LARP1

LARP1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4ZC4, 5C0V
Identifikatori
Aliasi	LARP1
Vanjski ID-jevi	OMIM: 612059 MGI: 1890165 HomoloGene: 9089 GeneCards: LARP1
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	154,817,605 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	57,952,860 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• RNA cap binding; • translation activator activity; • translation initiation factor binding; • GO:0001948, GO:0016582 vezivanje za proteine; • eukaryotic initiation factor 4E binding; • mRNA 3'-UTR binding; • mRNA 5'-UTR binding; • vezivanje sa RNK; • cadherin binding; • RNA 7-methylguanosine cap binding; • ribosomal small subunit binding;
Ćelijska komponenta	• citoplazma; • TORC1 complex; • membrana; • polysome; • cytoplasmic stress granule; • polysomal ribosome;
Biološki proces	• translational initiation; • positive regulation of macroautophagy; • positive regulation of viral genome replication; • Ćelijska proliferacija; • TOR signaling; • Biosinteza bjelančevina; • positive regulation of translation; • negative regulation of translation; • TORC1 signaling; • mRNA stabilization; • cellular response to rapamycin; • response to amino acid starvation; • regulation of translation; • negative regulation of translational initiation;
	Izvori:Amigo / QuickGO
Ortolozi
	23367
	73158
	ENSG00000155506
	ENSMUSG00000037331
	Q6PKG0
	Q6ZQ58
NM_015315; NM_033551; NM_001367713; NM_001367714; NM_001367715;
	NM_001367716; NM_001367717; NM_001367718; NM_001367719
	NM_028451
NP_056130; NP_001354642; NP_001354643; NP_001354644; NP_001354645;
	NP_001354646; NP_001354647; NP_001354648; NP_291029
	NP_082727
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

La-srodni protein 1 (LARP1) jest protein od kDa, koji je kod ljudi kodiran genom LARP1 sa hromosoma 5.^[5]^[6]^[7] LARP1 je nova sisarska meta na signalnom putu rapamicinskog kompleksa 1 (mTORC1), često hiperaktiviranog sklopa u karcinomu koji regulira rast i proliferaciju ćelija prvenstveno regulacijom sinteze proteina.^[8]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.096 aminokiselina, а molekulska težina 123.510 Da.^[9]

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
MATQVEPLLP	GGATLLQAEE	HGGLVRKKPP	PAPEGKGEPG	PNDVRGGEPD
GSARRPRPPC	AKPHKEGTGQ	QERESPRPLQ	LPGAEGPAIS	DGEEGGGEPG
AGGGAAGAAG	AGRRDFVEAP	PPKVNPWTKN	ALPPVLTTVN	GQSPPEHSAP
AKVVRAAVPK	QRKGSKVGDF	GDAINWPTPG	EIAHKSVQPQ	SHKPQPTRKL
PPKKDMKEQE	KGEGSDSKES	PKTKSDESGE	EKNGDEDCQR	GGQKKKGNKH
KWVPLQIDMK	PEVPREKLAS	RPTRPPEPRH	IPANRGEIKG	SESATYVPVA
PPTPAWQPEI	KPEPAWHDQD	ETSSVKSDGA	GGARASFRGR	GRGRGRGRGR
GRGGTRTHFD	YQFGYRKFDG	VEGPRTPKYM	NNITYYFDNV	SSTELYSVDQ
ELLKDYIKRQ	IEYYFSVDNL	ERDFFLRRKM	DADGFLPITL	IASFHRVQAL
TTDISLIFAA	LKDSKVVEIV	DEKVRRREEP	EKWPLPPIVD	YSQTDFSQLL
NCPEFVPRQH	YQKETESAPG	SPRAVTPVPT	KTEEVSNLKT	LPKGLSASLP
DLDSENWIEV	KKRPRPSPAR	PKKSEESRFS	HLTSLPQQLP	SQQLMSKDQD
EQEELDFLFD	EEMEQMDGRK	NTFTAWSDEE	SDYEIDDRDV	NKILIVTQTP
HYMRRHPGGD	RTGNHTSRAK	MSAELAKVIN	DGLFYYEQDL	WAEKFEPEYS
QIKQEVENFK	KVNMISREQF	DTLTPEPPVD	PNQEVPPGPP	RFQQVPTDAL
ANKLFGAPEP	STIARSLPTT	VPESPNYRNT	RTPRTPRTPQ	LKDSSQTSRF
YPVVKEGRTL	DAKMPRKRKT	RHSSNPPLES	HVGWVMDSRE	HRPRTASISS
SPSEGTPTVG	SYGCTPQSLP	KFQHPSHELL	KENGFTQHVY	HKYRRRCLNE
RKRLGIGQSQ	EMNTLFRFWS	FFLRDHFNKK	MYEEFKQLAL	EDAKEGYRYG
LECLFRYYSY	GLEKKFRLDI	FKDFQEETVK	DYEAGQLYGL	EKFWAFLKYS
KAKNLDIDPK	LQEYLGKFRR	LEDFRVDPPM	GEEGNHKRHS	VVAGGGGGEG
RKRCPSQSSS	RPAAMISQPP	TPPTGQPVRE	DAKWTSQHSN	TQTLGK

Funkcija

LARP1 je najveći od sedam članova porodice proteina LARP (ostali su: LARP1B, LARP3 (poznat i kao originalni La ili SSB), LARP4A, LARP4B, LARP6 i LARP7).^[10] Svi LARP oni, uključujući ljudske LARP, sadrže po dva konzervirana područja. Prva konzervirana regija dijeli homologiju s La proteinima (naziva se La motiv, dok je druga konzervirana regija (nazvana LA-motiv) ograničena na LARP proteine. LARP1 i 1B takođe sadrže konzerviranu "DM15 regiju" unutar svog C-kraja.^[11] Ova regija je jedinstvena i pokazalo se da je potrebna za vezanje RNK. Mišji Larp1 eksprimiran je u dorzalnim korijenima ganglija i kičmenoj moždini, kao i u organima u razvoju koje karakteriziraju interakcije epitel-mezenhim.^[6] Ljudski LARP1 prisutan je u niskim razinama u normalnim, neembrionskim ćelijama, ali je visoko izražen u epitelnim karcinomima (kao što su na jajnicima, debelom crijevu, prostati, nemaloćelijski pluća, hepatoćelijski i grliću maternice).^[12]^[13]^[14]^[15] Neka istraživanja pokazala su da visoka razina proteina LARP1 korelira s lošijom prognozom kod pacijenata s rakom.^[16]^[17]

LARP1 se veže i regulira translaciju terminalnih oligopirimidinskih motiva (TOP iRNK) i može direktno stupiti u interakciju s 5' kap iRNK.^[18]^[19] Također je pokazano da stupa u interakciju s 3' krajem i kodirajućim regijama (CDS) ostalih gena.^[18] LARP1 protein kolokalizira sa stresnim granulama i P-tijelima,^[20] koji funkcioniraju u skladištenju i razgradnji RNK. Predloženo je da LARP1 funkcionira u P-tijelima, kako bi smanjio broj konzerviranih iRNK Ras-MAPK. Grupa homologa LARP1-a može funkcionirati u kontroli ekspresije ključnih razvojnih regulatora.^[20]

Nekoliko je studija pokazalo da nedostatak LARP1 selektivno utiče na regrutiranje TOP iRNK u polisomima. U nekim ćelijamama raka, nedostatak LARP1 smanjuje proliferaciju i aktivira apoptotsku ćelijsku smrt.^[14] Iako je prijavljeno smanjenje količine proteina kodiranih sa TOP iRNK u utišanim ćelijama LARP1, neki vjeruju da to može biti jednostavno objašnjeno smanjenim brojem TOP transkripata iRNK u ćelijama s nedostatkom LARP1.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000155506 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000037331 - 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.
^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (oktobar 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
^ ^a ^b Chauvet S, Maurel-Zaffran C, Miassod R, Jullien N, Pradel J, Aragnol D (juli 2000). "dlarp, a new candidate Hox target in Drosophila whose orthologue in mouse is expressed at sites of epithelium/mesenchymal interactions". Developmental Dynamics. 218 (3): 401–13. doi:10.1002/1097-0177(200007)218:3<401::AID-DVDY1009>3.0.CO;2-6. PMID 10878606.
^ Db=gene&Cmd=ShowDetailView&TermToSearch=23367 "Entrez Gene: LARP1 La ribonucleoprotein domain family, member 1" Provjerite vrijednost parametra |url= (pomoć).
^ Tcherkezian J, Cargnello M, Romeo Y, Huttlin EL, Lavoie G, Gygi SP, Roux PP (Feb 2014). "Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5'TOP mRNA translation". Genes Dev. 28 (4): 357–71. doi:10.1101/gad.231407.113. PMC 3937514. PMID 24532714.
^ "UniProt, Q6PKG0" (jezik: engleski). Pristupljeno 16. 10. 2021.
^ Bousquet-Antonelli C, Deragon JM (maj 2009). "A comprehensive analysis of the La-motif protein superfamily". RNA. 15 (5): 750–64. doi:10.1261/rna.1478709. PMC 2673062. PMID 19299548.
^ Lahr RM, Mack SM, Héroux A, Blagden SP, Bousquet-Antonelli C, Deragon JM, Berman AJ (septembar 2015). "The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence". Nucleic Acids Research. 43 (16): 8077–88. doi:10.1093/nar/gkv748. PMC 4652764. PMID 26206669.
^ Stavraka C, Blagden S (oktobar 2015). "The La-Related Proteins, a Family with Connections to Cancer". Biomolecules. 5 (4): 2701–22. doi:10.3390/biom5042701. PMC 4693254. PMID 26501340.
^ Mura M, Hopkins TG, Michael T, Abd-Latip N, Weir J, Aboagye E, Mauri F, Jameson C, Sturge J, Gabra H, Bushell M, Willis AE, Curry E, Blagden SP (septembar 2015). "LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression". Oncogene. 34 (39): 5025–36. doi:10.1038/onc.2014.428. PMC 4430325. PMID 25531318.
^ ^a ^b Hopkins TG, Mura M, Al-Ashtal HA, Lahr RM, Abd-Latip N, Sweeney K, et al. (februar 2016). "The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer". Nucleic Acids Research. 44 (3): 1227–46. doi:10.1093/nar/gkv1515. PMC 4756840. PMID 26717985.
^ Xie C, Huang L, Xie S, Xie D, Zhang G, Wang P, Peng L, Gao Z (oktobar 2013). "LARP1 predict the prognosis for early-stage and AFP-normal hepatocellular carcinoma". Journal of Translational Medicine. 11: 272. doi:10.1186/1479-5876-11-272. PMC 3814951. PMID 24159927.
^ Ye L, Lin ST, Mi YS, Liu Y, Ma Y, Sun HM, Peng ZH, Fan JW (novembar 2016). "Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target". Tumour Biology. 37 (11): 14585–14594. doi:10.1007/s13277-016-5332-3. PMC 5126195. PMID 27614686.
^ Xu Z, Xu J, Lu H, Lin B, Cai S, Guo J, Zang F, Chen R (decembar 2017). "LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma". Oncology Reports. 38 (6): 3659–3667. doi:10.3892/or.2017.6040. PMID 29039571.
^ ^a ^b Hong S, Freeberg MA, Han T, Kamath A, Yao Y, Fukuda T, Suzuki T, Kim JK, Inoki K (juni 2017). "LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs". eLife. 6. doi:10.7554/elife.25237. PMC 5484620. PMID 28650797.
^ Lahr RM, Fonseca BD, Ciotti GE, Al-Ashtal HA, Jia JJ, Niklaus MR, Blagden SP, Alain T, Berman AJ (april 2017). "La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs". eLife. 6. doi:10.7554/elife.24146. PMC 5419741. PMID 28379136.
^ ^a ^b Nykamp K, Lee MH, Kimble J (juli 2008). "C. elegans La-related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis". RNA. 14 (7): 1378–89. doi:10.1261/rna.1066008. PMC 2441978. PMID 18515547.

Dopunska literatura

Horke S, Reumann K, Schweizer M, Will H, Heise T (juni 2004). "Nuclear trafficking of La protein depends on a newly identified nucleolar localization signal and the ability to bind RNA". The Journal of Biological Chemistry. 279 (25): 26563–70. doi:10.1074/jbc.M401017200. PMID 15060081.
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (august 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T (august 2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Current Biology. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660. S2CID 2371325.
Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (oktobar 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (novembar 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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000155506 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000037331 - 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.

[pmid9872452-5] Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (oktobar 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.

[pmid10878606-6] Chauvet S, Maurel-Zaffran C, Miassod R, Jullien N, Pradel J, Aragnol D (juli 2000). "dlarp, a new candidate Hox target in Drosophila whose orthologue in mouse is expressed at sites of epithelium/mesenchymal interactions". Developmental Dynamics. 218 (3): 401–13. doi:10.1002/1097-0177(200007)218:3<401::AID-DVDY1009>3.0.CO;2-6. PMID 10878606.

[entrez-7] Db=gene&Cmd=ShowDetailView&TermToSearch=23367 "Entrez Gene: LARP1 La ribonucleoprotein domain family, member 1" Provjerite vrijednost parametra |url= (pomoć).

[8] Tcherkezian J, Cargnello M, Romeo Y, Huttlin EL, Lavoie G, Gygi SP, Roux PP (Feb 2014). "Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5'TOP mRNA translation". Genes Dev. 28 (4): 357–71. doi:10.1101/gad.231407.113. PMC 3937514. PMID 24532714.

[UniProt-9] "UniProt, Q6PKG0" (jezik: engleski). Pristupljeno 16. 10. 2021.

[10] Bousquet-Antonelli C, Deragon JM (maj 2009). "A comprehensive analysis of the La-motif protein superfamily". RNA. 15 (5): 750–64. doi:10.1261/rna.1478709. PMC 2673062. PMID 19299548.

[11] Lahr RM, Mack SM, Héroux A, Blagden SP, Bousquet-Antonelli C, Deragon JM, Berman AJ (septembar 2015). "The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence". Nucleic Acids Research. 43 (16): 8077–88. doi:10.1093/nar/gkv748. PMC 4652764. PMID 26206669.

[12] Stavraka C, Blagden S (oktobar 2015). "The La-Related Proteins, a Family with Connections to Cancer". Biomolecules. 5 (4): 2701–22. doi:10.3390/biom5042701. PMC 4693254. PMID 26501340.

[13] Mura M, Hopkins TG, Michael T, Abd-Latip N, Weir J, Aboagye E, Mauri F, Jameson C, Sturge J, Gabra H, Bushell M, Willis AE, Curry E, Blagden SP (septembar 2015). "LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression". Oncogene. 34 (39): 5025–36. doi:10.1038/onc.2014.428. PMC 4430325. PMID 25531318.

[Hopkins_2016-14] Hopkins TG, Mura M, Al-Ashtal HA, Lahr RM, Abd-Latip N, Sweeney K, et al. (februar 2016). "The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer". Nucleic Acids Research. 44 (3): 1227–46. doi:10.1093/nar/gkv1515. PMC 4756840. PMID 26717985.

[15] Xie C, Huang L, Xie S, Xie D, Zhang G, Wang P, Peng L, Gao Z (oktobar 2013). "LARP1 predict the prognosis for early-stage and AFP-normal hepatocellular carcinoma". Journal of Translational Medicine. 11: 272. doi:10.1186/1479-5876-11-272. PMC 3814951. PMID 24159927.

[16] Ye L, Lin ST, Mi YS, Liu Y, Ma Y, Sun HM, Peng ZH, Fan JW (novembar 2016). "Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target". Tumour Biology. 37 (11): 14585–14594. doi:10.1007/s13277-016-5332-3. PMC 5126195. PMID 27614686.

[17] Xu Z, Xu J, Lu H, Lin B, Cai S, Guo J, Zang F, Chen R (decembar 2017). "LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma". Oncology Reports. 38 (6): 3659–3667. doi:10.3892/or.2017.6040. PMID 29039571.

[Hong_2017-18] Hong S, Freeberg MA, Han T, Kamath A, Yao Y, Fukuda T, Suzuki T, Kim JK, Inoki K (juni 2017). "LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs". eLife. 6. doi:10.7554/elife.25237. PMC 5484620. PMID 28650797.

[Lahr_Fonseca_Ciotti_Al-Ashtal_p.-19] Lahr RM, Fonseca BD, Ciotti GE, Al-Ashtal HA, Jia JJ, Niklaus MR, Blagden SP, Alain T, Berman AJ (april 2017). "La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs". eLife. 6. doi:10.7554/elife.24146. PMC 5419741. PMID 28379136.

[Nykamp_2008-20] Nykamp K, Lee MH, Kimble J (juli 2008). "C. elegans La-related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis". RNA. 14 (7): 1378–89. doi:10.1261/rna.1066008. PMC 2441978. PMID 18515547.

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