PELI2

PELI2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	3EGA, 3EGB
Identifikatori
Aliasi	PELI2
Vanjski ID-jevi	OMIM: 614798 MGI: 1891445 HomoloGene: 41431 GeneCards: PELI2
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	56,301,524 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	48,519,032 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • ubiquitin-ubiquitin ligase activity; • protein serine/threonine kinase activity; • aktivnost sa transferazom; • GO:1904264, GO:1904822, GO:0090622, GO:0090302 ubiquitin protein ligase activity;
Ćelijska komponenta	• citosol;
Biološki proces	• positive regulation of I-kappaB kinase/NF-kappaB signaling; • positive regulation of protein phosphorylation; • protein ubiquitination; • positive regulation of MAPK cascade; • protein polyubiquitination; • protein phosphorylation; • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor; • Toll signaling pathway; • interleukin-1-mediated signaling pathway; • regulation of Toll signaling pathway;
	Izvori:Amigo / QuickGO
Ortolozi
	57161
	93834
	ENSG00000139946
	ENSMUSG00000021846
	Q9HAT8
	Q8BST6
	NM_021255
	NM_033602
	NP_067078
	NP_291080
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Homolog 2 proteina pelino je protein koji je kod ljudi kodiran genom PELI2.^[5]^[6]^[7]

Resch et al. (2001) utvrdili su da se gen PELI2 sastoji od šest egzona. Hibridnom radijacijskom analizom zračenja, mapirali su gen PELI2 u hromosomu 14, sekvenca q21.^[8]^[8]

Pellino proteini, poput PELI2, su međukomponente u urođenim signalnim kaskadama imunskog odgovora koje iniciraju Toll-liki receptori (TLR) i IL1R, a u interakciji su sa homologom Drosophila pelle IRAK1, TRAF6 i NFKB (sažetak Jensen i Whitehead, 2003).

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 420 aminokiselina, a molekulska težina 46 435 Da.^[9]

10	20	30	40	50
MFSPGQEEHC	APNKEPVKYG	ELVVLGYNGA	LPNGDRGRRK	SRFALYKRPK
ANGVKPSTVH	VISTPQASKA	ISCKGQHSIS	YTLSRNQTVV	VEYTHDKDTD
MFQVGRSTES	PIDFVVTDTI	SGSQNTDEAQ	ITQSTISRFA	CRIVCDRNEP
YTARIFAAGF	DSSKNIFLGE	KAAKWKNPDG	HMDGLTTNGV	LVMHPRGGFT
EESQPGVWRE	ISVCGDVYTL	RETRSAQQRG	KLVESETNVL	QDGSLIDLCG
ATLLWRTADG	LFHTPTQKHI	EALRQEINAA	RPQCPVGLNT	LAFPSINRKE
VVEEKQPWAY	LSCGHVHGYH	NWGHRSDTEA	NERECPMCRT	VGPYVPLWLG
CEAGFYVDAG	PPTHAFTPCG	HVCSEKSAKY	WSQIPLPHGT	HAFHAACPFC
ATQLVGEQNC	IKLIFQGPID

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

Pretragom baze podataka, Resch et al. (2001) identificirali su mišje i ljudske homologe Drosophila pellino. Ljudski gen PELI2 kodira protein od 420 aminokiselina.

Funkcija gena

Koprecipitacijom i Western blot analizom, Jensen i Whitehead (2003) pokazali su da PELI2 komunicira s proteinima TRAF6 i TAK1 (MAP3K7), oba nizvodno od IRAK1 u kaskadi TLR / IL1R, ali ne i MYD88, uzvodni protein . Međutim, PELI2, ali ne i PELI1, promovirao je aktivaciju JUN-a i ELK1 fosforilacijom JNK-a (MAPK8).^[10]

Koristeći 2-hibridni skrining kvasca za proteine u interakciji s IRAK4 , Strelow et al. (2003) identificirali su PELI2. Analiza imunoprecipitacije pokazala je interakciju sa IRAK1 i IRAK4, nezavisno od aktivnosti njihovih kinaza. PELI2 je fosforiliran putem kinaza aktivnih IRAK1 i IRAK4. Predložili su da bi PELI2 mogao biti molekula skele koja povezuje signalizaciju receptora Toll/interleukin-1 (TIR) sa općim ćelijskim procesima.^[11] Koristeći snimak faga, nakon čega slijedi analiza imunoprecipitacije, Liu et al. (2004) identificirali su PELI2 i SOCS3, kao interaktivne partnere BCL10, što je odgovor na stimulaciju lipopolisaharida (LPS) u TLR putu. Interakcija se odvija preko ostataka 169 do 233 PELI2 i neizravno je blokirana ekspresijom SOCS3.^[12]

Kim et al. (2012) pokazali su da nokdaun PELI2, ali ne i PELI1, ukida IL1 i LPS-induciranu ubikvitinaciju IRAK1 na lys63 i smanjuje ubikvitinaciju preko lys48. PELI2 je također potreban za aktivaciju NFKB-a zavisnu od TAK1. RT-PCR analiza pokazala je da je PELI2 nokdaun smanjio ekspresiju KC (CXCL1), IL6 i TNF induciranu IL1– i LPS-om u mišjim makrofazima u kasnim vremenskim tačkama, praćenu raspadanjem upalnih gena iRNK. Nokdaun je također umanjio aktivaciju JNK i ERK (MAPK3). Zaključili su da PELI2 ima kritičnu ulogu u posttranskripcijskoj kontroli posredovanoj TLR/IL1R-om.^[13]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000139946 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021846 - 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.
^ Resch K, Jockusch H, Schmitt-John T (Apr 2001). "Assignment of homologous genes, Peli1/PELI1 and Peli2/PELI2, for the Pelle adaptor protein Pellino to mouse chromosomes 11 and 14 and human chromosomes 2p13.3 and 14q21, respectively, by physical and radiation hybrid mapping". Cytogenet Cell Genet. 92 (1–2): 172–4. doi:10.1159/000056895. PMID 11306823.
^ Strelow A, Kollewe C, Wesche H (Jul 2003). "Characterization of Pellino2, a substrate of IRAK1 and IRAK4". FEBS Lett. 547 (1–3): 157–61. doi:10.1016/S0014-5793(03)00697-5. PMID 12860405.
^ "Entrez Gene: PELI2 pellino homolog 2 (Drosophila)".
^ ^a ^b Resch, K., Jockusch, H., Schmitt-John, T. Assignment of homologous genes, Peli1/PELI1 and Peli2/PELI2, for the Pelle adaptor protein Pellino to mouse chromosomes 11 and 14 and human chromosomes 2p13.3 and 14q21, respectively, by physical and radiation hybrid mapping. Cytogenet. Cell Genet. 92: 172-174, 2001. PubMed: 11306823
^ "UniProt, Q9HAT8". Pristupljeno 28. 7. 2021.
^ Jensen, L. E., Whitehead, A. S. Pellino2 activates the mitogen activated protein kinase pathway. FEBS Lett. 545: 199-202, 2003. PubMed: 12804775
^ Strelow, A., Kollewe, C., Wesche, H. Characterization of Pellino2, a substrate of IRAK1 and IRAK4. FEBS Lett. 547: 157-161, 2003. PubMed: 12860405
^ Liu, Y., Dong, W., Chen, L., Xiang, R., Xiao, H., De. G., Wang, Z., Qi, Y. BCL10 mediates lipopolysaccharide/Toll-like receptor-4 signaling through interaction with Pellino2. J. Biol. Chem. 279: 37436-37444, 2004. PubMed: 15213237
^ Kim, T. W., Yu, M., Zhou, H., Cui, W., Wang, J., DiCorleto, P., Fox, P., Xiao, H., Li, X. Pellino 2 is critical for Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated post-transcriptional control. J. Biol. Chem. 287: 25686-25695, 2012. PubMed: 22669975

Dopunska literatura

Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
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.
Liu Y, Dong W, Chen L, et al. (2004). "BCL10 mediates lipopolysaccharide/toll-like receptor-4 signaling through interaction with Pellino2". J. Biol. Chem. 279 (36): 37436–44. doi:10.1074/jbc.M400241200. PMID 15213237.
Jensen LE, Whitehead AS (2003). "Pellino2 activates the mitogen activated protein kinase pathway". FEBS Lett. 545 (2–3): 199–202. doi:10.1016/S0014-5793(03)00533-7. PMID 12804775.
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.
Yu KY, Kwon HJ, Norman DA, et al. (2002). "Cutting edge: mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling". J. Immunol. 169 (8): 4075–8. doi:10.4049/jimmunol.169.8.4075. PMID 12370331.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000139946 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021846 - 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.

[pmid11306823-5] Resch K, Jockusch H, Schmitt-John T (Apr 2001). "Assignment of homologous genes, Peli1/PELI1 and Peli2/PELI2, for the Pelle adaptor protein Pellino to mouse chromosomes 11 and 14 and human chromosomes 2p13.3 and 14q21, respectively, by physical and radiation hybrid mapping". Cytogenet Cell Genet. 92 (1–2): 172–4. doi:10.1159/000056895. PMID 11306823.

[pmid12860405-6] Strelow A, Kollewe C, Wesche H (Jul 2003). "Characterization of Pellino2, a substrate of IRAK1 and IRAK4". FEBS Lett. 547 (1–3): 157–61. doi:10.1016/S0014-5793(03)00697-5. PMID 12860405.

[entrez-7] "Entrez Gene: PELI2 pellino homolog 2 (Drosophila)".

[Resch,_K._p13-8] Resch, K., Jockusch, H., Schmitt-John, T. Assignment of homologous genes, Peli1/PELI1 and Peli2/PELI2, for the Pelle adaptor protein Pellino to mouse chromosomes 11 and 14 and human chromosomes 2p13.3 and 14q21, respectively, by physical and radiation hybrid mapping. Cytogenet. Cell Genet. 92: 172-174, 2001. PubMed: 11306823

[UniProt-9] "UniProt, Q9HAT8". Pristupljeno 28. 7. 2021.

[10] Jensen, L. E., Whitehead, A. S. Pellino2 activates the mitogen activated protein kinase pathway. FEBS Lett. 545: 199-202, 2003. PubMed: 12804775

[11] Strelow, A., Kollewe, C., Wesche, H. Characterization of Pellino2, a substrate of IRAK1 and IRAK4. FEBS Lett. 547: 157-161, 2003. PubMed: 12860405

[12] Liu, Y., Dong, W., Chen, L., Xiang, R., Xiao, H., De. G., Wang, Z., Qi, Y. BCL10 mediates lipopolysaccharide/Toll-like receptor-4 signaling through interaction with Pellino2. J. Biol. Chem. 279: 37436-37444, 2004. PubMed: 15213237

[13] Kim, T. W., Yu, M., Zhou, H., Cui, W., Wang, J., DiCorleto, P., Fox, P., Xiao, H., Li, X. Pellino 2 is critical for Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated post-transcriptional control. J. Biol. Chem. 287: 25686-25695, 2012. PubMed: 22669975

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