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Protein

Protein SET

Gene

Set

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. 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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protein SET
Alternative name(s):
Phosphatase 2A inhibitor I2PP2A
Short name:
I-2PP2A
Template-activating factor I
Short name:
TAF-I
Gene namesi
Name:Set
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1860267. Set.

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Endoplasmic reticulum By similarity
  • Nucleusnucleoplasm By similarity

  • Note: In the cytoplasm, found both in the cytosol and associated with the endoplasmic reticulum. The SET complex is associated with the endoplasmic reticulum. Following CTL attack and cleavage by GZMA, 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 (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi4 – 41K → Q: Almost abolishes N-terminal methylation at A-2. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 289288Protein SETPRO_0000185663Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N,N,N-trimethylalanine; by NTM11 Publication
Modified residuei7 – 71PhosphoserineBy similarity
Modified residuei23 – 231N6-acetyllysineCombined sources
Modified residuei67 – 671N6-acetyllysineCombined sources
Modified residuei145 – 1451PhosphotyrosineCombined sources
Modified residuei149 – 1491N6-acetyllysineBy similarity
Cross-linki153 – 153Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei171 – 1711N6-acetyllysineBy similarity
Isoform 2 (identifier: Q9EQU5-2)
Modified residuei11 – 111N6-acetyllysineBy similarity
Modified residuei15 – 151PhosphoserineBy similarity
Modified residuei23 – 231PhosphothreonineBy similarity

Post-translational modificationi

Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group.
N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated.1 Publication
Isoform 2 is cleaved after Lys-176 by GZMA. The cleavage inhibits its nucelosome assembly activity and disrupts the inhibition on NME1 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9EQU5.
MaxQBiQ9EQU5.
PaxDbiQ9EQU5.
PRIDEiQ9EQU5.

PTM databases

iPTMnetiQ9EQU5.
PhosphoSiteiQ9EQU5.

Expressioni

Gene expression databases

BgeeiQ9EQU5.
CleanExiMM_SET.
ExpressionAtlasiQ9EQU5. baseline and differential.
GenevisibleiQ9EQU5. MM.

Interactioni

Subunit structurei

Headphone-shaped homodimer. 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 omponent of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1, but not NME2 or TREX2. Within this complex, directly interacts with ANP32A, NME1, HMGB2 and TREX1; the interaction with ANP32A is enhanced after cleavage. Interacts with APBB1, CHTOP, SETBP1, SGOL1.1 Publication

Protein-protein interaction databases

BioGridi207808. 101 interactions.
IntActiQ9EQU5. 69 interactions.
MINTiMINT-1854783.
STRINGi10090.ENSMUSP00000099930.

Structurei

3D structure databases

ProteinModelPortaliQ9EQU5.
SMRiQ9EQU5. Positions 37-235.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni31 – 7747DimerizationBy similarityAdd
BLAST
Regioni78 – 224147Earmuff domainBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi226 – 27752Asp/Glu-rich (highly acidic)Add
BLAST

Domaini

A long alpha helix in the N-terminus mediates dimerization, while the earmuff domain is responsible for core histone and dsDNA binding. The C-terminal acidic domain mediates the inhibition of histone acetyltransferases and is required for the DNA replication stimulatory activity (By similarity).By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1508. Eukaryota.
ENOG410XQRX. LUCA.
GeneTreeiENSGT00530000062882.
HOGENOMiHOG000232096.
HOVERGENiHBG014779.
InParanoidiQ9EQU5.
KOiK11290.
OMAiVSEPVNI.
PhylomeDBiQ9EQU5.
TreeFamiTF313386.

Family and domain databases

InterProiIPR002164. NAP_family.
[Graphical view]
PANTHERiPTHR11875. PTHR11875. 1 hit.
PfamiPF00956. NAP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9EQU5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAPKRQSAIL PQPKKPRPAA APKLEDKSAS PGLPKGEKEQ QEAIEHIDEV
60 70 80 90 100
QNEIDRLNEQ ASEEILKVEQ KYNKLRQPFF QKRSELIAKI PNFWVTTFVN
110 120 130 140 150
HPQVSALLGE EDEEALHYLT RVEVTEFEDI KSGYRIDFYF DENPYFENKV
160 170 180 190 200
LSKEFHLNES GDPSSKSTEI KWKSGKDLTK RSSQTQNKAS RKRQHEEPES
210 220 230 240 250
FFTWFTDHSD AGADELGEVI KDDIWPNPLQ YYLVPDMDDE EGEAEDDDDD
260 270 280
DEEEEGLEDI DEEGDEDEGE EDDDEDEGEE GEEDEGEDD
Length:289
Mass (Da):33,378
Last modified:March 1, 2001 - v1
Checksum:iB8FDD71A78107019
GO
Isoform 2 (identifier: Q9EQU5-2) [UniParc]FASTAAdd to basket

Also known as: TAF-I beta

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MAPKRQSAILPQPKKPRPAAAPKLEDKSASPGLPKG → MSAPTAKASKKELNSNHDGADETS

Show »
Length:277
Mass (Da):32,105
Checksum:i1CE428503676EC72
GO
Isoform 3 (identifier: Q9EQU5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     83-146: RSELIAKIPN...DFYFDENPYF → STTWFPTWMM...TKARMISTED
     147-289: Missing.

Show »
Length:146
Mass (Da):17,461
Checksum:i4CB164D648435078
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti91 – 911P → L in BAA34736 (PubMed:11231286).Curated
Sequence conflicti184 – 1841Q → L in BAA34736 (PubMed:11231286).Curated
Sequence conflicti207 – 2071D → A in BAA34736 (PubMed:11231286).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3636MAPKR…GLPKG → MSAPTAKASKKELNSNHDGA DETS in isoform 2. 2 PublicationsVSP_009869Add
BLAST
Alternative sequencei83 – 14664RSELI…ENPYF → STTWFPTWMMKKERQKMMMT TTKRRRGWKILMKKEMRMKV KKMTMRMKGRKERRTKARMI STED in isoform 3. 1 PublicationVSP_009870Add
BLAST
Alternative sequencei147 – 289143Missing in isoform 3. 1 PublicationVSP_009871Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044937 mRNA. Translation: BAB20793.1.
AK011630 mRNA. Translation: BAB27745.1.
AK019960 mRNA. Translation: BAB31936.1.
BX005298 Genomic DNA. Translation: CAM18951.1.
BC018255 mRNA. Translation: AAH18255.1.
AB015613 mRNA. Translation: BAA34736.1.
CCDSiCCDS15866.1. [Q9EQU5-1]
CCDS57162.1. [Q9EQU5-2]
RefSeqiNP_001191804.1. NM_001204875.1. [Q9EQU5-2]
NP_076360.1. NM_023871.4. [Q9EQU5-1]
UniGeneiMm.326055.
Mm.335942.

Genome annotation databases

EnsembliENSMUST00000067996; ENSMUSP00000070002; ENSMUSG00000054766. [Q9EQU5-2]
ENSMUST00000102866; ENSMUSP00000099930; ENSMUSG00000054766. [Q9EQU5-1]
GeneIDi56086.
KEGGimmu:56086.
UCSCiuc008jaw.2. mouse. [Q9EQU5-1]
uc008jax.2. mouse. [Q9EQU5-3]
uc008jay.2. mouse. [Q9EQU5-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044937 mRNA. Translation: BAB20793.1.
AK011630 mRNA. Translation: BAB27745.1.
AK019960 mRNA. Translation: BAB31936.1.
BX005298 Genomic DNA. Translation: CAM18951.1.
BC018255 mRNA. Translation: AAH18255.1.
AB015613 mRNA. Translation: BAA34736.1.
CCDSiCCDS15866.1. [Q9EQU5-1]
CCDS57162.1. [Q9EQU5-2]
RefSeqiNP_001191804.1. NM_001204875.1. [Q9EQU5-2]
NP_076360.1. NM_023871.4. [Q9EQU5-1]
UniGeneiMm.326055.
Mm.335942.

3D structure databases

ProteinModelPortaliQ9EQU5.
SMRiQ9EQU5. Positions 37-235.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207808. 101 interactions.
IntActiQ9EQU5. 69 interactions.
MINTiMINT-1854783.
STRINGi10090.ENSMUSP00000099930.

PTM databases

iPTMnetiQ9EQU5.
PhosphoSiteiQ9EQU5.

Proteomic databases

EPDiQ9EQU5.
MaxQBiQ9EQU5.
PaxDbiQ9EQU5.
PRIDEiQ9EQU5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000067996; ENSMUSP00000070002; ENSMUSG00000054766. [Q9EQU5-2]
ENSMUST00000102866; ENSMUSP00000099930; ENSMUSG00000054766. [Q9EQU5-1]
GeneIDi56086.
KEGGimmu:56086.
UCSCiuc008jaw.2. mouse. [Q9EQU5-1]
uc008jax.2. mouse. [Q9EQU5-3]
uc008jay.2. mouse. [Q9EQU5-2]

Organism-specific databases

CTDi6418.
MGIiMGI:1860267. Set.

Phylogenomic databases

eggNOGiKOG1508. Eukaryota.
ENOG410XQRX. LUCA.
GeneTreeiENSGT00530000062882.
HOGENOMiHOG000232096.
HOVERGENiHBG014779.
InParanoidiQ9EQU5.
KOiK11290.
OMAiVSEPVNI.
PhylomeDBiQ9EQU5.
TreeFamiTF313386.

Miscellaneous databases

PROiQ9EQU5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9EQU5.
CleanExiMM_SET.
ExpressionAtlasiQ9EQU5. baseline and differential.
GenevisibleiQ9EQU5. MM.

Family and domain databases

InterProiIPR002164. NAP_family.
[Graphical view]
PANTHERiPTHR11875. PTHR11875. 1 hit.
PfamiPF00956. NAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Up-regulation of I-2PP2A/SET gene expression in rat primary hepatomas and regenerating livers."
    Fukukawa C., Shima H., Tamura N., Ogawa K., Kikuchi K.
    Cancer Lett. 161:89-95(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: C57BL/6 X DBA/2.
    Tissue: Blastocyst.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
    Strain: C57BL/6J.
    Tissue: Embryo.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: Czech II.
    Tissue: Mammary tumor.
  5. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-222 (ISOFORM 2).
    Tissue: Embryo.
  6. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
    Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
    J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-145, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Mast cell.
  7. "Evolutionary divergence of enzymatic mechanisms for posttranslational polyglycylation."
    Rogowski K., Juge F., van Dijk J., Wloga D., Strub J.-M., Levilliers N., Thomas D., Bre M.-H., Van Dorsselaer A., Gaertig J., Janke C.
    Cell 137:1076-1087(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCYLATION.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  9. "NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein."
    Tooley C.E., Petkowski J.J., Muratore-Schroeder T.L., Balsbaugh J.L., Shabanowitz J., Sabat M., Minor W., Hunt D.F., Macara I.G.
    Nature 466:1125-1128(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE OF INITIATOR METHIONINE, METHYLATION AT ALA-2, MUTAGENESIS OF LYS-4.
  10. "Five friends of methylated chromatin target of protein-arginine-methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation to desumoylation."
    Fanis P., Gillemans N., Aghajanirefah A., Pourfarzad F., Demmers J., Esteghamat F., Vadlamudi R.K., Grosveld F., Philipsen S., van Dijk T.B.
    Mol. Cell. Proteomics 11:1263-1273(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CHTOP.
  11. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-23 AND LYS-67, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.

Entry informationi

Entry nameiSET_MOUSE
AccessioniPrimary (citable) accession number: Q9EQU5
Secondary accession number(s): A2BE95
, Q9CY82, Q9D0A9, Q9Z181
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: March 1, 2001
Last modified: June 8, 2016
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.