ID   UBP43_HUMAN             Reviewed;        1123 AA.
AC   Q70EL4; A6NDT9; B7ZLT9; B7ZVX5; Q8N2C5; Q96DQ6;
DT   19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 2.
DT   13-SEP-2023, entry version 142.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 43;
DE            EC=3.4.19.12;
DE   AltName: Full=Deubiquitinating enzyme 43;
DE   AltName: Full=Ubiquitin thioesterase 43;
DE   AltName: Full=Ubiquitin-specific-processing protease 43;
GN   Name=USP43;
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 1), AND TISSUE 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] (ISOFORMS 2 AND 3).
RC   TISSUE=Amygdala;
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=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
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   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1041, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
CC   -!- FUNCTION: May recognize and hydrolyze the peptide bond at the C-
CC       terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin
CC       precursors as well as that of ubiquitinated proteins (By similarity).
CC       {ECO:0000250}.
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=4;
CC       Name=1;
CC         IsoId=Q70EL4-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q70EL4-2; Sequence=VSP_020466, VSP_020468;
CC       Name=3;
CC         IsoId=Q70EL4-3; Sequence=VSP_020467;
CC       Name=4;
CC         IsoId=Q70EL4-4; Sequence=VSP_046779;
CC   -!- TISSUE SPECIFICITY: Expressed in brain, aorta and lung at low levels.
CC       {ECO:0000269|PubMed:14715245}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB70869.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AJ583817; CAE47744.2; -; mRNA.
DR   EMBL; AK055188; BAB70869.1; ALT_FRAME; mRNA.
DR   EMBL; AK090821; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC027045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC118755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471108; EAW90022.1; -; Genomic_DNA.
DR   EMBL; BC136368; AAI36369.1; -; mRNA.
DR   EMBL; BC144041; AAI44042.1; -; mRNA.
DR   EMBL; BC171759; AAI71759.1; -; mRNA.
DR   CCDS; CCDS45610.1; -. [Q70EL4-1]
DR   CCDS; CCDS58516.1; -. [Q70EL4-4]
DR   RefSeq; NP_001254505.1; NM_001267576.1. [Q70EL4-4]
DR   RefSeq; NP_694942.3; NM_153210.4. [Q70EL4-1]
DR   RefSeq; XP_011521944.1; XM_011523642.2.
DR   RefSeq; XP_016879649.1; XM_017024160.1. [Q70EL4-3]
DR   RefSeq; XP_016879650.1; XM_017024161.1. [Q70EL4-3]
DR   AlphaFoldDB; Q70EL4; -.
DR   BioGRID; 125884; 56.
DR   IntAct; Q70EL4; 34.
DR   MINT; Q70EL4; -.
DR   STRING; 9606.ENSP00000285199; -.
DR   MEROPS; C19.976; -.
DR   GlyGen; Q70EL4; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q70EL4; -.
DR   PhosphoSitePlus; Q70EL4; -.
DR   BioMuta; USP43; -.
DR   DMDM; 296452852; -.
DR   EPD; Q70EL4; -.
DR   jPOST; Q70EL4; -.
DR   MassIVE; Q70EL4; -.
DR   MaxQB; Q70EL4; -.
DR   PaxDb; Q70EL4; -.
DR   PeptideAtlas; Q70EL4; -.
DR   ProteomicsDB; 68549; -. [Q70EL4-1]
DR   ProteomicsDB; 68550; -. [Q70EL4-2]
DR   ProteomicsDB; 68551; -. [Q70EL4-3]
DR   ProteomicsDB; 7268; -.
DR   Antibodypedia; 6274; 161 antibodies from 25 providers.
DR   DNASU; 124739; -.
DR   Ensembl; ENST00000285199.12; ENSP00000285199.6; ENSG00000154914.17. [Q70EL4-1]
DR   Ensembl; ENST00000570475.5; ENSP00000458963.1; ENSG00000154914.17. [Q70EL4-4]
DR   GeneID; 124739; -.
DR   KEGG; hsa:124739; -.
DR   MANE-Select; ENST00000285199.12; ENSP00000285199.6; NM_153210.5; NP_694942.3.
DR   UCSC; uc010cod.5; human. [Q70EL4-1]
DR   AGR; HGNC:20072; -.
DR   CTD; 124739; -.
DR   DisGeNET; 124739; -.
DR   GeneCards; USP43; -.
DR   HGNC; HGNC:20072; USP43.
DR   HPA; ENSG00000154914; Low tissue specificity.
DR   neXtProt; NX_Q70EL4; -.
DR   OpenTargets; ENSG00000154914; -.
DR   PharmGKB; PA134865304; -.
DR   VEuPathDB; HostDB:ENSG00000154914; -.
DR   eggNOG; KOG1868; Eukaryota.
DR   eggNOG; KOG1870; Eukaryota.
DR   GeneTree; ENSGT00940000158772; -.
DR   HOGENOM; CLU_001060_6_0_1; -.
DR   InParanoid; Q70EL4; -.
DR   OMA; LAVEWDC; -.
DR   OrthoDB; 5474185at2759; -.
DR   PhylomeDB; Q70EL4; -.
DR   TreeFam; TF106278; -.
DR   PathwayCommons; Q70EL4; -.
DR   Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR   SignaLink; Q70EL4; -.
DR   BioGRID-ORCS; 124739; 18 hits in 1196 CRISPR screens.
DR   ChiTaRS; USP43; human.
DR   GenomeRNAi; 124739; -.
DR   Pharos; Q70EL4; Tbio.
DR   PRO; PR:Q70EL4; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q70EL4; Protein.
DR   Bgee; ENSG00000154914; Expressed in oviduct epithelium and 156 other tissues.
DR   ExpressionAtlas; Q70EL4; baseline and differential.
DR   Genevisible; Q70EL4; HS.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0019785; F:ISG15-specific peptidase activity; TAS:Reactome.
DR   GO; GO:0016579; P:protein deubiquitination; IEA:InterPro.
DR   GO; GO:0019985; P:translesion synthesis; TAS:Reactome.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR   CDD; cd02674; Peptidase_C19R; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 2.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR21646:SF20; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 43; 1.
DR   Pfam; PF00443; UCH; 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.
PE   1: Evidence at protein level;
KW   Alternative splicing; Hydrolase; Methylation; Phosphoprotein; Protease;
KW   Reference proteome; Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..1123
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 43"
FT                   /id="PRO_0000249521"
FT   DOMAIN          101..710
FT                   /note="USP"
FT   REGION          1..102
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          202..221
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          795..826
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          854..886
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          959..1049
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1068..1099
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        68..87
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        959..981
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        110
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        668
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   MOD_RES         746
FT                   /note="Asymmetric dimethylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BUM9"
FT   MOD_RES         969
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BUM9"
FT   MOD_RES         1041
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   VAR_SEQ         1..488
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_020466"
FT   VAR_SEQ         1..311
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_020467"
FT   VAR_SEQ         489..553
FT                   /note="HLRRPGGPPHVKLAVEWDSSVKERLFGSLQEERAQDADSVWQQQQAHQQHSC
FT                   TLDECFQFYTKEE -> MPTVCGSSSRRISSTAVPWMNVFSSTPRRSRSRPGGPCPGRE
FT                   GGWLPLVGWPRAAGASQSGWFAF (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_020468"
FT   VAR_SEQ         666..670
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_046779"
FT   CONFLICT        168
FT                   /note="K -> FQ (in Ref. 1; CAE47744)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        212
FT                   /note="K -> Q (in Ref. 1; CAE47744)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        976
FT                   /note="G -> E (in Ref. 2; BAB70869)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1123 AA;  122809 MW;  3B4FE86EC619173C CRC64;
     MDLGPGDAAG GGPLAPRPRR RRSLRRLFSR FLLALGSRSR PGDSPPRPQP GHCDGDGEGG
     FACAPGPVPA APGSPGEERP PGPQPQLQLP AGDGARPPGA QGLKNHGNTC FMNAVVQCLS
     NTDLLAEFLA LGRYRAAPGR AEVTEQLAAL VRALWTREYT PQLSAEFKNA VSKYGSQFQG
     NSQHDALEFL LWLLDRVHED LEGSSRGPVS EKLPPEATKT SENCLSPSAQ LPLGQSFVQS
     HFQAQYRSSL TCPHCLKQSN TFDPFLCVSL PIPLRQTRFL SVTLVFPSKS QRFLRVGLAV
     PILSTVAALR KMVAEEGGVP ADEVILVELY PSGFQRSFFD EEDLNTIAEG DNVYAFQVPP
     SPSQGTLSAH PLGLSASPRL AAREGQRFSL SLHSESKVLI LFCNLVGSGQ QASRFGPPFL
     IREDRAVSWA QLQQSILSKV RHLMKSEAPV QNLGSLFSIR VVGLSVACSY LSPKDSRPLC
     HWAVDRVLHL RRPGGPPHVK LAVEWDSSVK ERLFGSLQEE RAQDADSVWQ QQQAHQQHSC
     TLDECFQFYT KEEQLAQDDA WKCPHCQVLQ QGMVKLSLWT LPDILIIHLK RFCQVGERRN
     KLSTLVKFPL SGLNMAPHVA QRSTSPEAGL GPWPSWKQPD CLPTSYPLDF LYDLYAVCNH
     HGNLQGGHYT AYCRNSLDGQ WYSYDDSTVE PLREDEVNTR GAYILFYQKR NSIPPWSASS
     SMRGSTSSSL SDHWLLRLGS HAGSTRGSLL SWSSAPCPSL PQVPDSPIFT NSLCNQEKGG
     LEPRRLVRGV KGRSISMKAP TTSRAKQGPF KTMPLRWSFG SKEKPPGASV ELVEYLESRR
     RPRSTSQSIV SLLTGTAGED EKSASPRSNV ALPANSEDGG RAIERGPAGV PCPSAQPNHC
     LAPGNSDGPN TARKLKENAG QDIKLPRKFD LPLTVMPSVE HEKPARPEGQ KAMNWKESFQ
     MGSKSSPPSP YMGFSGNSKD SRRGTSELDR PLQGTLTLLR SVFRKKENRR NERAEVSPQV
     PPVSLVSGGL SPAMDGQAPG SPPALRIPEG LARGLGSRLE RDVWSAPSSL RLPRKASRAP
     RGSALGMSQR TVPGEQASYG TFQRVKYHTL SLGRKKTLPE SSF
//