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Protein

Protein SET

Gene

Set

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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):
Liver regeneration-related protein LRRGR00002
Phosphatase 2A inhibitor I2PP2A
Short name:
I-2PP2A
Template-activating factor I
Short name:
TAF-I
Gene namesi
Name:Set
ORF Names:Ab1-115
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi1307467. 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 289288Protein SETPRO_0000185664Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N,N,N-trimethylalanineBy similarity
Modified residuei7 – 71PhosphoserineBy similarity
Modified residuei23 – 231N6-acetyllysineBy similarity
Modified residuei28 – 281PhosphoserineBy similarity
Modified residuei62 – 621PhosphoserineBy similarity
Modified residuei67 – 671N6-acetyllysineBy similarity
Modified residuei145 – 1451PhosphotyrosineBy similarity
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: Q63945-2)
Modified residuei11 – 111N6-acetyllysineBy similarity
Modified residuei15 – 151PhosphoserineBy similarity
Modified residuei23 – 231PhosphothreonineBy similarity

Post-translational modificationi

Isoform 2 is phosphorylated on Ser-15 and Thr-23.By similarity
Isoform 2 is acetylated on Lys-11.By similarity
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 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ63945.
PRIDEiQ63945.

PTM databases

iPTMnetiQ63945.
PhosphoSiteiQ63945.

Expressioni

Tissue specificityi

Widely expressed, with higher expression in brain, thymus, spleen and bone marrow, and lower expression in heart, liver and muscle.1 Publication

Developmental stagei

Higher expression in neonatal kidney than in adult. In the neonatal kidney, expressed more strongly in primitive nephrons undergoing early morphogenesis than in more developed structures. In 1-day old rat kidney, restricted to the first recognizable primitive nephron structures. Up-regulated after partial hepatectomy, with a peak after 24 hours.

Gene expression databases

BgeeiENSRNOG00000034241.
ExpressionAtlasiQ63945. baseline.
GenevisibleiQ63945. RN.

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 (By similarity).By similarity

Protein-protein interaction databases

BioGridi258860. 1 interaction.
IntActiQ63945. 2 interactions.
STRINGi10116.ENSRNOP00000039454.

Structurei

3D structure databases

ProteinModelPortaliQ63945.
SMRiQ63945. 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 biasi238 – 28952Asp/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.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000232096.
HOVERGENiHBG014779.
InParanoidiQ63945.
KOiK11290.
OMAiVSEPVNI.
PhylomeDBiQ63945.
TreeFamiTF313386.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q63945-1) [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 PQPKKPRPVA 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):33,406
Last modified:January 1, 1999 - v2
Checksum:iE6EDD9DC4F1074E3
GO
Isoform 2 (identifier: Q63945-2) [UniParc]FASTAAdd to basket
Also known as: TAF-I beta

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

Show »
Length:277
Mass (Da):32,105
Checksum:i1CE428503676EC72
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti88 – 881A → T in AAP92538 (Ref. 2) Curated
Sequence conflicti181 – 1811R → C in AAP92538 (Ref. 2) Curated
Sequence conflicti273 – 2731D → N in AAP92538 (Ref. 2) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3636MAPKR…GLPKG → MSAPTAKASKKELNSNHDGA DETS in isoform 2. 1 PublicationVSP_050443Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68589 mRNA. Translation: AAC60681.1.
S68987 mRNA. Translation: AAC60682.1.
AY325137 mRNA. Translation: AAP92538.1.
RefSeqiNP_001012522.1. NM_001012504.1.
UniGeneiRn.76937.

Genome annotation databases

EnsembliENSRNOT00000081787; ENSRNOP00000070331; ENSRNOG00000025892. [Q63945-1]
GeneIDi307947.
KEGGirno:307947.
UCSCiRGD:1307467. rat. [Q63945-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68589 mRNA. Translation: AAC60681.1.
S68987 mRNA. Translation: AAC60682.1.
AY325137 mRNA. Translation: AAP92538.1.
RefSeqiNP_001012522.1. NM_001012504.1.
UniGeneiRn.76937.

3D structure databases

ProteinModelPortaliQ63945.
SMRiQ63945. Positions 37-235.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi258860. 1 interaction.
IntActiQ63945. 2 interactions.
STRINGi10116.ENSRNOP00000039454.

PTM databases

iPTMnetiQ63945.
PhosphoSiteiQ63945.

Proteomic databases

PaxDbiQ63945.
PRIDEiQ63945.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000081787; ENSRNOP00000070331; ENSRNOG00000025892. [Q63945-1]
GeneIDi307947.
KEGGirno:307947.
UCSCiRGD:1307467. rat. [Q63945-1]

Organism-specific databases

CTDi6418.
RGDi1307467. Set.

Phylogenomic databases

eggNOGiKOG1508. Eukaryota.
ENOG410XQRX. LUCA.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000232096.
HOVERGENiHBG014779.
InParanoidiQ63945.
KOiK11290.
OMAiVSEPVNI.
PhylomeDBiQ63945.
TreeFamiTF313386.

Miscellaneous databases

PROiQ63945.

Gene expression databases

BgeeiENSRNOG00000034241.
ExpressionAtlasiQ63945. baseline.
GenevisibleiQ63945. RN.

Family and domain databases

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

Entry informationi

Entry nameiSET_RAT
AccessioniPrimary (citable) accession number: Q63945
Secondary accession number(s): Q7TPA3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: January 1, 1999
Last modified: September 7, 2016
This is version 119 of the entry and version 2 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. 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.