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Protein

Protein SET

Gene

SET

Organism
Homo sapiens (Human)
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.2 Publications

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • histone binding Source: UniProtKB
  • protein phosphatase inhibitor activity Source: ProtInc
  • protein phosphatase regulator activity Source: UniProtKB

GO - Biological processi

  • DNA replication Source: ProtInc
  • negative regulation of histone acetylation Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • nucleosome assembly Source: ProtInc
  • nucleosome disassembly Source: UniProtKB
  • regulation of mRNA stability Source: Reactome
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionChaperone, DNA-binding
Biological processHost-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-2299718 Condensation of Prophase Chromosomes
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA
SIGNORiQ01105

Names & Taxonomyi

Protein namesi
Recommended name:
Protein SET
Alternative name(s):
HLA-DR-associated protein II
Inhibitor of granzyme A-activated DNase
Short name:
IGAAD
PHAPII
Phosphatase 2A inhibitor I2PP2A
Short name:
I-2PP2A
Template-activating factor I
Short name:
TAF-I
Gene namesi
Name:SET
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000119335.16
HGNCiHGNC:10760 SET
MIMi600960 gene
neXtProtiNX_Q01105

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

Involvement in diseasei

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei283 – 284Breakpoint for translocation to form SET-CAN oncogene2

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi6418
OpenTargetsiENSG00000119335
PharmGKBiPA35678

Polymorphism and mutation databases

BioMutaiSET
DMDMi46397790

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001856622 – 290Protein SETAdd BLAST289

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N,N,N-trimethylalanineBy similarity1
Modified residuei7PhosphoserineCombined sources1
Modified residuei28PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1
Modified residuei68N6-acetyllysineBy similarity1
Modified residuei146PhosphotyrosineBy similarity1
Modified residuei150N6-acetyllysineCombined sources1
Cross-linki154Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residuei172N6-acetyllysineCombined sources1
Isoform 2 (identifier: Q01105-2)
Modified residuei11N6-acetyllysineCombined sources1
Modified residuei15PhosphoserineCombined sources1
Modified residuei24PhosphoserineCombined sources1

Post-translational modificationi

Isoform 2 is phosphorylated on Ser-15 and Ser-24.
Isoform 2 is acetylated on Lys-11.
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 (By similarity).By similarity
N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated (By similarity).By similarity
Isoform 2 is cleaved after Lys-176 by GZMA. The cleavage inhibits its nucelosome assembly activity and disrupts the inhibition on NME1.3 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ01105
PaxDbiQ01105
PeptideAtlasiQ01105
PRIDEiQ01105
TopDownProteomicsiQ01105-1 [Q01105-1]
Q01105-2 [Q01105-2]

PTM databases

iPTMnetiQ01105
PhosphoSitePlusiQ01105
SwissPalmiQ01105

Expressioni

Tissue specificityi

Widely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor.

Gene expression databases

BgeeiENSG00000119335
CleanExiHS_SET
ExpressionAtlasiQ01105 baseline and differential
GenevisibleiQ01105 HS

Organism-specific databases

HPAiCAB005232
HPA063683

Interactioni

Subunit structurei

Headphone-shaped homodimer. Isoforms 1 and 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, 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. Interacts with herpes simplex virus 1 VP22.9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112316, 130 interactors
CORUMiQ01105
DIPiDIP-33561N
IntActiQ01105, 101 interactors
MINTiQ01105
STRINGi9606.ENSP00000361777

Structurei

Secondary structure

1290
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi37 – 88Combined sources52
Helixi94 – 100Combined sources7
Helixi103 – 106Combined sources4
Helixi111 – 116Combined sources6
Helixi117 – 119Combined sources3
Beta strandi120 – 127Combined sources8
Beta strandi135 – 141Combined sources7
Beta strandi145 – 148Combined sources4
Beta strandi150 – 156Combined sources7
Beta strandi166 – 168Combined sources3
Helixi203 – 206Combined sources4
Helixi215 – 223Combined sources9
Turni224 – 227Combined sources4
Helixi230 – 233Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2E50X-ray2.30A/B/P/Q38-238[»]
ProteinModelPortaliQ01105
SMRiQ01105
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ01105

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni31 – 78DimerizationAdd BLAST48
Regioni79 – 225Earmuff domainAdd BLAST147

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi239 – 290Asp/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.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1508 Eukaryota
ENOG410XQRX LUCA
GeneTreeiENSGT00530000062882
HOGENOMiHOG000232096
HOVERGENiHBG014779
InParanoidiQ01105
KOiK11290
OMAiPVALMNH
OrthoDBiEOG091G00YT
PhylomeDBiQ01105
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 (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q01105-1) [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
MAPKRQSPLP PQKKKPRPPP ALGPEETSAS AGLPKKGEKE QQEAIEHIDE
60 70 80 90 100
VQNEIDRLNE QASEEILKVE QKYNKLRQPF FQKRSELIAK IPNFWVTTFV
110 120 130 140 150
NHPQVSALLG EEDEEALHYL TRVEVTEFED IKSGYRIDFY FDENPYFENK
160 170 180 190 200
VLSKEFHLNE SGDPSSKSTE IKWKSGKDLT KRSSQTQNKA SRKRQHEEPE
210 220 230 240 250
SFFTWFTDHS DAGADELGEV IKDDIWPNPL QYYLVPDMDD EEGEGEEDDD
260 270 280 290
DDEEEEGLED IDEEGDEDEG EEDEDDDEGE EGEEDEGEDD
Length:290
Mass (Da):33,489
Last modified:April 13, 2004 - v3
Checksum:iF4664118171EF230
GO
Isoform 2 (identifier: Q01105-2) [UniParc]FASTAAdd to basket
Also known as: TAF-I beta

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG → MSAPAAKVSKKELNSNHDGADETS

Show »
Length:277
Mass (Da):32,103
Checksum:i52A6F516686010CE
GO
Isoform 3 (identifier: Q01105-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG → MPRSHQPPPPPH

Show »
Length:265
Mass (Da):30,993
Checksum:iA9B69B63736E06F4
GO
Isoform 4 (identifier: Q01105-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKG → MGCRDLLPSLKPTLL

Note: Gene prediction based on EST data.
Show »
Length:268
Mass (Da):31,272
Checksum:i6A34101DDEDA4B02
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078653233 – 290Missing Probable disease-associated mutation found in a patient with congenital microcephaly and moderate intellecutal disability. 1 PublicationAdd BLAST58
Isoform 2 (identifier: Q01105-2)
Natural varianti4P → QCombined sourcesCorresponds to variant dbSNP:rs1141138Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0098681 – 37MAPKR…LPKKG → MSAPAAKVSKKELNSNHDGA DETS in isoform 2. 9 PublicationsAdd BLAST37
Alternative sequenceiVSP_0451751 – 37MAPKR…LPKKG → MPRSHQPPPPPH in isoform 3. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_0467411 – 37MAPKR…LPKKG → MGCRDLLPSLKPTLL in isoform 4. CuratedAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AK300609 mRNA Translation: BAG62304.1
AL356481 Genomic DNA No translation available.
AL359678 Genomic DNA No translation available.
BC032749 mRNA Translation: AAH32749.1
EF534308 mRNA Translation: ABP96841.1
CCDSiCCDS48037.1 [Q01105-1]
CCDS59149.1 [Q01105-4]
CCDS6907.1 [Q01105-2]
PIRiA57984 A45018
I59377
RefSeqiNP_001116293.1, NM_001122821.1 [Q01105-1]
NP_001234929.1, NM_001248000.1 [Q01105-4]
NP_001234930.1, NM_001248001.1
NP_003002.2, NM_003011.3 [Q01105-2]
UniGeneiHs.436687

Genome annotation databases

EnsembliENST00000322030; ENSP00000318012; ENSG00000119335 [Q01105-2]
ENST00000372686; ENSP00000361771; ENSG00000119335 [Q01105-3]
ENST00000372692; ENSP00000361777; ENSG00000119335 [Q01105-1]
ENST00000409104; ENSP00000387321; ENSG00000119335 [Q01105-4]
GeneIDi6418
KEGGihsa:6418
UCSCiuc004bvu.5 human [Q01105-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSET_HUMAN
AccessioniPrimary (citable) accession number: Q01105
Secondary accession number(s): A5A5H4
, A6NGV1, B4DUE2, Q15541, Q5VXV1, Q5VXV2, Q6FHZ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 13, 2004
Last modified: May 23, 2018
This is version 191 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

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