q8NHU3; P23763-3: VAMP1; NbExp=3; IntAct=EBI-10977284, EBI-12097582;
CC Q8NHU3; O95159: ZFPL1; NbExp=3; IntAct=EBI-10977284, EBI-718439;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14685263,
CC ECO:0000269|PubMed:30779713}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:14685263,
CC ECO:0000269|PubMed:18370930}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Primarily localized at the plasma membrane with a
CC small fraction at the Golgi apparatus. {ECO:0000269|PubMed:14685263}.
CC -!- TISSUE SPECIFICITY: Brain, heart, kidney, liver, muscle and stomach.
CC Also expressed in a number of cell lines such as carcinoma HeLa cells,
CC hepatoma Hep-G2 cells, and colon carcinoma Caco-2 cells.
CC {ECO:0000269|PubMed:14685263}.
CC -!- PTM: Palmitoylated on Cys-331, Cys-332, Cys-343 and Cys-348; which
CC plays an important role in plasma membrane localization.
CC {ECO:0000269|PubMed:19233134}.
CC -!- DISEASE: Calvarial doughnut lesions with bone fragility (CDL)
CC [MIM:126550]: A rare autosomal dominant bone disease characterized by
CC low bone density, distinctive X-ray translucencies of the skull,
CC multiple fractures, elevated serum alkaline phosphatase, and dental
CC caries. Patients present with childhood onset of primary osteoporosis
CC and typical sclerotic doughnut-shaped lesions in the cranial bones.
CC {ECO:0000269|PubMed:30779713}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Calvarial doughnut lesions with bone fragility and
CC spondylometaphyseal dysplasia (CDLSMD) [MIM:126550]: A severe form of
CC calvarial doughnut lesions with bone fragility, a rare autosomal
CC dominant disease characterized by low bone density, distinctive X-ray
CC translucencies of the skull, multiple fractures, elevated serum
CC alkaline phosphatase, and dental caries. CDLSMD patients show neonatal
CC onset of fractures, severe short stature, marked cranial sclerosis, and
CC spondylometaphyseal dysplasia. {ECO:0000269|PubMed:30779713}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry.
CC -!- MISCELLANEOUS: Overexpression of the human protein in mouse causes
CC increased non-HDL-sphingomyelin and non-HDL cholesterol levels,
CC decreased HDL-sphingomyelin and HDL-cholesterol levels and increases
CC the atherogenic potential of non-HDL lipoprotein particles.
CC -!- SIMILARITY: Belongs to the sphingomyelin synthase family.
CC {ECO:0000305}.
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DR EMBL; AF452717; AAP13352.1; -; mRNA.
DR EMBL; AK290344; BAF83033.1; -; mRNA.
DR EMBL; AK314049; BAG36758.1; -; mRNA.
DR EMBL; CH471057; EAX06211.1; -; Genomic_DNA.
DR EMBL; BC028705; AAH28705.1; -; mRNA.
DR EMBL; BC041369; AAH41369.1; -; mRNA.
DR EMBL; AC096564; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS3677.1; -.
DR RefSeq; NP_001129729.1; NM_001136257.1.
DR RefSeq; NP_001129730.1; NM_001136258.1.
DR RefSeq; NP_689834.1; NM_152621.5.
DR RefSeq; XP_011530000.1; XM_011531698.2.
DR RefSeq; XP_011530001.1; XM_011531699.2.
DR RefSeq; XP_011530002.1; XM_011531700.2.
DR RefSeq; XP_011530003.1; XM_011531701.2.
DR RefSeq; XP_011530004.1; XM_011531702.2.
DR RefSeq; XP_016863328.1; XM_017007839.1.
DR RefSeq; XP_016863329.1; XM_017007840.1.
DR AlphaFoldDB; Q8NHU3; -.
DR BioGRID; 127938; 27.
DR IntAct; Q8NHU3; 12.
DR STRING; 9606.ENSP00000378176; -.
DR BindingDB; Q8NHU3; -.
DR ChEMBL; CHEMBL3112379; -.
DR GuidetoPHARMACOLOGY; 2521; -.
DR SwissLipids; SLP:000000172; -.
DR iPTMnet; Q8NHU3; -.
DR PhosphoSitePlus; Q8NHU3; -.
DR SwissPalm; Q8NHU3; -.
DR BioMuta; SGMS2; -.
DR DMDM; 44888519; -.
DR EPD; Q8NHU3; -.
DR jPOST; Q8NHU3; -.
DR MassIVE; Q8NHU3; -.
DR MaxQB; Q8NHU3; -.
DR PaxDb; Q8NHU3; -.
DR PeptideAtlas; Q8NHU3; -.
DR PRIDE; Q8NHU3; -.
DR ProteomicsDB; 73758; -.
DR Antibodypedia; 15282; 255 antibodies from 25 providers.
DR DNASU; 166929; -.
DR Ensembl; ENST00000359079.8; ENSP00000351981.4; ENSG00000164023.15.
DR Ensembl; ENST00000394684.8; ENSP00000378176.4; ENSG00000164023.15.
DR Ensembl; ENST00000394686.3; ENSP00000378178.3; ENSG00000164023.15.
DR Ensembl; ENST00000690982.1; ENSP00000508566.1; ENSG00000164023.15.
DR GeneID; 166929; -.
DR KEGG; hsa:166929; -.
DR MANE-Select; ENST00000690982.1; ENSP00000508566.1; NM_001375905.1; NP_001362834.1.
DR UCSC; uc003hyl.6; human.
DR CTD; 166929; -.
DR DisGeNET; 166929; -.
DR GeneCards; SGMS2; -.
DR HGNC; HGNC:28395; SGMS2.
DR HPA; ENSG00000164023; Low tissue specificity.
DR MalaCards; SGMS2; -.
DR MIM; 126550; phenotype.
DR MIM; 611574; gene.
DR neXtProt; NX_Q8NHU3; -.
DR OpenTargets; ENSG00000164023; -.
DR PharmGKB; PA162403069; -.
DR VEuPathDB; HostDB:ENSG00000164023; -.
DR eggNOG; KOG3058; Eukaryota.
DR GeneTree; ENSGT00940000157370; -.
DR HOGENOM; CLU_027104_0_1_1; -.
DR InParanoid; Q8NHU3; -.
DR OMA; VNWAFTV; -.
DR OrthoDB; 599210at2759; -.
DR PhylomeDB; Q8NHU3; -.
DR TreeFam; TF314547; -.
DR BRENDA; 2.7.8.27; 2681.
DR PathwayCommons; Q8NHU3; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; Q8NHU3; -.
DR BioGRID-ORCS; 166929; 9 hits in 1072 CRISPR screens.
DR ChiTaRS; SGMS2; human.
DR GenomeRNAi; 166929; -.
DR Pharos; Q8NHU3; Tchem.
DR PRO; PR:Q8NHU3; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8NHU3; protein.
DR Bgee; ENSG00000164023; Expressed in tibia and 169 other tissues.
DR ExpressionAtlas; Q8NHU3; baseline and differential.
DR Genevisible; Q8NHU3; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0030173; C:integral component of Golgi membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0047493; F:ceramide cholinephosphotransferase activity; IDA:UniProtKB.
DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0033188; F:sphingomyelin synthase activity; IDA:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0030500; P:regulation of bone mineralization; IMP:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR GO; GO:0006686; P:sphingomyelin biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR045221; Sphingomyelin_synth-like.
DR InterPro; IPR025749; Sphingomyelin_synth-like_dom.
DR PANTHER; PTHR21290; PTHR21290; 1.
DR Pfam; PF14360; PAP2_C; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Golgi apparatus; Kinase; Lipid metabolism;
KW Lipoprotein; Membrane; Palmitate; Reference proteome;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..365
FT /note="Phosphatidylcholine:ceramide
FT cholinephosphotransferase 2"
FT /id="PRO_0000221072"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 128..148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 275..295
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 296..365
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 229
FT /evidence="ECO:0000269|PubMed:18694848"
FT ACT_SITE 272
FT /evidence="ECO:0000269|PubMed:18694848"
FT ACT_SITE 276
FT /evidence="ECO:0000269|PubMed:18694848"
FT LIPID 331
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19233134"
FT LIPID 332
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19233134"
FT LIPID 343
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19233134"
FT LIPID 348
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19233134"
FT VARIANT 21
FT /note="T -> M (in dbSNP:rs17038204)"
FT /id="VAR_052025"
FT VARIANT 50..365
FT /note="Missing (in CDL; loss of enzymatic activity; does
FT not localize to plasma membrane)"
FT /evidence="ECO:0000269|PubMed:30779713"
FT /id="VAR_082674"
FT VARIANT 62
FT /note="I -> S (in CDLSMD; unknown pathological
FT significance; no effect on enzymatic activity; does not
FT localize to plasma membrane; accumulates in the endoplasmic
FT reticulum)"
FT /evidence="ECO:0000269|PubMed:30779713"
FT /id="VAR_082675"
FT VARIANT 64
FT /note="M -> R (in CDLSMD; unknown pathological
FT significance; no effect on enzymatic activity; does not
FT localize to plasma membrane; accumulates in the endoplasmic
FT reticulum)"
FT /evidence="ECO:0000269|PubMed:30779713"
FT /id="VAR_082676"
FT MUTAGEN 227
FT /note="S->A: Abolishes enzyme activity by about 70%. No
FT change in subcellular location."
FT /evidence="ECO:0000269|PubMed:18694848"
FT MUTAGEN 229
FT /note="H->A: Completely abolishes enzyme activity. No
FT change in subcellular location."
FT /evidence="ECO:0000269|PubMed:18694848"
FT MUTAGEN 272
FT /note="H->A: Completely abolishes enzyme activity. No
FT change in subcellular location."
FT /evidence="ECO:0000269|PubMed:18694848"
FT MUTAGEN 276
FT /note="D->E,A: Completely abolishes enzyme activity. No
FT change in subcellular location."
FT /evidence="ECO:0000269|PubMed:18694848,
FT ECO:0000269|PubMed:30779713"
FT MUTAGEN 331..332
FT /note="CC->AA: Little effect on palmitoylation; when
FT associated with A-343 or A-348. Abolishes palmitoylation
FT and dramatically reduces plasma membrane localization; when
FT associated with A-343 and A-348."
FT /evidence="ECO:0000269|PubMed:19233134"
FT MUTAGEN 343
FT /note="C->A: Strongly decreases palmitoylation; when
FT associated with A-348. Abolishes palmitoylation and
FT dramatically reduces plasma membrane localization; when
FT associated with 331-A-A-332 and A-348."
FT /evidence="ECO:0000269|PubMed:19233134"
FT MUTAGEN 348
FT /note="C->A: Strongly decreases palmitoylation; when
FT associated with A-343. Abolishes palmitoylation and
FT dramatically reduces plasma membrane localization; when
FT associated with 331-A-A-332 and A-343."
FT /evidence="ECO:0000269|PubMed:19233134"
FT CONFLICT 313
FT /note="W -> R (in Ref. 2; BAF83033)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 365 AA; 42280 MW; 49B3560AFB87CF40 CRC64;
MDIIETAKLE EHLENQPSDP TNTYARPAEP VEEENKNGNG KPKSLSSGLR KGTKKYPDYI
QIAMPTESRN KFPLEWWKTG IAFIYAVFNL VLTTVMITVV HERVPPKELS PPLPDKFFDY
IDRVKWAFSV SEINGIILVG LWITQWLFLR YKSIVGRRFC FIIGTLYLYR CITMYVTTLP
VPGMHFQCAP KLNGDSQAKV QRILRLISGG GLSITGSHIL CGDFLFSGHT VTLTLTYLFI
KEYSPRHFWW YHLICWLLSA AGIICILVAH EHYTIDVIIA YYITTRLFWW YHSMANEKNL
KVSSQTNFLS RAWWFPIFYF FEKNVQGSIP CCFSWPLSWP PGCFKSSCKK YSRVQKIGED
NEKST
