TRI33_HUMAN
ID TRI33_HUMAN Reviewed; 1127 AA.
AC Q9UPN9; O95855; Q5TG72; Q5TG73; Q5TG74; Q9C017; Q9UJ79;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM33;
DE EC=2.3.2.27;
DE AltName: Full=Ectodermin homolog;
DE AltName: Full=RET-fused gene 7 protein;
DE Short=Protein Rfg7;
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM33 {ECO:0000305};
DE AltName: Full=Transcription intermediary factor 1-gamma;
DE Short=TIF1-gamma;
DE AltName: Full=Tripartite motif-containing protein 33;
GN Name=TRIM33; Synonyms=KIAA1113, RFG7, TIF1G;
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 ALPHA), FUNCTION, SUBUNIT, AND VARIANT
RP THR-840.
RX PubMed=10022127; DOI=10.1038/sj.onc.1202655;
RA Venturini L., You J., Stadler M., Galien R., Lallemand V., Koken M.H.M.,
RA Mattei M.-G., Ganser A., Chambon P., Losson R., De The H.;
RT "TIF1gamma, a novel member of the transcriptional intermediary factor 1
RT family.";
RL Oncogene 18:1209-1217(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA), AND VARIANT THR-840.
RX PubMed=11331580; DOI=10.1093/emboj/20.9.2140;
RA Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L.,
RA Riganelli D., Zanaria E., Messali S., Cainarca S., Guffanti A., Minucci S.,
RA Pelicci P.G., Ballabio A.;
RT "The tripartite motif family identifies cell compartments.";
RL EMBO J. 20:2140-2151(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA), AND VARIANT
RP THR-840.
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 76-1127 (ISOFORMS ALPHA AND BETA),
RP CHROMOSOMAL TRANSLOCATION WITH RET, AND VARIANT THR-840.
RC TISSUE=Thyroid;
RX PubMed=10439047; DOI=10.1038/sj.onc.1202824;
RA Klugbauer S., Rabes H.M.;
RT "The transcription coactivator HTIF1 and a related protein are fused to the
RT RET receptor tyrosine kinase in childhood papillary thyroid carcinomas.";
RL Oncogene 18:4388-4393(1999).
RN [6]
RP SUBUNIT.
RX PubMed=12096914; DOI=10.1016/s0022-2836(02)00477-1;
RA Peng H., Feldman I., Rauscher F.J. III;
RT "Hetero-oligomerization among the TIF family of RBCC/TRIM domain-containing
RT nuclear cofactors: a potential mechanism for regulating the switch between
RT coactivation and corepression.";
RL J. Mol. Biol. 320:629-644(2002).
RN [7]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, UBIQUITINATION OF SMAD4,
RP INTERACTION WITH SMAD4, MUTAGENESIS OF CYS-125 AND CYS-128, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15820681; DOI=10.1016/j.cell.2005.01.033;
RA Dupont S., Zacchigna L., Cordenonsi M., Soligo S., Adorno M., Rugge M.,
RA Piccolo S.;
RT "Germ-layer specification and control of cell growth by Ectodermin, a Smad4
RT ubiquitin ligase.";
RL Cell 121:87-99(2005).
RN [8]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH SMAD2 AND SMAD3, INTERACTION
RP WITH SMAD2 AND SMAD3, AND SUBCELLULAR LOCATION.
RX PubMed=16751102; DOI=10.1016/j.cell.2006.03.045;
RA He W., Dorn D.C., Erdjument-Bromage H., Tempst P., Moore M.A., Massague J.;
RT "Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the
RT TGFbeta pathway.";
RL Cell 125:929-941(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862; THR-1102 AND SER-1105,
RP 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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SMAD2 AND SMAD4.
RX PubMed=19135894; DOI=10.1016/j.cell.2008.10.051;
RA Dupont S., Mamidi A., Cordenonsi M., Montagner M., Zacchigna L., Adorno M.,
RA Martello G., Stinchfield M.J., Soligo S., Morsut L., Inui M., Moro S.,
RA Modena N., Argenton F., Newfeld S.J., Piccolo S.;
RT "FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling,
RT controls Smad4 monoubiquitination.";
RL Cell 136:123-135(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-763; LYS-769 AND LYS-953, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862; THR-1102 AND SER-1105,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862; THR-1102 AND SER-1105,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862; THR-1051 AND SER-1119,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [16]
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).
RN [17]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-515; ARG-535; ARG-577; ARG-591;
RP ARG-598 AND ARG-604, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-334; LYS-763; LYS-769; LYS-776;
RP LYS-793; LYS-953; LYS-1007 AND LYS-1057, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [19]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-776 AND LYS-793, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [20]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-763; LYS-769; LYS-776; LYS-793;
RP LYS-861; LYS-1057 AND LYS-1118, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-763; LYS-769; LYS-776; LYS-793
RP AND LYS-1057, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [22]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-329; LYS-481; LYS-504; LYS-527;
RP LYS-763; LYS-769; LYS-774; LYS-776; LYS-793; LYS-796; LYS-861; LYS-953;
RP LYS-1043; LYS-1057 AND LYS-1118, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [23]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-580; SER-696; LYS-811; SER-885; MET-961
RP AND THR-1090.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4
CC ubiquitination, nuclear exclusion and degradation via the ubiquitin
CC proteasome pathway. According to PubMed:16751102, does not promote a
CC decrease in the level of endogenous SMAD4. May act as a transcriptional
CC repressor. Inhibits the transcriptional response to TGF-beta/BMP
CC signaling cascade. Plays a role in the control of cell proliferation.
CC Its association with SMAD2 and SMAD3 stimulates erythroid
CC differentiation of hematopoietic stem/progenitor (By similarity).
CC Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent
CC TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its
CC ability to form a stable complex with activated SMAD2/3 resulting in
CC inhibition of TGF-beta/BMP signaling cascade). {ECO:0000250,
CC ECO:0000269|PubMed:10022127, ECO:0000269|PubMed:15820681,
CC ECO:0000269|PubMed:16751102, ECO:0000269|PubMed:19135894}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homooligomer and heterooligomer with TRIM24 and TRIM28 family
CC members. Interacts with SMAD4 in unstimulated cells. Found in a complex
CC with SMAD2 and SMAD3 upon addition of TGF-beta. Interacts with SMAD2
CC and SMAD3. Interacts with SMAD4 under basal and induced conditions and,
CC upon TGF-beta signaling, with activated SMAD2. Forms a ternary complex
CC with SMAD4 and SMAD2 upon TGF-beta signaling.
CC {ECO:0000269|PubMed:10022127, ECO:0000269|PubMed:12096914,
CC ECO:0000269|PubMed:15820681, ECO:0000269|PubMed:16751102,
CC ECO:0000269|PubMed:19135894}.
CC -!- INTERACTION:
CC Q9UPN9; Q15796: SMAD2; NbExp=6; IntAct=EBI-2214398, EBI-1040141;
CC Q9UPN9; Q13485: SMAD4; NbExp=6; IntAct=EBI-2214398, EBI-347263;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15820681,
CC ECO:0000269|PubMed:16751102, ECO:0000269|PubMed:19135894}. Note=In
CC discrete nuclear dots resembling nuclear bodies. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha;
CC IsoId=Q9UPN9-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=Q9UPN9-2; Sequence=VSP_005774;
CC -!- TISSUE SPECIFICITY: Expressed in stem cells at the bottom of the crypts
CC of the colon (at protein level). Expressed in colon adenomas and
CC adenocarcinomas (at protein level). Expressed in brain, lung, liver,
CC spleen, thymus, prostate, kidney, testis, heart, placenta, pancreas,
CC small intestine, ovary, colon, skeletal muscle and hematopoietic
CC progenitors.
CC -!- PTM: Sumoylated with SUMO1. {ECO:0000250|UniProtKB:Q99PP7}.
CC -!- DISEASE: Note=A chromosomal aberration involving TRIM33 is found in
CC papillary thyroid carcinomas (PTCs). Translocation t(1;10)(p13;q11)
CC with RET. The translocation generates the TRIM33/RET (PTC7) oncogene.
CC {ECO:0000269|PubMed:10439047}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD17259.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA83065.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF119043; AAD17259.1; ALT_FRAME; mRNA.
DR EMBL; AF220136; AAG53509.1; -; mRNA.
DR EMBL; AF220137; AAG53510.1; -; mRNA.
DR EMBL; AB029036; BAA83065.1; ALT_INIT; mRNA.
DR EMBL; AL035410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL390241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AJ132948; CAB55313.1; -; mRNA.
DR CCDS; CCDS872.1; -. [Q9UPN9-1]
DR CCDS; CCDS873.1; -. [Q9UPN9-2]
DR RefSeq; NP_056990.3; NM_015906.3. [Q9UPN9-1]
DR RefSeq; NP_148980.2; NM_033020.2. [Q9UPN9-2]
DR PDB; 3U5M; X-ray; 3.08 A; A/B/C/D/E/F/G/H/I/J/K/L=882-1087.
DR PDB; 3U5N; X-ray; 1.95 A; A/B=882-1087.
DR PDB; 3U5O; X-ray; 2.70 A; A/B/C/D/E/F/G/H=882-1087.
DR PDB; 3U5P; X-ray; 2.80 A; A/B/C/D/E/F/G/H=882-1087.
DR PDB; 5MR8; X-ray; 1.74 A; A=882-1090.
DR PDBsum; 3U5M; -.
DR PDBsum; 3U5N; -.
DR PDBsum; 3U5O; -.
DR PDBsum; 3U5P; -.
DR PDBsum; 5MR8; -.
DR AlphaFoldDB; Q9UPN9; -.
DR SMR; Q9UPN9; -.
DR BioGRID; 119625; 237.
DR CORUM; Q9UPN9; -.
DR DIP; DIP-54262N; -.
DR IntAct; Q9UPN9; 85.
DR MINT; Q9UPN9; -.
DR STRING; 9606.ENSP00000351250; -.
DR BindingDB; Q9UPN9; -.
DR ChEMBL; CHEMBL2176772; -.
DR GlyGen; Q9UPN9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UPN9; -.
DR PhosphoSitePlus; Q9UPN9; -.
DR BioMuta; TRIM33; -.
DR DMDM; 313104270; -.
DR EPD; Q9UPN9; -.
DR jPOST; Q9UPN9; -.
DR MassIVE; Q9UPN9; -.
DR MaxQB; Q9UPN9; -.
DR PaxDb; Q9UPN9; -.
DR PeptideAtlas; Q9UPN9; -.
DR PRIDE; Q9UPN9; -.
DR ProteomicsDB; 85392; -. [Q9UPN9-1]
DR ProteomicsDB; 85393; -. [Q9UPN9-2]
DR ABCD; Q9UPN9; 1 sequenced antibody.
DR Antibodypedia; 1303; 441 antibodies from 36 providers.
DR DNASU; 51592; -.
DR Ensembl; ENST00000358465.7; ENSP00000351250.2; ENSG00000197323.12. [Q9UPN9-1]
DR Ensembl; ENST00000369543.6; ENSP00000358556.2; ENSG00000197323.12. [Q9UPN9-2]
DR GeneID; 51592; -.
DR KEGG; hsa:51592; -.
DR MANE-Select; ENST00000358465.7; ENSP00000351250.2; NM_015906.4; NP_056990.3.
DR UCSC; uc001eew.3; human. [Q9UPN9-1]
DR CTD; 51592; -.
DR DisGeNET; 51592; -.
DR GeneCards; TRIM33; -.
DR HGNC; HGNC:16290; TRIM33.
DR HPA; ENSG00000197323; Low tissue specificity.
DR MalaCards; TRIM33; -.
DR MIM; 605769; gene.
DR neXtProt; NX_Q9UPN9; -.
DR OpenTargets; ENSG00000197323; -.
DR Orphanet; 146; Differentiated thyroid carcinoma.
DR PharmGKB; PA38118; -.
DR VEuPathDB; HostDB:ENSG00000197323; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000156361; -.
DR InParanoid; Q9UPN9; -.
DR OMA; WCVECEE; -.
DR OrthoDB; 756911at2759; -.
DR PhylomeDB; Q9UPN9; -.
DR TreeFam; TF106455; -.
DR PathwayCommons; Q9UPN9; -.
DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR SignaLink; Q9UPN9; -.
DR SIGNOR; Q9UPN9; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 51592; 35 hits in 1139 CRISPR screens.
DR ChiTaRS; TRIM33; human.
DR GeneWiki; TRIM33; -.
DR GenomeRNAi; 51592; -.
DR Pharos; Q9UPN9; Tchem.
DR PRO; PR:Q9UPN9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UPN9; protein.
DR Bgee; ENSG00000197323; Expressed in endometrium epithelium and 207 other tissues.
DR ExpressionAtlas; Q9UPN9; baseline and differential.
DR Genevisible; Q9UPN9; HS.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0070410; F:co-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0070412; F:R-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:Reactome.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR Gene3D; 1.20.920.10; -; 1.
DR Gene3D; 3.30.40.10; -; 2.
DR IDEAL; IID00505; -.
DR InterPro; IPR003649; Bbox_C.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00439; Bromodomain; 1.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR PRINTS; PR00503; BROMODOMAIN.
DR SMART; SM00502; BBC; 1.
DR SMART; SM00336; BBOX; 2.
DR SMART; SM00297; BROMO; 1.
DR SMART; SM00249; PHD; 2.
DR SMART; SM00184; RING; 2.
DR SUPFAM; SSF47370; SSF47370; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50014; BROMODOMAIN_2; 1.
DR PROSITE; PS50119; ZF_BBOX; 2.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Bromodomain;
KW Chromosomal rearrangement; Coiled coil; DNA-binding; Isopeptide bond;
KW Metal-binding; Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Repressor; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1127
FT /note="E3 ubiquitin-protein ligase TRIM33"
FT /id="PRO_0000056395"
FT DOMAIN 974..1046
FT /note="Bromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT ZN_FING 125..154
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 212..259
FT /note="B box-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT ZN_FING 271..312
FT /note="B box-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT ZN_FING 887..934
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 1..147
FT /note="Necessary for E3 ubiquitin-protein ligase activity
FT and repression of SMAD4 signaling and transcriptional
FT repression"
FT REGION 1..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 299..401
FT /note="Necessary for oligomerization"
FT REGION 536..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 608..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 673..692
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 703..818
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1088..1127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 299..401
FT /evidence="ECO:0000255"
FT COMPBIAS 100..118
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..774
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1106..1127
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 217
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 220
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 245
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 279
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 304
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT SITE 964..965
FT /note="Breakpoint for translocation to form TRIM33-RET
FT oncogene"
FT MOD_RES 515
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 515
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 535
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 577
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 591
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99PP7"
FT MOD_RES 591
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 598
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 604
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 763
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 769
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 793
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99PP7"
FT MOD_RES 803
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99PP7"
FT MOD_RES 815
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99PP7"
FT MOD_RES 862
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 951
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99PP7"
FT MOD_RES 953
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1051
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1102
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 1105
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 1119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 329
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 334
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 481
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 504
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 527
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 763
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 769
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 774
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 776
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 776
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 793
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 793
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 796
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 861
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 953
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1007
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 1043
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1057
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1118
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1041..1057
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:10439047,
FT ECO:0000303|PubMed:11331580"
FT /id="VSP_005774"
FT VARIANT 67
FT /note="V -> A (in dbSNP:rs6691166)"
FT /id="VAR_029494"
FT VARIANT 580
FT /note="M -> I (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042376"
FT VARIANT 696
FT /note="L -> S (in dbSNP:rs56151583)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042377"
FT VARIANT 811
FT /note="E -> K (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042378"
FT VARIANT 840
FT /note="I -> T (in dbSNP:rs6537825)"
FT /evidence="ECO:0000269|PubMed:10022127,
FT ECO:0000269|PubMed:10439047, ECO:0000269|PubMed:10470851,
FT ECO:0000269|PubMed:11331580"
FT /id="VAR_024616"
FT VARIANT 885
FT /note="P -> S (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042379"
FT VARIANT 961
FT /note="V -> M (in dbSNP:rs55688622)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042380"
FT VARIANT 1090
FT /note="P -> T (in dbSNP:rs55784699)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042381"
FT MUTAGEN 125
FT /note="C->A: Abolishes E3 activity but does not affect
FT interaction with SMAD4; when associated with A-128."
FT /evidence="ECO:0000269|PubMed:15820681"
FT MUTAGEN 128
FT /note="C->A: Abolishes E3 activity but does not affect
FT interaction with SMAD4; when associated with A-125."
FT /evidence="ECO:0000269|PubMed:15820681"
FT CONFLICT 89
FT /note="V -> E (in Ref. 5; CAB55313)"
FT /evidence="ECO:0000305"
FT CONFLICT 451..453
FT /note="PAA -> LLH (in Ref. 5; CAB55313)"
FT /evidence="ECO:0000305"
FT CONFLICT 909
FT /note="F -> S (in Ref. 5; CAB55313)"
FT /evidence="ECO:0000305"
FT CONFLICT 1037
FT /note="R -> T (in Ref. 1; AAD17259)"
FT /evidence="ECO:0000305"
FT STRAND 888..890
FT /evidence="ECO:0007829|PDB:3U5N"
FT TURN 891..893
FT /evidence="ECO:0007829|PDB:5MR8"
FT STRAND 897..901
FT /evidence="ECO:0007829|PDB:5MR8"
FT STRAND 903..906
FT /evidence="ECO:0007829|PDB:5MR8"
FT TURN 911..913
FT /evidence="ECO:0007829|PDB:5MR8"
FT STRAND 914..916
FT /evidence="ECO:0007829|PDB:5MR8"
FT STRAND 918..920
FT /evidence="ECO:0007829|PDB:3U5P"
FT TURN 929..931
FT /evidence="ECO:0007829|PDB:5MR8"
FT STRAND 934..936
FT /evidence="ECO:0007829|PDB:5MR8"
FT HELIX 944..949
FT /evidence="ECO:0007829|PDB:5MR8"
FT TURN 950..952
FT /evidence="ECO:0007829|PDB:5MR8"
FT HELIX 960..974
FT /evidence="ECO:0007829|PDB:5MR8"
FT HELIX 980..982
FT /evidence="ECO:0007829|PDB:5MR8"
FT HELIX 993..996
FT /evidence="ECO:0007829|PDB:5MR8"
FT HELIX 1003..1009
FT /evidence="ECO:0007829|PDB:5MR8"
FT STRAND 1011..1013
FT /evidence="ECO:0007829|PDB:3U5O"
FT HELIX 1021..1038
FT /evidence="ECO:0007829|PDB:5MR8"
FT HELIX 1061..1080
FT /evidence="ECO:0007829|PDB:5MR8"
FT STRAND 1081..1083
FT /evidence="ECO:0007829|PDB:3U5O"
SQ SEQUENCE 1127 AA; 122533 MW; 7A36013799E9933C CRC64;
MAENKGGGEA ESGGGGSGSA PVTAGAAGPA AQEAEPPLTA VLVEEEEEEG GRAGAEGGAA
GPDDGGVAAA SSGSAQAASS PAASVGTGVA GGAVSTPAPA PASAPAPGPS AGPPPGPPAS
LLDTCAVCQQ SLQSRREAEP KLLPCLHSFC LRCLPEPERQ LSVPIPGGSN GDIQQVGVIR
CPVCRQECRQ IDLVDNYFVK DTSEAPSSSD EKSEQVCTSC EDNASAVGFC VECGEWLCKT
CIEAHQRVKF TKDHLIRKKE DVSESVGASG QRPVFCPVHK QEQLKLFCET CDRLTCRDCQ
LLEHKEHRYQ FLEEAFQNQK GAIENLLAKL LEKKNYVHFA ATQVQNRIKE VNETNKRVEQ
EIKVAIFTLI NEINKKGKSL LQQLENVTKE RQMKLLQQQN DITGLSRQVK HVMNFTNWAI
ASGSSTALLY SKRLITFQLR HILKARCDPV PAANGAIRFH CDPTFWAKNV VNLGNLVIES
KPAPGYTPNV VVGQVPPGTN HISKTPGQIN LAQLRLQHMQ QQVYAQKHQQ LQQMRMQQPP
APVPTTTTTT QQHPRQAAPQ MLQQQPPRLI SVQTMQRGNM NCGAFQAHQM RLAQNAARIP
GIPRHSGPQY SMMQPHLQRQ HSNPGHAGPF PVVSVHNTTI NPTSPTTATM ANANRGPTSP
SVTAIELIPS VTNPENLPSL PDIPPIQLED AGSSSLDNLL SRYISGSHLP PQPTSTMNPS
PGPSALSPGS SGLSNSHTPV RPPSTSSTGS RGSCGSSGRT AEKTSLSFKS DQVKVKQEPG
TEDEICSFSG GVKQEKTEDG RRSACMLSSP ESSLTPPLST NLHLESELDA LASLENHVKI
EPADMNESCK QSGLSSLVNG KSPIRSLMHR SARIGGDGNN KDDDPNEDWC AVCQNGGDLL
CCEKCPKVFH LTCHVPTLLS FPSGDWICTF CRDIGKPEVE YDCDNLQHSK KGKTAQGLSP
VDQRKCERLL LYLYCHELSI EFQEPVPASI PNYYKIIKKP MDLSTVKKKL QKKHSQHYQI
PDDFVADVRL IFKNCERFNE MMKVVQVYAD TQEINLKADS EVAQAGKAVA LYFEDKLTEI
YSDRTFAPLP EFEQEEDDGE VTEDSDEDFI QPRRKRLKSD ERPVHIK
