SAP18_MOUSE
ID SAP18_MOUSE Reviewed; 153 AA.
AC O55128; Q545L4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Histone deacetylase complex subunit SAP18;
DE AltName: Full=18 kDa Sin3-associated polypeptide;
DE AltName: Full=Sin3-associated polypeptide p18;
GN Name=Sap18;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RX PubMed=9511770; DOI=10.1016/s0378-1119(97)00648-3;
RA Boehmelt G., Antonio L., Iscove N.N.;
RT "Cloning of the murine transcriptional corepressor component SAP18 and
RT differential expression of its mRNA in the hematopoietic hierarchy.";
RL Gene 207:267-275(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Heart, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF THE ASAP COMPLEX, X-RAY
RP CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-143, FUNCTION OF THE ASAP COMPLEX,
RP IDENTIFICATION IN THE PSAP COMPLEX, FUNCTION OF THE PSAP COMPLEX,
RP INTERACTION WITH RNPS1, ACIN1 AND PNN, AND MUTAGENESIS OF CYS-26.
RX PubMed=22388736; DOI=10.1038/nsmb.2242;
RA Murachelli A.G., Ebert J., Basquin C., Le Hir H., Conti E.;
RT "The structure of the ASAP core complex reveals the existence of a Pinin-
RT containing PSAP complex.";
RL Nat. Struct. Mol. Biol. 19:378-386(2012).
CC -!- FUNCTION: Component of the SIN3-repressing complex. Enhances the
CC ability of SIN3-HDAC1-mediated transcriptional repression. When
CC tethered to the promoter, it can direct the formation of a repressive
CC complex to core histone proteins. Auxiliary component of the splicing-
CC dependent multiprotein exon junction complex (EJC) deposited at splice
CC junction on mRNAs. The EJC is a dynamic structure consisting of core
CC proteins and several peripheral nuclear and cytoplasmic associated
CC factors that join the complex only transiently either during EJC
CC assembly or during subsequent mRNA metabolism. Component of the ASAP
CC and PSAP complexes which bind RNA in a sequence-independent manner and
CC are proposed to be recruited to the EJC prior to or during the splicing
CC process and to regulate specific excision of introns in specific
CC transcription subsets. The ASAP complex can inhibit mRNA processing
CC during in vitro splicing reactions. The ASAP complex promotes apoptosis
CC and is disassembled after induction of apoptosis. Involved in the
CC splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic
CC genes); specifically inhibits the formation of proapoptotic isoforms
CC such as Bcl-X(S); the activity is different from the established EJC
CC assembly and function (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:22388736}.
CC -!- SUBUNIT: Found in a mRNA splicing-dependent exon junction complex
CC (EJC). Component of the heterotrimeric ASAP (apoptosis- and splicing-
CC associated protein) and PSAP complexes consisting of RNPS1, SAP18 and
CC either ACIN1 or PNN, respectively; the ASAP and PSAP complexes probably
CC are formed mutually exclusive. For the ASAP complex, the association of
CC SAP18 seems to require a preformed RNPS1:ACIN1 complex. Forms a complex
CC with SIN3A and HDAC1. Interacts with SUFU.
CC {ECO:0000269|PubMed:22388736}.
CC -!- INTERACTION:
CC O55128; Q9Z0P7: Sufu; NbExp=6; IntAct=EBI-3508332, EBI-3508336;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O00422}. Cytoplasm
CC {ECO:0000250|UniProtKB:O00422}. Nucleus speckle
CC {ECO:0000250|UniProtKB:O00422}. Note=Shuttles between the nucleus and
CC the cytoplasm (By similarity). Colocalizes with ACIN1 and SRSF2 in
CC nuclear speckles (By similarity). {ECO:0000250|UniProtKB:O00422}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested; highest levels in
CC the brain, kidney and muscle; lowest levels in lung spleen, liver,
CC intestine and testis, and moderate levels in salivary gland and heart.
CC {ECO:0000269|PubMed:9511770}.
CC -!- SIMILARITY: Belongs to the SAP18 family. {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; Z97062; CAB09797.1; -; mRNA.
DR EMBL; AK005189; BAB23871.1; -; mRNA.
DR EMBL; AK006647; BAB24687.1; -; mRNA.
DR EMBL; AK085992; BAC39588.1; -; mRNA.
DR EMBL; BC006625; AAH06625.1; -; mRNA.
DR RefSeq; NP_033145.2; NM_009119.3.
DR PDB; 4A6Q; X-ray; 1.50 A; A=6-143.
DR PDB; 4A8X; X-ray; 1.90 A; C=14-143.
DR PDB; 4A90; X-ray; 1.90 A; A/B=1-143.
DR PDBsum; 4A6Q; -.
DR PDBsum; 4A8X; -.
DR PDBsum; 4A90; -.
DR AlphaFoldDB; O55128; -.
DR BMRB; O55128; -.
DR SMR; O55128; -.
DR BioGRID; 203070; 20.
DR DIP; DIP-59924N; -.
DR IntAct; O55128; 7.
DR STRING; 10090.ENSMUSP00000073697; -.
DR iPTMnet; O55128; -.
DR PhosphoSitePlus; O55128; -.
DR EPD; O55128; -.
DR MaxQB; O55128; -.
DR PaxDb; O55128; -.
DR PeptideAtlas; O55128; -.
DR PRIDE; O55128; -.
DR ProteomicsDB; 256916; -.
DR DNASU; 20220; -.
DR GeneID; 20220; -.
DR KEGG; mmu:20220; -.
DR CTD; 10284; -.
DR MGI; MGI:1277978; Sap18.
DR eggNOG; KOG3391; Eukaryota.
DR InParanoid; O55128; -.
DR OrthoDB; 1622057at2759; -.
DR PhylomeDB; O55128; -.
DR Reactome; R-MMU-3214815; HDACs deacetylate histones.
DR BioGRID-ORCS; 20220; 23 hits in 78 CRISPR screens.
DR PRO; PR:O55128; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O55128; protein.
DR GO; GO:0061574; C:ASAP complex; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0035145; C:exon-exon junction complex; ISO:MGI.
DR GO; GO:0000118; C:histone deacetylase complex; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR Gene3D; 3.10.20.550; -; 1.
DR InterPro; IPR017250; Hist_deAcase_cplx_SAP18.
DR InterPro; IPR010516; SAP18.
DR InterPro; IPR042534; SAP18_sf.
DR PANTHER; PTHR13082; PTHR13082; 1.
DR Pfam; PF06487; SAP18; 1.
DR PIRSF; PIRSF037637; HDAC_SAP18; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Isopeptide bond; mRNA processing;
KW mRNA splicing; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O00422"
FT CHAIN 2..153
FT /note="Histone deacetylase complex subunit SAP18"
FT /id="PRO_0000220976"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..153
FT /note="Involved in splicing regulation activity"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O00422"
FT CROSSLNK 13
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O00422"
FT MUTAGEN 26
FT /note="C->R: Impairs interactions with RNPS1, ACIN1 and
FT PNN; reduces ASAP and PSAP complex assemblies."
FT /evidence="ECO:0000269|PubMed:22388736"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:4A6Q"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:4A6Q"
FT STRAND 28..39
FT /evidence="ECO:0007829|PDB:4A6Q"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:4A6Q"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:4A8X"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:4A6Q"
FT HELIX 66..76
FT /evidence="ECO:0007829|PDB:4A6Q"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:4A6Q"
FT STRAND 86..94
FT /evidence="ECO:0007829|PDB:4A6Q"
FT STRAND 96..110
FT /evidence="ECO:0007829|PDB:4A6Q"
FT TURN 116..119
FT /evidence="ECO:0007829|PDB:4A6Q"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:4A6Q"
FT STRAND 132..138
FT /evidence="ECO:0007829|PDB:4A6Q"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:4A6Q"
SQ SEQUENCE 153 AA; 17595 MW; 68FE63E6EAD04E6F CRC64;
MAVESRVTQE EIKKEPEKPI DREKTCPLLL RVFTTNNGRH HRMDEFSRGN VPSSELQIYT
WMDATLKELT SLVKEVYPEA RKKGTHFNFA IVFMDLKRPG YRVKEIGSTM SGRKGTDDSM
TLQSQKFQIG DYLDIAITPP NRAPPSSGRM RPY
