DegronMD - Q00839(HNRNPU)

FUNCTION: DNA- and RNA-binding protein involved in several cellular processes such as nuclear chromatin organization, telomere-length regulation, transcription, mRNA alternative splicing and stability, Xist-mediated transcriptional silencing and mitotic cell progression (PubMed:10490622, PubMed:18082603, PubMed:19029303, PubMed:22325991, PubMed:25986610, PubMed:28622508). Plays a role in the regulation of interphase large-scale gene-rich chromatin organization through chromatin-associated RNAs (caRNAs) in a transcription-dependent manner, and thereby maintains genomic stability (PubMed:1324173, PubMed:8174554, PubMed:28622508). Required for the localization of the long non-coding Xist RNA on the inactive chromosome X (Xi) and the subsequent initiation and maintenance of X-linked transcriptional gene silencing during X-inactivation (By similarity). Plays a role as a RNA polymerase II (Pol II) holoenzyme transcription regulator (PubMed:8174554, PubMed:9353307, PubMed:10490622, PubMed:15711563, PubMed:19617346, PubMed:23811339). Promotes transcription initiation by direct association with the core-TFIIH basal transcription factor complex for the assembly of a functional pre-initiation complex with Pol II in a actin-dependent manner (PubMed:10490622, PubMed:15711563). Blocks Pol II transcription elongation activity by inhibiting the C-terminal domain (CTD) phosphorylation of Pol II and dissociates from Pol II pre-initiation complex prior to productive transcription elongation (PubMed:10490622). Positively regulates CBX5-induced transcriptional gene silencing and retention of CBX5 in the nucleus (PubMed:19617346). Negatively regulates glucocorticoid-mediated transcriptional activation (PubMed:9353307). Key regulator of transcription initiation and elongation in embryonic stem cells upon leukemia inhibitory factor (LIF) signaling (By similarity). Involved in the long non-coding RNA H19-mediated Pol II transcriptional repression (PubMed:23811339). Participates in the circadian regulation of the core clock component ARNTL/BMAL1 transcription (By similarity). Plays a role in the regulation of telomere length (PubMed:18082603). Plays a role as a global pre-mRNA alternative splicing modulator by regulating U2 small nuclear ribonucleoprotein (snRNP) biogenesis (PubMed:22325991). Plays a role in mRNA stability (PubMed:17174306, PubMed:17289661, PubMed:19029303). Component of the CRD-mediated complex that promotes MYC mRNA stabilization (PubMed:19029303). Enhances the expression of specific genes, such as tumor necrosis factor TNFA, by regulating mRNA stability, possibly through binding to the 3'-untranslated region (UTR) (PubMed:17174306). Plays a role in mitotic cell cycle regulation (PubMed:21242313, PubMed:25986610). Involved in the formation of stable mitotic spindle microtubules (MTs) attachment to kinetochore, spindle organization and chromosome congression (PubMed:21242313). Phosphorylation at Ser-59 by PLK1 is required for chromosome alignement and segregation and progression through mitosis (PubMed:25986610). Contributes also to the targeting of AURKA to mitotic spindle MTs (PubMed:21242313). Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides (PubMed:1628625, PubMed:8068679, PubMed:8174554, PubMed:9204873, PubMed:9405365). Binds to chromatin-associated RNAs (caRNAs) (PubMed:28622508). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements in a chromatin-associated RNAs (caRNAs)-dependent manner (PubMed:7509195, PubMed:1324173, PubMed:9204873, PubMed:9405365, PubMed:10671544, PubMed:11003645, PubMed:11909954, PubMed:28622508). Binds to the Xist RNA (PubMed:26244333). Binds the long non-coding H19 RNA (PubMed:23811339). Binds to SMN1/2 pre-mRNAs at G/U-rich regions (PubMed:22325991). Binds to small nuclear RNAs (snRNAs) (PubMed:22325991). Binds to the 3'-UTR of TNFA mRNA (PubMed:17174306). Binds (via RNA-binding RGG-box region) to the long non-coding Xist RNA; this binding is direct and bridges the Xist RNA and the inactive chromosome X (Xi) (By similarity). Also negatively regulates embryonic stem cell differentiation upon LIF signaling (By similarity). Required for embryonic development (By similarity). Binds to brown fat long non-coding RNA 1 (Blnc1); facilitates the recruitment of Blnc1 by ZBTB7B required to drive brown and beige fat development and thermogenesis (By similarity). {ECO:0000250|UniProtKB:Q8VEK3, ECO:0000269|PubMed:10490622, ECO:0000269|PubMed:10671544, ECO:0000269|PubMed:11003645, ECO:0000269|PubMed:11909954, ECO:0000269|PubMed:1324173, ECO:0000269|PubMed:15711563, ECO:0000269|PubMed:1628625, ECO:0000269|PubMed:17174306, ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:18082603, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19617346, ECO:0000269|PubMed:21242313, ECO:0000269|PubMed:22325991, ECO:0000269|PubMed:23811339, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26244333, ECO:0000269|PubMed:28622508, ECO:0000269|PubMed:7509195, ECO:0000269|PubMed:8068679, ECO:0000269|PubMed:8174554, ECO:0000269|PubMed:9204873, ECO:0000269|PubMed:9353307, ECO:0000269|PubMed:9405365}.; FUNCTION: (Microbial infection) Negatively regulates immunodeficiency virus type 1 (HIV-1) replication by preventing the accumulation of viral mRNA transcripts in the cytoplasm. {ECO:0000269|PubMed:16916646}. 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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.G763V	TCGA-23-2649	OV	TCGA	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.2778
p.G763V	DO31779	OV	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.2778
p.G744V	TCGA-55-8299	LUAD	TCGA	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.0833
p.G744V	DO25927	LUAD	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.0833
p.G745R	TCGA-CR-7402	HNSC	TCGA	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.1111
p.G745R	DO15727	HNSC	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.1111
p.P757L	TCGA-L5-A4OP	ESCA	TCGA	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation altering degron motif	0.6471
p.Y765H	TCGA-MH-A562	KIRP	TCGA	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.2222
p.Y765H	DO48495	KIRP	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.2222
p.G750S	DO222455	ESCA	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.25
p.G750S	DO232761	PBCA	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.25
p.A756S	DO228917	LICA	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation altering degron motif	0.7588
p.R755S	DO229027	LICA	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation altering degron motif	0.6316
p.R755S	DO231201	LUSC	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation altering degron motif	0.6316
p.R762C	DO229052	LICA	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.3056
p.Y765S	DO220850	MELA	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation rewiring degron network	0.2222
p.G761D	DO229213	THCA	ICGC	YPRAPVFPG	DEG_SIAH_1	753:761	Mutation altering degron motif	0.6087

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

HNRNPU

UniProt ID: Q00839

Entrez ID: 3192

Protein name: Heterogeneous nuclear ribonucleoprotein U (hnRNP U) (GRIP120) (Nuclear p120 ribonucleoprotein) (Scaffold-attachment factor A) (SAF-A) (p120) (pp120)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for HNRNPU in