USP9X

This gene is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation. Mutations in this gene have been associated with Turner syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Ubiquitin Specific Peptidase 9, X-Linked

Deubiquitinase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins (PubMed:19135894, PubMed:25944111, PubMed:18254724, PubMed:22371489, PubMed:29626158).
May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin (PubMed:19135894, PubMed:25944111, PubMed:22371489, PubMed:18254724, PubMed:29626158).
Specifically hydrolyzes 'Lys-63'-, 'Lys-48'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitins chains (PubMed:25944111, PubMed:18254724, PubMed:33378666).
Essential component of TGF-beta/BMP signaling cascade (PubMed:19135894).
Specifically deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33 (PubMed:19135894).
Deubiquitinates alkylation repair enzyme ALKBH3 (PubMed:25944111).
OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111).
Deubiquitinates mTORC2 complex component RICTOR at 'Lys-294' by removing 'Lys-63'-linked polyubiquitin chains, stabilizing RICTOR and enhancing its binding to MTOR, thus promoting mTORC2 complex assembly (PubMed:33378666).
Regulates chromosome alignment and segregation in mitosis by regulating the localization of BIRC5/survivin to mitotic centromeres (PubMed:16322459).
Involved in axonal growth and neuronal cell migration (PubMed:24607389).
Regulates cellular clock function by enhancing the protein stability and transcriptional activity of the core circadian protein BMAL1 via its deubiquitinating activity (PubMed:29626158).
Acts as a regulator of peroxisome import by mediating deubiquitination of PEX5: specifically deubiquitinates PEX5 monoubiquitinated at 'Cys-11' following its retrotranslocation into the cytosol, resetting PEX5 for a subsequent import cycle (PubMed:22371489).
Deubiquitinates PEG10 (By similarity).

Biological Process amyloid fibril formation Source:Reactome
Biological Process axon extension Source:UniProtKB1 Publication
Biological Process BMP signaling pathway Source:UniProtKB1 Publication
Biological Process cell cycle Source:UniProtKB-KW
Biological Process cell division Source:UniProtKB-KW
Biological Process cell migration Source:GO_Central1 Publication
Biological Process chromosome segregation Source:UniProtKB-KW
Biological Process female gamete generation Source:ProtInc1 Publication
Biological Process monoubiquitinated protein deubiquitination Source:UniProtKB1 Publication
Biological Process negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source:UniProtKB1 Publication
Biological Process negative regulation of transcription by RNA polymerase II Source:Reactome
Biological Process neuron migration Source:UniProtKB1 Publication
Biological Process positive regulation of DNA demethylation Source:UniProtKB1 Publication
Biological Process positive regulation of protein binding Source:UniProtKB1 Publication
Biological Process positive regulation of TORC2 signaling Source:UniProtKB1 Publication
Biological Process protein deubiquitination Source:UniProtKB1 Publication
Biological Process protein deubiquitination involved in ubiquitin-dependent protein catabolic process Source:UniProtKB1 Publication
Biological Process protein import into peroxisome matrix, receptor recycling Source:UniProtKB1 Publication
Biological Process protein K63-linked deubiquitination Source:UniProtKB1 Publication
Biological Process protein localization Source:Reactome
Biological Process protein stabilization Source:UniProtKB2 Publications
Biological Process protein ubiquitination Source:Reactome
Biological Process regulation of circadian rhythm Source:UniProtKB1 Publication
Biological Process rhythmic process Source:UniProtKB-KW
Biological Process transforming growth factor beta receptor signaling pathway Source:UniProtKB1 Publication

Cytoplasm, cytosol
Cell projection, growth cone
Cytoplasm, cytoskeleton, cilium axoneme

Intellectual developmental disorder, X-linked 99 (XLID99):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations.
Intellectual developmental disorder, X-linked 99, syndromic, female-restricted (MRXS99F):
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning, associated with impairments in adaptive behavior and manifested during the developmental period. MRXS99F affected females manifest intellectual disability, developmental delay, facial dysmorphism, short stature, and distinct congenital malformations comprising choanal atresia, anal abnormalities, post-axial polydactyly, heart defects, hypomastia, cleft palate/bifid uvula, progressive scoliosis, and structural brain abnormalities. Inheritance is X-linked dominant.