Reviewed,
UniProtKB/Swiss-Prot Q01105 (SET_HUMAN)
Last modified
November 25, 2008.
Version 88.
History...
Clusters with 100%,
90%,
50% identity |
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Names and origin
| Protein names | Recommended name: Protein SET Alternative name(s): Phosphatase 2A inhibitor I2PP2A Short name=I-2PP2A Template-activating factor I Short name=TAF-I HLA-DR-associated protein II PHAPII Inhibitor of granzyme A-activated DNase Short name=IGAAD | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 290 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone binding. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher. |
| Subunit structure | Isoform 1 and isoform 2 interact directly with each other and with ANP32A within the tripartite INHAT (inhibitor of acetyltransferases) complex. Isoform 1 and isoform 2 interact also with histones. Isoform 2 is a component of the SET complex, which also contains ANP32A, APEX1, HMGB2 and NME1, but not NME2. Within this complex, directly interacts with NME1 and with HMGB2. Interacts with SETBP1. |
| Subcellular location | Cytoplasm › cytosol. Endoplasmic reticulum. Nucleus › nucleoplasm. Note= In the cytoplasm, found both in the cytosol and associated with the endoplasmic reticulum. Following CTL attack, moves rapidly to the nucleus, where it is found in the nucleoplasm, avoiding the nucleolus. Similar translocation to the nucleus is also observed for lymphocyte-activated killer cells after the addition of calcium. The SET complex is associated with the endoplasmic reticulum. |
| Tissue specificity | Widely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor. |
| Domain | The C-terminal acidic domain mediates the inhibition of histone acetyltransferases and is required for the DNA replication stimulatory activity. |
| Post-translational modification | Isoform 2 is phosphorylated on Ser-15 and Thr-23. Isoform 2 is acetylated on Lys-11. |
| Involvement in disease | A chromosomal aberration involving SET is found in some cases of acute undifferentiated leukemia (AUL). Translocation t(6;9)(q21;q34.1) with NUP214/CAN. |
| Sequence similarities | Belongs to the nucleosome assembly protein (NAP) family. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CSNK2A1 | P68400 | 1 | EBI-1053182,EBI-347804 | |
| DGKE | P52429 | 1 | EBI-1053182,EBI-1057499 | |
| Eef1a1 | P10126 | 1 | EBI-1053182,EBI-773865 | From a different organism. |
| RGS20 | O76081 | 1 | EBI-1053182,EBI-1052678 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | |||||||||
| Isoform 1 (identifier: Q01105-1) Also known as: TAF-I alpha; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | |||||||||
| Isoform 2 (identifier: Q01105-2) Also known as: TAF-I beta; The sequence of this isoform differs from the canonical sequence as follows: 1-37: MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG → MSAPAAKVSKKELNSNHDGADETS | |||||||||
| Notes: Acetylated on Lys-11. Phosphorylated on Ser-15 and Thr-23. | |||||||||
Sequence annotation (Features) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
| Natural variant | 4 | 1 | P → Q: dbSNP rs1141138. | ||||||
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 290 | 290 | Protein SET | PRO_0000185662 | ||||||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||||||
| Compositional bias | 239 – 290 | 52 | Asp/Glu-rich (highly acidic) | |||||||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||||||
| Site | 283 – 284 | 2 | Breakpoint for translocation to form SET-CAN oncogene | |||||||||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||||||||
| Modified residue | 7 | 1 | Phosphoserine | |||||||||||||||||||||||||||||||
| Modified residue | 30 | 1 | Phosphoserine By similarity | |||||||||||||||||||||||||||||||
| Modified residue | 146 | 1 | Phosphotyrosine By similarity | |||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 37 | 37 | MAPKR…LPKKG → MSAPAAKVSKKELNSNHDGA DETS in isoform 2. | VSP_009868 | ||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||
| Helix | 38 – 88 | 51 | ||||||||||||||||||||||||||||||||
| Helix | 94 – 100 | 7 | ||||||||||||||||||||||||||||||||
| Helix | 103 – 106 | 4 | ||||||||||||||||||||||||||||||||
| Helix | 111 – 116 | 6 | ||||||||||||||||||||||||||||||||
| Helix | 117 – 119 | 3 | ||||||||||||||||||||||||||||||||
| Beta strand | 120 – 127 | 8 | ||||||||||||||||||||||||||||||||
| Beta strand | 135 – 141 | 7 | ||||||||||||||||||||||||||||||||
| Beta strand | 145 – 148 | 4 | ||||||||||||||||||||||||||||||||
| Beta strand | 150 – 156 | 7 | ||||||||||||||||||||||||||||||||
| Beta strand | 166 – 168 | 3 | ||||||||||||||||||||||||||||||||
| Helix | 203 – 206 | 4 | ||||||||||||||||||||||||||||||||
| Helix | 215 – 223 | 9 | ||||||||||||||||||||||||||||||||
| Turn | 224 – 227 | 4 | ||||||||||||||||||||||||||||||||
| Helix | 230 – 233 | 4 | ||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene." von Lindern M., van Baal S., Wiegant J., Raap A., Hagemeijer A., Grosveld G. Mol. Cell. Biol. 12:3346-3355(1992) [PubMed: 1630450] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). |
| [2] | "Purification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII." Vaesen M., Barnikol-Watanabe S., Goetz H., Adil Awni L., Cole T., Zimmermann B., Kratzin H.D., Hilschmann N. Biol. Chem. Hoppe-Seyler 375:113-126(1994) [PubMed: 8192856] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE. |
| [3] | "Replication factor encoded by a putative oncogene, set, associated with myeloid leukemogenesis." Nagata K., Kawase H., Handa H., Yano K., Yamasaki M., Ishimi Y., Okuda A., Kikuchi A., Matsumoto K. Proc. Natl. Acad. Sci. U.S.A. 92:4279-4283(1995) [PubMed: 7753797] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 14-35; 40-60; 75-90 AND 155-167, ACTIVATION OF DNA REPLICATION. Tissue: Cervix carcinoma. |
| [4] | "The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A." Li M., Makkinje A., Damuni Z. J. Biol. Chem. 271:11059-11062(1996) [PubMed: 8626647] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Kidney. |
| [5] | "Inhibitors of protein phosphatase-2A from human brain structures, immunocytological localization and activities towards dephosphorylation of the Alzheimer type hyperphosphorylated tau." Tsujio I., Zaidi T., Xu J., Kotula L., Grundke-Iqbal I., Iqbal K. FEBS Lett. 579:363-372(2005) [PubMed: 15642345] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain. |
| [6] | "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). |
| [7] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain. |
| [8] | "DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. Dunham I.Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [9] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis. |
| [10] | "Identification and characterization of SET, a nuclear phosphoprotein encoded by the translocation break point in acute undifferentiated leukemia." Adachi Y., Pavlaki G.N., Copeland T.D. J. Biol. Chem. 269:2258-2262(1994) [PubMed: 8294483] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION. |
| [11] | "A relative factor in human rectum carcinoma." Wang L.C., Chen Y. Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-241 (ISOFORM 2). |
| [12] | "Expression of SET, an inhibitor of protein phosphatase 2A, in renal development and Wilms' tumor." Carlson S.G., Eng E., Kim E.-G., Perlman E.J., Copeland T.D., Ballermann B.J. J. Am. Soc. Nephrol. 9:1873-1880(1998) [PubMed: 9773788] [Abstract] Cited for: EXPRESSION IN THE KIDNEY. |
| [13] | "Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the Set oncoprotein." Seo S.-B., McNamara P., Heo S., Turner A., Lane W.S., Chakravarti D. Cell 104:119-130(2001) [PubMed: 11163245] [Abstract] Cited for: INHIBITION OF HISTONE ACETYLATION. |
| [14] | "Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET." Minakuchi M., Kakazu N., Gorrin-Rivas M.J., Abe T., Copeland T.D., Ueda K., Adachi Y. Eur. J. Biochem. 268:1340-1351(2001) [PubMed: 11231286] [Abstract] Cited for: INTERACTION WITH SETBP1. Tissue: Cervix carcinoma. |
| [15] | "HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A." Fan Z., Beresford P.J., Zhang D., Lieberman J. Mol. Cell. Biol. 22:2810-2820(2002) [PubMed: 11909973] [Abstract] Cited for: INTERACTION WITH HMGB2. |
| [16] | "Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor." Fan Z., Beresford P.J., Oh D.Y., Zhang D., Lieberman J. Cell 112:659-672(2003) [PubMed: 12628186] [Abstract] Cited for: NME1 INHIBITION, SUBCELLULAR LOCATION, DESCRIPTION OF THE SET COMPLEX. |
| [17] | Erratum Fan Z., Beresford P.J., Oh D.Y., Zhang D., Lieberman J. Cell 115:241-241(2003) |
| [18] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7 (ISOFORM 1) AND SER-15 (ISOFORM 2), MASS SPECTROMETRY. Tissue: Epithelium. |
| [19] | "Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-11 (ISOFORM 2), MASS SPECTROMETRY. Tissue: Epithelium. |
| [20] | "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, MASS SPECTROMETRY. Tissue: Epithelium. |
| [21] | "Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-23 (ISOFORM 2), MASS SPECTROMETRY. |
| [22] | "Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, MASS SPECTROMETRY. |
| [23] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M93651 mRNA. Translation: AAA60318.1. X75091 mRNA. Translation: CAA52982.1. D45198 mRNA. Translation: BAA08139.1. U51924 mRNA. Translation: AAC50460.1. AY349172 mRNA. Translation: AAQ79833.1. CR536543 mRNA. Translation: CAG38780.1. CR542050 mRNA. Translation: CAG46847.1. AK223556 mRNA. Translation: BAD97276.1. AL356481 Genomic DNA. Translation: CAH71410.1. BC032749 mRNA. Translation: AAH32749.1. EF534308 mRNA. Translation: ABP96841.1. | |||||||||||||
| PIR | A45018. A57984. I59377. | ||||||||||||
| RefSeq | NP_001116293.1. NP_003002.2. | ||||||||||||
| UniGene | Hs.436687 Hs.596814 | ||||||||||||
3D structure databases | |||||||||||||
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| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | Q01105. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q01105. | ||||||||||||
Proteomic databases | |||||||||||||
| PeptideAtlas | Q01105. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000119335. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 6418. | ||||||||||||
| KEGG | hsa:6418. | ||||||||||||
Organism-specific databases | |||||||||||||
| H-InvDB | HIX0008434. HIX0056875. HIX0057468. | ||||||||||||
| HGNC | HGNC:10760. SET. | ||||||||||||
| HPA | CAB005232. | ||||||||||||
| MIM | 600960. gene. | ||||||||||||
| Orphanet | 98835. Undifferentiated acute leukaemia. | ||||||||||||
| PharmGKB | PA35678. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
| GeneCards | Search... | ||||||||||||

Clusters with