Protein: Protein lin-28 homolog B (Lin-28B) (Q6ZN17)
Organism: Homo sapiens (Human)
Function: Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA. Does not act on pri-miR21. The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation. This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent. Interaction with target pre-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop. Mediates MYC-induced let-7 repression (By similarity). When overexpressed, isoform 1 stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.
Subcellular location: Nucleus. Nucleus, nucleolus {ECO:0000269|PubMed:22118463}. Cytoplasm {ECO:0000269|PubMed:16971064}. Note=Predominantly nucleolar (PubMed:22118463). In Huh7 cells, predominantly cytoplasmic, with only a subset of cells exhibiting strong nuclear staining; however, the specificity of the polyclonal antibody used in these experiments has not been not documented (PubMed:16971064). {ECO:0000269|PubMed:16971064, ECO:0000269|PubMed:22118463}.
Sequence: MAEGGASKGGGEEPGKLPEPAEEESQVLRGTGHCKWFNVRMGFGFISMINREGSPLDIPVDVFVHQSKLFMEGFRSLKEGEPVEFTFKKSSKGLESIRVTGPGGSPCLGSERRPKGKTLQKRKPKGDRCYNCGGLDHHAKECSLPPQPKKCHYCQSIMHMVANCPHKNVAQPPASSQGRQEAESQPCTSTLPREVGGGHGCTSPPFPQEARAEISERSGRSPQEASSTKSSIAPEEQSKKGPSVQKRKKT
InterPro domains: - IPR011129: Cold-shock domain (domain) [31-102]
- IPR051373: Lin-28 homolog RNA-binding protein (family) [3-250]
- IPR054081: Lin-28A-like, second zinc knuckle (domain) [148-179]
- IPR036875: Zinc finger, CCHC-type superfamily (homologous_superfamily) [122-168]
- IPR001878: Zinc finger, CCHC-type (domain) [128-166]
- IPR002059: Cold-shock protein Csp, DNA-binding (domain) [29-101]
- IPR012340: Nucleic acid-binding, OB-fold (homologous_superfamily) [21-110]
Interaction partners: - Terminal uridylyltransferase 4
- High mobility group AT-hook 2
- Insulin-like growth factor 2 mRNA-binding protein 1
- Ribonuclease 3
- Endoribonuclease Dicer
- E3 ubiquitin-protein ligase TRIM71
- Developmental pluripotency-associated protein 3
- Myc proto-oncogene protein
- Transcription factor SOX-2
- Speckle targeted PIP5K1A-regulated poly
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0060090 (molecular adaptor activity), GO:0044877 (protein-containing complex binding), GO:0030674 (protein-macromolecule adaptor activity), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0043021 (ribonucleoprotein complex binding), GO:0003723 (RNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0098727 (maintenance of cell number), GO:0009893 (positive regulation of metabolic process), GO:0019827 (stem cell population maintenance), GO:0044238 (primary metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0044248 (cellular catabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009891 (positive regulation of biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0034655 (nucleobase-containing compound catabolic process), GO:0044270 (cellular nitrogen compound catabolic process), GO:0034250 (positive regulation of amide metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051246 (regulation of protein metabolic process), GO:0019439 (aromatic compound catabolic process), GO:0046700 (heterocycle catabolic process), GO:0010628 (positive regulation of gene expression), GO:0010468 (regulation of gene expression), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0009057 (macromolecule catabolic process), GO:0034248 (regulation of amide metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0044265 (cellular macromolecule catabolic process), GO:0031326 (regulation of cellular biosynthetic process), GO:1901361 (organic cyclic compound catabolic process), GO:0051247 (positive regulation of protein metabolic process), GO:0010467 (gene expression), GO:0010629 (negative regulation of gene expression), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0016070 (RNA metabolic process), GO:0031047 (RNA-mediated gene silencing), GO:0006401 (RNA catabolic process), GO:0006396 (RNA processing), GO:2000112 (regulation of cellular macromolecule biosynthetic process), GO:0006417 (regulation of translation), GO:0045727 (positive regulation of translation), GO:0010608 (post-transcriptional regulation of gene expression), GO:0034470 (ncRNA processing), GO:0031123 (RNA 3'-end processing), GO:2000765 (regulation of cytoplasmic translation), GO:0070918 (regulatory ncRNA processing), GO:2000767 (positive regulation of cytoplasmic translation), GO:0034661 (ncRNA catabolic process), GO:0034660 (ncRNA metabolic process), GO:0035196 (miRNA processing), GO:0010586 (miRNA metabolic process), GO:0031054 (pre-miRNA processing)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005730 (nucleolus), GO:0005634 (nucleus)