Molecule Information

General Information of the Molecule (ID: Mol00413)

• Name: Heterogeneous nuclear ribonucleoprotein U (HNRNPU) ,Homo sapiens
• Synonyms: hnRNP U; GRIP120; Nuclear p120 ribonucleoprotein; Scaffold-attachment factor A; SAF-A; p120; pp120; C1orf199; HNRPU; SAFA; U21.1
• Molecule Type: Protein
• Gene Name: HNRNPU
• Gene ID: 3192
• Location: chr1:244840638-244864560[-]
• Sequence:
  MSSSPVNVKKLKVSELKEELKKRRLSDKGLKAELMERLQAALDDEEAGGRPAMEPGNGSL
  DLGGDSAGRSGAGLEQEAAAGGDEEEEEEEEEEEGISALDGDQMELGEENGAAGAADSGP
  MEEEEAASEDENGDDQGFQEGEDELGDEEEGAGDENGHGEQQPQPPATQQQQPQQQRGAA
  KEAAGKSSGPTSLFAVTVAPPGARQGQQQAGGKKKAEGGGGGGRPGAPAAGDGKTEQKGG
  DKKRGVKRPREDHGRGYFEYIEENKYSRAKSPQPPVEEEDEHFDDTVVCLDTYNCDLHFK
  ISRDRLSASSLTMESFAFLWAGGRASYGVSKGKVCFEMKVTEKIPVRHLYTKDIDIHEVR
  IGWSLTTSGMLLGEEEFSYGYSLKGIKTCNCETEDYGEKFDENDVITCFANFESDEVELS
  YAKNGQDLGVAFKISKEVLAGRPLFPHVLCHNCAVEFNFGQKEKPYFPIPEEYTFIQNVP
  LEDRVRGPKGPEEKKDCEVVMMIGLPGAGKTTWVTKHAAENPGKYNILGTNTIMDKMMVA
  GFKKQMADTGKLNTLLQRAPQCLGKFIEIAARKKRNFILDQTNVSAAAQRRKMCLFAGFQ
  RKAVVVCPKDEDYKQRTQKKAEVEGKDLPEHAVLKMKGNFTLPEVAECFDEITYVELQKE
  EAQKLLEQYKEESKKALPPEKKQNTGSKKSNKNKSGKNQFNRGGGHRGRGGFNMRGGNFR
  GGAPGNRGGYNRRGNMPQRGGGGGGSGGIGYPYPRAPVFPGRGSYSNRGNYNRGGMPNRG
  NYNQNFRGRGNNRGYKNQSQGYNQWQQGQFWGQKPWSQHYHQGYY
• 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. 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 ARNTL/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-59 by PLK1 is required for chromosome alignement and segregation and progression through mitosis. Contributes also to the targeting of AURKA to mitotic spindle MTs. Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides. Binds to chromatin-associated RNAs (caRNAs). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements 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. 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.
• Uniprot ID: HNRPU_HUMAN
• Ensembl ID: ENSG00000153187
• HGNC ID: HGNC:5048

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung squamous cell carcinoma [1]

• Sensitive Disease: Lung squamous cell carcinoma [ICD-11: 2C25.3]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: Sk-MES-1 cells; Lung; Homo sapiens (Human); CVCL_0630
• In Vitro Model: 16HBE cells; Lung; Homo sapiens (Human); CVCL_0112
• In Vitro Model: A549-DDP cells; Lung; Homo sapiens (Human); CVCL_IP03
• In Vitro Model: NCl-H226 cells; Lung; Homo sapiens (Human); CVCL_1544
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS Cell Proliferation Assay; EdU assay; Flow cytometry assay
• Mechanism Description: Long noncoding RNA SFTA1P promoted apoptosis and increased cisplatin chemosensitivity via regulating the hnRNP-U-GADD45A axis in lung squamous cell carcinoma. SFTA1P could up-regulate hnRNP-U expression. hnRNP-U enhanced cisplatin-induced apoptosis through up-regulation of GADD45A.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.35E-26; Fold-change: -4.76E-01; Z-score: -1.15E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 7.29E-23; Fold-change: -4.46E-01; Z-score: -1.22E+00

References

• Ref 1: Long noncoding RNA SFTA1P promoted apoptosis and increased cisplatin chemosensitivity via regulating the hnRNP-U-GADD45A axis in lung squamous cell carcinoma. Oncotarget. 2017 Oct 27;8(57):97476-97489. doi: 10.18632/oncotarget.22138. eCollection 2017 Nov 14.