USP26 (ubiquitin specific peptidase 26)

Gene

• Entrez ID: 83844
• Gene name: Ubiquitin specific peptidase 26
• Gene symbol: USP26
• Synonyms (NCBI Gene): SPGFX6
• Chromosome: X
• Chromosome location: Xq26.2
• Summary: This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases and is a deubiquitinating enzyme (DUB) with His and Cys domains. It is specifically expressed in testis tissue. Mutations in this gene have been associated with Sert

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT735749	hsa-miR-203a-5p	Luciferase reporter assay, Western blotting, qRT-PCR	32760222

Transcription factors

Transcription factor	Regulation	Reference
AR	Unknown	20501646

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000082	Process	G1/S transition of mitotic cell cycle	IBA
GO:0004843	Function	Cysteine-type deubiquitinase activity	IBA
GO:0004843	Function	Cysteine-type deubiquitinase activity	IEA
GO:0005515	Function	Protein binding	IPI	20501646, 28839133, 35156780
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	20501646
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0005856	Component	Cytoskeleton	IEA
GO:0005929	Component	Cilium	IEA
GO:0006508	Process	Proteolysis	IEA
GO:0007283	Process	Spermatogenesis	IMP	34202084
GO:0008233	Function	Peptidase activity	IEA
GO:0008234	Function	Cysteine-type peptidase activity	IEA
GO:0016579	Process	Protein deubiquitination	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0031514	Component	Motile cilium	IEA
GO:0031647	Process	Regulation of protein stability	IBA
GO:0032435	Process	Negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP	28839133
GO:0036126	Component	Sperm flagellum	IMP	34202084
GO:0042995	Component	Cell projection	IEA
GO:0060765	Process	Regulation of androgen receptor signaling pathway	IMP	20501646
GO:0101005	Function	Deubiquitinase activity	IDA	20501646
GO:0101005	Function	Deubiquitinase activity	IEA
GO:1990380	Function	K48-linked deubiquitinase activity	IDA	28839133

Other IDs

• MIM: 300309
• HGNC: 13485
• e!Ensembl: ENSG00000134588

Protein

• UniProt ID: Q9BXU7
• Protein name: Ubiquitin carboxyl-terminal hydrolase 26 (EC 3.4.19.12) (Deubiquitinating enzyme 26) (Ubiquitin thioesterase 26) (Ubiquitin-specific-processing protease 26)
• Protein function: Deubiquitinase regulating several biological processes through the deubiquitination of components of these processes (PubMed:20501646, PubMed:28839133). Involved in somatic cell reprogramming through the 'Lys-48'-linked deubiquitination and stab
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16674	UCH_N	1 → 104	N-terminal of ubiquitin carboxyl-terminal hydrolase 37	Domain
  PF00443	UCH	295 → 883	Ubiquitin carboxyl-terminal hydrolase	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in testis. {ECO:0000269|PubMed:34202084}.
• Sequence:

  MAALFLRGFVQIGNCKTGISKSKEAFIEAVERKKKDRLVLYFKSGKYSTFRLSDNIQNVV
  LKSYRGNQNHLHLTLQNNNGLFIEGLSSTDAEQLKIFLDRVHQNEVQPPVRPGKGGSVFS
  STTQKEINKTSFHKVDEKSSSKSFEIAKGSGTGVLQRMPLLTSKLTLTCGELSENQHKKR
  KRMLSSSSEMNEEFLKENNSVEYKKSKADCSRCVSYNREKQLKLKELEENKKLECESSCI
  MNATGNPYLDDIGLLQALTEKMVLVFLLQQGYSDGYTKWDKLKLFFELFPEKICHGLPNL
  GNTCYMNAVLQSLLSIPSFADDLLNQSFPWGKIPLNALTMCLARLLFFKDTYNIEIKEML
  LLNLKKAISAAAEIFHGNAQNDAHEFLAHCLDQLKDNMEKLNTIWKPKSEFGEDNFPKQV
  FADDPDTSGFSCPVITNFELELLHSIACKACGQVILKTELNNYLSINLPQRIKAHPSSIQ
  STFDLFFGAEELEYKCAKCEHKTSVGVHSFSRLPRILIVHLKRYSLNEFCALKKNDQEVI
  ISKYLKVSSHCNEGTRPPLPLSEDGEITDFQLLKVIRKMTSGNISVSWPATKESKDILAP
  HIGSDKESEQKKGQTVFKGASRRQQQKYLGKNSKPNELESVYSGDRAFIEKEPLAHLMTY
  LEDTSLCQFHKAGGKPASSPGTPLSKVDFQTVPENPKRKKYVKTSKFVAFDRIINPTKDL
  YEDKNIRIPERFQKVSEQTQQCDGMRICEQAPQQALPQSFPKPGTQGHTKNLLRPTKLNL
  QKSNRNSLLALGSNKNPRNKDILDKIKSKAKETKRNDDKGDHTYRLISVVSHLGKTLKSG
  HYICDAYDFEKQIWFTYDDMRVLGIQEAQMQEDRRCTGYIFFYMHNEIFEEMLKREENAQ
  LNSKEVEETLQKE

• Sequence length: 913

Pathways

Reactome:

Ub-specific processing proteases

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Male infertility	Pathogenic	rs2524103427	RCV004585024	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spermatogenic failure, X-linked, 6	Pathogenic	rs747682836, rs1446375255, rs2524103427	RCV003153258 RCV003153259 RCV003459816	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
HIV-1 INFECTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
USP26-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Abortion Habitual	Associate	23779098	★☆☆☆☆ Found in Text Mining only
Abortion Spontaneous	Associate	23779098	★☆☆☆☆ Found in Text Mining only
Airway Obstruction	Associate	23779098	★☆☆☆☆ Found in Text Mining only
Arrest of spermatogenesis	Associate	17968467, 18958354, 32202304	★☆☆☆☆ Found in Text Mining only
Asthenozoospermia	Associate	34202084	★☆☆☆☆ Found in Text Mining only
Azoospermia	Associate	18958354, 23779098, 25739334, 32410375	★☆☆☆☆ Found in Text Mining only
Azoospermia Nonobstructive	Associate	27089915	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Associate	28381482	★☆☆☆☆ Found in Text Mining only
Infertility	Associate	32202304	★☆☆☆☆ Found in Text Mining only
Infertility Male	Associate	17968467, 23779098, 32202304, 32410375, 34202084	★☆☆☆☆ Found in Text Mining only
Oligospermia	Associate	18958354, 32202304	★☆☆☆☆ Found in Text Mining only
Sertoli Cell Only Syndrome	Associate	32410375	★☆☆☆☆ Found in Text Mining only
Thyroid Carcinoma Anaplastic	Associate	35397626	★☆☆☆☆ Found in Text Mining only