SET_RAT
ID SET_RAT Reviewed; 289 AA.
AC Q63945; Q7TPA3;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1999, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Protein SET;
DE AltName: Full=Liver regeneration-related protein LRRGR00002;
DE AltName: Full=Phosphatase 2A inhibitor I2PP2A;
DE Short=I-2PP2A;
DE AltName: Full=Template-activating factor I;
DE Short=TAF-I;
GN Name=Set; ORFNames=Ab1-115;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney;
RX PubMed=7508204; DOI=10.1152/ajprenal.1994.266.1.f155;
RA Kim E.-G., Choi M.E., Ballermann B.J.;
RT "Spatially restricted expression of set mRNA in developing rat kidney.";
RL Am. J. Physiol. 266:F155-F161(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Xu C.S., Li W.Q., Li Y.C., Ma H., Wang L., Wang S.F., Han H.P., Wang G.P.,
RA Chai L.Q., Yuan J.Y., Yang K.J., Yan H.M., Chang C.F., Zhao L.F., Shi J.B.,
RA Rahman S., Wang Q.N., Zhang J.B.;
RT "Liver regeneration after PH.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=11078917; DOI=10.1016/s0304-3835(00)00598-x;
RA Fukukawa C., Shima H., Tamura N., Ogawa K., Kikuchi K.;
RT "Up-regulation of I-2PP2A/SET gene expression in rat primary hepatomas and
RT regenerating livers.";
RL Cancer Lett. 161:89-95(2000).
CC -!- FUNCTION: Multitasking protein, involved in apoptosis, transcription,
CC nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic
CC activity is mediated by inhibition of the GZMA-activated DNase, NME1.
CC In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA
CC cleaves SET, disrupting its binding to NME1 and releasing NME1
CC inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein
CC phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-
CC mediated acetylation of histones (HAT) and nucleosomes, most probably
CC by masking the accessibility of lysines of histones to the acetylases.
CC The predominant target for inhibition is histone H4. HAT inhibition
CC leads to silencing of HAT-dependent transcription and prevents active
CC demethylation of DNA. Both isoforms stimulate DNA replication of the
CC adenovirus genome complexed with viral core proteins; however, isoform
CC 2 specific activity is higher (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Headphone-shaped homodimer. Isoform 1 and isoform 2 interact
CC directly with each other and with ANP32A within the tripartite INHAT
CC (inhibitor of acetyltransferases) complex. Isoform 1 and isoform 2
CC interact also with histones. Isoform 2 is a omponent of the SET
CC complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and
CC TREX1, but not NME2 or TREX2. Within this complex, directly interacts
CC with ANP32A, NME1, HMGB2 and TREX1; the interaction with ANP32A is
CC enhanced after cleavage. Interacts with APBB1, CHTOP, SETBP1, SGO1 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Endoplasmic
CC reticulum {ECO:0000250}. Nucleus, nucleoplasm {ECO:0000250}. Note=In
CC the cytoplasm, found both in the cytosol and associated with the
CC endoplasmic reticulum. The SET complex is associated with the
CC endoplasmic reticulum. Following CTL attack and cleavage by GZMA, moves
CC rapidly to the nucleus, where it is found in the nucleoplasm, avoiding
CC the nucleolus. Similar translocation to the nucleus is also observed
CC for lymphocyte-activated killer cells after the addition of calcium (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=TAF-I alpha;
CC IsoId=Q63945-1; Sequence=Displayed;
CC Name=2; Synonyms=TAF-I beta;
CC IsoId=Q63945-2; Sequence=VSP_050443;
CC -!- TISSUE SPECIFICITY: Widely expressed, with higher expression in brain,
CC thymus, spleen and bone marrow, and lower expression in heart, liver
CC and muscle. {ECO:0000269|PubMed:11078917}.
CC -!- DEVELOPMENTAL STAGE: Higher expression in neonatal kidney than in
CC adult. In the neonatal kidney, expressed more strongly in primitive
CC nephrons undergoing early morphogenesis than in more developed
CC structures. In 1-day old rat kidney, restricted to the first
CC recognizable primitive nephron structures. Up-regulated after partial
CC hepatectomy, with a peak after 24 hours.
CC -!- DOMAIN: A long alpha helix in the N-terminus mediates dimerization,
CC while the earmuff domain is responsible for core histone and dsDNA
CC binding. The C-terminal acidic domain mediates the inhibition of
CC histone acetyltransferases and is required for the DNA replication
CC stimulatory activity (By similarity). {ECO:0000250}.
CC -!- PTM: Isoform 2 is phosphorylated on Ser-15 and Ser-24. {ECO:0000250}.
CC -!- PTM: Isoform 2 is acetylated on Lys-11. {ECO:0000250}.
CC -!- PTM: Some glutamate residues are glycylated by TTLL8. This modification
CC occurs exclusively on glutamate residues and results in a glycine chain
CC on the gamma-carboxyl group (By similarity). {ECO:0000250}.
CC -!- PTM: N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly
CC trimethylated (By similarity). {ECO:0000250}.
CC -!- PTM: [Isoform 2]: Cleaved after Lys-176 by GZMA. The cleavage inhibits
CC its nucleosome assembly activity and disrupts the inhibition on NME1
CC (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nucleosome assembly protein (NAP) family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; S68589; AAC60681.1; -; mRNA.
DR EMBL; S68987; AAC60682.1; -; mRNA.
DR EMBL; AY325137; AAP92538.1; -; mRNA.
DR RefSeq; NP_001012522.1; NM_001012504.1.
DR AlphaFoldDB; Q63945; -.
DR SMR; Q63945; -.
DR BioGRID; 258860; 2.
DR IntAct; Q63945; 3.
DR MINT; Q63945; -.
DR STRING; 10116.ENSRNOP00000039454; -.
DR iPTMnet; Q63945; -.
DR PhosphoSitePlus; Q63945; -.
DR jPOST; Q63945; -.
DR PaxDb; Q63945; -.
DR PRIDE; Q63945; -.
DR Ensembl; ENSRNOT00000102290; ENSRNOP00000077721; ENSRNOG00000025892. [Q63945-2]
DR GeneID; 307947; -.
DR KEGG; rno:307947; -.
DR UCSC; RGD:1307467; rat. [Q63945-1]
DR CTD; 646817; -.
DR RGD; 1307467; Set.
DR VEuPathDB; HostDB:ENSRNOG00000025892; -.
DR eggNOG; KOG1508; Eukaryota.
DR GeneTree; ENSGT00940000161818; -.
DR HOGENOM; CLU_051687_4_0_1; -.
DR InParanoid; Q63945; -.
DR OMA; WPVALMN; -.
DR OrthoDB; 1191764at2759; -.
DR PhylomeDB; Q63945; -.
DR TreeFam; TF313386; -.
DR Reactome; R-RNO-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-RNO-450520; HuR (ELAVL1) binds and stabilizes mRNA.
DR PRO; PR:Q63945; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000025892; Expressed in ovary and 19 other tissues.
DR ExpressionAtlas; Q63945; baseline and differential.
DR Genevisible; Q63945; RN.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0045446; P:endothelial cell differentiation; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006334; P:nucleosome assembly; IEA:InterPro.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR InterPro; IPR037231; NAP-like_sf.
DR InterPro; IPR002164; NAP_family.
DR PANTHER; PTHR11875; PTHR11875; 1.
DR Pfam; PF00956; NAP; 1.
DR SUPFAM; SSF143113; SSF143113; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Alternative splicing; Chaperone; Cytoplasm; DNA-binding;
KW Endoplasmic reticulum; Isopeptide bond; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9EQU5"
FT CHAIN 2..289
FT /note="Protein SET"
FT /id="PRO_0000185664"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 31..77
FT /note="Dimerization"
FT /evidence="ECO:0000250"
FT REGION 78..224
FT /note="Earmuff domain"
FT /evidence="ECO:0000250"
FT REGION 157..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..203
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..289
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N,N,N-trimethylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQU5"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01105"
FT MOD_RES 23
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQU5"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01105"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01105"
FT MOD_RES 67
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQU5"
FT MOD_RES 145
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQU5"
FT MOD_RES 149
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01105"
FT MOD_RES 171
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01105"
FT CROSSLNK 153
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q01105"
FT VAR_SEQ 1..36
FT /note="MAPKRQSAILPQPKKPRPVAAPKLEDKSASPGLPKG -> MSAPTAKASKKE
FT LNSNHDGADETS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7508204"
FT /id="VSP_050443"
FT CONFLICT 88
FT /note="A -> T (in Ref. 2; AAP92538)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="R -> C (in Ref. 2; AAP92538)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="D -> N (in Ref. 2; AAP92538)"
FT /evidence="ECO:0000305"
FT MOD_RES Q63945-2:11
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000305"
FT MOD_RES Q63945-2:15
FT /note="Phosphoserine"
FT /evidence="ECO:0000305"
FT MOD_RES Q63945-2:24
FT /note="Phosphoserine"
FT /evidence="ECO:0000305"
SQ SEQUENCE 289 AA; 33406 MW; E6EDD9DC4F1074E3 CRC64;
MAPKRQSAIL PQPKKPRPVA APKLEDKSAS PGLPKGEKEQ QEAIEHIDEV QNEIDRLNEQ
ASEEILKVEQ KYNKLRQPFF QKRSELIAKI PNFWVTTFVN HPQVSALLGE EDEEALHYLT
RVEVTEFEDI KSGYRIDFYF DENPYFENKV LSKEFHLNES GDPSSKSTEI KWKSGKDLTK
RSSQTQNKAS RKRQHEEPES FFTWFTDHSD AGADELGEVI KDDIWPNPLQ YYLVPDMDDE
EGEAEDDDDD DEEEEGLEDI DEEGDEDEGE EDDDEDEGEE GEEDEGEDD
