pre-miRNA Information | |
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pre-miRNA | hsa-mir-4307 |
Genomic Coordinates | chr14: 26908642 - 26908725 |
Description | Homo sapiens miR-4307 stem-loop |
Comment | None |
RNA Secondary Structure | ![]() |
Mature miRNA Information | ||||||||||||||||||||||||||||
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Mature miRNA | hsa-miR-4307 | |||||||||||||||||||||||||||
Sequence | 56| AAUGUUUUUUCCUGUUUCC |74 | |||||||||||||||||||||||||||
Evidence | Experimental | |||||||||||||||||||||||||||
Experiments | SOLiD | |||||||||||||||||||||||||||
SNPs in miRNA |
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Putative Targets |
miRNA Expression profile | |
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Human miRNA Tissue Atlas | |
Circulating MicroRNA Expression Profiling |
Gene Information | |||||||||||||||||||||
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Gene Symbol | INIP | ||||||||||||||||||||
Synonyms | C9orf80, HSPC043, MISE, SOSSC, SSBIP1, hSSBIP1 | ||||||||||||||||||||
Description | INTS3 and NABP interacting protein | ||||||||||||||||||||
Transcript | NM_021218 | ||||||||||||||||||||
Expression | |||||||||||||||||||||
Putative miRNA Targets on INIP | |||||||||||||||||||||
3'UTR of INIP (miRNA target sites are highlighted) |
>INIP|NM_021218|3'UTR 1 AGAAAACATTTGCGATGGAAAAGTGACTTTGTAATATCAAATGCCAAAGCTACTATCATTCAGTGCTACATGAACTGTGA 81 CTTTAAGAATTTTGGTGAACTTTGATATTTTTTGTTTGTCTGAAAGAAAGGAATGTGTAAGTGAAAGCTGAAAGAAGAAT 161 AACCAGGATGATGAGAGCTGTGGAAGCTGTATCGTCCAAGGAATTGATTATGTACCGTGACTGTAACTTTTTTGTAATGC 241 TGTTTAACTCTCAATCAGACTGTGAACTGGATGGTCACGAAGTCATTCCCCAACTCCTAGCAAGTTTGACTGAATATATC 321 ATGTCCACAGTAGATTTTCAAGAATCATTTATAGTACTTAACTTTAAAGAAACAAGGCTGCTTTTAAAAAATGAACTAAT 401 AGGCTTAAATCAATTGCATCCATATTTGCTGTTTATAGGATTGCTATCAGTATACCTTTTGCGTTTATAGTCAACATGTA 481 TCATCCTGAAATATTCTTTCTGGACTTATAACTACTTCCCCCTTTTTCACTTTAAAACAAACCTCAAGAATAAATTACTA 561 ACCAGTCTTAACCATCTTTTATAAACATATGCTCTTATAAATGTTGTGACTAGATGCAATTAAAAATAATAGGGAATGTG 641 GTAGGTTTTTAATTTGTACATCCTCTTATTTAGTGTTACCACATAAATGATGAGTTTGTGTGGTTCTGTTTTCCATTTTT 721 GTTCTAACTGAAAACTTTTTGGCTGGGCACGGTGCCTCATGCCTGTAATCCCAGCACTTTGGGAGGCCAAGGCGGGCAGA 801 TCACTTGAGATCAGGAGTTTGAGACCAGCCTGGCCAACATGGTGAAACCCTGTCTCTACTAAAAGTATAAAAAATTAGCC 881 ATGTGTGGTGGCACACGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCAGGAGAATCGCTTGAACCTGGGAGGCAGGGG 961 TTGCAGTGAGCTGAGACGGTGTCACTGCACTCCAGCCTGGGTGACAGTGAGTCTTTGTCTCAAAGAAAAAAAGAAAAAGA 1041 AAACTTATGCAAGTCGAGCTCCTTTTTAATTAAGTAGGAAGGGATTAGGTTAAGAAAGTCTCTCAACATGACCCATCTTT 1121 AGCAGTATCTGGGGTGCTTATTTAAGTATGCAGTCCCACTACCCTACCCTAGTCCTACAGAATTAGAATCTGATTCAAAA 1201 TAAAGTCTGAAAACCATGAGATAGAGAATTCTATGAAATATCTTGTACAGATTTTCGTGATATATTTATACACGCATGGG 1281 TTTGTAGATCCCTGAAACTTAGAGGTCATTTAGCTAAAATCTACATTTTTTTTAACTTTTAATAGGATTGAAATGATATT 1361 TTACACTGTATCACAGATACAGTATTTTATATAACTTTTTGTAACTGACCTTATCTTGGCCTTGAGTCCCATCCTCTCTG 1441 GTGGTAGCGTAAAACTGAAAATTCCAGTTTGGGTCAATATTTAGTGAAAGTTCTACTTTCTTTTCAGAGAGTTTGTTCCC 1521 CCCTTTCTTCCTTAGATGTTTTCAAACACACAGCCCCATCCTACTCAAACCAAGTGAAGCAAGAGTGGACAATTCTAGAA 1601 TTGGCTGTGCCATGTAGGTTTTTTTTAGAATTTGAACTGATTTCCTTCATTTTGATGAGGTGGCAACTGTCCCCATTGTA 1681 ATGGTCACCATTGCAGCGAGGATAGCCTTACTTCTGCGGCGCAGAGCTCCTCAGGGGGCCTCTGGCTCCTGTCCTTCCTC 1761 AGGTCCATCCAACTACTCCTTGGGCCTCCTTATGGTAGCCCTCATTGTCTTGAGTTGATTTCACTAGGTTTCTGTTCTCT 1841 GTCATCTGCAACATAACTGACATGGTTCTAAATCTGTCTCTAAGGAGATAACACATTAGTATATTTTCTACACTATTGAA 1921 GCCTCTACCTAATGTATGACTTTTGTAGCTCAGGTAAAGAGATCTTTTTACCAGTGTTATCGTTTCTAGTCTGTTTGTTA 2001 GTCTTCTTTTAAATAGATATGGCCTAAATCCTGTATTCCTGGCTAGGAAGCACTTCTCTCCACCCCTCTGCTTTGAGTTA 2081 CAAATTCAATTCAATTTCCTATGTATTTATTAATACCTACAGATAAAGTACTGTGCTTTGGGGGACACAAAGGTGACTGG 2161 TACCTGCTCTTTTAGGAGGTCACCGTGCAGAGGATCCTATTCTGGTACACCAATAGTTATAAAGCAAGCCACAGCCTAGG 2241 CAACATAGTGAGACCCCTGTCTCTACTAAAAAATTAAAAAAAAAAAAAAAAGATTGGCTAGGTGTGCTGGTGCATGCATA 2321 GAGTCCCAGCCACTCGGGAGGCTGAGGTGGGAGGATTGCTTGAGCCTGGGAGGTTGAGGCTGCAGTGGGCCATGATTGCA 2401 CAACTTGGCAACAGAGTGAGACCCTGTCTCTAAATCAATCAATCAAGCGAGCCAGAATGCAGTAGTGGCCTGAGAGAGGC 2481 ATCCTGGAACGCAGTGCGGTCTGGCTAGGCTTAGAAGTATTCATGTGATTTTTACCTGACAAGGGAAGGAAGAGCTGCTC 2561 CACGTGCAGAGCAAGGTTTCAGAATGAGAGGAGAAGAGCAGGCACTGCAGAGGGTGAGGGAAAGGGCAGCAGTGGACTGG 2641 GAAGCCCTCAGGTGGAGGTCAGCATTGCTTCCCTCAGATCATGGGTGAATTTGAGGAACTCAGTTAATATCTTTGTATGT 2721 TCCTCCCTCCATAAGGTGAGAACAAGCACATGCTCTGCCCATGTCAGAAATTGTCTAGACTAGTGTTTTTCAAAGTGCAA 2801 AAGCCTCAACCCATTACTGAGTTGAGAAGCCAACTTAATGGTTTAACAGGATTGACCAGCATTTTTTCCGAAAAAATCAA 2881 AAACATCTGAGTGTACTGCATATAGAAATAGGTGGTTTTGCCTCATGAATATTCTGTTTCTGTGTGTTCCTATATTTTAC 2961 TTTGTATTGTGTTGGTTTTTTAAGAGACAGTCCTGCTCTGTCATCCAGGCTGGAGTGCAGTGGTATAATCATAGCTCACT 3041 GCAAGACTCCTTGAATCCCTGGGCTCAAGCAATCCTCAACCCTTAGCCTCCCAAGTAGCTGAGACTACAGGCACATGCCA 3121 CCATGCCCAGCTAATTTTTTTTTTTTTTTAATTTTTGTAGAGACAGCATCTTGCTATGTTGCCCAGGCTGGTCTTGAACT 3201 CTTGGCCTCAAGCAGTCCTCTCGATCCTCCCACCTTGGCCTCCTAAAGTGCTGAGATTACAGGTGTGAGCCACTGCATCT 3281 GGCTTACTTATTTTGTCTATTGTCTGTTCCACTAGTATGTAAAGTCTTAGAGAGCAAGAATTTTTGTTTATTTCTTTCTC 3361 TTCCTCCTTTCCTTTCTTCCTCTTTTACTTCGTTCACTACTGTATTCCACATAAAATATATTTGGCATATAGTAGGTGTT 3441 CAATATGTTGAAGGAATGAAAGAATTTATAGACTTGAGTTGCAATATAAAATGTATTTTTTTTTACTGTGAGTTATGGCA 3521 AAAAAAGTTTTGAAAGCCGCTTCTAAATAATGCAGATGTCAGTGCTTTGACCCTGGAATAAAAACTGAAA Target sites
Provided by authors
Predicted by miRanda
DRVs
SNPs
DRVs & SNPs
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miRNA-target interactions (Predicted by miRanda) |
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DRVs in gene 3'UTRs | |||||||||||||||||||||
SNPs in gene 3'UTRs |
Experimental Support 1 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | hESCs (WA-09) |
Disease | 58493.0 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
"PAR-CLIP data was present in SRR359787. RNA binding protein: AGO2. Condition:4-thiouridine
... - Lipchina I; Elkabetz Y; Hafner M; Sheridan et al., 2011, Genes & development. |
Article |
- Lipchina I; Elkabetz Y; Hafner M; Sheridan et al. - Genes & development, 2011
MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due to the lack of genome-wide strategies to identify their targets. Here, we performed comprehensive microRNA profiling in hESCs and in purified neural and mesenchymal derivatives. Using a combination of AGO cross-linking and microRNA perturbation experiments, together with computational prediction, we identified the targets of the miR-302/367 cluster, the most abundant microRNAs in hESCs. Functional studies identified novel roles of miR-302/367 in maintaining pluripotency and regulating hESC differentiation. We show that in addition to its role in TGF-beta signaling, miR-302/367 promotes bone morphogenetic protein (BMP) signaling by targeting BMP inhibitors TOB2, DAZAP2, and SLAIN1. This study broadens our understanding of microRNA function in hESCs and is a valuable resource for future studies in this area.
LinkOut: [PMID: 22012620]
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CLIP-seq Support 1 for dataset SRR359787 | |
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Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | hESCs (WA-09) / 4-thiouridine, RNase T1 |
Location of target site | ENST00000374242.4 | 3UTR | UCUUAACCAUCUUUUAUAAACAUAUGCUCUUAUAAAUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 22012620 / SRX103431 |
CLIP-seq Viewer | Link |
MiRNA-Target Expression Profile | |||||||
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MiRNA-Target Expression Profile (TCGA) | |||||||
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107 hsa-miR-4307 Target Genes:
Functional analysis:
ID![]() |
Target | Description | Validation methods |
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Strong evidence | Less strong evidence | |||||||||||
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MIRT091681 | RARB | retinoic acid receptor beta | ![]() |
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2 | 6 | ||||||
MIRT097311 | AGGF1 | angiogenic factor with G-patch and FHA domains 1 | ![]() |
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2 | 2 | ||||||
MIRT099878 | SOX4 | SRY-box 4 | ![]() |
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2 | 2 | ||||||
MIRT114514 | ARF6 | ADP ribosylation factor 6 | ![]() |
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2 | 2 | ||||||
MIRT163479 | WNT5A | Wnt family member 5A | ![]() |
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2 | 2 | ||||||
MIRT186633 | COX20 | COX20, cytochrome c oxidase assembly factor | ![]() |
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2 | 8 | ||||||
MIRT194921 | TNRC6A | trinucleotide repeat containing 6A | ![]() |
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2 | 2 | ||||||
MIRT230189 | AKAP17A | A-kinase anchoring protein 17A | ![]() |
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2 | 2 | ||||||
MIRT281397 | MAPK6 | mitogen-activated protein kinase 6 | ![]() |
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2 | 2 | ||||||
MIRT328018 | RLIM | ring finger protein, LIM domain interacting | ![]() |
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2 | 2 | ||||||
MIRT354896 | SEC62 | SEC62 homolog, preprotein translocation factor | ![]() |
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2 | 2 | ||||||
MIRT361422 | PNRC1 | proline rich nuclear receptor coactivator 1 | ![]() |
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2 | 2 | ||||||
MIRT442526 | MOB3B | MOB kinase activator 3B | ![]() |
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2 | 2 | ||||||
MIRT442629 | NUDT12 | nudix hydrolase 12 | ![]() |
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2 | 2 | ||||||
MIRT442685 | SLC39A9 | solute carrier family 39 member 9 | ![]() |
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2 | 2 | ||||||
MIRT444131 | BRCA2 | BRCA2, DNA repair associated | ![]() |
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2 | 2 | ||||||
MIRT444174 | RBM7 | RNA binding motif protein 7 | ![]() |
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2 | 2 | ||||||
MIRT446045 | TPR | translocated promoter region, nuclear basket protein | ![]() |
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2 | 2 | ||||||
MIRT447984 | LINC00598 | long intergenic non-protein coding RNA 598 | ![]() |
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2 | 2 | ||||||
MIRT460527 | S100A11 | S100 calcium binding protein A11 | ![]() |
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2 | 4 | ||||||
MIRT466861 | STX6 | syntaxin 6 | ![]() |
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2 | 2 | ||||||
MIRT468806 | SAP18 | Sin3A associated protein 18 | ![]() |
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2 | 6 | ||||||
MIRT480269 | C8orf4 | chromosome 8 open reading frame 4 | ![]() |
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2 | 2 | ||||||
MIRT493119 | MKNK2 | MAP kinase interacting serine/threonine kinase 2 | ![]() |
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2 | 6 | ||||||
MIRT499168 | YRDC | yrdC N6-threonylcarbamoyltransferase domain containing | ![]() |
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2 | 8 | ||||||
MIRT500507 | ZBTB34 | zinc finger and BTB domain containing 34 | ![]() |
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2 | 2 | ||||||
MIRT503021 | CAND1 | cullin associated and neddylation dissociated 1 | ![]() |
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2 | 2 | ||||||
MIRT505314 | TOR1AIP2 | torsin 1A interacting protein 2 | ![]() |
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2 | 2 | ||||||
MIRT506123 | PMAIP1 | phorbol-12-myristate-13-acetate-induced protein 1 | ![]() |
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2 | 8 | ||||||
MIRT509346 | CYP20A1 | cytochrome P450 family 20 subfamily A member 1 | ![]() |
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2 | 4 | ||||||
MIRT509446 | POU2F2 | POU class 2 homeobox 2 | ![]() |
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2 | 6 | ||||||
MIRT509598 | PEX26 | peroxisomal biogenesis factor 26 | ![]() |
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2 | 2 | ||||||
MIRT516008 | GPN2 | GPN-loop GTPase 2 | ![]() |
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2 | 2 | ||||||
MIRT516120 | SRPX2 | sushi repeat containing protein, X-linked 2 | ![]() |
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2 | 4 | ||||||
MIRT522126 | NELL2 | neural EGFL like 2 | ![]() |
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2 | 2 | ||||||
MIRT523018 | IL1RAPL1 | interleukin 1 receptor accessory protein like 1 | ![]() |
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2 | 4 | ||||||
MIRT524015 | DONSON | downstream neighbor of SON | ![]() |
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2 | 2 | ||||||
MIRT526307 | JAKMIP2 | janus kinase and microtubule interacting protein 2 | ![]() |
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2 | 2 | ||||||
MIRT526789 | SGCD | sarcoglycan delta | ![]() |
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2 | 2 | ||||||
MIRT529141 | CLCC1 | chloride channel CLIC like 1 | ![]() |
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2 | 2 | ||||||
MIRT531336 | GDPD1 | glycerophosphodiester phosphodiesterase domain containing 1 | ![]() |
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2 | 2 | ||||||
MIRT531573 | ILDR1 | immunoglobulin like domain containing receptor 1 | ![]() |
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2 | 2 | ||||||
MIRT531831 | MTPAP | mitochondrial poly(A) polymerase | ![]() |
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2 | 2 | ||||||
MIRT534994 | PRR11 | proline rich 11 | ![]() |
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2 | 6 | ||||||
MIRT535419 | PDZD8 | PDZ domain containing 8 | ![]() |
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2 | 2 | ||||||
MIRT535534 | PAK2 | p21 (RAC1) activated kinase 2 | ![]() |
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2 | 2 | ||||||
MIRT536649 | INIP | INTS3 and NABP interacting protein | ![]() |
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2 | 2 | ||||||
MIRT543498 | MDM2 | MDM2 proto-oncogene | ![]() |
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2 | 4 | ||||||
MIRT545392 | PM20D2 | peptidase M20 domain containing 2 | ![]() |
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2 | 2 | ||||||
MIRT545881 | ZNF200 | zinc finger protein 200 | ![]() |
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2 | 4 | ||||||
MIRT547931 | HNRNPR | heterogeneous nuclear ribonucleoprotein R | ![]() |
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2 | 2 | ||||||
MIRT548109 | GDAP2 | ganglioside induced differentiation associated protein 2 | ![]() |
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2 | 2 | ||||||
MIRT549370 | ANKS1A | ankyrin repeat and sterile alpha motif domain containing 1A | ![]() |
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2 | 2 | ||||||
MIRT549934 | RPL7L1 | ribosomal protein L7 like 1 | ![]() |
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2 | 4 | ||||||
MIRT550455 | MYADM | myeloid associated differentiation marker | ![]() |
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2 | 4 | ||||||
MIRT550640 | AR | androgen receptor | ![]() |
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2 | 2 | ||||||
MIRT550815 | FAM229B | family with sequence similarity 229 member B | ![]() |
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2 | 2 | ||||||
MIRT551258 | OPCML | opioid binding protein/cell adhesion molecule like | ![]() |
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2 | 2 | ||||||
MIRT551768 | MED21 | mediator complex subunit 21 | ![]() |
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2 | 2 | ||||||
MIRT552214 | ATP5S | ATP synthase, H+ transporting, mitochondrial Fo complex subunit s (factor B) | ![]() |
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2 | 2 | ||||||
MIRT555472 | POGZ | pogo transposable element derived with ZNF domain | ![]() |
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2 | 2 | ||||||
MIRT556008 | MZT1 | mitotic spindle organizing protein 1 | ![]() |
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2 | 2 | ||||||
MIRT557878 | FEM1B | fem-1 homolog B | ![]() |
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2 | 4 | ||||||
MIRT558486 | DBN1 | drebrin 1 | ![]() |
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2 | 2 | ||||||
MIRT560859 | GAL3ST3 | galactose-3-O-sulfotransferase 3 | ![]() |
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2 | 2 | ||||||
MIRT561521 | AZF1 | azoospermia factor 1 | ![]() |
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2 | 2 | ||||||
MIRT562090 | KIAA0895 | KIAA0895 | ![]() |
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2 | 2 | ||||||
MIRT563065 | ZNF28 | zinc finger protein 28 | ![]() |
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2 | 2 | ||||||
MIRT563487 | ZWINT | ZW10 interacting kinetochore protein | ![]() |
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2 | 2 | ||||||
MIRT564286 | CTCF | CCCTC-binding factor | ![]() |
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2 | 2 | ||||||
MIRT565627 | SLC16A1 | solute carrier family 16 member 1 | ![]() |
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2 | 2 | ||||||
MIRT566508 | PAWR | pro-apoptotic WT1 regulator | ![]() |
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2 | 2 | ||||||
MIRT566978 | LBR | lamin B receptor | ![]() |
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2 | 2 | ||||||
MIRT567180 | IGFBP5 | insulin like growth factor binding protein 5 | ![]() |
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2 | 2 | ||||||
MIRT568432 | GDNF | glial cell derived neurotrophic factor | ![]() |
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2 | 2 | ||||||
MIRT570092 | KANSL1L | KAT8 regulatory NSL complex subunit 1 like | ![]() |
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2 | 2 | ||||||
MIRT570565 | PABPC1 | poly(A) binding protein cytoplasmic 1 | ![]() |
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2 | 2 | ||||||
MIRT571385 | JKAMP | JNK1/MAPK8-associated membrane protein | ![]() |
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2 | 2 | ||||||
MIRT572053 | GPATCH8 | G-patch domain containing 8 | ![]() |
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2 | 2 | ||||||
MIRT572333 | CACNA1A | calcium voltage-gated channel subunit alpha1 A | ![]() |
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2 | 2 | ||||||
MIRT574528 | PEG10 | paternally expressed 10 | ![]() |
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2 | 2 | ||||||
MIRT575818 | Igfbp4 | insulin-like growth factor binding protein 4 | ![]() |
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2 | 2 | ||||||
MIRT608587 | PPP2R1B | protein phosphatase 2 scaffold subunit Abeta | ![]() |
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2 | 4 | ||||||
MIRT610442 | TSPAN15 | tetraspanin 15 | ![]() |
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2 | 2 | ||||||
MIRT614994 | GABRB1 | gamma-aminobutyric acid type A receptor beta1 subunit | ![]() |
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2 | 2 | ||||||
MIRT615014 | ERGIC2 | ERGIC and golgi 2 | ![]() |
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2 | 2 | ||||||
MIRT615078 | CISD3 | CDGSH iron sulfur domain 3 | ![]() |
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2 | 2 | ||||||
MIRT616180 | SYT7 | synaptotagmin 7 | ![]() |
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2 | 2 | ||||||
MIRT617191 | CDH13 | cadherin 13 | ![]() |
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2 | 2 | ||||||
MIRT617287 | GTF2H3 | general transcription factor IIH subunit 3 | ![]() |
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2 | 2 | ||||||
MIRT618714 | ESD | esterase D | ![]() |
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2 | 2 | ||||||
MIRT621825 | TIMM8B | translocase of inner mitochondrial membrane 8 homolog B | ![]() |
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2 | 2 | ||||||
MIRT624139 | DLX3 | distal-less homeobox 3 | ![]() |
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2 | 2 | ||||||
MIRT625991 | IBA57 | IBA57 homolog, iron-sulfur cluster assembly | ![]() |
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2 | 2 | ||||||
MIRT626344 | BLOC1S4 | biogenesis of lysosomal organelles complex 1 subunit 4 | ![]() |
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2 | 2 | ||||||
MIRT634899 | ZNF701 | zinc finger protein 701 | ![]() |
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2 | 2 | ||||||
MIRT637848 | SLC2A9 | solute carrier family 2 member 9 | ![]() |
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2 | 2 | ||||||
MIRT639514 | FYB | FYN binding protein 1 | ![]() |
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2 | 2 | ||||||
MIRT642468 | RSL1D1 | ribosomal L1 domain containing 1 | ![]() |
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2 | 2 | ||||||
MIRT653670 | SLC26A7 | solute carrier family 26 member 7 | ![]() |
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2 | 2 | ||||||
MIRT655192 | PHAX | phosphorylated adaptor for RNA export | ![]() |
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2 | 2 | ||||||
MIRT657011 | KCNMB4 | potassium calcium-activated channel subfamily M regulatory beta subunit 4 | ![]() |
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2 | 2 | ||||||
MIRT661008 | ABCB11 | ATP binding cassette subfamily B member 11 | ![]() |
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2 | 2 | ||||||
MIRT665816 | TMEM161B | transmembrane protein 161B | ![]() |
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2 | 2 | ||||||
MIRT683852 | ZNF208 | zinc finger protein 208 | ![]() |
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2 | 2 | ||||||
MIRT700436 | PURB | purine rich element binding protein B | ![]() |
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2 | 2 | ||||||
MIRT700517 | PTPN14 | protein tyrosine phosphatase, non-receptor type 14 | ![]() |
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2 | 2 |
miRNA-Drug Associations | ||||||||||||||||||
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miRNA-Drug Resistance Associations | ||||||||||||||||||||||||||||||||||||||||||||||||||
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