Details of Host Protein

Host Protein General Information (ID: PT0599)
Protein Name	HUMAN la-related protein 1 (LARP1)	Gene Name	LARP1
Host Species	Homo sapiens	Uniprot Entry Name	LARP1_HUMAN
Protein Families	LARP family
Subcellular Location	Cytoplasm Cytoplasmic granule
External Link
	NCBI Gene ID	23367
	Uniprot ID	Q6PKG0
	Ensembl ID	ENSG00000155506
	HGNC ID	HGNC:29531
Function in Host	RNA-binding protein that regulates the translation ofspecific target mRNA species downstream of the mTORC1 complex, infunction of growth signals and nutrient availability. Interacts on the one hand with the3' poly-A tails that are present in all mRNA molecules, and on theother hand with the 7-methylguanosine cap structure of mRNAs containinga 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAsencoding ribosomal proteins and several components of the translationmachinery. The interactionwith the 5' end of mRNAs containing a 5'TOP motif leads totranslational repression by preventing the binding of EIF4G1. When mTORC1 is activated, LARP1 is phosphorylated and dissociates fromthe 5' untranslated region (UTR) of mRNA. Does not prevent binding of EIF4G1 to mRNAs that lacka 5'TOP motif. Interacts with the free 40S ribosomesubunit and with ribosomes, both monosomes and polysomes. Under normal nutrient availability, interacts primarily with the 3'untranslated region (UTR) of mRNAs encoding ribosomal proteins andincreases protein synthesis. Associates with actively translating ribosomes and stimulatestranslation of mRNAs containing a 5'TOP motif, thereby regulatingprotein synthesis, and as a consequence, cell growth and proliferation. Stabilizes mRNAs species with a5'TOP motif, which is required to prevent apoptosis. [1-9] Click to Show/Hide
3D Structure	PDB ID: 4ZC4 FASTA Download 2D PNG Download PDB File Download

Function of This Protein During Virus Infection
Virus Name	SARS-COV-2	Protein Function	Anti-viral	[10]
Infected Tissue	Lung	Infection Time	24h; 48 h
Infected Cell	Calu-3 cells (Human lung cancer cell line)	Cellosaurus ID	CVCL_0609
Method Description	To detect the role of host protein LARP1 in viral infection, LARP1 protein knockout Calu-3 cells were infected with SARS-COV-2 for 24 - 48 h , and the effects on infection was detected through qRT-PCR.
Results	It is reported that Knockdown of LARP1 increases SARS-CoV-2 RNA levels compared with control group.

Host Protein - Virus RNA Network

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Full List of Virus RNA Interacting with This Protien
*RNA Region: 3'-UTR (hCoV-19/Not Specified Virus Strain )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[11]
Strains Name	hCoV-19/Not Specified Virus Strain
RNA Binding Region	3'-UTR
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Infection Cells	Huh7 cells (human liver cell line); Calu-3 cells (human lung cancer cell line) (CVCL_0336;CVCL_0609 )
Cell Originated Tissue	Liver; Lung
Interaction Score	P-value < 0.05
Method Description	RNA pull-down assays; liquid chromatography with tandem mass spectrometry (LC-MS/MS); Wilcoxon test; MS2 affinity purification coupled with liquid chromatography-mass spectrometry (MAMS)
*RNA Region: 5'-UTR (hCoV-19/South Korea/KCDC03/2020 )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[10]
Strains Name	hCoV-19/South Korea/KCDC03/2020
Strains Family	Alpha (B.1.1.7)
RNA Binding Region	5'-UTR
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Interaction Type	Directly bind to SARS-CoV-23 RNA's 5' UTR region
Infection Cells	Vero cells (epithelial kidney cell) Vero cells (epithelial kidney cell) (CVCL_0059 )
Cell Originated Tissue	kidney
Infection Time	24 h
Interaction Score	P-adjust < 0.05
Method Description	Modified RNA antisense purification coupled with mass spectrometry (RAP-MS); label-free quantification (LFQ); liquid chromatography with tandem mass spectrometry (LC-MS/MS)
*RNA Region: Not Specified Virus Region (hCov-OC43/VR-759 Quebec/2019 )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[10]
Strains Name	hCov-OC43/VR-759 Quebec/2019
Strains Family	Beta
RNA Binding Region	Not Specified Virus Region
Virus Name	Human coronavirus OC43 (HCov-OC43)
Infection Cells	HCT-8 cells (Human ileocaecal adenocarcinoma cell) HCT-8 cells (Human ileocaecal adenocarcinoma cell) (CVCL_2478 )
Cell Originated Tissue	Ileocecum
Infection Time	12h; 24; 36h; 48h
Interaction Score	p_value < 0.05; FDR < 10%
Method Description	Modified RNA antisense purification coupled with mass spectrometry (RAP-MS); label-free quantification (LFQ); liquid chromatography with tandem mass spectrometry (LC-MS/MS)
*RNA Region: Not Specified Virus Region (hCoV-19/Not Specified Virus Strain )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[12]
Strains Name	hCoV-19/Not Specified Virus Strain
RNA Binding Region	Not Specified Virus Region
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Infection Cells	Huh7 cells (liver carcinoma cell) Huh7 cells (liver carcinoma cell) (CVCL_0336 )
Cell Originated Tissue	Liver
Infection Time	24h
Interaction Score	log2FC = 4.01006E+14
Method Description	RNA antisense purification and quantitative mass spectrometry (RAP-MS); Tandem mass tag (TMT) labelling; liquid chromatography tandem mass spectrometry (LC-MS/MS); Westernblot
*RNA Region: Not Specified Virus Region (hCoV-19/England/02/2020 )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[13]
Strains Name	hCoV-19/England/02/2020
Strains Family	Beta (B.1.351)
RNA Binding Region	Not Specified Virus Region
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Infection Cells	Calu-3 cells (Human lung cancer cell) Calu-3 cells (Human lung cancer cell) (CVCL_0609 )
Cell Originated Tissue	Lung
Infection Time	24 h
Interaction Score	P-adjust = 0.008
Method Description	UV protein-RNA crosslinking; RNA interactome capture (cRIC); RNA antisense purification coupled with mass spectrometry (RAP-MS)

Differential Gene Expression During SARS-COV-2 Infection

GEO Accession: GSE152641

Sample Type: Blood

Samples Details: Healthy Control: 24; COVID-19: 62

Platform: GPL24676 Illumina NovaSeq 6000

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GEO Accession: GSE162835

Sample Type: Nasopharyngeal Swabs

Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3

Platform: GPL24676 Illumina NovaSeq 6000

PNG Download

GEO Accession: GSE175779

Sample Type: Human Bronchial Epithelial Cells

Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)

Platform: GPL18573 Illumina NextSeq 500

PNG Download

Protein Phosphorylation after Virus Infection
S1040 [14] PNG Download
S1056 [14] PNG Download
S143 [14] PNG Download
S220 [14] PNG Download
S517 [14] PNG Download
S521 [15] PNG Download
S521 [14] PNG Download
S546 [15] PNG Download
S546 [14] PNG Download
S548 [15] PNG Download
S548 [14] PNG Download
S75 [14] PNG Download
S766 [15] PNG Download
S766 [14] PNG Download
S774 [15] PNG Download
S774 [14] PNG Download
S823 [14] PNG Download
S824 [15] PNG Download
S824 [14] PNG Download
S830 [14] PNG Download
S847 [14] PNG Download
S849 [14] PNG Download
S853 [14] PNG Download
S90 [14] PNG Download
T1071 [15] PNG Download
T1071 [14] PNG Download
T1074 [14] PNG Download
T137 [14] PNG Download
T138 [14] PNG Download
T376 [14] PNG Download
T515 [14] PNG Download
T526 [15] PNG Download
T526 [14] PNG Download
T647 [14] PNG Download
T649 [15] PNG Download
T649 [14] PNG Download
T724 [14] PNG Download
T769 [14] PNG Download
T865 [14] PNG Download

Potential Drug(s) that Targets This Protein
Drug Name	DrunkBank ID	Pubchem ID	TTD ID	REF
(-)-Rapamycin	DB12017	.	D0V15HJ	[16]
Rapamycin	DB12016	.	D0V14HJ	[16]
Sapanisertib	DB11836	45375953	D03DPZ	[17]
Sapanisertib	DB12015	.	D0V13HJ	[16]
SIROLIMUS	DB00877	5284616	D03LJR	[17]
Ulocuplumab	DB12018	.	D0V16HJ	[16]
Ulocuplumab	DB12018	.	D0V16HJ	[16]

Protein Sequence Information
MATQVEPLLPGGATLLQAEEHGGLVRKKPPPAPEGKGEPGPNDVRGGEPDGSARRPRPPCAKPHKEGTGQQERESPRPLQLPGAEGPAISDGEEGGGEPGAGGGAAGAAGAGRRDFVEAPPPKVNPWTKNALPPVLTTVNGQSPPEHSAPAKVVRAAVPKQRKGSKVGDFGDAINWPTPGEIAHKSVQPQSHKPQPTRKLPPKKDMKEQEKGEGSDSKESPKTKSDESGEEKNGDEDCQRGGQKKKGNKHKWVPLQIDMKPEVPREKLASRPTRPPEPRHIPANRGEIKGSESATYVPVAPPTPAWQPEIKPEPAWHDQDETSSVKSDGAGGARASFRGRGRGRGRGRGRGRGGTRTHFDYQFGYRKFDGVEGPRTPKYMNNITYYFDNVSSTELYSVDQELLKDYIKRQIEYYFSVDNLERDFFLRRKMDADGFLPITLIASFHRVQALTTDISLIFAALKDSKVVEIVDEKVRRREEPEKWPLPPIVDYSQTDFSQLLNCPEFVPRQHYQKETESAPGSPRAVTPVPTKTEEVSNLKTLPKGLSASLPDLDSENWIEVKKRPRPSPARPKKSEESRFSHLTSLPQQLPSQQLMSKDQDEQEELDFLFDEEMEQMDGRKNTFTAWSDEESDYEIDDRDVNKILIVTQTPHYMRRHPGGDRTGNHTSRAKMSAELAKVINDGLFYYEQDLWAEKFEPEYSQIKQEVENFKKVNMISREQFDTLTPEPPVDPNQEVPPGPPRFQQVPTDALANKLFGAPEPSTIARSLPTTVPESPNYRNTRTPRTPRTPQLKDSSQTSRFYPVVKEGRTLDAKMPRKRKTRHSSNPPLESHVGWVMDSREHRPRTASISSSPSEGTPTVGSYGCTPQSLPKFQHPSHELLKENGFTQHVYHKYRRRCLNERKRLGIGQSQEMNTLFRFWSFFLRDHFNKKMYEEFKQLALEDAKEGYRYGLECLFRYYSYGLEKKFRLDIFKDFQEETVKDYEAGQLYGLEKFWAFLKYSKAKNLDIDPKLQEYLGKFRRLEDFRVDPPMGEEGNHKRHSVVAGGGGGEGRKRCPSQSSSRPAAMISQPPTPPTGQPVREDAKWTSQHSNTQTLGK Click to Show/Hide

References
1	Autogenous Control of 5 TOP mRNA Stability by 40S Ribosomes. Mol Cell. 2017 Jul 6;67(1):55-70.e4.
2	Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5 TOP mRNA translation. Genes Dev. 2014 Feb 15;28(4):357-71.
3	La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region. Nucleic Acids Res. 2018 Feb 16;46(3):1457-1469.
4	LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs. Elife. 2017 Jun 26;6:e25237.
5	La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs. Elife. 2017 Apr 7;6:e24146.
6	The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5 TOP sequence. Nucleic Acids Res. 2015 Sep 18;43(16):8077-88.
7	La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). J Biol Chem. 2015 Jun 26;290(26):15996-6020.
8	LARP1 specifically recognizes the 3 terminus of poly(A) mRNA. FEBS Lett. 2013 Jul 11;587(14):2173-8.
9	The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration. Nucleic Acids Res. 2010 Sep;38(16):5542-53.
10	The SARS-CoV-2 RNA interactome. Mol Cell. 2021 Jul 1;81(13):2838-2850.e6.
11	Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
12	The SARS-CoV-2 RNA-protein interactome in infected human cells. Nat Microbiol. 2021 Mar;6(3):339-353.
13	Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection. Mol Cell. 2021 Jul 1;81(13):2851-2867.e7.
14	Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
15	The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
16	A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv. 2020 Mar 22;2020.03.22.002386.
17	A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 Jul;583(7816):459-468.

Details of Host Protein

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