Full text data of SET
SET
[Confidence: low (only semi-automatic identification from reviews)]
Protein SET (HLA-DR-associated protein II; Inhibitor of granzyme A-activated DNase; IGAAD; PHAPII; Phosphatase 2A inhibitor I2PP2A; I-2PP2A; Template-activating factor I; TAF-I)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein SET (HLA-DR-associated protein II; Inhibitor of granzyme A-activated DNase; IGAAD; PHAPII; Phosphatase 2A inhibitor I2PP2A; I-2PP2A; Template-activating factor I; TAF-I)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q01105
ID SET_HUMAN Reviewed; 290 AA.
AC Q01105; A5A5H4; A6NGV1; B4DUE2; Q15541; Q5VXV1; Q5VXV2; Q6FHZ5;
read moreDT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 3.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Protein SET;
DE AltName: Full=HLA-DR-associated protein II;
DE AltName: Full=Inhibitor of granzyme A-activated DNase;
DE Short=IGAAD;
DE AltName: Full=PHAPII;
DE AltName: Full=Phosphatase 2A inhibitor I2PP2A;
DE Short=I-2PP2A;
DE AltName: Full=Template-activating factor I;
DE Short=TAF-I;
GN Name=SET;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1630450;
RA von Lindern M., van Baal S., Wiegant J., Raap A., Hagemeijer A.,
RA Grosveld G.;
RT "Can, a putative oncogene associated with myeloid leukemogenesis, may
RT be activated by fusion of its 3' half to different genes:
RT characterization of the set gene.";
RL Mol. Cell. Biol. 12:3346-3355(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8192856;
RA Vaesen M., Barnikol-Watanabe S., Goetz H., Adil Awni L., Cole T.,
RA Zimmermann B., Kratzin H.D., Hilschmann N.;
RT "Purification and characterization of two putative HLA class II
RT associated proteins: PHAPI and PHAPII.";
RL Biol. Chem. Hoppe-Seyler 375:113-126(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF
RP 14-35; 40-60; 75-90 AND 155-167, AND ACTIVATION OF DNA REPLICATION.
RC TISSUE=Cervix carcinoma;
RX PubMed=7753797; DOI=10.1073/pnas.92.10.4279;
RA Nagata K., Kawase H., Handa H., Yano K., Yamasaki M., Ishimi Y.,
RA Okuda A., Kikuchi A., Matsumoto K.;
RT "Replication factor encoded by a putative oncogene, set, associated
RT with myeloid leukemogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4279-4283(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=8626647; DOI=10.1074/jbc.271.19.11059;
RA Li M., Makkinje A., Damuni Z.;
RT "The myeloid leukemia-associated protein SET is a potent inhibitor of
RT protein phosphatase 2A.";
RL J. Biol. Chem. 271:11059-11062(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15642345; DOI=10.1016/j.febslet.2004.11.097;
RA Tsujio I., Zaidi T., Xu J., Kotula L., Grundke-Iqbal I., Iqbal K.;
RT "Inhibitors of protein phosphatase-2A from human brain structures,
RT immunocytological localization and activities towards
RT dephosphorylation of the Alzheimer type hyperphosphorylated tau.";
RL FEBS Lett. 579:363-372(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RX PubMed=8294483;
RA Adachi Y., Pavlaki G.N., Copeland T.D.;
RT "Identification and characterization of SET, a nuclear phosphoprotein
RT encoded by the translocation break point in acute undifferentiated
RT leukemia.";
RL J. Biol. Chem. 269:2258-2262(1994).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-241 (ISOFORM 2).
RA Wang L.C., Chen Y.;
RT "A relative factor in human rectum carcinoma.";
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP EXPRESSION IN THE KIDNEY.
RX PubMed=9773788;
RA Carlson S.G., Eng E., Kim E.-G., Perlman E.J., Copeland T.D.,
RA Ballermann B.J.;
RT "Expression of SET, an inhibitor of protein phosphatase 2A, in renal
RT development and Wilms' tumor.";
RL J. Am. Soc. Nephrol. 9:1873-1880(1998).
RN [14]
RP INHIBITION OF HISTONE ACETYLATION.
RX PubMed=11163245; DOI=10.1016/S0092-8674(01)00196-9;
RA Seo S.-B., McNamara P., Heo S., Turner A., Lane W.S., Chakravarti D.;
RT "Regulation of histone acetylation and transcription by INHAT, a human
RT cellular complex containing the Set oncoprotein.";
RL Cell 104:119-130(2001).
RN [15]
RP INTERACTION WITH SETBP1.
RC TISSUE=Cervix carcinoma;
RX PubMed=11231286; DOI=10.1046/j.1432-1327.2001.02000.x;
RA Minakuchi M., Kakazu N., Gorrin-Rivas M.J., Abe T., Copeland T.D.,
RA Ueda K., Adachi Y.;
RT "Identification and characterization of SEB, a novel protein that
RT binds to the acute undifferentiated leukemia-associated protein SET.";
RL Eur. J. Biochem. 268:1340-1351(2001).
RN [16]
RP INTERACTION WITH HMGB2.
RX PubMed=11909973; DOI=10.1128/MCB.22.8.2810-2820.2002;
RA Fan Z., Beresford P.J., Zhang D., Lieberman J.;
RT "HMG2 interacts with the nucleosome assembly protein SET and is a
RT target of the cytotoxic T-lymphocyte protease granzyme A.";
RL Mol. Cell. Biol. 22:2810-2820(2002).
RN [17]
RP NME1 INHIBITION, SUBCELLULAR LOCATION, AND DESCRIPTION OF THE SET
RP COMPLEX.
RX PubMed=12628186; DOI=10.1016/S0092-8674(03)00150-8;
RA Fan Z., Beresford P.J., Oh D.Y., Zhang D., Lieberman J.;
RT "Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-
RT mediated apoptosis, and the nucleosome assembly protein SET is its
RT inhibitor.";
RL Cell 112:659-672(2003).
RN [18]
RP ERRATUM.
RA Fan Z., Beresford P.J., Oh D.Y., Zhang D., Lieberman J.;
RL Cell 115:241-241(2003).
RN [19]
RP SUBCELLULAR LOCATION.
RX PubMed=12524539; DOI=10.1038/ni885;
RA Fan Z., Beresford P.J., Zhang D., Xu Z., Novina C.D., Yoshida A.,
RA Pommier Y., Lieberman J.;
RT "Cleaving the oxidative repair protein Ape1 enhances cell death
RT mediated by granzyme A.";
RL Nat. Immunol. 4:145-153(2003).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [21]
RP INTERACTION WITH SGOL1.
RX PubMed=16541025; DOI=10.1038/nature04663;
RA Kitajima T.S., Sakuno T., Ishiguro K., Iemura S., Natsume T.,
RA Kawashima S.A., Watanabe Y.;
RT "Shugoshin collaborates with protein phosphatase 2A to protect
RT cohesin.";
RL Nature 441:46-52(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [23]
RP 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 [24]
RP INTERACTION WITH APBB1.
RX PubMed=19343227; DOI=10.1371/journal.pone.0005071;
RA Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J.,
RA Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D.;
RT "FE65 binds Teashirt, inhibiting expression of the primate-specific
RT caspase-4.";
RL PLoS ONE 4:E5071-E5071(2009).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-132; LYS-150 AND LYS-172,
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-11 (ISOFORM 2), AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-15 AND SER-24 (ISOFORM 2), AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [27]
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.,
RA Buerckstuemmer T., 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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15 AND SER-24 (ISOFORM
RP 2), AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 38-238, DNA-BINDING, DOMAINS,
RP AND SUBUNIT.
RX PubMed=17360516; DOI=10.1073/pnas.0603762104;
RA Muto S., Senda M., Akai Y., Sato L., Suzuki T., Nagai R., Senda T.,
RA Horikoshi M.;
RT "Relationship between the structure of SET/TAF-Ibeta/INHAT and its
RT histone chaperone activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:4285-4290(2007).
CC -!- FUNCTION: Multitasking protein, involved in apoptosis,
CC transcription, nucleosome assembly and histone chaperoning.
CC Isoform 2 anti-apoptotic activity is mediated by inhibition of the
CC GZMA-activated DNase, NME1. In the course of cytotoxic T-
CC lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting
CC its binding to NME1 and releasing NME1 inhibition. Isoform 1 and
CC isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform
CC 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation
CC of histones (HAT) and nucleosomes, most probably by masking the
CC accessibility of lysines of histones to the acetylases. The
CC predominant target for inhibition is histone H4. HAT inhibition
CC leads to silencing of HAT-dependent transcription and prevents
CC active demethylation of DNA. Both isoforms stimulate DNA
CC replication of the adenovirus genome complexed with viral core
CC proteins; however, isoform 2 specific activity is higher.
CC -!- SUBUNIT: Interacts with CHTOP (By similarity). Headphone-shaped
CC homodimer. Isoform 1 and isoform 2 interact directly with each
CC other and with ANP32A within the tripartite INHAT (inhibitor of
CC acetyltransferases) complex. Isoform 1 and isoform 2 interact also
CC with histones. Isoform 2 is a component of the SET complex, which
CC also contains ANP32A, APEX1, HMGB2 and NME1, but not NME2. Within
CC this complex, directly interacts with NME1 and with HMGB2.
CC Interacts with SETBP1. Interacts with SGOL1. Interacts with APBB1.
CC -!- INTERACTION:
CC Q00987:MDM2; NbExp=2; IntAct=EBI-1053182, EBI-389668;
CC P10644:PRKAR1A; NbExp=2; IntAct=EBI-1053182, EBI-476431;
CC P63000:RAC1; NbExp=8; IntAct=EBI-1053182, EBI-413628;
CC Q15573:TAF1A; NbExp=2; IntAct=EBI-1053182, EBI-2510647;
CC Q53T94:TAF1B; NbExp=3; IntAct=EBI-1053182, EBI-1560239;
CC Q15572:TAF1C; NbExp=4; IntAct=EBI-1053182, EBI-2510659;
CC P20226:TBP; NbExp=4; IntAct=EBI-1053182, EBI-355371;
CC P17480:UBTF; NbExp=4; IntAct=EBI-1053182, EBI-396235;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum.
CC Nucleus, nucleoplasm. Note=In the cytoplasm, found both in the
CC cytosol and associated with the endoplasmic reticulum. Following
CC CTL attack, moves rapidly to the nucleus, where it is found in the
CC nucleoplasm, avoiding the nucleolus. Similar translocation to the
CC nucleus is also observed for lymphocyte-activated killer cells
CC after the addition of calcium. The SET complex is associated with
CC the endoplasmic reticulum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=TAF-I alpha;
CC IsoId=Q01105-1; Sequence=Displayed;
CC Name=2; Synonyms=TAF-I beta;
CC IsoId=Q01105-2; Sequence=VSP_009868;
CC Note=Variant in position: 4:P->Q (in dbSNP:rs1141138). Contains
CC a N6-acetyllysine at position 11. Contains a phosphoserine at
CC position 15. Contains a phosphoserine at position 24;
CC Name=3;
CC IsoId=Q01105-3; Sequence=VSP_045175;
CC Name=4;
CC IsoId=Q01105-4; Sequence=VSP_046741;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Widely expressed. Low levels in quiescent
CC cells during serum starvation, contact inhibition or
CC differentiation. Highly expressed in Wilms' tumor.
CC -!- DOMAIN: A long alpha helix in the N-terminus mediates
CC dimerization, while the earmuff domain is responsible for core
CC histone and dsDNA binding. The C-terminal acidic domain mediates
CC the inhibition of histone acetyltransferases and is required for
CC the DNA replication stimulatory activity.
CC -!- PTM: Isoform 2 is phosphorylated on Ser-15 and Thr-23.
CC -!- PTM: Isoform 2 is acetylated on Lys-11.
CC -!- PTM: Some glutamate residues are glycylated by TTLL8. This
CC modification occurs exclusively on glutamate residues and results
CC in a glycine chain on the gamma-carboxyl group (By similarity).
CC -!- PTM: N-terminus of isoform 1 is methylated by METTL11A/NTM1.
CC Mainly trimethylated (By similarity).
CC -!- DISEASE: Note=A chromosomal aberration involving SET is found in
CC some cases of acute undifferentiated leukemia (AUL). Translocation
CC t(6;9)(q21;q34.1) with NUP214/CAN.
CC -!- SIMILARITY: Belongs to the nucleosome assembly protein (NAP)
CC family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SETID42272ch9q34.html";
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DR EMBL; M93651; AAA60318.1; -; mRNA.
DR EMBL; X75091; CAA52982.1; -; mRNA.
DR EMBL; D45198; BAA08139.1; -; mRNA.
DR EMBL; U51924; AAC50460.1; -; mRNA.
DR EMBL; AY349172; AAQ79833.1; -; mRNA.
DR EMBL; CR536543; CAG38780.1; -; mRNA.
DR EMBL; CR542050; CAG46847.1; -; mRNA.
DR EMBL; AK223556; BAD97276.1; -; mRNA.
DR EMBL; AK300609; BAG62304.1; -; mRNA.
DR EMBL; AL356481; CAH71410.1; -; Genomic_DNA.
DR EMBL; AL359678; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032749; AAH32749.1; -; mRNA.
DR EMBL; EF534308; ABP96841.1; -; mRNA.
DR PIR; A57984; A45018.
DR PIR; I59377; I59377.
DR RefSeq; NP_001116293.1; NM_001122821.1.
DR RefSeq; NP_001234929.1; NM_001248000.1.
DR RefSeq; NP_001234930.1; NM_001248001.1.
DR RefSeq; NP_003002.2; NM_003011.3.
DR UniGene; Hs.436687; -.
DR PDB; 2E50; X-ray; 2.30 A; A/B/P/Q=38-238.
DR PDBsum; 2E50; -.
DR ProteinModelPortal; Q01105; -.
DR SMR; Q01105; 38-236.
DR DIP; DIP-33561N; -.
DR IntAct; Q01105; 75.
DR MINT; MINT-4990855; -.
DR STRING; 9606.ENSP00000361777; -.
DR PhosphoSite; Q01105; -.
DR DMDM; 46397790; -.
DR PaxDb; Q01105; -.
DR PeptideAtlas; Q01105; -.
DR PRIDE; Q01105; -.
DR DNASU; 6418; -.
DR Ensembl; ENST00000322030; ENSP00000318012; ENSG00000119335.
DR Ensembl; ENST00000372686; ENSP00000361771; ENSG00000119335.
DR Ensembl; ENST00000372688; ENSP00000361773; ENSG00000119335.
DR Ensembl; ENST00000372692; ENSP00000361777; ENSG00000119335.
DR Ensembl; ENST00000409104; ENSP00000387321; ENSG00000119335.
DR GeneID; 6418; -.
DR KEGG; hsa:6418; -.
DR UCSC; uc011mbj.2; human.
DR CTD; 6418; -.
DR GeneCards; GC09P131445; -.
DR HGNC; HGNC:10760; SET.
DR HPA; CAB005232; -.
DR MIM; 600960; gene.
DR neXtProt; NX_Q01105; -.
DR PharmGKB; PA35678; -.
DR eggNOG; NOG260846; -.
DR HOGENOM; HOG000232096; -.
DR HOVERGEN; HBG014779; -.
DR InParanoid; Q01105; -.
DR KO; K11290; -.
DR OMA; FEIENGG; -.
DR PhylomeDB; Q01105; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; SET; human.
DR EvolutionaryTrace; Q01105; -.
DR GeneWiki; Protein_SET; -.
DR GenomeRNAi; 6418; -.
DR NextBio; 24926; -.
DR PRO; PR:Q01105; -.
DR ArrayExpress; Q01105; -.
DR Bgee; Q01105; -.
DR CleanEx; HS_SET; -.
DR Genevestigator; Q01105; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; TAS:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; TAS:ProtInc.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0035067; P:negative regulation of histone acetylation; TAS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IGI:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0006913; P:nucleocytoplasmic transport; NAS:UniProtKB.
DR GO; GO:0006334; P:nucleosome assembly; TAS:ProtInc.
DR GO; GO:0006337; P:nucleosome disassembly; TAS:UniProtKB.
DR InterPro; IPR002164; NAP_family.
DR PANTHER; PTHR11875; PTHR11875; 1.
DR Pfam; PF00956; NAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chaperone;
KW Chromosomal rearrangement; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Endoplasmic reticulum;
KW Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Polymorphism;
KW Proto-oncogene; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 290 Protein SET.
FT /FTId=PRO_0000185662.
FT REGION 31 78 Dimerization.
FT REGION 79 225 Earmuff domain.
FT COMPBIAS 239 290 Asp/Glu-rich (highly acidic).
FT SITE 283 284 Breakpoint for translocation to form SET-
FT CAN oncogene.
FT MOD_RES 2 2 N,N,N-trimethylalanine (By similarity).
FT MOD_RES 7 7 Phosphoserine.
FT MOD_RES 132 132 N6-acetyllysine.
FT MOD_RES 146 146 Phosphotyrosine (By similarity).
FT MOD_RES 150 150 N6-acetyllysine.
FT MOD_RES 172 172 N6-acetyllysine.
FT CROSSLNK 154 154 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VAR_SEQ 1 37 MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG ->
FT MSAPAAKVSKKELNSNHDGADETS (in isoform 2).
FT /FTId=VSP_009868.
FT VAR_SEQ 1 37 MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG ->
FT MPRSHQPPPPPH (in isoform 3).
FT /FTId=VSP_045175.
FT VAR_SEQ 1 37 MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG ->
FT MGCRDLLPSLKPTLL (in isoform 4).
FT /FTId=VSP_046741.
FT HELIX 38 88
FT HELIX 94 100
FT HELIX 103 106
FT HELIX 111 116
FT HELIX 117 119
FT STRAND 120 127
FT STRAND 135 141
FT STRAND 145 148
FT STRAND 150 156
FT STRAND 166 168
FT HELIX 203 206
FT HELIX 215 223
FT TURN 224 227
FT HELIX 230 233
SQ SEQUENCE 290 AA; 33489 MW; F4664118171EF230 CRC64;
MAPKRQSPLP PQKKKPRPPP ALGPEETSAS AGLPKKGEKE QQEAIEHIDE VQNEIDRLNE
QASEEILKVE QKYNKLRQPF FQKRSELIAK IPNFWVTTFV NHPQVSALLG EEDEEALHYL
TRVEVTEFED IKSGYRIDFY FDENPYFENK VLSKEFHLNE SGDPSSKSTE IKWKSGKDLT
KRSSQTQNKA SRKRQHEEPE SFFTWFTDHS DAGADELGEV IKDDIWPNPL QYYLVPDMDD
EEGEGEEDDD DDEEEEGLED IDEEGDEDEG EEDEDDDEGE EGEEDEGEDD
//
ID SET_HUMAN Reviewed; 290 AA.
AC Q01105; A5A5H4; A6NGV1; B4DUE2; Q15541; Q5VXV1; Q5VXV2; Q6FHZ5;
read moreDT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 3.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Protein SET;
DE AltName: Full=HLA-DR-associated protein II;
DE AltName: Full=Inhibitor of granzyme A-activated DNase;
DE Short=IGAAD;
DE AltName: Full=PHAPII;
DE AltName: Full=Phosphatase 2A inhibitor I2PP2A;
DE Short=I-2PP2A;
DE AltName: Full=Template-activating factor I;
DE Short=TAF-I;
GN Name=SET;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1630450;
RA von Lindern M., van Baal S., Wiegant J., Raap A., Hagemeijer A.,
RA Grosveld G.;
RT "Can, a putative oncogene associated with myeloid leukemogenesis, may
RT be activated by fusion of its 3' half to different genes:
RT characterization of the set gene.";
RL Mol. Cell. Biol. 12:3346-3355(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8192856;
RA Vaesen M., Barnikol-Watanabe S., Goetz H., Adil Awni L., Cole T.,
RA Zimmermann B., Kratzin H.D., Hilschmann N.;
RT "Purification and characterization of two putative HLA class II
RT associated proteins: PHAPI and PHAPII.";
RL Biol. Chem. Hoppe-Seyler 375:113-126(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF
RP 14-35; 40-60; 75-90 AND 155-167, AND ACTIVATION OF DNA REPLICATION.
RC TISSUE=Cervix carcinoma;
RX PubMed=7753797; DOI=10.1073/pnas.92.10.4279;
RA Nagata K., Kawase H., Handa H., Yano K., Yamasaki M., Ishimi Y.,
RA Okuda A., Kikuchi A., Matsumoto K.;
RT "Replication factor encoded by a putative oncogene, set, associated
RT with myeloid leukemogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4279-4283(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=8626647; DOI=10.1074/jbc.271.19.11059;
RA Li M., Makkinje A., Damuni Z.;
RT "The myeloid leukemia-associated protein SET is a potent inhibitor of
RT protein phosphatase 2A.";
RL J. Biol. Chem. 271:11059-11062(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15642345; DOI=10.1016/j.febslet.2004.11.097;
RA Tsujio I., Zaidi T., Xu J., Kotula L., Grundke-Iqbal I., Iqbal K.;
RT "Inhibitors of protein phosphatase-2A from human brain structures,
RT immunocytological localization and activities towards
RT dephosphorylation of the Alzheimer type hyperphosphorylated tau.";
RL FEBS Lett. 579:363-372(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RX PubMed=8294483;
RA Adachi Y., Pavlaki G.N., Copeland T.D.;
RT "Identification and characterization of SET, a nuclear phosphoprotein
RT encoded by the translocation break point in acute undifferentiated
RT leukemia.";
RL J. Biol. Chem. 269:2258-2262(1994).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-241 (ISOFORM 2).
RA Wang L.C., Chen Y.;
RT "A relative factor in human rectum carcinoma.";
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP EXPRESSION IN THE KIDNEY.
RX PubMed=9773788;
RA Carlson S.G., Eng E., Kim E.-G., Perlman E.J., Copeland T.D.,
RA Ballermann B.J.;
RT "Expression of SET, an inhibitor of protein phosphatase 2A, in renal
RT development and Wilms' tumor.";
RL J. Am. Soc. Nephrol. 9:1873-1880(1998).
RN [14]
RP INHIBITION OF HISTONE ACETYLATION.
RX PubMed=11163245; DOI=10.1016/S0092-8674(01)00196-9;
RA Seo S.-B., McNamara P., Heo S., Turner A., Lane W.S., Chakravarti D.;
RT "Regulation of histone acetylation and transcription by INHAT, a human
RT cellular complex containing the Set oncoprotein.";
RL Cell 104:119-130(2001).
RN [15]
RP INTERACTION WITH SETBP1.
RC TISSUE=Cervix carcinoma;
RX PubMed=11231286; DOI=10.1046/j.1432-1327.2001.02000.x;
RA Minakuchi M., Kakazu N., Gorrin-Rivas M.J., Abe T., Copeland T.D.,
RA Ueda K., Adachi Y.;
RT "Identification and characterization of SEB, a novel protein that
RT binds to the acute undifferentiated leukemia-associated protein SET.";
RL Eur. J. Biochem. 268:1340-1351(2001).
RN [16]
RP INTERACTION WITH HMGB2.
RX PubMed=11909973; DOI=10.1128/MCB.22.8.2810-2820.2002;
RA Fan Z., Beresford P.J., Zhang D., Lieberman J.;
RT "HMG2 interacts with the nucleosome assembly protein SET and is a
RT target of the cytotoxic T-lymphocyte protease granzyme A.";
RL Mol. Cell. Biol. 22:2810-2820(2002).
RN [17]
RP NME1 INHIBITION, SUBCELLULAR LOCATION, AND DESCRIPTION OF THE SET
RP COMPLEX.
RX PubMed=12628186; DOI=10.1016/S0092-8674(03)00150-8;
RA Fan Z., Beresford P.J., Oh D.Y., Zhang D., Lieberman J.;
RT "Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-
RT mediated apoptosis, and the nucleosome assembly protein SET is its
RT inhibitor.";
RL Cell 112:659-672(2003).
RN [18]
RP ERRATUM.
RA Fan Z., Beresford P.J., Oh D.Y., Zhang D., Lieberman J.;
RL Cell 115:241-241(2003).
RN [19]
RP SUBCELLULAR LOCATION.
RX PubMed=12524539; DOI=10.1038/ni885;
RA Fan Z., Beresford P.J., Zhang D., Xu Z., Novina C.D., Yoshida A.,
RA Pommier Y., Lieberman J.;
RT "Cleaving the oxidative repair protein Ape1 enhances cell death
RT mediated by granzyme A.";
RL Nat. Immunol. 4:145-153(2003).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [21]
RP INTERACTION WITH SGOL1.
RX PubMed=16541025; DOI=10.1038/nature04663;
RA Kitajima T.S., Sakuno T., Ishiguro K., Iemura S., Natsume T.,
RA Kawashima S.A., Watanabe Y.;
RT "Shugoshin collaborates with protein phosphatase 2A to protect
RT cohesin.";
RL Nature 441:46-52(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [23]
RP 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 [24]
RP INTERACTION WITH APBB1.
RX PubMed=19343227; DOI=10.1371/journal.pone.0005071;
RA Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J.,
RA Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D.;
RT "FE65 binds Teashirt, inhibiting expression of the primate-specific
RT caspase-4.";
RL PLoS ONE 4:E5071-E5071(2009).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-132; LYS-150 AND LYS-172,
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-11 (ISOFORM 2), AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-15 AND SER-24 (ISOFORM 2), AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [27]
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.,
RA Buerckstuemmer T., 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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15 AND SER-24 (ISOFORM
RP 2), AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 38-238, DNA-BINDING, DOMAINS,
RP AND SUBUNIT.
RX PubMed=17360516; DOI=10.1073/pnas.0603762104;
RA Muto S., Senda M., Akai Y., Sato L., Suzuki T., Nagai R., Senda T.,
RA Horikoshi M.;
RT "Relationship between the structure of SET/TAF-Ibeta/INHAT and its
RT histone chaperone activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:4285-4290(2007).
CC -!- FUNCTION: Multitasking protein, involved in apoptosis,
CC transcription, nucleosome assembly and histone chaperoning.
CC Isoform 2 anti-apoptotic activity is mediated by inhibition of the
CC GZMA-activated DNase, NME1. In the course of cytotoxic T-
CC lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting
CC its binding to NME1 and releasing NME1 inhibition. Isoform 1 and
CC isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform
CC 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation
CC of histones (HAT) and nucleosomes, most probably by masking the
CC accessibility of lysines of histones to the acetylases. The
CC predominant target for inhibition is histone H4. HAT inhibition
CC leads to silencing of HAT-dependent transcription and prevents
CC active demethylation of DNA. Both isoforms stimulate DNA
CC replication of the adenovirus genome complexed with viral core
CC proteins; however, isoform 2 specific activity is higher.
CC -!- SUBUNIT: Interacts with CHTOP (By similarity). Headphone-shaped
CC homodimer. Isoform 1 and isoform 2 interact directly with each
CC other and with ANP32A within the tripartite INHAT (inhibitor of
CC acetyltransferases) complex. Isoform 1 and isoform 2 interact also
CC with histones. Isoform 2 is a component of the SET complex, which
CC also contains ANP32A, APEX1, HMGB2 and NME1, but not NME2. Within
CC this complex, directly interacts with NME1 and with HMGB2.
CC Interacts with SETBP1. Interacts with SGOL1. Interacts with APBB1.
CC -!- INTERACTION:
CC Q00987:MDM2; NbExp=2; IntAct=EBI-1053182, EBI-389668;
CC P10644:PRKAR1A; NbExp=2; IntAct=EBI-1053182, EBI-476431;
CC P63000:RAC1; NbExp=8; IntAct=EBI-1053182, EBI-413628;
CC Q15573:TAF1A; NbExp=2; IntAct=EBI-1053182, EBI-2510647;
CC Q53T94:TAF1B; NbExp=3; IntAct=EBI-1053182, EBI-1560239;
CC Q15572:TAF1C; NbExp=4; IntAct=EBI-1053182, EBI-2510659;
CC P20226:TBP; NbExp=4; IntAct=EBI-1053182, EBI-355371;
CC P17480:UBTF; NbExp=4; IntAct=EBI-1053182, EBI-396235;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum.
CC Nucleus, nucleoplasm. Note=In the cytoplasm, found both in the
CC cytosol and associated with the endoplasmic reticulum. Following
CC CTL attack, moves rapidly to the nucleus, where it is found in the
CC nucleoplasm, avoiding the nucleolus. Similar translocation to the
CC nucleus is also observed for lymphocyte-activated killer cells
CC after the addition of calcium. The SET complex is associated with
CC the endoplasmic reticulum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=TAF-I alpha;
CC IsoId=Q01105-1; Sequence=Displayed;
CC Name=2; Synonyms=TAF-I beta;
CC IsoId=Q01105-2; Sequence=VSP_009868;
CC Note=Variant in position: 4:P->Q (in dbSNP:rs1141138). Contains
CC a N6-acetyllysine at position 11. Contains a phosphoserine at
CC position 15. Contains a phosphoserine at position 24;
CC Name=3;
CC IsoId=Q01105-3; Sequence=VSP_045175;
CC Name=4;
CC IsoId=Q01105-4; Sequence=VSP_046741;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Widely expressed. Low levels in quiescent
CC cells during serum starvation, contact inhibition or
CC differentiation. Highly expressed in Wilms' tumor.
CC -!- DOMAIN: A long alpha helix in the N-terminus mediates
CC dimerization, while the earmuff domain is responsible for core
CC histone and dsDNA binding. The C-terminal acidic domain mediates
CC the inhibition of histone acetyltransferases and is required for
CC the DNA replication stimulatory activity.
CC -!- PTM: Isoform 2 is phosphorylated on Ser-15 and Thr-23.
CC -!- PTM: Isoform 2 is acetylated on Lys-11.
CC -!- PTM: Some glutamate residues are glycylated by TTLL8. This
CC modification occurs exclusively on glutamate residues and results
CC in a glycine chain on the gamma-carboxyl group (By similarity).
CC -!- PTM: N-terminus of isoform 1 is methylated by METTL11A/NTM1.
CC Mainly trimethylated (By similarity).
CC -!- DISEASE: Note=A chromosomal aberration involving SET is found in
CC some cases of acute undifferentiated leukemia (AUL). Translocation
CC t(6;9)(q21;q34.1) with NUP214/CAN.
CC -!- SIMILARITY: Belongs to the nucleosome assembly protein (NAP)
CC family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SETID42272ch9q34.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; M93651; AAA60318.1; -; mRNA.
DR EMBL; X75091; CAA52982.1; -; mRNA.
DR EMBL; D45198; BAA08139.1; -; mRNA.
DR EMBL; U51924; AAC50460.1; -; mRNA.
DR EMBL; AY349172; AAQ79833.1; -; mRNA.
DR EMBL; CR536543; CAG38780.1; -; mRNA.
DR EMBL; CR542050; CAG46847.1; -; mRNA.
DR EMBL; AK223556; BAD97276.1; -; mRNA.
DR EMBL; AK300609; BAG62304.1; -; mRNA.
DR EMBL; AL356481; CAH71410.1; -; Genomic_DNA.
DR EMBL; AL359678; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032749; AAH32749.1; -; mRNA.
DR EMBL; EF534308; ABP96841.1; -; mRNA.
DR PIR; A57984; A45018.
DR PIR; I59377; I59377.
DR RefSeq; NP_001116293.1; NM_001122821.1.
DR RefSeq; NP_001234929.1; NM_001248000.1.
DR RefSeq; NP_001234930.1; NM_001248001.1.
DR RefSeq; NP_003002.2; NM_003011.3.
DR UniGene; Hs.436687; -.
DR PDB; 2E50; X-ray; 2.30 A; A/B/P/Q=38-238.
DR PDBsum; 2E50; -.
DR ProteinModelPortal; Q01105; -.
DR SMR; Q01105; 38-236.
DR DIP; DIP-33561N; -.
DR IntAct; Q01105; 75.
DR MINT; MINT-4990855; -.
DR STRING; 9606.ENSP00000361777; -.
DR PhosphoSite; Q01105; -.
DR DMDM; 46397790; -.
DR PaxDb; Q01105; -.
DR PeptideAtlas; Q01105; -.
DR PRIDE; Q01105; -.
DR DNASU; 6418; -.
DR Ensembl; ENST00000322030; ENSP00000318012; ENSG00000119335.
DR Ensembl; ENST00000372686; ENSP00000361771; ENSG00000119335.
DR Ensembl; ENST00000372688; ENSP00000361773; ENSG00000119335.
DR Ensembl; ENST00000372692; ENSP00000361777; ENSG00000119335.
DR Ensembl; ENST00000409104; ENSP00000387321; ENSG00000119335.
DR GeneID; 6418; -.
DR KEGG; hsa:6418; -.
DR UCSC; uc011mbj.2; human.
DR CTD; 6418; -.
DR GeneCards; GC09P131445; -.
DR HGNC; HGNC:10760; SET.
DR HPA; CAB005232; -.
DR MIM; 600960; gene.
DR neXtProt; NX_Q01105; -.
DR PharmGKB; PA35678; -.
DR eggNOG; NOG260846; -.
DR HOGENOM; HOG000232096; -.
DR HOVERGEN; HBG014779; -.
DR InParanoid; Q01105; -.
DR KO; K11290; -.
DR OMA; FEIENGG; -.
DR PhylomeDB; Q01105; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; SET; human.
DR EvolutionaryTrace; Q01105; -.
DR GeneWiki; Protein_SET; -.
DR GenomeRNAi; 6418; -.
DR NextBio; 24926; -.
DR PRO; PR:Q01105; -.
DR ArrayExpress; Q01105; -.
DR Bgee; Q01105; -.
DR CleanEx; HS_SET; -.
DR Genevestigator; Q01105; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; TAS:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; TAS:ProtInc.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0035067; P:negative regulation of histone acetylation; TAS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IGI:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0006913; P:nucleocytoplasmic transport; NAS:UniProtKB.
DR GO; GO:0006334; P:nucleosome assembly; TAS:ProtInc.
DR GO; GO:0006337; P:nucleosome disassembly; TAS:UniProtKB.
DR InterPro; IPR002164; NAP_family.
DR PANTHER; PTHR11875; PTHR11875; 1.
DR Pfam; PF00956; NAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chaperone;
KW Chromosomal rearrangement; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Endoplasmic reticulum;
KW Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Polymorphism;
KW Proto-oncogene; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 290 Protein SET.
FT /FTId=PRO_0000185662.
FT REGION 31 78 Dimerization.
FT REGION 79 225 Earmuff domain.
FT COMPBIAS 239 290 Asp/Glu-rich (highly acidic).
FT SITE 283 284 Breakpoint for translocation to form SET-
FT CAN oncogene.
FT MOD_RES 2 2 N,N,N-trimethylalanine (By similarity).
FT MOD_RES 7 7 Phosphoserine.
FT MOD_RES 132 132 N6-acetyllysine.
FT MOD_RES 146 146 Phosphotyrosine (By similarity).
FT MOD_RES 150 150 N6-acetyllysine.
FT MOD_RES 172 172 N6-acetyllysine.
FT CROSSLNK 154 154 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VAR_SEQ 1 37 MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG ->
FT MSAPAAKVSKKELNSNHDGADETS (in isoform 2).
FT /FTId=VSP_009868.
FT VAR_SEQ 1 37 MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG ->
FT MPRSHQPPPPPH (in isoform 3).
FT /FTId=VSP_045175.
FT VAR_SEQ 1 37 MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG ->
FT MGCRDLLPSLKPTLL (in isoform 4).
FT /FTId=VSP_046741.
FT HELIX 38 88
FT HELIX 94 100
FT HELIX 103 106
FT HELIX 111 116
FT HELIX 117 119
FT STRAND 120 127
FT STRAND 135 141
FT STRAND 145 148
FT STRAND 150 156
FT STRAND 166 168
FT HELIX 203 206
FT HELIX 215 223
FT TURN 224 227
FT HELIX 230 233
SQ SEQUENCE 290 AA; 33489 MW; F4664118171EF230 CRC64;
MAPKRQSPLP PQKKKPRPPP ALGPEETSAS AGLPKKGEKE QQEAIEHIDE VQNEIDRLNE
QASEEILKVE QKYNKLRQPF FQKRSELIAK IPNFWVTTFV NHPQVSALLG EEDEEALHYL
TRVEVTEFED IKSGYRIDFY FDENPYFENK VLSKEFHLNE SGDPSSKSTE IKWKSGKDLT
KRSSQTQNKA SRKRQHEEPE SFFTWFTDHS DAGADELGEV IKDDIWPNPL QYYLVPDMDD
EEGEGEEDDD DDEEEEGLED IDEEGDEDEG EEDEDDDEGE EGEEDEGEDD
//
MIM
600960
*RECORD*
*FIELD* NO
600960
*FIELD* TI
*600960 SET TRANSLOCATION, MYELOID LEUKEMIA-ASSOCIATED; SET
;;INHIBITOR OF GZMA-ACTIVATED DNase; IGAAD
read more*FIELD* TX
CLONING
The translocation (6;9)(p23q34) is the hallmark of a specific subtype of
acute myeloid leukemia (AML) characterized by a poor prognosis and a
young age of onset. It is classified in the French-American-British
(FAB) system mostly as M2/M4 and rarely as M1 or refractive anemia with
excess of blast cells (RAEB). On chromosome 9, breakpoints take place in
a specific intron, denoted icb-9, of a large gene named Cain (CAN;
114350). On chromosome 6, breakpoints occur in a single intron, icb-6,
of a gene named DEK (125264). In a patient with acute undifferentiated
leukemia and an apparently normal karyotype, von Lindern et al. (1992)
found a breakpoint in icb-9 of the CAN gene in a bone marrow sample but
detected no breakpoint in DEK. They isolated and characterized a novel
gene, named SET (suppressor of variegation, enhancer of zeste, and
Trithorax), that was fused to CAN in the leukemic cells of this patient.
A chimeric SET-CAN transcript whose sequence predicted a fusion protein
of 155 kD was detected. The SET gene encodes transcripts of 2.0 and 2.7
kb that result from the use of alternative polyadenylation sites. Both
transcripts contained the open reading frame for a putative protein with
a predicted molecular mass of 32 kD. The SET sequence showed homology
with the yeast nucleosome assembly protein NAP-I. The only common
sequence motif of SET and DEK proteins is an acidic region. SET has a
long acidic tail, of which a large part is present in the predicted
SET-CAN fusion protein.
GENE FUNCTION
Carlson et al. (1998) studied the role of SET in the regulation of renal
cell proliferation and tumorigenesis. The mRNA encoding SET was
expressed at much higher levels in transformed human and rodent cell
lines than in cultured renal epithelial and primary endothelial cells.
Consistent with a role for SET in cell proliferation, SET mRNA
expression was markedly reduced in cells rendered quiescent by serum
starvation, contact inhibition, or differentiation. Previous findings
during renal development were extended by demonstrating that SET protein
expression is also much greater in developing rat and human kidney than
in fully differentiated, mature kidney. Finally, high levels of SET mRNA
and SET protein expression were found in Wilms tumor but not in renal
cell carcinoma, adult polycystic kidney disease, or in transitional cell
carcinoma. The SET domain (Tschiersch et al., 1994) is found in proteins
that are involved in embryonic development (Tripoulas et al., 1996).
Granzyme A (GZMA; 140050) induces a caspase-independent cell death
pathway characterized by single-stranded DNA nicks and other features of
apoptosis. A GZMA-activated DNase (GAAD) is in an endoplasmic
reticulum-associated complex containing pp32 (600832) and the GZMA
substrates SET, HMG2 (163906), and APE1 (107748). Fan et al. (2003)
showed that GAAD is NM23H1 (156490), a nucleoside diphosphate kinase
implicated in suppression of tumor metastasis, and its specific
inhibitor (IGAAD) is SET. NM23H1 bound SET and was released from
inhibition by GZMA cleavage of SET. After GZMA loading or cytotoxic T
lymphocyte attack, SET and NM23H1 translocated to the nucleus and SET
was degraded, allowing NM23H1 to nick chromosomal DNA. GZMA-treated
cells with silenced NM23H1 expression were resistant to GZMA-mediated
DNA damage and cytolysis, while cells overexpressing NM23H1 were more
sensitive.
By yeast 2-hybrid analysis using the N-terminal 277 amino acids of SET
as bait, Minakuchi et al. (2001) identified SET-binding protein-1
(SETBP1; 611060). Deletion and mutagenesis analysis revealed that amino
acids 182 to 223 of SET interacted with amino acids 1238 to 1434 of
SETBP1. Immunoprecipitation analysis verified that SETBP1 interacted
with endogenous SET in a human osteosarcoma cell line.
Ischemia and seizure cause excessive neuronal excitation that is
associated with brain acidosis and neuronal cell death. Liu et al.
(2008) found that the neurotoxin kainic acid activated lysosomal
asparagine endopeptidase (AEP, or LGMN; 602620) in mouse brain and
triggered degradation of Set, followed by DNA nicking and neuronal cell
death. Pike-L (CENTG1; 605476) strongly bound Set in the nucleus and
protected Set from proteolytic cleavage by Aep in vitro and in vivo,
thereby diminishing DNA damage and neuronal cell death. Kainic acid or
stroke failed to provoke DNA nicking and neuronal cell death in
Aep-deficient mice.
MAPPING
By fluorescence in situ hybridization, von Lindern et al. (1992)
assigned the SET gene to 9q34, centromeric of ABL (189980).
*FIELD* RF
1. Carlson, S. G.; Eng, E.; Kim, E.-G.; Perlman, E. J.; Copeland,
T. D.; Ballermann, B. J.: Expression of SET, an inhibitor of protein
phosphatase 2A, in renal development and Wilms' tumor. J. Am. Soc.
Nephrol. 9: 1873-1880, 1998.
2. Fan, Z.; Beresford, P. J.; Oh, D. Y.; Zhang, D.; Lieberman, J.
: Tumor suppressor NM23-H1 is a granzyme A-activated DNase during
CTL-mediated apoptosis, and the nucleosome assembly protein SET is
its inhibitor. Cell 112: 659-672, 2003. Note: Erratum: Cell 115:
241 only, 2003.
3. Liu, Z.; Jang, S.-W.; Liu, X.; Cheng, D.; Peng, J.; Yepes, M.;
Li, X.; Matthews, S.; Watts, C.; Asano, M.; Hara-Nishimura, I.; Luo,
H. R.; Ye, K.: Neuroprotective actions of PIKE-L by inhibition of
SET proteolytic degradation by asparagine endopeptidase. Molec. Cell 29:
665-678, 2008.
4. Minakuchi, M.; Kakazu, N.; Gorrin-Rivas, M. J.; Abe, T.; Copeland,
T. D.; Ueda, K.; Adachi, Y.: Identification and characterization
of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated
protein SET. Europ. J. Biochem. 268: 1340-1351, 2001.
5. Tripoulas, N.; LaJeunesse, D.; Gildea, J.; Shearn, A.: The Drosophila
ash1 gene product, which is localized at specific sites on polytene
chromosomes, contains a SET domain and a PHD finger. Genetics 143:
913-928, 1996.
6. Tschiersch, B.; Hofmann, A.; Krauss, V.; Dorn, R.; Korge, G.; Reuter,
G.: The protein encoded by the Drosophila position-effect variegation
suppressor gene Su(var)3-9 combines domains of antagonistic regulators
of homeotic gene complexes. EMBO J. 13: 3822-3831, 1994.
7. von Lindern, M.; van Baal, S.; Wiegant, J.; Raap, A.; Hagemeijer,
A.; Grosveld, G.: 'can,' a putative oncogene associated with myeloid
leukemogenesis, may be activated by fusion of its 3-prime half to
different genes: characterization of the 'set' gene. Molec. Cell.
Biol. 12: 3346-3355, 1992.
*FIELD* CN
Patricia A. Hartz - updated: 5/30/2008
Patricia A. Hartz - updated: 5/23/2007
Stylianos E. Antonarakis - updated: 4/14/2003
Ada Hamosh - updated: 5/11/1999
Victor A. McKusick - updated: 7/8/1998
*FIELD* CD
Victor A. McKusick: 12/18/1995
*FIELD* ED
mgross: 06/03/2008
terry: 5/30/2008
mgross: 5/23/2007
mgross: 6/20/2006
carol: 9/17/2003
mgross: 4/14/2003
mcapotos: 4/11/2001
terry: 4/9/2001
alopez: 5/17/1999
terry: 5/11/1999
dholmes: 7/22/1998
carol: 7/13/1998
terry: 7/8/1998
terry: 6/4/1998
mark: 12/18/1995
*RECORD*
*FIELD* NO
600960
*FIELD* TI
*600960 SET TRANSLOCATION, MYELOID LEUKEMIA-ASSOCIATED; SET
;;INHIBITOR OF GZMA-ACTIVATED DNase; IGAAD
read more*FIELD* TX
CLONING
The translocation (6;9)(p23q34) is the hallmark of a specific subtype of
acute myeloid leukemia (AML) characterized by a poor prognosis and a
young age of onset. It is classified in the French-American-British
(FAB) system mostly as M2/M4 and rarely as M1 or refractive anemia with
excess of blast cells (RAEB). On chromosome 9, breakpoints take place in
a specific intron, denoted icb-9, of a large gene named Cain (CAN;
114350). On chromosome 6, breakpoints occur in a single intron, icb-6,
of a gene named DEK (125264). In a patient with acute undifferentiated
leukemia and an apparently normal karyotype, von Lindern et al. (1992)
found a breakpoint in icb-9 of the CAN gene in a bone marrow sample but
detected no breakpoint in DEK. They isolated and characterized a novel
gene, named SET (suppressor of variegation, enhancer of zeste, and
Trithorax), that was fused to CAN in the leukemic cells of this patient.
A chimeric SET-CAN transcript whose sequence predicted a fusion protein
of 155 kD was detected. The SET gene encodes transcripts of 2.0 and 2.7
kb that result from the use of alternative polyadenylation sites. Both
transcripts contained the open reading frame for a putative protein with
a predicted molecular mass of 32 kD. The SET sequence showed homology
with the yeast nucleosome assembly protein NAP-I. The only common
sequence motif of SET and DEK proteins is an acidic region. SET has a
long acidic tail, of which a large part is present in the predicted
SET-CAN fusion protein.
GENE FUNCTION
Carlson et al. (1998) studied the role of SET in the regulation of renal
cell proliferation and tumorigenesis. The mRNA encoding SET was
expressed at much higher levels in transformed human and rodent cell
lines than in cultured renal epithelial and primary endothelial cells.
Consistent with a role for SET in cell proliferation, SET mRNA
expression was markedly reduced in cells rendered quiescent by serum
starvation, contact inhibition, or differentiation. Previous findings
during renal development were extended by demonstrating that SET protein
expression is also much greater in developing rat and human kidney than
in fully differentiated, mature kidney. Finally, high levels of SET mRNA
and SET protein expression were found in Wilms tumor but not in renal
cell carcinoma, adult polycystic kidney disease, or in transitional cell
carcinoma. The SET domain (Tschiersch et al., 1994) is found in proteins
that are involved in embryonic development (Tripoulas et al., 1996).
Granzyme A (GZMA; 140050) induces a caspase-independent cell death
pathway characterized by single-stranded DNA nicks and other features of
apoptosis. A GZMA-activated DNase (GAAD) is in an endoplasmic
reticulum-associated complex containing pp32 (600832) and the GZMA
substrates SET, HMG2 (163906), and APE1 (107748). Fan et al. (2003)
showed that GAAD is NM23H1 (156490), a nucleoside diphosphate kinase
implicated in suppression of tumor metastasis, and its specific
inhibitor (IGAAD) is SET. NM23H1 bound SET and was released from
inhibition by GZMA cleavage of SET. After GZMA loading or cytotoxic T
lymphocyte attack, SET and NM23H1 translocated to the nucleus and SET
was degraded, allowing NM23H1 to nick chromosomal DNA. GZMA-treated
cells with silenced NM23H1 expression were resistant to GZMA-mediated
DNA damage and cytolysis, while cells overexpressing NM23H1 were more
sensitive.
By yeast 2-hybrid analysis using the N-terminal 277 amino acids of SET
as bait, Minakuchi et al. (2001) identified SET-binding protein-1
(SETBP1; 611060). Deletion and mutagenesis analysis revealed that amino
acids 182 to 223 of SET interacted with amino acids 1238 to 1434 of
SETBP1. Immunoprecipitation analysis verified that SETBP1 interacted
with endogenous SET in a human osteosarcoma cell line.
Ischemia and seizure cause excessive neuronal excitation that is
associated with brain acidosis and neuronal cell death. Liu et al.
(2008) found that the neurotoxin kainic acid activated lysosomal
asparagine endopeptidase (AEP, or LGMN; 602620) in mouse brain and
triggered degradation of Set, followed by DNA nicking and neuronal cell
death. Pike-L (CENTG1; 605476) strongly bound Set in the nucleus and
protected Set from proteolytic cleavage by Aep in vitro and in vivo,
thereby diminishing DNA damage and neuronal cell death. Kainic acid or
stroke failed to provoke DNA nicking and neuronal cell death in
Aep-deficient mice.
MAPPING
By fluorescence in situ hybridization, von Lindern et al. (1992)
assigned the SET gene to 9q34, centromeric of ABL (189980).
*FIELD* RF
1. Carlson, S. G.; Eng, E.; Kim, E.-G.; Perlman, E. J.; Copeland,
T. D.; Ballermann, B. J.: Expression of SET, an inhibitor of protein
phosphatase 2A, in renal development and Wilms' tumor. J. Am. Soc.
Nephrol. 9: 1873-1880, 1998.
2. Fan, Z.; Beresford, P. J.; Oh, D. Y.; Zhang, D.; Lieberman, J.
: Tumor suppressor NM23-H1 is a granzyme A-activated DNase during
CTL-mediated apoptosis, and the nucleosome assembly protein SET is
its inhibitor. Cell 112: 659-672, 2003. Note: Erratum: Cell 115:
241 only, 2003.
3. Liu, Z.; Jang, S.-W.; Liu, X.; Cheng, D.; Peng, J.; Yepes, M.;
Li, X.; Matthews, S.; Watts, C.; Asano, M.; Hara-Nishimura, I.; Luo,
H. R.; Ye, K.: Neuroprotective actions of PIKE-L by inhibition of
SET proteolytic degradation by asparagine endopeptidase. Molec. Cell 29:
665-678, 2008.
4. Minakuchi, M.; Kakazu, N.; Gorrin-Rivas, M. J.; Abe, T.; Copeland,
T. D.; Ueda, K.; Adachi, Y.: Identification and characterization
of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated
protein SET. Europ. J. Biochem. 268: 1340-1351, 2001.
5. Tripoulas, N.; LaJeunesse, D.; Gildea, J.; Shearn, A.: The Drosophila
ash1 gene product, which is localized at specific sites on polytene
chromosomes, contains a SET domain and a PHD finger. Genetics 143:
913-928, 1996.
6. Tschiersch, B.; Hofmann, A.; Krauss, V.; Dorn, R.; Korge, G.; Reuter,
G.: The protein encoded by the Drosophila position-effect variegation
suppressor gene Su(var)3-9 combines domains of antagonistic regulators
of homeotic gene complexes. EMBO J. 13: 3822-3831, 1994.
7. von Lindern, M.; van Baal, S.; Wiegant, J.; Raap, A.; Hagemeijer,
A.; Grosveld, G.: 'can,' a putative oncogene associated with myeloid
leukemogenesis, may be activated by fusion of its 3-prime half to
different genes: characterization of the 'set' gene. Molec. Cell.
Biol. 12: 3346-3355, 1992.
*FIELD* CN
Patricia A. Hartz - updated: 5/30/2008
Patricia A. Hartz - updated: 5/23/2007
Stylianos E. Antonarakis - updated: 4/14/2003
Ada Hamosh - updated: 5/11/1999
Victor A. McKusick - updated: 7/8/1998
*FIELD* CD
Victor A. McKusick: 12/18/1995
*FIELD* ED
mgross: 06/03/2008
terry: 5/30/2008
mgross: 5/23/2007
mgross: 6/20/2006
carol: 9/17/2003
mgross: 4/14/2003
mcapotos: 4/11/2001
terry: 4/9/2001
alopez: 5/17/1999
terry: 5/11/1999
dholmes: 7/22/1998
carol: 7/13/1998
terry: 7/8/1998
terry: 6/4/1998
mark: 12/18/1995