ID   UBP38_MOUSE             Reviewed;        1042 AA.
AC   Q8BW70; Q8BWL1; Q8BX03;
DT   10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2003, sequence version 2.
DT   24-JAN-2024, entry version 148.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 38;
DE            EC=3.4.19.12;
DE   AltName: Full=Deubiquitinating enzyme 38;
DE   AltName: Full=Ubiquitin thioesterase 38;
DE   AltName: Full=Ubiquitin-specific-processing protease 38;
GN   Name=Usp38;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
RC   TISSUE=Embryonic heart, Embryonic stem cell, and Oviduct;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain, Olfactory epithelium, and Retina;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Heart, Liver, Pancreas, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=27692986; DOI=10.1016/j.molcel.2016.08.029;
RA   Lin M., Zhao Z., Yang Z., Meng Q., Tan P., Xie W., Qin Y., Wang R.F.,
RA   Cui J.;
RT   "USP38 Inhibits Type I Interferon Signaling by Editing TBK1 Ubiquitination
RT   through NLRP4 Signalosome.";
RL   Mol. Cell 64:267-281(2016).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=35238669; DOI=10.1073/pnas.2116279119;
RA   Yi X.M., Li M., Chen Y.D., Shu H.B., Li S.;
RT   "Reciprocal regulation of IL-33 receptor-mediated inflammatory response and
RT   pulmonary fibrosis by TRAF6 and USP38.";
RL   Proc. Natl. Acad. Sci. U.S.A. 119:e2116279119-e2116279119(2022).
CC   -!- FUNCTION: Deubiquitinating enzyme that plays a role in various cellular
CC       processes, including DNA repair, cell cycle regulation, and immune
CC       response (PubMed:27692986, PubMed:35238669). Plays a role in the
CC       inhibition of type I interferon signaling by mediating the 'Lys-33' to
CC       'Lys-48' ubiquitination transition of TBK1 leading to its degradation.
CC       Cleaves the ubiquitin chain from the histone demethylase LSD1/KDM1A and
CC       prevents it from degradation by the 26S proteasome, thus maintaining
CC       LSD1 protein level in cells. Plays a role in the DNA damage response by
CC       regulating the deacetylase activity of HDAC1. Mechanistically, removes
CC       the 'Lys-63'-linked ubiquitin chain promoting the deacetylase activity
CC       of HDAC1 in response to DNA damage. Acts also as a specific
CC       deubiquitinase of histone deacetylase 3/HDAC3 and cleaves its 'Lys-63'-
CC       linked ubiquitin chains to lower its histone deacetylase activity.
CC       Regulates MYC levels and cell proliferation via antagonizing ubiquitin
CC       E3 ligase FBXW7 thereby preventing MYC 'Lys-48'-linked ubiquitination
CC       and degradation. Participates in antiviral response by removing both
CC       'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of Zika virus
CC       envelope protein E. Constitutively associated with IL-33R/IL1RL1,
CC       deconjugates its 'Lys-27'-linked polyubiquitination resulting in its
CC       autophagic degradation. {ECO:0000250|UniProtKB:Q8NB14,
CC       ECO:0000269|PubMed:27692986, ECO:0000269|PubMed:35238669}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:Q8NB14};
CC   -!- SUBUNIT: Interacts with isoform 1 of FBXW7; this interaction prevents
CC       FBXW7-mediated degradation of MYC. {ECO:0000250|UniProtKB:Q8NB14}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8NB14}. Nucleus
CC       {ECO:0000250|UniProtKB:Q8NB14}. Note=In response to DNA damage,
CC       recruited to DNA damage sites in the nucleus.
CC       {ECO:0000250|UniProtKB:Q8NB14}.
CC   -!- DISRUPTION PHENOTYPE: USP38-deletion mice produce higher levels of IFN-
CC       beta, TNF-alpha, and IL-6 than WT mice in response to viral infection
CC       (PubMed:27692986). They are also more susceptible to inflammatory
CC       damage and death and developed more serious pulmonary fibrosis after
CC       bleomycin treatment (PubMed:35238669). {ECO:0000269|PubMed:27692986,
CC       ECO:0000269|PubMed:35238669}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR   EMBL; AK049287; BAC33659.2; -; mRNA.
DR   EMBL; AK052219; BAC34890.1; -; mRNA.
DR   EMBL; AK054116; BAC35661.1; -; mRNA.
DR   EMBL; BC054404; AAH54404.1; -; mRNA.
DR   EMBL; BC057122; AAH57122.1; -; mRNA.
DR   EMBL; BC058784; AAH58784.1; -; mRNA.
DR   CCDS; CCDS22444.1; -.
DR   RefSeq; NP_081830.2; NM_027554.2.
DR   AlphaFoldDB; Q8BW70; -.
DR   SMR; Q8BW70; -.
DR   BioGRID; 217020; 3.
DR   STRING; 10090.ENSMUSP00000039943; -.
DR   MEROPS; C19.056; -.
DR   iPTMnet; Q8BW70; -.
DR   PhosphoSitePlus; Q8BW70; -.
DR   EPD; Q8BW70; -.
DR   MaxQB; Q8BW70; -.
DR   PaxDb; 10090-ENSMUSP00000039943; -.
DR   ProteomicsDB; 298461; -.
DR   Pumba; Q8BW70; -.
DR   Antibodypedia; 27336; 156 antibodies from 26 providers.
DR   DNASU; 74841; -.
DR   Ensembl; ENSMUST00000042724.8; ENSMUSP00000039943.7; ENSMUSG00000038250.10.
DR   GeneID; 74841; -.
DR   KEGG; mmu:74841; -.
DR   UCSC; uc009mjd.1; mouse.
DR   AGR; MGI:1922091; -.
DR   CTD; 84640; -.
DR   MGI; MGI:1922091; Usp38.
DR   VEuPathDB; HostDB:ENSMUSG00000038250; -.
DR   eggNOG; KOG1864; Eukaryota.
DR   GeneTree; ENSGT00940000158403; -.
DR   HOGENOM; CLU_010910_0_0_1; -.
DR   InParanoid; Q8BW70; -.
DR   OMA; AFVCDSV; -.
DR   OrthoDB; 227085at2759; -.
DR   PhylomeDB; Q8BW70; -.
DR   TreeFam; TF324529; -.
DR   BioGRID-ORCS; 74841; 5 hits in 77 CRISPR screens.
DR   ChiTaRS; Usp38; mouse.
DR   PRO; PR:Q8BW70; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; Q8BW70; Protein.
DR   Bgee; ENSMUSG00000038250; Expressed in animal zygote and 241 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:MGI.
DR   GO; GO:0140311; F:protein sequestering activity; ISO:MGI.
DR   GO; GO:0045824; P:negative regulation of innate immune response; ISO:MGI.
DR   GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR   CDD; cd02664; Peptidase_C19H; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR033840; USP38.
DR   InterPro; IPR049407; Usp38-like_N.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF710; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 38; 1.
DR   Pfam; PF00443; UCH; 1.
DR   Pfam; PF21246; Usp38-like_N; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   Genevisible; Q8BW70; MM.
PE   1: Evidence at protein level;
KW   Cytoplasm; Hydrolase; Nucleus; Protease; Reference proteome;
KW   Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..1042
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 38"
FT                   /id="PRO_0000080669"
FT   DOMAIN          445..949
FT                   /note="USP"
FT   ACT_SITE        454
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        857
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   CONFLICT        90
FT                   /note="Q -> H (in Ref. 1; BAC35661)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        266
FT                   /note="S -> G (in Ref. 1; BAC33659)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        442
FT                   /note="T -> A (in Ref. 1; BAC34890)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        776
FT                   /note="V -> A (in Ref. 1; BAC33659)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1042 AA;  116102 MW;  B039BCA53E16B178 CRC64;
     MDKILEGLVS SSHPLPLKRM IVRKVVEFAE HWLDEAQCEA MFDLTTRLIL EGQDPFQRQV
     GHQVLEAYAR YHRPEFESFF NKTFVLGLLQ QGYHSVDRKD VAILDYIHNG LKLIMSCPSV
     LDLFSLLQVE VLRMVCERPE PVLCARLSDL LTDFVQCVPK GKLSVTFCQQ LVRTIGHFQC
     VSTQEKELRE YVSQVTKVST LLQNIWKAEP STLLPSLQEV FASISSTDAS FEPSVALASL
     VQHIPLQMIT VLIRSLTTDP NVKDASMTQA LCRMIDWLSW PLAQHVDTWV IALLKGLAAV
     QKFTILIDVT LLKIELVFNR LWFPLVRPGA LAVLSHMLLS FQHSPEAFHV IVPHIVNLVH
     SFRSDGLPSS TAFLVQLTEL VHCMMYHYSG FPDLYEPILE AVKDFPKPSE EKIKLILNQS
     AWTSQSNALA SCLSRLSGKS ETGKTGLINL GNTCYMNSVL QALFMATEFR RQVLSLNLNG
     CNSLMKKLQH LFAFLAHTQR EAYAPRIFFE ASRPPWFTPR SQQDCSEYLR FLLDRLHEEE
     KILRVQSSHK PSEGLDCAET CLQEVTSKVA VPTESPGTGD SEKTLIEKMF GGKLRTHICC
     LNCGSTSHKV EAFTDLSLAF CPSPSVEDLS FQDTASLPSA QDDGLMQTSV ADPEEEPVVY
     NPATAAFVCD SVVNQRVLGS PPVEFHCAES SSVPEESAKI LISKDVPQNP GGESTTSVTD
     LLNYFLAPEV LTGENQYYCE SCASLQNAEK TMQITEEPEY LILTLLRFSY DQKYHVRRKI
     LDNVSLPLVL ELPVKRTASF SSLSQSWSVD VDFTDINENL PKKLKPSGTE EAFCPKLVPY
     LLSSVVVHSG VSSESGHYYS YARNITGTES SYQMCPQSES LALAPSQSCL LGVESPNTVI
     EQDLENKEMS QEWFLFNDSR VTFTSFQSVQ KITSRFPKDT AYVLLYKKQS RANGIDSDNP
     ASGVWANGDP PLQKELMDAI TKDNKLYLQE QELNARARAL QAASASCSFR PNGFDDNDPP
     GSCGPTGGGG GGGFNTVGRL VF
//