USP4 (ubiquitin specific peptidase 4)

Gene

• Entrez ID: 7375
• Gene name: Ubiquitin specific peptidase 4
• Gene symbol: USP4
• Synonyms (NCBI Gene): UNP, Unph
• Chromosome: 3
• Chromosome location: 3p21.31
• Summary: The protein encoded by this gene is a protease that deubiquitinates target proteins such as ADORA2A and TRIM21. The encoded protein shuttles between the nucleus and cytoplasm and is involved in maintaining operational fidelity in the endoplasmic reticulum

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT438752	hsa-miR-148a-3p	Hep3B	24798342
MIRT438752	hsa-miR-148a-3p	Hep3B	24798342
MIRT739953	hsa-miR-1324	CLIP-seq
MIRT739950	hsa-miR-136	CLIP-seq
MIRT1479727	hsa-miR-28-3p	CLIP-seq
MIRT739952	hsa-miR-3145-5p	CLIP-seq
MIRT1479728	hsa-miR-3175	CLIP-seq
MIRT1479729	hsa-miR-320a	CLIP-seq
MIRT1479730	hsa-miR-320b	CLIP-seq
MIRT1479731	hsa-miR-320c	CLIP-seq
MIRT1479732	hsa-miR-320d	CLIP-seq
MIRT1479733	hsa-miR-320e	CLIP-seq
MIRT1479734	hsa-miR-4321	CLIP-seq
MIRT1479735	hsa-miR-4429	CLIP-seq
MIRT1479736	hsa-miR-4704-5p	CLIP-seq
MIRT1479737	hsa-miR-4706	CLIP-seq
MIRT739954	hsa-miR-4713-3p	CLIP-seq
MIRT1479738	hsa-miR-4749-5p	CLIP-seq
MIRT1479739	hsa-miR-4781-5p	CLIP-seq
MIRT739951	hsa-miR-508-5p	CLIP-seq
MIRT1479740	hsa-miR-875-3p	CLIP-seq
MIRT2144435	hsa-miR-193a-5p	CLIP-seq
MIRT2144436	hsa-miR-3925-3p	CLIP-seq
MIRT2144437	hsa-miR-4645-5p	CLIP-seq
MIRT2144438	hsa-miR-4673	CLIP-seq
MIRT1479736	hsa-miR-4704-5p	CLIP-seq
MIRT2144439	hsa-miR-766	CLIP-seq
MIRT739950	hsa-miR-136	CLIP-seq
MIRT2144435	hsa-miR-193a-5p	CLIP-seq
MIRT2364651	hsa-miR-3183	CLIP-seq
MIRT2364652	hsa-miR-342-5p	CLIP-seq
MIRT2364653	hsa-miR-3665	CLIP-seq
MIRT2144436	hsa-miR-3925-3p	CLIP-seq
MIRT2364654	hsa-miR-4326	CLIP-seq
MIRT2144437	hsa-miR-4645-5p	CLIP-seq
MIRT2364655	hsa-miR-4651	CLIP-seq
MIRT2364656	hsa-miR-4664-5p	CLIP-seq
MIRT2144438	hsa-miR-4673	CLIP-seq
MIRT2364657	hsa-miR-4723-3p	CLIP-seq
MIRT2364658	hsa-miR-510	CLIP-seq
MIRT2364659	hsa-miR-512-5p	CLIP-seq
MIRT2364660	hsa-miR-608	CLIP-seq
MIRT2364661	hsa-miR-657	CLIP-seq
MIRT2144439	hsa-miR-766	CLIP-seq
MIRT2463055	hsa-miR-3157-5p	CLIP-seq
MIRT2463056	hsa-miR-4760-3p	CLIP-seq
MIRT2463057	hsa-miR-548c-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000244	Process	Spliceosomal tri-snRNP complex assembly	IMP	20595234
GO:0002181	Process	Cytoplasmic translation	IDA	8706699, 34314702
GO:0004843	Function	Cysteine-type deubiquitinase activity	IDA	16316627, 16472766, 18728397, 30514904
GO:0004843	Function	Cysteine-type deubiquitinase activity	IEA
GO:0004843	Function	Cysteine-type deubiquitinase activity	TAS
GO:0005515	Function	Protein binding	IPI	11461834, 16339847, 20595234, 21522127, 23313255, 28604766
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	16339847, 20595234
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	16316627, 16339847, 20595234
GO:0005737	Component	Cytoplasm	IEA
GO:0005764	Component	Lysosome	TAS	9827704
GO:0005829	Component	Cytosol	TAS
GO:0006508	Process	Proteolysis	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0008234	Function	Cysteine-type peptidase activity	IEA
GO:0009267	Process	Cellular response to starvation	IDA	24529379
GO:0016579	Process	Protein deubiquitination	IDA	16316627, 16339847, 16472766
GO:0016579	Process	Protein deubiquitination	IEA
GO:0016579	Process	Protein deubiquitination	IMP	20595234
GO:0016579	Process	Protein deubiquitination	TAS
GO:0016787	Function	Hydrolase activity	IEA
GO:0031397	Process	Negative regulation of protein ubiquitination	IMP	16472766
GO:0031647	Process	Regulation of protein stability	IDA	16472766
GO:0031669	Process	Cellular response to nutrient levels	IDA	29236692, 29750193
GO:0031685	Function	Adenosine receptor binding	IPI	16339847
GO:0034394	Process	Protein localization to cell surface	IDA	16339847
GO:0038202	Process	TORC1 signaling	IDA	12087098, 29750193
GO:0042802	Function	Identical protein binding	IPI	22001210
GO:0045947	Process	Negative regulation of translational initiation	IDA	22578813
GO:0045948	Process	Positive regulation of translational initiation	IDA	1922062, 29750193
GO:0046872	Function	Metal ion binding	IEA
GO:1904262	Process	Negative regulation of TORC1 signaling	IDA	9045618, 12906785
GO:1904263	Process	Positive regulation of TORC1 signaling	IDA	29236692
GO:1904263	Process	Positive regulation of TORC1 signaling	IDA	30514904

Other IDs

• MIM: 603486
• HGNC: 12627
• e!Ensembl: ENSG00000114316

Protein

• UniProt ID: Q13107
• Protein name: Ubiquitin carboxyl-terminal hydrolase 4 (EC 3.4.19.12) (Deubiquitinating enzyme 4) (Ubiquitin thioesterase 4) (Ubiquitin-specific-processing protease 4) (Ubiquitous nuclear protein homolog)
• Protein function: Deubiquitinating enzyme that removes conjugated ubiquitin from target proteins (PubMed:16316627, PubMed:16339847, PubMed:16472766, PubMed:20595234, PubMed:22347420, PubMed:25404403, PubMed:28604766, PubMed:30514904). Deubiquitinates PDPK1 (PubMe
• PDB: 2Y6E, 5CTR
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF06337	DUSP	31 → 123	DUSP domain	Domain
  PF14836	Ubiquitin_3	139 → 226	Ubiquitin-like domain	Domain
  PF00443	UCH	302 → 920	Ubiquitin carboxyl-terminal hydrolase	Family

• Tissue specificity: TISSUE SPECIFICITY: Overexpressed in small cell tumors and adenocarcinomas of the lung compared to wild-type lung (at protein level). Expressed in the hippocampal neurons. {ECO:0000269|PubMed:16339847, ECO:0000269|PubMed:7784062}.
• Sequence:

  MAEGGGCRERPDAETQKSELGPLMRTTLQRGAQWYLIDSRWFKQWKKYVGFDSWDMYNVG
  EHNLFPGPIDNSGLFSDPESQTLKEHLIDELDYVLVPTEAWNKLLNWYGCVEGQQPIVRK
  VVEHGLFVKHCKVEVYLLELKLCENSDPTNVLSCHFSKADTIATIEKEMRKLFNIPAERE
  TRLWNKYMSNTYEQLSKLDNTVQDAGLYQGQVLVIEPQNEDGTWPRQTLQSKSSTAPSRN
  FTTSPKSSASPYSSVSASLIANGDSTSTCGMHSSGVSRGGSGFSASYNCQEPPSSHIQPG
  LCGLGNLGNTCFMNSALQCLSNTAPLTDYFLKDEYEAEINRDNPLGMKGEIAEAYAELIK
  QMWSGRDAHVAPRMFKTQVGRFAPQFSGYQQQDSQELLAFLLDGLHEDLNRVKKKPYLEL
  KDANGRPDAVVAKEAWENHRLRNDSVIVDTFHGLFKSTLVCPECAKVSVTFDPFCYLTLP
  LPLKKDRVMEVFLVPADPHCRPTQYRVTVPLMGAVSDLCEALSRLSGIAAENMVVADVYN
  HRFHKIFQMDEGLNHIMPRDDIFVYEVCSTSVDGSECVTLPVYFRERKSRPSSTSSASAL
  YGQPLLLSVPKHKLTLESLYQAVCDRISRYVKQPLPDEFGSSPLEPGACNGSRNSCEGED
  EEEMEHQEEGKEQLSETEGSGEDEPGNDPSETTQKKIKGQPCPKRLFTFSLVNSYGTADI
  NSLAADGKLLKLNSRSTLAMDWDSETRRLYYDEQESEAYEKHVSMLQPQKKKKTTVALRD
  CIELFTTMETLGEHDPWYCPNCKKHQQATKKFDLWSLPKILVVHLKRFSYNRYWRDKLDT
  VVEFPIRGLNMSEFVCNLSARPYVYDLIAVSNHYGAMGVGHYTAYAKNKLNGKWYYFDDS
  NVSLASEDQIVTKAAYVLFYQRRDDEFYKTPSLSSSGSSDGGTRPSSSQQGFGDDEACSM
  DTN

• Sequence length: 963

Pathways

Reactome:

TNFR1-induced proapoptotic signaling
Regulation of TNFR1 signaling
TNFR1-induced NFkappaB signaling pathway
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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CANNABIS DEPENDENCE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, HEPATOCELLULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ENDOMETRIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOOD DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	26883469, 29667299		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	25821221		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	22706160, 27049265, 27430936, 31219614, 31302495		★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	16360395		★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	27060135, 27990632	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	29667299	Inhibit	★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	26189775, 31251006		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	26669864, 31251006		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	26189775	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal carcinoma	Esophageal Carcinoma	BEFREE	28946564		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophagus Neoplasm	BEFREE	28946564		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	28946564	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	BEFREE	29573006		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	30362572		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	30655854		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	30655854, 30881035		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	35774799	Associate	★☆☆☆☆ Found in Text Mining only
Hypoalphalipoproteinemias	Hypoalphalipoproteinemia	Pubtator	28473662	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	24798342, 29396555, 30335615		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	40311306	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	22706160, 27049265, 27430936, 31219614, 31302495		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of esophagus	Esophagus Neoplasm	BEFREE	28946564		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	22029577, 26669864, 29667299, 30655854		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	26189775, 31251006		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	29542252		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	29542252	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	29573006		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	33531688, 36762777	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23313255, 24798342, 27430936, 28946564, 29396555, 30071870, 30881035		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	29573006		★☆☆☆☆ Found in Text Mining only
Rheumatic Heart Disease	Rheumatic Heart Disease	BEFREE	25821221, 28791349		★☆☆☆☆ Found in Text Mining only
Rheumatic Heart Disease	Rheumatic heart disease	Pubtator	28791349	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	23313255, 37308746	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of lung	Lung carcinoma	BEFREE	29667299		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	BEFREE	23313255		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	29573006		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	36336860, 37624791	Associate	★☆☆☆☆ Found in Text Mining only