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Symbol KHSRP contributors: mct/ - updated : 02-02-2018
HGNC name KH-type splicing regulatory protein
HGNC id 6316
TYPE functioning gene
STRUCTURE 11.71 kb     20 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
20 - 3262 73 711 widely expressed in somatic and germ cells where it is primarily nuclear 2008 19015122
- - - 52 - present in the cytoplasm of a subpopulation of germ cells 2008 19015122
  • binds directly to a 93-nt sequence (designated the F1 region) of the 3prime-UTR of the PGK2 mRNA and destabilizes PGK2 mRNA constructs in testis
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
     pharynx   highly
    Lymphoid/Immunelymph node   highly
    Nervousbrain     Homo sapiens
    Visualeye   highly
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticneutrophil Homo sapiens
    Lymphoid/ImmuneB cell Homo sapiens
    Lymphoid/Immunedendritic cell Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • a proline/glycine rich N terminal
  • a central RNA-binding domain with four domains capable of binding single-stranded nucleic acids, the so-called K-homology domains, KH1 to KH4 (third and fourth KH domains required for mRNA binding and degradation) , and responsible for its nucleic acid-binding activity
  • KH2 and KH3 interact and form the structural core of the KHSRP protein (KH23)
  • a proline, glycine, alanine and glutamine rich C terminal domain
    interspecies homolog to murine Khsrp
    homolog to rat Marta1
  • KHSRP family
  • CATEGORY regulatory , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
  • somatodendritic cytoplasm
  • shuttle between the nucleus and cytoplasm in response to extracellular stimuli, and its nuclear-cytoplasmic distribution varies substantially depending on cell type and conditions
  • basic FUNCTION
  • involving in neuron-specific splicing of the N1 exon of SRC
  • inducing the assembly of five other proteins, including the heterogeneous nuclear ribonucleoprotein F, onto the splicing enhancer
  • may be playing a role in nucleocytoplasmic mRNA targeting
  • having functions as a limiting factor in inflammatory gene expression
  • multifunctional RNA-binding protein that has been implicated in transcriptional regulation, neuro-specific alternative splicing and mRNA decay
  • involved in the etiology of milder forms of SMA
  • multi-domain RNA-binding protein that recruits the exosome-containing mRNA degradation complex to mRNAs coding for cellular proliferation and inflammatory response factors
  • with HNRNPA1 have antagonistic roles in the post-transcriptional regulation of MIRLET7A1, MIRLET7A2, MIRLET7A3 expression
  • function of KHSRP in innate immunity by negatively regulating IFN production
  • critical role for KHSRP in regulating pro-inflammatory mediators and have implications for a wide range of CNS inflammatory and autoimmune diseases
  • likely involved in Schwann cells (SCs) and neuronal differentiation by inducing CTNNB1 mRNA decay
  • ability of KHSRP to integrate different levels of gene expression is required for proper immune response, lipid metabolism, cell-fate decisions, tissue regeneration, and DNA damage response
  • KHSRP is an important regulator of circadian expression of lipid metabolism genes in the liver likely through controlling PER2 mRNA stability
  • controls important cellular functions as different as proliferation, differentiation, metabolism, and response to infectious agents
  • likely oncogenic role for KHSRP in lung cancer
  • is a nucleic acid binding protein, which negatively regulates the stability and/or translatability of many mRNA species encoding immune-relevant proteins
  • CELLULAR PROCESS nucleotide, RNA splicing
    text RNA processing/modification
    a component
  • spliceosomal subunit
    RNA RNA binding
    small molecule
  • interacting with MAP2
  • interacts with the Tudor domain of SMN, in a CARM1 methylation-dependent fashion
  • interacting with YWHAZ (impairment of exosome recruitment is mediated by the binding of the YWHAZ protein to KHSRP phosphorylated on Ser193)
  • KHSRP is a protein involved in AU-rich elements (AREs)-mediated translational silencing
  • subcellular localization of KHSRP is regulated by competing interactions with DDX1 or 14-3-3
  • KHSRP is an important regulator of mRNA stability and axonal length that works in direct opposition to ELAVL4 to regulate the levels of GAP43 and other AU-rich element (ARE)-containing neuronal mRNAs
  • KHSRP promotes decay of PER2 mRNA through an RNA-protein interaction and show that increased PER2 expression is responsible for the phase delay in cycling of several clock genes in the absence of KHSRP
  • PTH is a major regulator of both transcription and translation, and KHSRP binds SLC34A1 mRNA but its role in PTH regulation of SLC34A1 mRNA is not clear
  • DDX17 and KHSRP influence AGO2 stability by regulating miRNA levels in the cell and that loss of DDX17/KHSRP results in a decrease of unloaded AGO2
  • interaction between the Kelch domain of Kelch-like protein 12 (KLHL12) and the C-terminal domain of KHSRP contributed to KHSRP ubiquitination
  • KHSRP promotes the down-regulation of SPRY4 by a post-transcriptional mRNA regulation
  • cell & other
    Other regulated by phosphorylation of a serine within its N-terminal KH domain (KH1)
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    dysregulated in SMA1
    tumoral     --over  
    in human lung cancer
    the absence of KHSRP likely protects against the induction of inflammatory arthritis
    Variant & Polymorphism
    Candidate gene
    Therapy target promote tumor-relevant functions by at least partly employing the microtubule-destabilizing factor stathmin and represent a new potential target structure for hepatocellular carcinoma treatment