PRPSAP2

PRPSAP2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2JI4
Identifikatori
Aliasi	PRPSAP2
Vanjski ID-jevi	OMIM: 603762 MGI: 2384838 HomoloGene: 2073 GeneCards: PRPSAP2
Lokacija gena (čovjek)
Hrom.	Hromosom 17 (čovjek)
Kraj	18,931,287 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	61,652,914 bp
Ontologija gena
Molekularna funkcija	• ribose phosphate diphosphokinase activity; • GO:0048551 enzyme inhibitor activity; • magnesium ion binding; • GO:0001948, GO:0016582 vezivanje za proteine; • GO:0010576 enzyme regulator activity;
Ćelijska komponenta	• ribose phosphate diphosphokinase complex; • citoplazma; • GO:0009327 makromolekulani kompleks;
Biološki proces	• nucleotide biosynthetic process; • bone development; • nucleobase-containing compound metabolic process; • GO:0048553 negative regulation of catalytic activity; • nucleoside metabolic process; • 5-phosphoribose 1-diphosphate biosynthetic process; • purine nucleotide biosynthetic process; • GO:0048552 regulation of catalytic activity;
	Izvori:Amigo / QuickGO
Ortolozi
	5636
	212627
	ENSG00000141127
	ENSMUSG00000020528
	O60256
	Q8R574
NM_001243936; NM_001243940; NM_001243941; NM_001243942; NM_002767;
	NM_001353096; NM_001353097; NM_001353098; NM_001353099; NM_001353100; NM_001353101; NM_001353102; NM_001353103; NM_001353104; NM_001353105; NM_001353106; NM_001353107
NM_001164242; NM_001164243; NM_001164244; NM_144806; NM_001364086;
	NM_001364087; NM_001364088; NM_001364090
NP_001230865; NP_001230869; NP_001230870; NP_001230871; NP_002758;
	NP_001340025; NP_001340026; NP_001340027; NP_001340028; NP_001340029; NP_001340030; NP_001340031; NP_001340032; NP_001340033; NP_001340034; NP_001340035; NP_001340036
NP_001157714; NP_001157715; NP_001157716; NP_659055; NP_001351015;
	NP_001351016; NP_001351017; NP_001351019
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein 2 pridružen fosforibozil pirososfat-sintetazi je protein koji je kod ljudi kodirtan genom PRPSAP2.^[5]

Funkcija[uredi | uredi izvor]

Enzim fosforibozil pirofosfat-sintetaza (PRS) katalizira stvaranje fosforibozil-pirofosfata, koji je supstrat za sintezu nukleotida purina i pirimidina, histidina, triptofana i NAD-a. PRS postoji kao kompleks sa po dvije katalitske i pridružene podjedinice. Ovaj gen kodira nekatalitski povezanu podjedinicu PRS-a.^[5]

Dužina polipeptidnog lanca je 369 aminokiselina, a molekulska težina 40.926^[6].

Aminokiselinska sekvenca

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

10	20	30	40	50
MFCVTPPELE	TKMNITKGGL	VLFSANSNSS	CMELSKKIAE	RLGVEMGKVQ
VYQEPNRETR	VQIQESVRGK	DVFIIQTVSK	DVNTTIMELL	IMVYACKTSC
AKSIIGVIPY	FPYSKQCKMR	KRGSIVSKLL	ASMMCKAGLT	HLITMDLHQK
EIQGFFNIPV	DNLRASPFLL	QYIQEEIPDY	RNAVIVAKSP	ASAKRAQSFA
ERLRLGIAVI	HGEAQDAESD	LVDGRHSPPM	VRSVAAIHPS	LEIPMLIPKE
KPPITVVGDV	GGRIAIIVDD	IIDDVDSFLA	AAETLKERGA	YKIFVMATHG
LLSSDAPRRI	EESAIDEVVV	TNTIPHEVQK	LQCPKIKTVD	ISMILSEAIR
RIHNGESMSY	LFRNIGLDD

Modelni organizmi[uredi | uredi izvor]

Fenotip nokaut-miša *Pnpo*
Svojstvo	Fenotip
Vijabilnost homozigota	Normalno
Studija recesivne letalnosti	Nenormalno
Plodnost	Normalno
Tjelesna težina	Normalno
Test otvorenog polja: anksioznost	Nenormalno
Neurološka procjena	Normalno
Snaga stiska	Normalno
Test vruće ploče	Normalno
Dismorfologija	Normalno
Indirektna kalorimetrija	Normalno
Test tolerancije glukoze	Normalno
Slušni odgovor moždanog stabla	Normalno
DEXA	Normalno
Radiografija	Normalno
Tjelesna temperatura	Normalno
Morfologija ika	Normalno
Klinička hemija (nalaz)	Normalno
Plazmatski imunoglobulini	Nenormalno
Hematologija	Normalno
Leukociti periferne krvi	Normalno
Mikronukleus test	Normalno
Težina srca	Normalno
Histopatologija oka	Normalno
Salmonella infekcija	Normal^[7]
Citrobacter infekcija	Normal^[8]
Svi testovi i analize su iz ^[9]^[10]

U proučavanju PNPO funkcije, korišteni su modelni organizmi. Uvjetna linija nokaut-miševa, zvana Pnpo^{tm1a (KOMP) Wtsi},^[11]^[12] generirana je kao dio programa Međunarosnog konzorcija za miševe – visokopropusnog projekta mutageneze za generiranje i distribuciju životinjskih modela bolesti zainteresiranim naučnicima.^[13]^[14]^[15]

Muške i ženske životinje prolazile su standardizirani fenotipski skrining, kako bi se utvrdili efekti delecije.^[9]^[16] Od 24 izvedena testa ina mutantnim miševima, uočene su dvije značajne abnormalnosti.^[9] Tokom gestacije, nije utvrđen homozigotni mutantni embrion, pa tako nijedan nije preživio do odvikavanja. Preostali testovi su izvedeni na mutiranim heterozigotnim odraslim miševima; nisu opažene nikakve dodatne značajne abnormalnosti kod ovih životinja.^[9]

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000141127 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020528 - 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.
^ ^a ^b "Entrez Gene: phosphoribosyl pyrophosphate synthetase-associated protein 2". Pristupljeno 30. 8. 2011.
^ "UniProt, O60256". Pristupljeno 12. 9. 2017.
^ "Salmonella infection data for Pnpo". Wellcome Trust Sanger Institute.
^ "Citrobacter infection data for Pnpo". Wellcome Trust Sanger Institute.
^ ^a ^b ^c ^d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
^ "International Knockout Mouse Consortium". Arhivirano s originala, 3. 4. 2012. Pristupljeno 10. 6. 2021.
^ "Mouse Genome Informatics".
^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
^ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Dopunska literatura[uredi | uredi izvor]

Katashima R, Iwahana H, Fujimura M, et al. (1998). "Molecular cloning of a human cDNA for the 41-kDa phosphoribosylpyrophosphate synthetase-associated protein". Biochim. Biophys. Acta. 1396 (3): 245–50. doi:10.1016/S0167-4781(97)00217-0. PMID 9545573.
Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
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. S2CID 7827573.
Katashima R, Iwahana H, Fujimura M, et al. (1998). "Assignment of the human phosphoribosylpyrophosphate synthetase-associated protein 41 gene (PRPSAP2) to 17p11.2-p12". Genomics. 54 (1): 180–1. doi:10.1006/geno.1998.5432. PMID 9806849.
Low SK, Kuchiba A, Zembutsu H, et al. (2010). "Genome-wide association study of pancreatic cancer in Japanese population". PLOS ONE. 5 (7): e11824. Bibcode:2010PLoSO...511824L. doi:10.1371/journal.pone.0011824. PMC 2912284. PMID 20686608.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000141127 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020528 - 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.

[entrez-5] "Entrez Gene: phosphoribosyl pyrophosphate synthetase-associated protein 2". Pristupljeno 30. 8. 2011.

[UniProt-6] "UniProt, O60256". Pristupljeno 12. 9. 2017.

[''Salmonella''_infection-7] "Salmonella infection data for Pnpo". Wellcome Trust Sanger Institute.

[''Citrobacter''_infection-8] "Citrobacter infection data for Pnpo". Wellcome Trust Sanger Institute.

[mgp_reference-9] Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.

[10] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-11] "International Knockout Mouse Consortium". Arhivirano s originala, 3. 4. 2012. Pristupljeno 10. 6. 2021.

[mgi_allele_ref-12] "Mouse Genome Informatics".

[pmid21677750-13] Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-14] Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-15] Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.

[pmid21722353-16] van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]