ID   SAP18_HUMAN             Reviewed;         153 AA.
AC   O00422; B2R494; Q2TTR4; Q6IAW9; Q8N606; Q9UF14;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   19-MAR-2014, entry version 126.
DE   RecName: Full=Histone deacetylase complex subunit SAP18;
DE   AltName: Full=18 kDa Sin3-associated polypeptide;
DE   AltName: Full=2HOR0202;
DE   AltName: Full=Cell growth-inhibiting gene 38 protein;
DE   AltName: Full=Sin3-associated polypeptide p18;
GN   Name=SAP18; ORFNames=GIG38;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH SIN3A AND
RP   HDAC1.
RX   PubMed=9150135; DOI=10.1016/S0092-8674(00)80216-0;
RA   Zhang Y., Iratni R., Erdjument-Bromage H., Tempst P., Reinberg D.;
RT   "Histone deacetylases and SAP18, a novel polypeptide, are components
RT   of a human Sin3 complex.";
RL   Cell 89:357-364(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Kawasaki H., Housman D.E., Graybiel A.M.;
RT   "Characterization of proteins interacting with CAMPGEF.";
RL   Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Hair follicle dermal papilla;
RA   Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Chung H.J., Sohn M.Y.,
RA   Hwang S.Y., Im S.U., Jung E.J., Lee H.D., Kim J.C.;
RT   "A catalogue of genes in the human dermal papilla cells as identified
RT   by expressed sequence tags.";
RL   Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kim J.W.;
RT   "Identification of a human cell growth inhibiting gene.";
RL   Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057823; DOI=10.1038/nature02379;
RA   Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA   Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
RA   Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA   Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA   Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA   Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
RA   Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA   Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA   Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA   Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA   Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA   Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA   Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA   King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA   Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA   Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA   Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
RA   Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA   Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA   Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA   Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA   Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA   Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
RT   "The DNA sequence and analysis of human chromosome 13.";
RL   Nature 428:522-528(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Hypothalamus;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [10]
RP   IDENTIFICATION IN THE ASAP COMPLEX, AND FUNCTION OF THE ASAP COMPLEX.
RX   PubMed=12665594; DOI=10.1128/MCB.23.8.2981-2990.2003;
RA   Schwerk C., Prasad J., Degenhardt K., Erdjument-Bromage H., White E.,
RA   Tempst P., Kidd V.J., Manley J.L., Lahti J.M., Reinberg D.;
RT   "ASAP, a novel protein complex involved in RNA processing and
RT   apoptosis.";
RL   Mol. Cell. Biol. 23:2981-2990(2003).
RN   [11]
RP   IDENTIFICATION IN A MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX,
RP   IDENTIFICATION IN THE ASAP COMPLEX, SUBCELLULAR LOCATION, AND MASS
RP   SPECTROMETRY.
RX   PubMed=16314458; DOI=10.1261/rna.2155905;
RA   Tange T.O., Shibuya T., Jurica M.S., Moore M.J.;
RT   "Biochemical analysis of the EJC reveals two new factors and a stable
RT   tetrameric protein core.";
RL   RNA 11:1869-1883(2005).
RN   [12]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS], AND CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RNPS1 AND ACIN1, AND
RP   MUTAGENESIS OF ASP-118; THR-121 AND LYS-126.
RX   PubMed=20966198; DOI=10.1261/rna.2304410;
RA   Singh K.K., Erkelenz S., Rattay S., Dehof A.K., Hildebrandt A.,
RA   Schulze-Osthoff K., Schaal H., Schwerk C.;
RT   "Human SAP18 mediates assembly of a splicing regulatory multiprotein
RT   complex via its ubiquitin-like fold.";
RL   RNA 16:2442-2454(2010).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA   Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [15]
RP   FUNCTION.
RX   PubMed=22203037; DOI=10.1128/MCB.06130-11;
RA   Michelle L., Cloutier A., Toutant J., Shkreta L., Thibault P.,
RA   Durand M., Garneau D., Gendron D., Lapointe E., Couture S., Le Hir H.,
RA   Klinck R., Elela S.A., Prinos P., Chabot B.;
RT   "Proteins associated with the exon junction complex also control the
RT   alternative splicing of apoptotic regulators.";
RL   Mol. Cell. Biol. 32:954-967(2012).
RN   [16]
RP   STRUCTURE BY NMR OF 6-149, AND INTERACTION WITH SUFU.
RX   PubMed=17002296; DOI=10.1021/bi060687l;
RA   McCallum S.A., Bazan J.F., Merchant M., Yin J., Pan B.,
RA   de Sauvage F.J., Fairbrother W.J.;
RT   "Structure of SAP18: a ubiquitin fold in histone deacetylase complex
RT   assembly.";
RL   Biochemistry 45:11974-11982(2006).
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
CC       repressive complex to core histone proteins. Auxiliary component
CC       of the splicing-dependent multiprotein exon junction complex (EJC)
CC       deposited at splice junction on mRNAs. The EJC is a dynamic
CC       structure consisting of core proteins and several peripheral
CC       nuclear and cytoplasmic associated factors that join the complex
CC       only transiently either during EJC assembly or during subsequent
CC       mRNA metabolism. Component of the ASAP and PSAP complexes which
CC       bind RNA in a sequence-independent manner and are proposed to be
CC       recruited to the EJC prior to or during the splicing process and
CC       to regulate specific excision of introns in specific transcription
CC       subsets. The ASAP complex can inhibit mRNA processing during in
CC       vitro splicing reactions. The ASAP complex promotes apoptosis and
CC       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
CC       isoforms such as Bcl-X(S); the activity is different from the
CC       established EJC assembly and function.
CC   -!- SUBUNIT: Found in a mRNA splicing-dependent exon junction complex
CC       (EJC). Component of the heterotrimeric ASAP (apoptosis- and
CC       splicing-associated protein) and PSAP complexes consisting of
CC       RNPS1, SAP18 and either ACIN1 or PNN, respectively; the ASAP and
CC       PSAP complexes probably are formed mutually exclusive. For the
CC       ASAP complex, the association of SAP18 seems to require a
CC       preformed RNPS1:ACIN1 complex. Forms a complex with SIN3A and
CC       HDAC1. Interacts with SUFU.
CC   -!- INTERACTION:
CC       Q13547:HDAC1; NbExp=2; IntAct=EBI-1044156, EBI-301834;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Nucleus speckle.
CC       Note=Shuttles between the nucleus and the cytoplasm. Colocalizes
CC       with ACIN1 and SRSF2 in nuclear speckles.
CC   -!- TISSUE SPECIFICITY: Ubiquitous.
CC   -!- SIMILARITY: Belongs to the SAP18 family.
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DR   EMBL; U96915; AAC51322.1; -; mRNA.
DR   EMBL; U78303; AAF21220.1; -; mRNA.
DR   EMBL; AF153608; AAD41090.1; -; mRNA.
DR   EMBL; AY550970; AAT52216.1; -; mRNA.
DR   EMBL; CR457035; CAG33316.1; -; mRNA.
DR   EMBL; AK311748; BAG34691.1; -; mRNA.
DR   EMBL; AL158032; CAH69949.1; -; Genomic_DNA.
DR   EMBL; CH471075; EAX08291.1; -; Genomic_DNA.
DR   EMBL; BC030836; AAH30836.1; -; mRNA.
DR   RefSeq; NP_005861.2; NM_005870.4.
DR   UniGene; Hs.524899; -.
DR   PDB; 2HDE; NMR; -; A=6-149.
DR   PDBsum; 2HDE; -.
DR   ProteinModelPortal; O00422; -.
DR   SMR; O00422; 6-149.
DR   BioGrid; 115573; 92.
DR   DIP; DIP-33590N; -.
DR   IntAct; O00422; 12.
DR   MINT; MINT-5002140; -.
DR   STRING; 9606.ENSP00000371973; -.
DR   TCDB; 3.A.18.1.1; the nuclear mrna exporter (mrna-e) family.
DR   PhosphoSite; O00422; -.
DR   PaxDb; O00422; -.
DR   PeptideAtlas; O00422; -.
DR   PRIDE; O00422; -.
DR   DNASU; 10284; -.
DR   Ensembl; ENST00000607003; ENSP00000475925; ENSG00000150459.
DR   GeneID; 10284; -.
DR   KEGG; hsa:10284; -.
DR   UCSC; uc001uns.3; human.
DR   CTD; 10284; -.
DR   GeneCards; GC13P021714; -.
DR   H-InvDB; HIX0011163; -.
DR   HGNC; HGNC:10530; SAP18.
DR   HPA; CAB012273; -.
DR   HPA; HPA011352; -.
DR   MIM; 602949; gene.
DR   neXtProt; NX_O00422; -.
DR   PharmGKB; PA34940; -.
DR   eggNOG; NOG249491; -.
DR   HOGENOM; HOG000238745; -.
DR   HOVERGEN; HBG003465; -.
DR   InParanoid; O00422; -.
DR   KO; K14324; -.
DR   OrthoDB; EOG79SDZS; -.
DR   PhylomeDB; O00422; -.
DR   TreeFam; TF313032; -.
DR   SignaLink; O00422; -.
DR   ChiTaRS; SAP18; human.
DR   EvolutionaryTrace; O00422; -.
DR   GeneWiki; SAP18; -.
DR   GenomeRNAi; 10284; -.
DR   NextBio; 38964; -.
DR   PRO; PR:O00422; -.
DR   Bgee; O00422; -.
DR   CleanEx; HS_SAP18; -.
DR   Genevestigator; O00422; -.
DR   GO; GO:0061574; C:ASAP complex; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0000118; C:histone deacetylase complex; TAS:ProtInc.
DR   GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
DR   GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR   GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IDA:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR   GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR   GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR   InterPro; IPR017250; Hist_deAcase_cplx_SAP18.
DR   InterPro; IPR010516; SAP18.
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; Complete proteome; Cytoplasm;
KW   mRNA processing; mRNA splicing; Nucleus; Reference proteome;
KW   Repressor; Transcription; Transcription regulation.
FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    153       Histone deacetylase complex subunit
FT                                SAP18.
FT                                /FTId=PRO_0000220975.
FT   REGION       93    153       Involved in splicing regulation activity.
FT   MOD_RES       2      2       N-acetylalanine.
FT   MUTAGEN     118    118       D->A: Abolishes splicing regulation
FT                                activity and interaction with RNPS1 and
FT                                ACIN1; when associated with A-121.
FT   MUTAGEN     121    121       T->A: Abolishes splicing regulation
FT                                activity and interaction with RNPS1 and
FT                                ACIN1; when associated with A-118.
FT   MUTAGEN     126    126       K->A: No effect on splicing regulation
FT                                activity.
FT   CONFLICT    114    114       K -> E (in Ref. 2; AAF21220).
FT   CONFLICT    146    146       P -> T (in Ref. 9; AAH30836).
FT   TURN         22     24
FT   STRAND       28     37
FT   HELIX        43     45
FT   TURN         52     54
FT   STRAND       55     60
FT   HELIX        66     76
FT   HELIX        78     81
FT   STRAND       86     91
FT   STRAND       95     98
FT   STRAND      104    112
FT   HELIX       122    125
FT   STRAND      132    138
FT   STRAND      144    147
SQ   SEQUENCE   153 AA;  17561 MW;  C7E479FFE9CA5774 CRC64;
     MAVESRVTQE EIKKEPEKPI DREKTCPLLL RVFTTNNGRH HRMDEFSRGN VPSSELQIYT
     WMDATLKELT SLVKEVYPEA RKKGTHFNFA IVFTDVKRPG YRVKEIGSTM SGRKGTDDSM
     TLQSQKFQIG DYLDIAITPP NRAPPPSGRM RPY
//