SGPP1

SGPP1
Identifikatori
Aliasi	SGPP1
Vanjski ID-jevi	OMIM: 612826 MGI: 2135760 HomoloGene: 101696 GeneCards: SGPP1
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	63,728,065 bp
Lokacija gena (miš)
Hrom.	Hromosom 12 (miš)
Kraj	75,782,503 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• hydrolase activity; • sphingosine-1-phosphate phosphatase activity; • dihydrosphingosine-1-phosphate phosphatase activity;
Ćelijska komponenta	• integral component of membrane; • endoplasmic reticulum membrane; • Endoplazmatski retikulum; • membrana; • ćelijska membrana; • jedro; • nukleoplazma;
Biološki proces	• intrinsic apoptotic signaling pathway; • sphingosine metabolic process; • sphingolipid biosynthetic process; • extrinsic apoptotic signaling pathway; • GO:0098501, GO:0098502, GO:0006286 Defosforilacija; • sphinganine-1-phosphate metabolic process; • sphingolipid metabolic process; • ER to Golgi ceramide transport; • regulation of keratinocyte differentiation; • regulation of epidermis development;
	Izvori:Amigo / QuickGO
Ortolozi
	81537
	81535
	ENSG00000126821; ENSG00000285281
	ENSMUSG00000021054
	Q9BX95
	Q9JI99
	NM_030791
	NM_030750
	NP_110418
	NP_109675
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Sfingozin-1-fosfat fosfataza 1 je enzim jokoji je kod ljudi kodiran genom SGPP1.^[5]^[6]

Sfingozin-1-fosfat (S1P) je bioaktivni sfingolipidni metabolit koji regulira različite biološke procese. SGPP1 katalizira razgradnju S1P, putem spašavanja i recikliranja sfingozina u dugolančane keramide (Mandala et al., 2000; Le Stunff et al., 2007). Analizom baza podataka, Le Stunff et al. (2002) mapirali su gen SGPP1 na hromosomu 14, sekvenca 14q22.1.^[7]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 441 aminokiselina, a molekulska težina 49.108 Da.^[8].

10	20	30	40	50
MSLRQRLAQL	VGRLQDPQKV	ARFQRLCGVE	APPRRSADRR	EDEKAEAPLA
GDPRLRGRQP	GAPGGPQPPG	SDRNQCPAKP	DGGGAPNGVR	NGLAAELGPA
SPRRAGALRR	NSLTGEEGQL	ARVSNWPLYC	LFCFGTELGN	ELFYILFFPF
WIWNLDPLVG	RRLVVIWVLV	MYLGQCTKDI	IRWPRPASPP	VVKLEVFYNS
EYSMPSTHAM	SGTAIPISMV	LLTYGRWQYP	LIYGLILIPC	WCSLVCLSRI
YMGMHSILDI	IAGFLYTILI	LAVFYPFVDL	IDNFNQTHKY	APFIIIGLHL
ALGIFSFTLD	TWSTSRGDTA	EILGSGAGIA	CGSHVTYNMG	LVLDPSLDTL
PLAGPPITVT	LFGKAILRIL	IGMVFVLIIR	DVMKKITIPL	ACKIFNIPCD
DIRKARQHME	VELPYRYITY	GMVGFSITFF	VPYIFFFIGI	S

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Kloniranje i ekspresija[uredi | uredi izvor]

Analizom EST baze podataka, koristeći kvaščevu S1P fosfolipazu Lbp1 kao upit, nakon čega slijedi RACE biblioteke cDNK mišjeg mozga, Mandala et al. (2000) klonirani mišji Sgpp1, kojeg su nazvali Spp1. Izvedeni mišji protein od 430 aminokiselina ima 17% identiteta aminokiselina s kvascem Lbp1. Northern blot analizom otkriven je transkript od 3,8 kb u svim ispitivanim tkivima miša, s najvećom ekspresijom u jetri i bubrezima i najmanjom u skeletnim mišićima.^[9]

Analizom baza podataka, nakon čega slijedi RACE-PCR ljudske placentne cDNK, Le Stunff et al (2002) klonirali su SGPP1. Izvedeni protein od 441 aminokiseline dijeli 76% identiteta aminokiselina sa mišjim homologom. Transfekcija ćelija HJ293 ili jajnika kineskog hrčka (CHO) SGPP1 rezultirala je značajnim povećanjem aktivnosti SGPP1 u membranskim frakcijama. SGPP1 je bio vrlo specifičan prema dugolančanim sfingoidnim fosfatima i razgrađenim S1P, dihidro-S1P i fito-S1P. Aktivnost SGPP1 bila je neovisna o bilo kojim zahtjevima za kationom, uključujući Mg (2+), a EDTA nije inhibirala, ali jeste Zn (2+).^[10]

Funkcija gena[uredi | uredi izvor]

Mandala et al. (2000) pokazali su da je mišji Sgpp1 imao visoko specifičnu aktivnost dihidro-S1P fosfataze koja je funkcionalno nadopunjavala mutanta Lbp1 kvasca. Prekomjerna ekspresija mišjeg Sgpp1 uzrokovala je ćelijsku smrt u ćelijama NIH3T3.

Le Stunff et al. (2007) pokazali su da ekspresija SGPP1 povećava ugradnju sfingozina u dugolančane keramide u ćelijama HEK293. Koristeći inhibitore keramid-sintaze, pokazali su da je ovaj porast dugolančanog keramida posredovan putem recikliranja sfingozina/spašavanja, a ne de novo sintezom sfingozina. Zaključili su da SGPP1 regulira recikliranje sfingozina u dugolančane keramide, a sfingozin-kinaza-2 (SPHK2) djeluje sa SGPP1 za recikliranje sfingozina u keramid.

Koristeći divlji tip SGPP1 i katalitski neaktivni H208A-mutirani SGPP1, Peter et al. (2008) pokazali su da SGPP1 ima ulogu u regulaciji mišićnog tonusa u otpornim arterijama hrčka i da ovaj učinak zahtijeva aktivnost SGPP1 fosfataze. SGPP1 je modulirao vazokonstrikcijske efekte endogenog S1P. Inhibicija transmembranskog regulatora provodljivosti cistaste fibroze (CFTR) donekle je ublažila učinak SGPP1 na vaskularni tonus. Sugerirali su da CFTR može posredovati transport vanćelijskog S1P do unutarćelijski lokaliziranog SGPP1 radi razgradnje.^[11]

Reference[uredi | uredi izvor]

^ ^a ^b ^c ENSG00000285281 GRCh38: Ensembl release 89: ENSG00000126821, ENSG00000285281 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021054 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mandala SM, Thornton R, Galve-Roperh I, Poulton S, Peterson C, Olivera A, Bergstrom J, Kurtz MB, Spiegel S (Aug 2000). "Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1- phosphate and induces cell death". Proc Natl Acad Sci U S A. 97 (14): 7859–64. doi:10.1073/pnas.120146897. PMC 16635. PMID 10859351.
^ "Entrez Gene: SGPP1 sphingosine-1-phosphate phosphatase 1".
^ Le Stunff, H., Peterson, C., Thornton, R., Milstien, S., Mandala, S. M., Spiegel, S. Characterization of murine sphingosine-1-phosphate phosphohydrolase. J. Biol. Chem. 277: 8920-8927, 2002. PubMed: 11756451
^ "UniProt, Q9BX95". Pristupljeno 11. 9. 2017.
^ Mandala, S. M., Thornton, R., Galve-Roperh, I., Poulton, S., Peterson, C., Olivera, A., Bergstrom, J., Kurtz, M. B., Spiegel, S. Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1-phosphate and induces cell death. Proc. Nat. Acad. Sci. 97: 7859-7864, 2000. PubMed: 10859351
^ Le Stunff, H., Giussani, P., Maceyka, M., Lepine, S., Milstien, S., Spiegel, S. Recycling of sphingosine is regulated by the concerted actions of sphingosine-1-phosphate phosphohydrolase 1 and sphingosine kinase 2. J. Biol. Chem. 282: 34372-34380, 2007. PubMed: 17895250
^ Peter, B. F., Lidington, D., Harada, A., Bolz, H. J., Vogel, L., Heximer, S., Spiegel, S., Pohl, U., Bolz, S.-S. Role of sphingosine-1-phosphate phosphohydrolase 1 in the regulation of resistance artery tone. Circ. Res. 103: 315-324, 2008. PubMed: 18583713

Dopunska literatura[uredi | uredi izvor]

Ogawa C, Kihara A, Gokoh M, Igarashi Y (2003). "Identification and characterization of a novel human sphingosine-1-phosphate phosphohydrolase, hSPP2". J. Biol. Chem. 278 (2): 1268–72. doi:10.1074/jbc.M209514200. PMID 12411432.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Heilig R, Eckenberg R, Petit JL, et al. (2003). "The DNA sequence and analysis of human chromosome 14". Nature. 421 (6923): 601–7. doi:10.1038/nature01348. PMID 12508121.
Johnson KR, Johnson KY, Becker KP, et al. (2003). "Role of human sphingosine-1-phosphate phosphatase 1 in the regulation of intra- and extracellular sphingosine-1-phosphate levels and cell viability". J. Biol. Chem. 278 (36): 34541–7. doi:10.1074/jbc.M301741200. PMID 12815058.
Le Stunff H, Mikami A, Giussani P, et al. (2004). "Role of sphingosine-1-phosphate phosphatase 1 in epidermal growth factor-induced chemotaxis". J. Biol. Chem. 279 (33): 34290–7. doi:10.1074/jbc.M404907200. PMID 15180992.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Giussani P, Maceyka M, Le Stunff H, et al. (2006). "Sphingosine-1-phosphate phosphohydrolase regulates endoplasmic reticulum-to-golgi trafficking of ceramide". Mol. Cell. Biol. 26 (13): 5055–69. doi:10.1128/MCB.02107-05. PMC 1489178. PMID 16782891.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.

[refGRCh38Ensembl-1] ENSG00000285281 GRCh38: Ensembl release 89: ENSG00000126821, ENSG00000285281 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021054 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10859351-5] Mandala SM, Thornton R, Galve-Roperh I, Poulton S, Peterson C, Olivera A, Bergstrom J, Kurtz MB, Spiegel S (Aug 2000). "Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1- phosphate and induces cell death". Proc Natl Acad Sci U S A. 97 (14): 7859–64. doi:10.1073/pnas.120146897. PMC 16635. PMID 10859351.

[entrez-6] "Entrez Gene: SGPP1 sphingosine-1-phosphate phosphatase 1".

[7] Le Stunff, H., Peterson, C., Thornton, R., Milstien, S., Mandala, S. M., Spiegel, S. Characterization of murine sphingosine-1-phosphate phosphohydrolase. J. Biol. Chem. 277: 8920-8927, 2002. PubMed: 11756451

[UniProt-8] "UniProt, Q9BX95". Pristupljeno 11. 9. 2017.

[9] Mandala, S. M., Thornton, R., Galve-Roperh, I., Poulton, S., Peterson, C., Olivera, A., Bergstrom, J., Kurtz, M. B., Spiegel, S. Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1-phosphate and induces cell death. Proc. Nat. Acad. Sci. 97: 7859-7864, 2000. PubMed: 10859351

[10] Le Stunff, H., Giussani, P., Maceyka, M., Lepine, S., Milstien, S., Spiegel, S. Recycling of sphingosine is regulated by the concerted actions of sphingosine-1-phosphate phosphohydrolase 1 and sphingosine kinase 2. J. Biol. Chem. 282: 34372-34380, 2007. PubMed: 17895250

[11] Peter, B. F., Lidington, D., Harada, A., Bolz, H. J., Vogel, L., Heximer, S., Spiegel, S., Pohl, U., Bolz, S.-S. Role of sphingosine-1-phosphate phosphohydrolase 1 in the regulation of resistance artery tone. Circ. Res. 103: 315-324, 2008. PubMed: 18583713

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