Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol USP9X contributors: mct - updated : 05-09-2016
HGNC name ubiquitin specific peptidase 9, X-linked
HGNC id 12632
Corresponding disease
MRX99 mental retardation, X-linked 99
MRXS99F mental retardation, X-linked 99, syndromic, female-restricted
Location Xp11.4      Physical location : 40.944.887 - 41.095.830
Synonym name
  • ubiquitin specific protease 9, X chromosome (fat facets-like Drosophila)
  • Drosophila fat facets related, X-linked
  • deubiquitinating enzyme FAF-X
  • ubiquitin thioesterase FAF-X
  • Synonym symbol(s) DFFRX, FAF, FAM, USP9
    TYPE functioning gene
    text escaping inactivation
    STRUCTURE 150.94 kb     45 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map pter - DXS1368 - USP9X - DXS993 - DXS8012 - CASK - DXS1392 - DXS1387 - DXS7512 - DXS1379 - DXS1207 - DXS1201 - DXS8085 - DXS8330 - DXS8187 - [DXS228 - DXS77 - DXS7 - MAOA /MAOB - NDP - DXS8080 DXS8083 - cen
    Authors Sparkes (00)
    Physical map
    HYPM Xp21.1 monoamine oxidase A LOC340549 Xp21.1 similar to RIKEN cDNA 1700113O17 SYTL5 Xp21.1 synaptotagmin-like 5 SRPX Xp21.1 sushi-repeat-containing protein, X chromosome LOC286441 Xp21.1 hypothetical LOC286441 RPGR Xp21.1 retinitis pigmentosa GTPase regulator OTC Xp21.1 ornithine carbamoyltransferase LOC392442 X similar to BAG-family molecular chaperone regulator-1 (BCL-2 binding athanogene-1) (BAG-1) (Glucocorticoid receptor-associated protein RAP46) LOC392443 X similar to ferritin light chain LOC392444 X similar to Nucleolar transcription factor 1 (Upstream binding factor 1) (UBF-1) TM4SF2 Xp11.4-q11 transmembrane 4 superfamily member 2 LOC389845 X LOC389845 STRAIT11499 Xp11.4 hypothetical protein STRAIT11499 LOC389846 X hypothetical gene supported by BC043536 GAPDP1 Xp11.4-p11.23 glyceraldehyde-3-phosphate dehydrogenase pseudogene 1 LOC392445 X similar to 40S ribosomal protein S11 BCOR Xp11.4 BCL6 co-repressor LOC158624 Xp11.4 similar to IMP dehydrogenase (EC I - human ATP6AP2 Xq21 ATPase, H+ transporting, lysosomal accessory protein 2 LOC347411 Xp11.4 similar to ENSANGP00000015797 MGC39350 Xp11.4 hypothetical protein MGC39350 CRSP2 Xp11.2-p11.4 cofactor required for Sp1 transcriptional activation, subunit 2, 150kDa LOC392446 X similar to claudin 7; Clostridium perfringens enterotoxin receptor-like 2; claudin 9 MKRN4 Xp21.1 makorin, ring finger protein, 4 LOC392447 X similar to 60S ribosomal protein L32 LOC286444 Xp11.4 similar to ribosomal protein S2; 40S ribosomal protein S2 LOC392448 X similar to Chloride intracellular channel protein 4 (mc3s5/mtCLIC) USP9X Xp11.4 ubiquitin specific protease 9, X chromosome (fat facets-like Drosophila) DDX3X Xp11.3-p11.23 DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked NYX Xp11.4 nyctalopin CASK Xp11.4 calcium/calmodulin-dependent serine protein kinase (MAGUK family) LOC158781 Xp11.4 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta pseudogene GPR34 Xp11.4-p11.3 G protein-coupled receptor 34 GPR82 Xp11.4 G protein-coupled receptor 82 I-4 Xp11.4-Xp11.3 type 1 protein phosphatase inhibitor LOC139334 Xp11.4 similar to inosine monophosphate dehydrogenase 1 isoform b; sWSS2608 LOC392449 X similar to Nanog homeobox; homeobox transcription factor Nanog LOC389847 X similar to Amine oxidase [flavin-containing] A (Monoamine oxidase) (MAO-A) MAOA Xp11.23 monoamine oxidase A MAOB Xp11.23 monoamine oxidase B NDP Xp11.4 Norrie disease (pseudoglioma) LOC286398 Xp11.4 similar to RNA-binding region containing protein 2 (Hepatocellular carcinoma protein 1) (Splicing factor HCC1) FLJ22843 Xp11.4 hypothetical protein FLJ22843
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    45 - 12401 292 2570 - 2009 19135894
    isoform 3
    45 - 12353 - 2554 - 2009 19135894
    isoform 4
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Reproductivefemale systemuteruscervix highly
    Respiratorylung   highly
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, pregnancy
    Text embryo, at low levels
  • five highly conserved domains, domains I, II and III containing the expected catalytic triad Cys, Asp, His which defines cysteine proteases
  • catalytic and ubiquitin-like domains
  • C terminus of USP9X binds the regulator of neuronal cell migration Doublecortin
    interspecies homolog to murine Dres14
    homolog to Drosophila developmental gene fat facets related on the X
  • deubiquitin family
  • peptidase C19 family
  • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
  • interacting with MARCH7 in the cytosol
  • mostly cytosolic, but is also found in the nucleoplasm
  • localizes along the length of the ciliary axoneme
  • basic FUNCTION
  • may function as a ubiquitin-protein or polyubiquitin hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins
  • may play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin
  • can stabilize MARCH7, and deubiquitylate MARCH7 in the cytosol
  • deubiquitinase acting as essential and evolutionarily conserved component in TGFbeta and bone morphogenetic protein signaling, opposing the activity of Ectodermin/Tif1gamma (Ecto, TRIM33)
  • enhances the polarity and self-renewal of embryonic stem cell-derived neural progenitors
  • stabilizes MCL1 and thereby promotes cell survival
  • controlling the level of PSD, mediating its deubuiquitination and protecting from proteasomal degradation, thus regulating de nov tight junction assembly
  • is an elongated monomeric protein with the capacity to hydrolyze thioester, isopeptide, and peptide bonds
  • implicated in the participation in the PEX5-mediated peroxisomal protein import pathway
  • acts as a negative regulator of MTOR activity and muscle differentiation
  • is a major tumour suppressor gene with prognostic and therapeutic relevance in pancreatic ductal adenocarcinoma
  • is a novel regulator of SMURF1 and is required for SMURF1-dependent cellular physiology
  • required for normal neuronal cell migration
  • substrate-specific deubiquitylating enzyme, and thus regulates the proteome
  • role in de-ubiquitination of ciliary proteins
    TGFB pathway
    a component
  • component of the TGFB pathway
    small molecule
  • interacting with DCX to regulate cell adhesion
  • binding partner of ITCH (transient overexpression of FAM/USP9X resulted in the deubiquitylation of ITCH)
  • interacting with and deubiquitinating monoubiquitinated SMAD4, opposing the activity of Ectodermin/TIF1G (TRIM33), rather than stability
  • with TRIM33 act as antagonistic SMAD4 regulator during embryonic development
  • binding MCL1 and removing the Lys48-linked polyubiquitin chains
  • interacting with MCL1 (stabilizes MCL1 by reversing its polyubiquitination)
  • interacts with and deubiquitinates SNCA
  • involved in MCL1 protein turnover by preventing its degradation through the removal of conjugated ubiquitin
  • SMURF1 is known to bind the C terminus of USP9X and has established roles in cell migration
  • PMAIP1 over-expression caused a decrease in the USP9X/MCL1 interaction associated with an increase in the MCL1 polyubiquitinated forms
  • USP9X was found to be the most active deubiquitinase acting on ubiquitin-PEX5
  • novel MTOR and CRTC2 binding partner that negatively regulates MTOR activity and skeletal muscle differentiation
  • USP9X interacts with SMURF1 and stabilizes SMURF1 through deubiquitination
  • in B lymphocytes, USP9X is required for the induction of PRKCB activity after BCR-dependent activation
  • USP9X functions as a positive regulatory switch during T lymphocyte priming through removal of inhibitory monoubiquitination from ZAP70
  • USP9X is a deubiquitinase of PBX1
  • cell & other
    corresponding disease(s) MRX99 , MRXS99F
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    increased expression in follicular lymphomas and diffuse large B-cell lymphomas correlates with increased MCL1 expression and poor prognosis
    tumoral       loss of function
    inactivated in over 50p100 of the pancreatic ductal adenocarcinoma (PDA)
    constitutional     --low  
    lower levels of cytosolic USP9X and deubiquitinase activity in alpha-synucleinopathies may contribute to the accumulation and aggregation SNCA in Lewy bodies
    constitutional       loss of function
    resulted in changes to the neuronal cytoskeleton
    constitutional germinal mutation      
    associated with nonsyndromic X-linked intellectual disability
    Variant & Polymorphism
    Candidate gene
  • marker prognostic in follicular lymphomas and diffuse large B-cell lymphomas
  • Therapy target
    targeting the USP9X/PBX1 axis could be a potential therapeutic strategy for managing advanced prostate cancer
    therapy target in follicular lymphomas and diffuse large B-cell lymphomas