UBP34_HUMAN
ID UBP34_HUMAN Reviewed; 3546 AA.
AC Q70CQ2; A8MWD0; B3KWU9; O60316; O94834; Q3B777; Q6P6C9; Q7L8P6; Q8N3T9;
AC Q8TBW2; Q9UGA1;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 34;
DE EC=3.4.19.12 {ECO:0000269|PubMed:14715245, ECO:0000269|PubMed:21383061};
DE AltName: Full=Deubiquitinating enzyme 34;
DE AltName: Full=Ubiquitin thioesterase 34;
DE AltName: Full=Ubiquitin-specific-processing protease 34;
GN Name=USP34; Synonyms=KIAA0570, KIAA0729;
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 2), TISSUE SPECIFICITY, ENZYME
RP ACTIVITY, AND VARIANT THR-661.
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 VARIANT THR-661.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1723-2532 AND 2629-3546 (ISOFORM
RP 1).
RC TISSUE=Amygdala, and Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1821-3338.
RC TISSUE=Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2351-3546 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2561-3546 (ISOFORM 2), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3024-3546 (ISOFORM 3).
RC TISSUE=Brain, Colon, and Kidney;
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649, VARIANT [LARGE SCALE
RP ANALYSIS] THR-661, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-352; SER-3358; SER-3359 AND
RP SER-3406, AND IDENTIFICATION BY 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2488, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH AXIN1 AND AXIN2, AND
RP MUTAGENESIS OF CYS-1903.
RX PubMed=21383061; DOI=10.1128/mcb.01094-10;
RA Lui T.T., Lacroix C., Ahmed S.M., Goldenberg S.J., Leach C.A., Daulat A.M.,
RA Angers S.;
RT "The Ubiquitin specific protease USP34 regulates Axin stability and
RT Wnt/beta-catenin signaling.";
RL Mol. Cell. Biol. 31:2053-2065(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487; SER-3358; SER-3359;
RP THR-3381 AND SER-3386, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
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).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3503, AND IDENTIFICATION BY
RP 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: Ubiquitin hydrolase that can remove conjugated ubiquitin from
CC AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling
CC pathway. Acts as an activator of the Wnt signaling pathway downstream
CC of the beta-catenin destruction complex by deubiquitinating and
CC stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of
CC AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated
CC transcription. Recognizes and hydrolyzes 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.
CC {ECO:0000269|PubMed:21383061}.
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:0000269|PubMed:14715245,
CC ECO:0000269|PubMed:21383061};
CC -!- SUBUNIT: Interacts with AXIN1 and AXIN2. {ECO:0000269|PubMed:21383061}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q70CQ2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q70CQ2-2; Sequence=VSP_035639, VSP_035640;
CC Name=3;
CC IsoId=Q70CQ2-3; Sequence=VSP_035639, VSP_035640, VSP_020463;
CC -!- TISSUE SPECIFICITY: Expressed in brain at low level.
CC {ECO:0000269|PubMed:14715245}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI07762.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA25496.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAG54261.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ586138; CAE51938.1; -; mRNA.
DR EMBL; AB011142; BAA25496.2; ALT_INIT; mRNA.
DR EMBL; AC016747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL050092; CAB43264.1; -; mRNA.
DR EMBL; AL831918; CAD38579.1; -; mRNA.
DR EMBL; AK125898; BAG54261.1; ALT_INIT; mRNA.
DR EMBL; AB018272; BAA34449.1; -; mRNA.
DR EMBL; BC022783; AAH22783.1; -; mRNA.
DR EMBL; BC062325; AAH62325.1; -; mRNA.
DR EMBL; BC107761; AAI07762.1; ALT_FRAME; mRNA.
DR CCDS; CCDS42686.1; -. [Q70CQ2-1]
DR PIR; T00338; T00338.
DR PIR; T13057; T13057.
DR RefSeq; NP_055524.3; NM_014709.3. [Q70CQ2-1]
DR SMR; Q70CQ2; -.
DR BioGRID; 115085; 159.
DR IntAct; Q70CQ2; 27.
DR MINT; Q70CQ2; -.
DR STRING; 9606.ENSP00000381577; -.
DR MEROPS; C19.067; -.
DR iPTMnet; Q70CQ2; -.
DR PhosphoSitePlus; Q70CQ2; -.
DR BioMuta; USP34; -.
DR DMDM; 212276488; -.
DR EPD; Q70CQ2; -.
DR jPOST; Q70CQ2; -.
DR MassIVE; Q70CQ2; -.
DR MaxQB; Q70CQ2; -.
DR PaxDb; Q70CQ2; -.
DR PeptideAtlas; Q70CQ2; -.
DR PRIDE; Q70CQ2; -.
DR ProteomicsDB; 68521; -. [Q70CQ2-1]
DR ProteomicsDB; 68522; -. [Q70CQ2-2]
DR ProteomicsDB; 68523; -. [Q70CQ2-3]
DR Antibodypedia; 7689; 100 antibodies from 23 providers.
DR DNASU; 9736; -.
DR Ensembl; ENST00000398571.7; ENSP00000381577.2; ENSG00000115464.15. [Q70CQ2-1]
DR GeneID; 9736; -.
DR KEGG; hsa:9736; -.
DR MANE-Select; ENST00000398571.7; ENSP00000381577.2; NM_014709.4; NP_055524.3.
DR UCSC; uc002sbe.4; human. [Q70CQ2-1]
DR CTD; 9736; -.
DR DisGeNET; 9736; -.
DR GeneCards; USP34; -.
DR HGNC; HGNC:20066; USP34.
DR HPA; ENSG00000115464; Low tissue specificity.
DR MIM; 615295; gene.
DR neXtProt; NX_Q70CQ2; -.
DR OpenTargets; ENSG00000115464; -.
DR PharmGKB; PA134897042; -.
DR VEuPathDB; HostDB:ENSG00000115464; -.
DR eggNOG; KOG1866; Eukaryota.
DR GeneTree; ENSGT00940000158659; -.
DR HOGENOM; CLU_000109_0_0_1; -.
DR InParanoid; Q70CQ2; -.
DR OMA; LETRHNT; -.
DR OrthoDB; 625455at2759; -.
DR PhylomeDB; Q70CQ2; -.
DR TreeFam; TF323966; -.
DR PathwayCommons; Q70CQ2; -.
DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q70CQ2; -.
DR BioGRID-ORCS; 9736; 33 hits in 1125 CRISPR screens.
DR ChiTaRS; USP34; human.
DR GeneWiki; USP34; -.
DR GenomeRNAi; 9736; -.
DR Pharos; Q70CQ2; Tbio.
DR PRO; PR:Q70CQ2; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q70CQ2; protein.
DR Bgee; ENSG00000115464; Expressed in nipple and 204 other tissues.
DR ExpressionAtlas; Q70CQ2; baseline and differential.
DR Genevisible; Q70CQ2; 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; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:FlyBase.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR GO; GO:0016055; P:Wnt signaling pathway; TAS:Reactome.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR021905; DUF3517.
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 Pfam; PF12030; DUF3517; 1.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF48371; SSF48371; 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; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway;
KW Wnt signaling pathway.
FT CHAIN 1..3546
FT /note="Ubiquitin carboxyl-terminal hydrolase 34"
FT /id="PRO_0000249519"
FT DOMAIN 1894..2239
FT /note="USP"
FT REGION 502..535
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 550..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1459..1478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3331..3443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 515..535
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..608
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..679
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3334..3373
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3374..3409
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3422..3437
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1903
FT /note="Nucleophile"
FT /evidence="ECO:0000305"
FT ACT_SITE 2164
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZQ93"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZQ93"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 1469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZQ93"
FT MOD_RES 2488
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 3358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3359
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3381
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3386
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3406
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 3503
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..139
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14715245,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9628581,
FT ECO:0000303|PubMed:9872452"
FT /id="VSP_035639"
FT VAR_SEQ 140..162
FT /note="SKSSDPFSLWSTDEKEKLLLCVA -> MRRKNSYYVWQ (in isoform 2
FT and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14715245,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9628581,
FT ECO:0000303|PubMed:9872452"
FT /id="VSP_035640"
FT VAR_SEQ 2936..3018
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020463"
FT VARIANT 661
FT /note="M -> T (in dbSNP:rs6722430)"
FT /evidence="ECO:0000269|PubMed:14715245,
FT ECO:0000269|PubMed:9628581, ECO:0007744|PubMed:17525332"
FT /id="VAR_047106"
FT VARIANT 1663
FT /note="L -> R (in dbSNP:rs6723818)"
FT /id="VAR_047107"
FT VARIANT 2348
FT /note="D -> N (in dbSNP:rs4386306)"
FT /id="VAR_047108"
FT MUTAGEN 1903
FT /note="C->S: Loss of function."
FT /evidence="ECO:0000269|PubMed:21383061"
SQ SEQUENCE 3546 AA; 404233 MW; A31851911D990044 CRC64;
MCENCADLVE VLNEISDVEG GDGLQLRKEH TLKIFTYINS WTQRQCLCCF KEYKHLEIFN
QVVCALINLV IAQVQVLRDQ LCKHCTTINI DSTWQDESNQ AEEPLNIDRE CNEGSTERQK
SIEKKSNSTR ICNLTEEESS KSSDPFSLWS TDEKEKLLLC VAKIFQIQFP LYTAYKHNTH
PTIEDISTQE SNILGAFCDM NDVEVPLHLL RYVCLFCGKN GLSLMKDCFE YGTPETLPFL
IAHAFITVVS NIRIWLHIPA VMQHIIPFRT YVIRYLCKLS DQELRQSAAR NMADLMWSTV
KEPLDTTLCF DKESLDLAFK YFMSPTLTMR LAGLSQITNQ LHTFNDVCNN ESLVSDTETS
IAKELADWLI SNNVVEHIFG PNLHIEIIKQ CQVILNFLAA EGRLSTQHID CIWAAAQLKH
CSRYIHDLFP SLIKNLDPVP LRHLLNLVSA LEPSVHTEQT LYLASMLIKA LWNNALAAKA
QLSKQSSFAS LLNTNIPIGN KKEEEELRRT APSPWSPAAS PQSSDNSDTH QSGGSDIEMD
EQLINRTKHV QQRLSDTEES MQGSSDETAN SGEDGSSGPG SSSGHSDGSS NEVNSSHASQ
SAGSPGSEVQ SEDIADIEAL KEEDEDDDHG HNPPKSSCGT DLRNRKLESQ AGICLGDSQG
MSERNGTSSG TGKDLVFNTE SLPSVDNRMR MLDACSHSED PEHDISGEMN ATHIAQGSQE
SCITRTGDFL GETIGNELFN CRQFIGPQHH HHHHHHHHHH DGHMVDDMLS ADDVSCSSSQ
VSAKSEKNMA DFDGEESGCE EELVQINSHA ELTSHLQQHL PNLASIYHEH LSQGPVVHKH
QFNSNAVTDI NLDNVCKKGN TLLWDIVQDE DAVNLSEGLI NEAEKLLCSL VCWFTDRQIR
MRFIEGCLEN LGNNRSVVIS LRLLPKLFGT FQQFGSSYDT HWITMWAEKE LNMMKLFFDN
LVYYIQTVRE GRQKHALYSH SAEVQVRLQF LTCVFSTLGS PDHFRLSLEQ VDILWHCLVE
DSECYDDALH WFLNQVRSKD QHAMGMETYK HLFLEKMPQL KPETISMTGL NLFQHLCNLA
RLATSAYDGC SNSELCGMDQ FWGIALRAQS GDVSRAAIQY INSYYINGKT GLEKEQEFIS
KCMESLMIAS SSLEQESHSS LMVIERGLLM LKTHLEAFRR RFAYHLRQWQ IEGTGISSHL
KALSDKQSLP LRVVCQPAGL PDKMTIEMYP SDQVADLRAE VTHWYENLQK EQINQQAQLQ
EFGQSNRKGE FPGGLMGPVR MISSGHELTT DYDEKALHEL GFKDMQMVFV SLGAPRRERK
GEGVQLPASC LPPPQKDNIP MLLLLQEPHL TTLFDLLEML ASFKPPSGKV AVDDSESLRC
EELHLHAENL SRRVWELLML LPTCPNMLMA FQNISDEQSN DGFNWKELLK IKSAHKLLYA
LEIIEALGKP NRRIRRESTG SYSDLYPDSD DSSEDQVENS KNSWSCKFVA AGGLQQLLEI
FNSGILEPKE QESWTVWQLD CLACLLKLIC QFAVDPSDLD LAYHDVFAWS GIAESHRKRT
WPGKSRKAAG DHAKGLHIPR LTEVFLVLVQ GTSLIQRLMS VAYTYDNLAP RVLKAQSDHR
SRHEVSHYSM WLLVSWAHCC SLVKSSLADS DHLQDWLKKL TLLIPETAVR HESCSGLYKL
SLSGLDGGDS INRSFLLLAA STLLKFLPDA QALKPIRIDD YEEEPILKPG CKEYFWLLCK
LVDNIHIKDA SQTTLLDLDA LARHLADCIR SREILDHQDG NVEDDGLTGL LRLATSVVKH
KPPFKFSREG QEFLRDIFNL LFLLPSLKDR QQPKCKSHSS RAAAYDLLVE MVKGSVENYR
LIHNWVMAQH MQSHAPYKWD YWPHEDVRAE CRFVGLTNLG ATCYLASTIQ QLYMIPEARQ
AVFTAKYSED MKHKTTLLEL QKMFTYLMES ECKAYNPRPF CKTYTMDKQP LNTGEQKDMT
EFFTDLITKI EEMSPELKNT VKSLFGGVIT NNVVSLDCEH VSQTAEEFYT VRCQVADMKN
IYESLDEVTI KDTLEGDNMY TCSHCGKKVR AEKRACFKKL PRILSFNTMR YTFNMVTMMK
EKVNTHFSFP LRLDMTPYTE DFLMGKSERK EGFKEVSDHS KDSESYEYDL IGVTVHTGTA
DGGHYYSFIR DIVNPHAYKN NKWYLFNDAE VKPFDSAQLA SECFGGEMTT KTYDSVTDKF
MDFSFEKTHS AYMLFYKRME PEEENGREYK FDVSSELLEW IWHDNMQFLQ DKNIFEHTYF
GFMWQLCSCI PSTLPDPKAV SLMTAKLSTS FVLETFIHSK EKPTMLQWIE LLTKQFNNSQ
AACEWFLDRM ADDDWWPMQI LIKCPNQIVR QMFQRLCIHV IQRLRPVHAH LYLQPGMEDG
SDDMDTSVED IGGRSCVTRF VRTLLLIMEH GVKPHSKHLT EYFAFLYEFA KMGEEESQFL
LSLQAISTMV HFYMGTKGPE NPQVEVLSEE EGEEEEEEED ILSLAEEKYR PAALEKMIAL
VALLVEQSRS ERHLTLSQTD MAALTGGKGF PFLFQHIRDG INIRQTCNLI FSLCRYNNRL
AEHIVSMLFT SIAKLTPEAA NPFFKLLTML MEFAGGPPGM PPFASYILQR IWEVIEYNPS
QCLDWLAVQT PRNKLAHSWV LQNMENWVER FLLAHNYPRV RTSAAYLLVS LIPSNSFRQM
FRSTRSLHIP TRDLPLSPDT TVVLHQVYNV LLGLLSRAKL YVDAAVHGTT KLVPYFSFMT
YCLISKTEKL MFSTYFMDLW NLFQPKLSEP AIATNHNKQA LLSFWYNVCA DCPENIRLIV
QNPVVTKNIA FNYILADHDD QDVVLFNRGM LPAYYGILRL CCEQSPAFTR QLASHQNIQW
AFKNLTPHAS QYPGAVEELF NLMQLFIAQR PDMREEELED IKQFKKTTIS CYLRCLDGRS
CWTTLISAFR ILLESDEDRL LVVFNRGLIL MTESFNTLHM MYHEATACHV TGDLVELLSI
FLSVLKSTRP YLQRKDVKQA LIQWQERIEF AHKLLTLLNS YSPPELRNAC IDVLKELVLL
SPHDFLHTLV PFLQHNHCTY HHSNIPMSLG PYFPCRENIK LIGGKSNIRP PRPELNMCLL
PTMVETSKGK DDVYDRMLLD YFFSYHQFIH LLCRVAINCE KFTETLVKLS VLVAYEGLPL
HLALFPKLWT ELCQTQSAMS KNCIKLLCED PVFAEYIKCI LMDERTFLNN NIVYTFMTHF
LLKVQSQVFS EANCANLIST LITNLISQYQ NLQSDFSNRV EISKASASLN GDLRALALLL
SVHTPKQLNP ALIPTLQELL SKCRTCLQQR NSLQEQEAKE RKTKDDEGAT PIKRRRVSSD
EEHTVDSCIS DMKTETREVL TPTSTSDNET RDSSIIDPGT EQDLPSPENS SVKEYRMEVP
SSFSEDMSNI RSQHAEEQSN NGRYDDCKEF KDLHCSKDST LAEEESEFPS TSISAVLSDL
ADLRSCDGQA LPSQDPEVAL SLSCGHSRGL FSHMQQHDIL DTLCRTIEST IHVVTRISGK
GNQAAS
