PSTPIP2
Prolin-serin-treonin fosfatazno-interaktivni protein 2 je enzim koji je kod ljudi kodiran genom PSTPIP2.[4][5] Ovaj protein, poznat i kao makrofagni F-aktin-povezani i tirozin-fosforilirani protein (MAYP), član je porodice proteina Pombe Cdc15 homologije (PCH) koji pokazuju koordinaciju membranske i citoskeletne dinamike.[6]
| PSTPIP2 | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifikatori | |||||||||||||||||||||||||
| Aliasi | PSTPIP2 | ||||||||||||||||||||||||
| Vanjski ID-jevi | OMIM: 616046 MGI: 1335088 HomoloGene: 69150 GeneCards: PSTPIP2 | ||||||||||||||||||||||||
| |||||||||||||||||||||||||
| |||||||||||||||||||||||||
| |||||||||||||||||||||||||
| Ortolozi | |||||||||||||||||||||||||
| Vrste | Čovjek | Miš | |||||||||||||||||||||||
| Entrez | |||||||||||||||||||||||||
| Ensembl | |||||||||||||||||||||||||
| UniProt | |||||||||||||||||||||||||
| RefSeq (mRNK) | |||||||||||||||||||||||||
| RefSeq (bjelančevina) | |||||||||||||||||||||||||
| Lokacija (UCSC) | Chr 18: 45.98 – 46.07 Mb | n/a | |||||||||||||||||||||||
| PubMed pretraga | [2] | [3] | |||||||||||||||||||||||
| Wikipodaci | |||||||||||||||||||||||||
| |||||||||||||||||||||||||
Dužina polipeptidnog lanca je 334 aminokiseline, sa molekulskom težinom od 38.858.[7].
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 | ||||
|---|---|---|---|---|---|---|---|---|
| MTRSLFKGNF | WSADILSTIG | YDNIIQHLNN | GRKNCKEFED | FLKERAAIEE | ||||
| RYGKDLLNLS | RKKPCGQSEI | NTLKRALEVF | KQQVDNVAQC | HIQLAQSLRE | ||||
| EARKMEEFRE | KQKLQRKKTE | LIMDAIHKQK | SLQFKKTMDA | KKNYEQKCRD | ||||
| KDEAEQAVSR | SANLVNPKQQ | EKLFVKLATS | KTAVEDSDKA | YMLHIGTLDK | ||||
| VREEWQSEHI | KACEAFEAQE | CERINFFRNA | LWLHVNQLSQ | QCVTSDEMYE | ||||
| QVRKSLEMCS | IQRDIEYFVN | QRKTGQIPPA | PIMYENFYSS | QKNAVPAGKA | ||||
| TGPNLARRGP | LPIPKSSPDD | PNYSLVDDYS | LLYQ |
Funkcija
urediPstpip2 se selektivno eksprimira u makrofazima i makrofagnim prekursorima,[8][9] i to je aktin snop protein koji reguliše formiranje filopodija i makrofagnu pokretljivost.[10]
Profil ekspresije citokina
urediNedostatak PSTPIP2 dovodi do povišenih nivoa cirkulirajućeg medijatora upale in vivo. U asimptomatskih miševa povišeni su samo MIP-1α i IL-6, ali simptomatski miševi kojima nedostaje PSTPIP2 imaju povišene razine cirkulirajućeg IL-6, MIP-1α, TNF-α , CSF-1 i IP-10[11] i smanjene nivoe IL-13.[12][13]
Povezanost s bolestima
urediMisens mutacija I282N dovodi do makrofagno posredovane autoupalne bolesti zvane Lupo Pstpip2 (Pstpip2Lupo/Lupo ). Karakterizira je nekroza kože, upala šaka, ušiju i upalna resorpcija kostiju.[14] Druga mutacija u Pstpip2 , L98P, opisana je kod miševa s hroničnim multifokusnim osteomielitisom (cmo). Ova bolest je također autoupalna i uzrokuje upalni infiltrat [polimorfojedarni leukociti|[polimorfojedarnih leukocita]], makrofaga, limfocita, plazma-ćelija i osteoklasta. Kasnije se infiltrat zamjenjuje novim koštanim tkivom, što dovodi do pregiba repa i deformacija stražnjeg stopala. Na miševima CMO također nastaje upala uha u epidermi, dermi i hrskavici.[15]
Interakcije
urediPSTPIP2 komunicira s tirozin-fosfatazama iz porodice proteina bogatih prolinom, glutaminskom kiselinom, serinom i treoninom (PEST).[16] SHIP1 and Csk[17]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000152229 - 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.
- ^ Wu Y, Dowbenko D, Lasky LA (novembar 1998). "PSTPIP 2, a second tyrosine phosphorylated, cytoskeletal-associated protein that binds a PEST-type protein-tyrosine phosphatase". The Journal of Biological Chemistry. 273 (46): 30487–96. doi:10.1074/jbc.273.46.30487. PMID 9804817.
- ^ "Entrez Gene: PSTPIP2 proline-serine-threonine phosphatase interacting protein 2".
- ^ Chitu V, Stanley ER (mart 2007). "Pombe Cdc15 homology (PCH) proteins: coordinators of membrane-cytoskeletal interactions". Trends in Cell Biology. 17 (3): 145–56. doi:10.1016/j.tcb.2007.01.003. PMID 17296299.
- ^ "UniProt, Q9H939". Pristupljeno September, 2017. Provjerite vrijednost datuma u parametru:
|access-date=(pomoć) - ^ Yeung YG, Soldera S, Stanley ER (novembar 1998). "A novel macrophage actin-associated protein (MAYP) is tyrosine-phosphorylated following colony stimulating factor-1 stimulation". The Journal of Biological Chemistry. 273 (46): 30638–42. doi:10.1074/jbc.273.46.30638. PMID 9804836.
- ^ Grosse J, Chitu V, Marquardt A, Hanke P, Schmittwolf C, Zeitlmann L, Schropp P, Barth B, Yu P, Paffenholz R, Stumm G, Nehls M, Stanley ER (april 2006). "Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease". Blood. 107 (8): 3350–8. doi:10.1182/blood-2005-09-3556. PMC 1895761. PMID 16397132.
- ^ Chitu V, Pixley FJ, Macaluso F, Larson DR, Condeelis J, Yeung YG, Stanley ER (juni 2005). "The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages". Molecular Biology of the Cell. 16 (6): 2947–59. doi:10.1091/mbc.e04-10-0914. PMC 1142438. PMID 15788569.
- ^ Chitu V, Ferguson PJ, de Bruijn R, Schlueter AJ, Ochoa LA, Waldschmidt TJ, Yeung YG, Stanley ER (septembar 2009). "Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice". Blood. 114 (12): 2497–505. doi:10.1182/blood-2009-02-204925. PMC 2746474. PMID 19608749.
- ^ Doherty TM, Kastelein R, Menon S, Andrade S, Coffman RL (decembar 1993). "Modulation of murine macrophage function by IL-13". J. Immunol. 151 (12): 7151–60. PMID 7903102.
- ^ Martinez FO, Sica A, Mantovani A, Locati M (januar 2008). "Macrophage activation and polarization". Front. Biosci. 13 (13): 453–61. doi:10.2741/2692. PMID 17981560.
- ^ Greška kod citiranja: Nevaljana oznaka
<ref>; nije naveden tekst za reference s imenom: 0 - ^ Chitu V, Ferguson PJ, de Bruijn R, Schlueter AJ, Ochoa LA, Waldschmidt TJ, Yeung YG, Stanley ER (septembar 2009). "Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice". Blood. 114 (12): 2497–505. doi:10.1182/blood-2009-02-204925. PMC 2746474. PMID 19608749.
- ^ Veillette A, Rhee I, Souza CM, Davidson D (mart 2009). "PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders". Immunological Reviews. 228 (1): 312–24. doi:10.1111/j.1600-065x.2008.00747.x. PMID 19290936. S2CID 30394426.
- ^ Drobek A, Kralova J, Skopcova T, Kucova M, Novák P, Angelisová P, Otahal P, Alberich-Jorda M, Brdicka T (oktobar 2015). "PSTPIP2, a Protein Associated with Autoinflammatory Disease, Interacts with Inhibitory Enzymes SHIP1 and Csk". Journal of Immunology. 195 (7): 3416–26. doi:10.4049/jimmunol.1401494. PMID 26304991.
Dopunska literatura
uredi- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (januar 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (oktobar 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
- Pope SN, Lee IR (februar 2005). "Yeast two-hybrid identification of prostatic proteins interacting with human sex hormone-binding globulin". The Journal of Steroid Biochemistry and Molecular Biology. 94 (1–3): 203–8. doi:10.1016/j.jsbmb.2005.01.007. PMID 15862967. S2CID 9746088.
- Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S (septembar 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.