UBP40_HUMAN
ID UBP40_HUMAN Reviewed; 1235 AA.
AC Q9NVE5; Q6NX38; Q70EL0;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 40;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 40;
DE AltName: Full=Ubiquitin thioesterase 40;
DE AltName: Full=Ubiquitin-specific-processing protease 40;
GN Name=USP40;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), LACK OF ENZYME ACTIVITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=14715245; DOI=10.1016/j.bbrc.2003.12.050;
RA Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S.,
RA Lopez-Otin C.;
RT "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific
RT proteases.";
RL Biochem. Biophys. Res. Commun. 314:54-62(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 2-1142 (ISOFORM 1).
RC TISSUE=Esophagus, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-318 (ISOFORM 1).
RC TISSUE=Testis;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: May be catalytically inactive.
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;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NVE5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NVE5-2; Sequence=VSP_008595, VSP_008596, VSP_012819;
CC Name=3;
CC IsoId=Q9NVE5-3; Sequence=VSP_040938;
CC -!- TISSUE SPECIFICITY: Broadly expressed. {ECO:0000269|PubMed:14715245}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91807.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ583821; CAE47748.2; -; mRNA.
DR EMBL; AK001647; BAA91807.1; ALT_INIT; mRNA.
DR EMBL; AK124094; BAC85770.1; -; mRNA.
DR EMBL; AC019221; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC019072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC067300; AAH67300.1; -; mRNA.
DR CCDS; CCDS46547.1; -. [Q9NVE5-1]
DR RefSeq; NP_060688.1; NM_018218.2. [Q9NVE5-1]
DR AlphaFoldDB; Q9NVE5; -.
DR SMR; Q9NVE5; -.
DR BioGRID; 120525; 7.
DR IntAct; Q9NVE5; 1.
DR STRING; 9606.ENSP00000415434; -.
DR MEROPS; C19.069; -.
DR iPTMnet; Q9NVE5; -.
DR PhosphoSitePlus; Q9NVE5; -.
DR BioMuta; USP40; -.
DR DMDM; 59803114; -.
DR EPD; Q9NVE5; -.
DR jPOST; Q9NVE5; -.
DR MassIVE; Q9NVE5; -.
DR MaxQB; Q9NVE5; -.
DR PaxDb; Q9NVE5; -.
DR PeptideAtlas; Q9NVE5; -.
DR PRIDE; Q9NVE5; -.
DR ProteomicsDB; 82785; -. [Q9NVE5-1]
DR ProteomicsDB; 82786; -. [Q9NVE5-2]
DR ProteomicsDB; 82787; -. [Q9NVE5-3]
DR Antibodypedia; 965; 124 antibodies from 23 providers.
DR DNASU; 55230; -.
DR Ensembl; ENST00000251722.10; ENSP00000251722.6; ENSG00000085982.15. [Q9NVE5-1]
DR Ensembl; ENST00000409945.1; ENSP00000386664.1; ENSG00000085982.15. [Q9NVE5-2]
DR Ensembl; ENST00000427112.6; ENSP00000387898.2; ENSG00000085982.15. [Q9NVE5-1]
DR Ensembl; ENST00000450966.5; ENSP00000415434.1; ENSG00000085982.15. [Q9NVE5-3]
DR GeneID; 55230; -.
DR KEGG; hsa:55230; -.
DR UCSC; uc002vuo.1; human. [Q9NVE5-1]
DR CTD; 55230; -.
DR DisGeNET; 55230; -.
DR GeneCards; USP40; -.
DR HGNC; HGNC:20069; USP40.
DR HPA; ENSG00000085982; Low tissue specificity.
DR MIM; 610570; gene.
DR neXtProt; NX_Q9NVE5; -.
DR OpenTargets; ENSG00000085982; -.
DR PharmGKB; PA134909324; -.
DR VEuPathDB; HostDB:ENSG00000085982; -.
DR eggNOG; KOG1863; Eukaryota.
DR GeneTree; ENSGT00940000157267; -.
DR HOGENOM; CLU_009719_0_0_1; -.
DR InParanoid; Q9NVE5; -.
DR OMA; NHPQIFQ; -.
DR OrthoDB; 77113at2759; -.
DR PhylomeDB; Q9NVE5; -.
DR TreeFam; TF106281; -.
DR PathwayCommons; Q9NVE5; -.
DR SignaLink; Q9NVE5; -.
DR BioGRID-ORCS; 55230; 12 hits in 1122 CRISPR screens.
DR ChiTaRS; USP40; human.
DR GeneWiki; USP40; -.
DR GenomeRNAi; 55230; -.
DR Pharos; Q9NVE5; Tbio.
DR PRO; PR:Q9NVE5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NVE5; protein.
DR Bgee; ENSG00000085982; Expressed in adrenal tissue and 147 other tissues.
DR ExpressionAtlas; Q9NVE5; baseline and differential.
DR Genevisible; Q9NVE5; HS.
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; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0031647; P:regulation of protein stability; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR033384; USP40.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR PANTHER; PTHR24006:SF644; PTHR24006:SF644; 1.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..1235
FT /note="Ubiquitin carboxyl-terminal hydrolase 40"
FT /id="PRO_0000080670"
FT DOMAIN 41..482
FT /note="USP"
FT REGION 1180..1235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1180..1203
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 50
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 305
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT VAR_SEQ 1..824
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008595"
FT VAR_SEQ 1
FT /note="M -> MSLFLRVVFSFTM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14715245"
FT /id="VSP_040938"
FT VAR_SEQ 973..987
FT /note="ASGNEPAQVSLLYLG -> ENRMGFQQPVHHKEK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008596"
FT VAR_SEQ 988..1235
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_012819"
FT VARIANT 666
FT /note="V -> A (in dbSNP:rs838543)"
FT /id="VAR_017123"
FT VARIANT 1025
FT /note="T -> M (in dbSNP:rs34026756)"
FT /id="VAR_059753"
FT VARIANT 1111
FT /note="R -> C (in dbSNP:rs1048603)"
FT /id="VAR_017124"
FT CONFLICT 277..318
FT /note="CEQSELDDLEYIYDLFSVIIHKGGCYGGHYHVYIKDVDHLGN -> FFSFNQ
FT KMHNVCVNRRYGGSGMPLLRCGRCVGSAQPLSSVFR (in Ref. 4; AAH67300)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1235 AA; 140130 MW; BEB20702566D39A8 CRC64;
MFGDLFEEEY STVSNNQYGK GKKLKTKALE PPAPREFTNL SGIRNQGGTC YLNSLLQTLH
FTPEFREALF SLGPEELGLF EDKDKPDAKV RIIPLQLQRL FAQLLLLDQE AASTADLTDS
FGWTSNEEMR QHDVQELNRI LFSALETSLV GTSGHDLIYR LYHGTIVNQI VCKECKNVSE
RQEDFLDLTV AVKNVSGLED ALWNMYVEEE VFDCDNLYHC GTCDRLVKAA KSAKLRKLPP
FLTVSLLRFN FDFVKCERYK ETSCYTFPLR INLKPFCEQS ELDDLEYIYD LFSVIIHKGG
CYGGHYHVYI KDVDHLGNWQ FQEEKSKPDV NLKDLQSEEE IDHPLMILKA ILLEENNLIP
VDQLGQKLLK KIGISWNKKY RKQHGPLRKF LQLHSQIFLL SSDESTVRLL KNSSLQAESD
FQRNDQQIFK MLPPESPGLN NSISCPHWFD INDSKVQPIR EKDIEQQFQG KESAYMLFYR
KSQLQRPPEA RANPRYGVPC HLLNEMDAAN IELQTKRAEC DSANNTFELH LHLGPQYHFF
NGALHPVVSQ TESVWDLTFD KRKTLGDLRQ SIFQLLEFWE GDMVLSVAKL VPAGLHIYQS
LGGDELTLCE TEIADGEDIF VWNGVEVGGV HIQTGIDCEP LLLNVLHLDT SSDGEKCCQV
IESPHVFPAN AEVGTVLTAL AIPAGVIFIN SAGCPGGEGW TAIPKEDMRK TFREQGLRNG
SSILIQDSHD DNSLLTKEEK WVTSMNEIDW LHVKNLCQLE SEEKQVKISA TVNTMVFDIR
IKAIKELKLM KELADNSCLR PIDRNGKLLC PVPDSYTLKE AELKMGSSLG LCLGKAPSSS
QLFLFFAMGS DVQPGTEMEI VVEETISVRD CLKLMLKKSG LQGDAWHLRK MDWCYEAGEP
LCEEDATLKE LLICSGDTLL LIEGQLPPLG FLKVPIWWYQ LQGPSGHWES HQDQTNCTSS
WGRVWRATSS QGASGNEPAQ VSLLYLGDIE ISEDATLAEL KSQAMTLPPF LEFGVPSPAH
LRAWTVERKR PGRLLRTDRQ PLREYKLGRR IEICLEPLQK GENLGPQDVL LRTQVRIPGE
RTYAPALDLV WNAAQGGTAG SLRQRVADFY RLPVEKIEIA KYFPEKFEWL PISSWNQQIT
KRKKKKKQDY LQGAPYYLKD GDTIGVKNLL IDDDDDFSTI RDDTGKEKQK QRALGRRKSQ
EALHEQSSYI LSSAETPARP RAPETSLSIH VGSFR
