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Protein

Protein SET

Gene

Set

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionChaperone, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1860267 Set

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi4K → Q: Almost abolishes N-terminal methylation at A-2. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001856632 – 289Protein SETAdd BLAST288

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N,N,N-trimethylalanine; by NTM11 Publication1
Modified residuei7PhosphoserineBy similarity1
Modified residuei23N6-acetyllysineCombined sources1
Modified residuei28PhosphoserineBy similarity1
Modified residuei62PhosphoserineBy similarity1
Modified residuei67N6-acetyllysineCombined sources1
Modified residuei145PhosphotyrosineCombined sources1
Modified residuei149N6-acetyllysineBy similarity1
Cross-linki153Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei171N6-acetyllysineBy similarity1
Isoform 2 (identifier: Q9EQU5-2)
Modified residuei11N6-acetyllysineBy similarity1
Modified residuei15PhosphoserineBy similarity1
Modified residuei23PhosphothreonineBy similarity1

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
PaxDbiQ9EQU5
PeptideAtlasiQ9EQU5
PRIDEiQ9EQU5

PTM databases

iPTMnetiQ9EQU5
PhosphoSitePlusiQ9EQU5

Expressioni

Gene expression databases

BgeeiENSMUSG00000054766
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, SGO1.1 Publication

Protein-protein interaction databases

BioGridi207808, 101 interactors
IntActiQ9EQU5, 69 interactors
MINTiQ9EQU5
STRINGi10090.ENSMUSP00000099930

Structurei

3D structure databases

ProteinModelPortaliQ9EQU5
SMRiQ9EQU5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni31 – 77DimerizationBy similarityAdd BLAST47
Regioni78 – 224Earmuff domainBy similarityAdd BLAST147

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi226 – 277Asp/Glu-rich (highly acidic)Add BLAST52

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
OMAiPVALMNH
OrthoDBiEOG091G00YT
PhylomeDBiQ9EQU5
TreeFamiTF313386

Family and domain databases

InterProiView protein in InterPro
IPR037231 NAP-like_sf
IPR002164 NAP_family
PANTHERiPTHR11875 PTHR11875, 1 hit
PfamiView protein in Pfam
PF00956 NAP, 1 hit
SUPFAMiSSF143113 SSF143113, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti91P → L in BAA34736 (PubMed:11231286).Curated1
Sequence conflicti184Q → L in BAA34736 (PubMed:11231286).Curated1
Sequence conflicti207D → A in BAA34736 (PubMed:11231286).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0098691 – 36MAPKR…GLPKG → MSAPTAKASKKELNSNHDGA DETS in isoform 2. 2 PublicationsAdd BLAST36
Alternative sequenceiVSP_00987083 – 146RSELI…ENPYF → STTWFPTWMMKKERQKMMMT TTKRRRGWKILMKKEMRMKV KKMTMRMKGRKERRTKARMI STED in isoform 3. 1 PublicationAdd BLAST64
Alternative sequenceiVSP_009871147 – 289Missing in isoform 3. 1 PublicationAdd BLAST143

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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiSET_MOUSE
AccessioniPrimary (citable) accession number: Q9EQU5
Secondary accession number(s): A2BE95
, Q9CY82, Q9D0A9, Q9Z181
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: March 1, 2001
Last modified: May 23, 2018
This is version 139 of the entry and version 1 of the sequence. See 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

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