Protein: Heterogeneous nuclear ribonucleoprotein U (hnRNP U) (SP120) (Scaffold-attachment factor A) (SAF-A) (Q6IMY8)
Organism: Rattus norvegicus (Rat)
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. 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. 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). Required for the topoisomerase TOP2A protein stability and activity in a RNA-dependent manner. Plays a role as a RNA polymerase II (Pol II) holoenzyme transcription regulator. 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. 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. Positively regulates CBX5-induced transcriptional gene silencing and retention of CBX5 in the nucleus. Negatively regulates glucocorticoid-mediated transcriptional activation. Key regulator of transcription initiation and elongation in embryonic stem cells upon leukemia inhibitory factor (LIF) signaling. Involved in the long non-coding RNA H19-mediated Pol II transcriptional repression. Participates in the circadian regulation of the core clock component BMAL1 transcription. Plays a role in the regulation of telomere length. Plays a role as a global pre-mRNA alternative splicing modulator by regulating U2 small nuclear ribonucleoprotein (snRNP) biogenesis. Plays a role in mRNA stability. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. 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). Plays a role in mitotic cell cycle regulation. Involved in the formation of stable mitotic spindle microtubules (MTs) attachment to kinetochore, spindle organization and chromosome congression. Phosphorylation at Ser-58 by PLK1 is required for chromosome alignement and segregation and progression through mitosis. Contributes also to the targeting of AURKA to mitotic spindle MTs (By similarity). Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides. Binds to chromatin-associated RNAs (caRNAs) (By similarity). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements in DNA. Associates with chromatin in a chromatin-associated RNAs (caRNAs)-dependent manner. Binds to the Xist RNA. Binds the long non-coding H19 RNA. Binds to SMN1/2 pre-mRNAs at G/U-rich regions. Binds to small nuclear RNAs (snRNAs). Binds to the 3'-UTR of TNFA mRNA. 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). Also negatively regulates embryonic stem cell differentiation upon LIF signaling. 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).
Subcellular location: Nucleus {ECO:0000250|UniProtKB:Q00839}. Nucleus matrix {ECO:0000250|UniProtKB:Q00839}. Chromosome {ECO:0000250|UniProtKB:Q00839}. Nucleus speckle {ECO:0000250|UniProtKB:Q00839}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q00839}. Chromosome, centromere, kinetochore {ECO:0000250|UniProtKB:Q00839}. Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:Q00839}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q00839}. Midbody {ECO:0000250|UniProtKB:Q00839}. Cytoplasm {ECO:0000250|UniProtKB:Q00839}. Cell surface {ECO:0000250|UniProtKB:Q00839}. Cytoplasmic granule {ECO:0000250|UniProtKB:Q00839}. Note=Localizes at inactive X chromosome (Xi) regions. Localizes in the nucleus during interphase. At metaphase, localizes with mitotic spindle microtubules (MTs). At anaphase, localizes in the mitotic spindle midzone. Localizes in spindle MTs proximal to spindle poles in a TPX2- and AURKA-dependent manner. The Ser-58 phosphorylated form localizes to centrosomes during prophase and metaphase, to mitotic spindles in anaphase and to the midbody during cytokinesis. Colocalizes with SMARCA4 in the nucleus (By similarity). Colocalizes with CBX5 in the nucleus. Colocalizes with NR3C1 in nuclear speckles. Localized in cytoplasmic ribonucleoprotein (RNP) granules containing untranslated mRNAs. {ECO:0000250|UniProtKB:Q00839, ECO:0000250|UniProtKB:Q8VEK3}.
InterPro domains:
- IPR036361: SAP domain superfamily (homologous_superfamily) [1-53]
- IPR035778: Heterogeneous nuclear ribonucleoprotein U, SPRY domain (domain) [262-437]
- IPR003877: SPRY domain (domain) [305-437]
- IPR013320: Concanavalin A-like lectin/glucanase domain superfamily (homologous_superfamily) [258-440]
- IPR001870: B30.2/SPRY domain (domain) [242-438]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [468-644]
- IPR043136: B30.2/SPRY domain superfamily (homologous_superfamily) [260-471]
- IPR003034: SAP domain (domain) [8-42]
Sequence:
MSSSPVNVKKLKVSELKEELKKRRLSDKGLKADLMDRLQAALDNEAGGRPAMEPGNGSLDLGGDAAGRSGAGLEQEAAAGAEDDEEEEGIAALDGDQMELGEENGAAGAADAGAMEEEEAASEDENGDDQGFQEGEDELGDEEEGAGDENGHGEQQSQPPAAAQQASQQRGPGKEAAGKSSGPTSLFAVTVAPPGARQGQQQAGGDGKTEQKAGDKKRGVKRPREDHGRGYFEYIEENKYSRAKSPQPPVEEEDEHFDDTVVCLDTYNCDLHFKISRDRLSASSLTMESFAFLWAGGRASYGVSKGKVCFEMKVTEKIPVRHLYTKDIDIHEVRIGWSLTTSGMLLGEEEFSYGYSLKGIKTCNCETEDYGEKFDENDVITCFANFETDEVELSYAKNGQDLGVAFKISKEVLADRPLFPHVLCHNCAVEFNFGQKEKPYFPIPEDCTFIQNVPLEDRVRGPKGPEEKKDCEVVMMIGLPGAGKTTWVTKHAAENPGKYNILGTNTIMDKMMVAGFKKQMADTGKLNTLLQRAPQCLGKFIEIAARKKRNFILDQTNVSAAAQRRKMCLFAGFQRKAVVVCPKDEDYKQRTQKKAEVEGKDLPEHAVLKMKGNFTLPEVAECFDEITYVELQKEEAQKLLEQYKEESKKALPPEKKQNTGSKKSNKNKSGKNQFNRGGGHRGRGGFNMRGGNFRGGAPGNRGGYNRRGNMPQRGGGGGSGGIGYPYPRGPVFPGRGGYSNRGNYNRGGMPNRGNYNQNFRGRGNNRGYKNQSQGYNQWQQGQFWGQKPWSQHYHQGYY
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0065008 (regulation of biological quality), GO:0051641 (cellular localization), GO:0031503 (protein-containing complex localization), GO:0048522 (positive regulation of cellular process), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0007017 (microtubule-based process), GO:0051640 (organelle localization), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0051656 (establishment of organelle localization), GO:0042391 (regulation of membrane potential), GO:0006810 (transport), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0051649 (establishment of localization in cell), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0050803 (regulation of synapse structure or activity), GO:0000226 (microtubule cytoskeleton organization), GO:0080090 (regulation of primary metabolic process), GO:0051128 (regulation of cellular component organization), GO:0009891 (positive regulation of biosynthetic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0050807 (regulation of synapse organization), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0033043 (regulation of organelle organization), GO:0051252 (regulation of RNA metabolic process), GO:0006996 (organelle organization), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0010468 (regulation of gene expression), GO:0007010 (cytoskeleton organization), GO:0007005 (mitochondrion organization), GO:0047497 (mitochondrion transport along microtubule), GO:1902680 (positive regulation of RNA biosynthetic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045893 (positive regulation of DNA-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045944 (positive regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)