Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

USP9X

contributors: mct - updated : 05-09-2019

HGNC name	ubiquitin specific peptidase 9, X-linked
HGNC id	12632

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001039590 45 - 12401 NP_001034679 292 2570 - 2009 19135894 isoform 3 NM_001039591 45 - 12353 NP_001034680 - 2554 - 2009 19135894 isoform 4

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine pituitary     highly Reproductive female system uterus cervix   highly Respiratory lung       highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	embryo, at low levels

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	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

HOMOLOGY

interspecies	homolog to murine Dres14
	homolog to Drosophila developmental gene fat facets related on the X

Homologene

FAMILY	deubiquitin family
	peptidase C19 family

CATEGORY

enzyme , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus,nucleoplasm
text	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

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

TGFB pathway

a component

component of the TGFB pathway

INTERACTION

DNA

RNA

small molecule

protein	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 novel regulator of the translation initiation process via deubiquitination of EIF4A1, which offers new insight in understanding the pivotal role of USP9X in malignancies and neurodevelopmental disorders
	deubiquitinase, USP9X interacts with ZBTB38, deubiquitinates it, and stabilizes it
	USP9X is a deubiquitinase of PBX1

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

MRX99 , MRXS99F

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	marker prognostic in follicular lymphomas and diffuse large B-cell lymphomas
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate targeting the USP9X/PBX1 axis could be a potential therapeutic strategy for managing advanced prostate cancer cancer hemopathy   therapy target in follicular lymphomas and diffuse large B-cell lymphomas

ANIMAL & CELL MODELS