DegronMD - Q14671(PUM1)

FUNCTION: Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (PubMed:21572425, PubMed:18328718, PubMed:21653694, PubMed:21397187). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233). {ECO:0000250|UniProtKB:Q80U78, ECO:0000269|PubMed:18328718, ECO:0000269|PubMed:18776931, ECO:0000269|PubMed:20818387, ECO:0000269|PubMed:20860814, ECO:0000269|PubMed:21397187, ECO:0000269|PubMed:21572425, ECO:0000269|PubMed:21653694, ECO:0000269|PubMed:22345517, ECO:0000269|PubMed:22955276, ECO:0000269|PubMed:25340845, ECO:0000269|PubMed:25768905, ECO:0000269|PubMed:26724866, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:29474920}. View more >>

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GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S220I	TCGA-AP-A051	UCEC	TCGA	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation blocking phosphorylation signal	0.6389
p.S220I	DO42673	UCEC	ICGC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation blocking phosphorylation signal	0.6389
p.G215E	TCGA-DU-6407	LGG	TCGA	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.0556
p.G215E	DO22295	LGG	ICGC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.0556
p.G238V	TCGA-DU-7294	LGG	TCGA	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.0833
p.G238V	DO22333	LGG	ICGC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.0833
p.P215H	DO20776	KIRP	ICGC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.0556
p.Q234K	DO229034	LICA	ICGC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.1944
p.V222G	DO23527	LIRI	ICGC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.25
p.V219I	DO232224	PBCA	ICGC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.1667
p.G225V	DO41903	UCEC	ICGC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation altering degron motif	0.7532
p.R236I	ACH-001973	Metastasis	CCLE	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation rewiring degron network	0.1389
p.R237H	SNU-175	large intestine	COSMIC	VLSSS	DEG_SPOP_SBC_1	225:229	Mutation blocking ubiquitination signal	0.5556

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PUM1

UniProt ID: Q14671

Entrez ID: 9698

Protein name: Pumilio homolog 1 (HsPUM) (Pumilio-1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PUM1 in