Protein: Ubiquitin carboxyl-terminal hydrolase 38 (Q8NB14)
Organism: Homo sapiens (Human)
Function: Deubiquitinating enzyme that plays a role in various cellular processes, including DNA repair, cell cycle regulation, and immune response. Plays a role in the inhibition of type I interferon signaling by mediating the 'Lys-33' to 'Lys-48' ubiquitination transition of TBK1 leading to its degradation. Cleaves the ubiquitin chain from the histone demethylase LSD1/KDM1A and prevents it from degradation by the 26S proteasome, thus maintaining LSD1 protein level in cells. Plays a role in the DNA damage response by regulating the deacetylase activity of HDAC1 . Mechanistically, removes the 'Lys-63'-linked ubiquitin chain promoting the deacetylase activity of HDAC1 in response to DNA damage. Acts also as a specific deubiquitinase of histone deacetylase 3/HDAC3 and cleaves its 'Lys-63'-linked ubiquitin chains to lower its histone deacetylase activity . Regulates MYC levels and cell proliferation via antagonizing ubiquitin E3 ligase FBXW7 thereby preventing MYC 'Lys-48'- linked ubiquitination and degradation. Participates in antiviral response by removing both 'Lys-48'-linked and 'Lys-63'- linked polyubiquitination of Zika virus envelope protein E . Constitutively associated with IL-33R/IL1RL1, deconjugates its 'Lys-27'-linked polyubiquitination resulting in its autophagic degradation
Subcellular location: Cytoplasm. Nucleus. Note=In response to DNA damage, recruited to DNA damage sites in the nucleus
InterPro domains:
- IPR018200: Ubiquitin specific protease, conserved site (conserved_site) [446-858]
- IPR001394: Peptidase C19, ubiquitin carboxyl-terminal hydrolase (domain) [445-946]
- IPR028889: Ubiquitin specific protease UPS, catalytic domain (domain) [445-949]
- IPR038765: Papain-like cysteine peptidase superfamily (homologous_superfamily) [440-949]
- IPR033840: Ubiquitin-specific peptidase 38 (domain) [446-947]
- IPR049407: Ubiquitin carboxyl-terminal hydrolase 38-like, N-terminal domain (domain) [48-384]
- IPR050164: Ubiquitin carboxyl-terminal hydrolases (family) [266-950]
Sequence:
MDKILEGLVSSSHPLPLKRVIVRKVVESAEHWLDEAQCEAMFDLTTRLILEGQDPFQRQVGHQVLEAYARYHRPEFESFFNKTFVLGLLHQGYHSLDRKDVAILDYIHNGLKLIMSCPSVLDLFSLLQVEVLRMVCERPEPQLCARLSDLLTDFVQCIPKGKLSITFCQQLVRTIGHFQCVSTQERELREYVSQVTKVSNLLQNIWKAEPATLLPSLQEVFASISSTDASFEPSVALASLVQHIPLQMITVLIRSLTTDPNVKDASMTQALCRMIDWLSWPLAQHVDTWVIALLKGLAAVQKFTILIDVTLLKIELVFNRLWFPLVRPGALAVLSHMLLSFQHSPEAFHLIVPHVVNLVHSFKNDGLPSSTAFLVQLTELIHCMMYHYSGFPDLYEPILEAIKDFPKPSEEKIKLILNQSAWTSQSNSLASCLSRLSGKSETGKTGLINLGNTCYMNSVIQALFMATDFRRQVLSLNLNGCNSLMKKLQHLFAFLAHTQREAYAPRIFFEASRPPWFTPRSQQDCSEYLRFLLDRLHEEEKILKVQASHKPSEILECSETSLQEVASKAAVLTETPRTSDGEKTLIEKMFGGKLRTHIRCLNCRSTSQKVEAFTDLSLAFCPSSSLENMSVQDPASSPSIQDGGLMQASVPGPSEEPVVYNPTTAAFICDSLVNEKTIGSPPNEFYCSENTSVPNESNKILVNKDVPQKPGGETTPSVTDLLNYFLAPEILTGDNQYYCENCASLQNAEKTMQITEEPEYLILTLLRFSYDQKYHVRRKILDNVSLPLVLELPVKRITSFSSLSESWSVDVDFTDLSENLAKKLKPSGTDEASCTKLVPYLLSSVVVHSGISSESGHYYSYARNITSTDSSYQMYHQSEALALASSQSHLLGRDSPSAVFEQDLENKEMSKEWFLFNDSRVTFTSFQSVQKITSRFPKDTAYVLLYKKQHSTNGLSGNNPTSGLWINGDPPLQKELMDAITKDNKLYLQEQELNARARALQAASASCSFRPNGFDDNDPPGSCGPTGGGGGGGFNTVGRLVF
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140096 (catalytic activity, acting on a protein), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0008233 (peptidase activity), GO:0008234 (cysteine-type peptidase activity), GO:0019783 (ubiquitin-like protein peptidase activity), GO:0101005 (deubiquitinase activity), GO:0004843 (cysteine-type deubiquitinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0043170 (macromolecule metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0019538 (protein metabolic process), GO:0006508 (proteolysis), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0070646 (protein modification by small protein removal), GO:0070647 (protein modification by small protein conjugation or removal), GO:0016579 (protein deubiquitination)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)