PIP4K2A
Fosfatidilinozitol-5-fosfat 4-kinaza tip-2 alfa je enzim koji je kodiran genom PIP4K2A.[5][6][7]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 406 aminokiselina, а molekulska težina 46.225 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MATPGNLGSS | VLASKTKTKK | KHFVAQKVKL | FRASDPLLSV | LMWGVNHSIN | ||||
| ELSHVQIPVM | LMPDDFKAYS | KIKVDNHLFN | KENMPSHFKF | KEYCPMVFRN | ||||
| LRERFGIDDQ | DFQNSLTRSA | PLPNDSQARS | GARFHTSYDK | RYIIKTITSE | ||||
| DVAEMHNILK | KYHQYIVECH | GITLLPQFLG | MYRLNVDGVE | IYVIVTRNVF | ||||
| SHRLSVYRKY | DLKGSTVARE | ASDKEKAKEL | PTLKDNDFIN | EGQKIYIDDN | ||||
| NKKVFLEKLK | KDVEFLAQLK | LMDYSLLVGI | HDVERAEQEE | VECEENDGEE | ||||
| EGESDGTHPV | GTPPDSPGNT | LNSSPPLAPG | EFDPNIDVYG | IKCHENSPRK | ||||
| EVYFMAIIDI | LTHYDAKKKA | AHAAKTVKHG | AGAEISTVNP | EQYSKRFLDF | ||||
| IGHILT |
Funkcija
urediFosfatidilinositol 4,5-bisfosfat, prekursor drugog glasnika fosfatidilinozitolskih signalnih puteva, smatra se uključenim u regulaciju sekrecije, ćelijske proliferacije, diferencijaciju i pokretljivost. Protein kodiran ovim genom jedan je iz porodice enzima koji mogu katalizirati fosforilaciju fosfatidilinozitol-4-fosfata na petom hidroksilu mio-inozitolskog prstena za stvaranje fosfatidilinositol-4,5-bisfosfata.
Aminokiselinska sekvenca ovog enzima ne pokazuje homologije s drugim kinazama, ali rekombinantni protein pokazuje aktivnost kinaze. Ovaj gen je član porodice fosfatidilinositol-4-fosfat 5-kinaza.[7]
Klinički značaj
urediPutem studije šire asocijacije na genomu (GWAS), primijećeno je da su neki od jednonukleotidnih polimorfizama (SNP-ovi) koji se nalaze u ovom genu značajno povezani sa osjetljivošću djetinjstvenu akutnu limfoblastnu leukemiju u etnički raznolikim populacijama.[9][10]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000150867 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026737 - 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.
- ^ Boronenkov IV, Anderson RA (februar 1995). "The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases". The Journal of Biological Chemistry. 270 (7): 2881–4. doi:10.1074/jbc.270.7.2881. PMID 7852364.
- ^ Rameh LE, Tolias KF, Duckworth BC, Cantley LC (novembar 1997). "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate". Nature. 390 (6656): 192–6. doi:10.1038/36621. PMID 9367159. S2CID 4403301.
- ^ a b "Entrez Gene: PIP5K2A phosphatidylinositol-4-phosphate 5-kinase, type II, alpha".
- ^ "UniProt, P48426". Pristupljeno 4. 9. 2021.
- ^ Xu H, Yang W, Perez-Andreu V, Devidas M, Fan Y, Cheng C, et al. (maj 2013). "Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations". Journal of the National Cancer Institute. 105 (10): 733–42. doi:10.1093/jnci/djt042. PMC 3691938. PMID 23512250.
- ^ Liao F, Yin D, Zhang Y, Hou Q, Zheng Z, Yang L, Shu Y, Xu H, Li Y (maj 2016). "Association Between PIP4K2A Polymorphisms and Acute Lymphoblastic Leukemia Susceptibility". Medicine. 95 (18): e3542. doi:10.1097/MD.0000000000003542. PMC 4863780. PMID 27149463.
Dopunaka literatura
uredi- Loijens JC, Boronenkov IV, Parker GJ, Anderson RA (1996). "The phosphatidylinositol 4-phosphate 5-kinase family". Advances in Enzyme Regulation. 36: 115–40. doi:10.1016/0065-2571(95)00005-4. PMID 8869744.
- Niiro H, Clark EA (novembar 2003). "Branches of the B cell antigen receptor pathway are directed by protein conduits Bam32 and Carma1". Immunity. 19 (5): 637–40. doi:10.1016/S1074-7613(03)00303-0. PMID 14614850.
- Carpenter CL (april 2004). "Btk-dependent regulation of phosphoinositide synthesis". Biochemical Society Transactions. 32 (Pt 2): 326–9. doi:10.1042/BST0320326. PMID 15046600.
- Tolias KF, Cantley LC, Carpenter CL (juli 1995). "Rho family GTPases bind to phosphoinositide kinases". The Journal of Biological Chemistry. 270 (30): 17656–9. doi:10.1074/jbc.270.30.17656. PMID 7629060.
- Divecha N, Truong O, Hsuan JJ, Hinchliffe KA, Irvine RF (august 1995). "The cloning and sequence of the C isoform of PtdIns4P 5-kinase". The Biochemical Journal. 309 (3): 715–9. doi:10.1042/bj3090715. PMC 1135690. PMID 7639683.
- Rozenvayn N, Flaumenhaft R (mart 2003). "Protein kinase C mediates translocation of type II phosphatidylinositol 5-phosphate 4-kinase required for platelet alpha-granule secretion". The Journal of Biological Chemistry. 278 (10): 8126–34. doi:10.1074/jbc.M206493200. PMID 12509423.
- Saito K, Tolias KF, Saci A, Koon HB, Humphries LA, Scharenberg A, Rawlings DJ, Kinet JP, Carpenter CL (novembar 2003). "BTK regulates PtdIns-4,5-P2 synthesis: importance for calcium signaling and PI3K activity". Immunity. 19 (5): 669–78. doi:10.1016/S1074-7613(03)00297-8. PMID 14614854.
- Schwab SG, Knapp M, Sklar P, Eckstein GN, Sewekow C, Borrmann-Hassenbach M, Albus M, Becker T, Hallmayer JF, Lerer B, Maier W, Wildenauer DB (septembar 2006). "Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia". Molecular Psychiatry. 11 (9): 837–46. doi:10.1038/sj.mp.4001864. PMID 16801950.
- Bakker SC, Hoogendoorn ML, Hendriks J, Verzijlbergen K, Caron S, Verduijn W, Selten JP, Pearson PL, Kahn RS, Sinke RJ (mart 2007). "The PIP5K2A and RGS4 genes are differentially associated with deficit and non-deficit schizophrenia". Genes, Brain, and Behavior. 6 (2): 113–9. doi:10.1111/j.1601-183X.2006.00234.x. PMID 17410640. S2CID 32120485.
- He Z, Li Z, Shi Y, Tang W, Huang K, Ma G, Zhou J, Meng J, Li H, Feng G, He L (august 2007). "The PIP5K2A gene and schizophrenia in the Chinese population--a case-control study". Schizophrenia Research. 94 (1–3): 359–65. doi:10.1016/j.schres.2007.04.013. PMID 17555944. S2CID 34716299.