ISY1_HUMAN
ID ISY1_HUMAN Reviewed; 285 AA.
AC Q9ULR0; Q96IL2; Q9BT05;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 3.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Pre-mRNA-splicing factor ISY1 homolog;
GN Name=ISY1; Synonyms=KIAA1160;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis from
RT size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lung, Ovary, and Testis;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SPLICEOSOMAL C
RP COMPLEX, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=11991638; DOI=10.1017/s1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-247, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [5]
RP IDENTIFICATION AS PART OF THE XAB2 COMPLEX.
RX PubMed=17981804; DOI=10.1074/jbc.m706647200;
RA Kuraoka I., Ito S., Wada T., Hayashida M., Lee L., Saijo M., Nakatsu Y.,
RA Matsumoto M., Matsunaga T., Handa H., Qin J., Nakatani Y., Tanaka K.;
RT "Isolation of XAB2 complex involved in pre-mRNA splicing, transcription,
RT and transcription-coupled repair.";
RL J. Biol. Chem. 283:940-950(2008).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-127, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
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., Buerckstuemmer T.,
RA 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE IB COMPLEX,
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=25599396; DOI=10.1038/nsmb.2951;
RA De I., Bessonov S., Hofele R., dos Santos K., Will C.L., Urlaub H.,
RA Luhrmann R., Pena V.;
RT "The RNA helicase Aquarius exhibits structural adaptations mediating its
RT recruitment to spliceosomes.";
RL Nat. Struct. Mol. Biol. 22:138-144(2015).
RN [10] {ECO:0007744|PDB:5YZG}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.10 ANGSTROMS), FUNCTION, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=29301961; DOI=10.1126/science.aar6401;
RA Zhan X., Yan C., Zhang X., Lei J., Shi Y.;
RT "Structure of a human catalytic step I spliceosome.";
RL Science 359:537-545(2018).
CC -!- FUNCTION: Component of the spliceosome C complex required for the
CC selective processing of microRNAs during embryonic stem cell
CC differentiation (By similarity). Required for the biogenesis of all
CC miRNAs from the pri-miR-17-92 primary transcript except miR-92a (By
CC similarity). Only required for the biogenesis of miR-290 and miR-96
CC from the pri-miR-290-295 and pri-miR-96-183 primary transcripts,
CC respectively (By similarity). Required during the transition of
CC embryonic stem cells (ESCs) from the naive to primed state (By
CC similarity). By enhancing miRNA biogenesis, promotes exit of ESCs from
CC the naive state to an intermediate state of poised pluripotency, which
CC precedes transition to the primed state (By similarity). Involved in
CC pre-mRNA splicing as component of the spliceosome.
CC {ECO:0000250|UniProtKB:Q69ZQ2, ECO:0000269|PubMed:29301961,
CC ECO:0000305|PubMed:11991638, ECO:0000305|PubMed:25599396}.
CC -!- SUBUNIT: Identified in the spliceosome C complex (PubMed:11991638,
CC PubMed:29301961). Component of the XAB2 complex, a multimeric protein
CC complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE
CC (PubMed:17981804). Identified in a pentameric intron-binding (IB)
CC complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is
CC incorporated into the spliceosome as a preassembled complex
CC (PubMed:25599396). The IB complex does not contain PRPF19
CC (PubMed:25599396). Interacts with CPSF3; this interaction is in an RNA
CC independent manner (By similarity). Interacts with the microprocessor
CC complex subunits DGCR8 and DROSHA; this interaction is in an RNA
CC dependent manner (By similarity). {ECO:0000250|UniProtKB:Q69ZQ2,
CC ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:17981804,
CC ECO:0000269|PubMed:25599396, ECO:0000269|PubMed:29301961}.
CC -!- INTERACTION:
CC Q9ULR0; O60306: AQR; NbExp=6; IntAct=EBI-2557660, EBI-2512328;
CC Q9ULR0; P27797: CALR; NbExp=3; IntAct=EBI-2557660, EBI-1049597;
CC Q9ULR0; P24863: CCNC; NbExp=3; IntAct=EBI-2557660, EBI-395261;
CC Q9ULR0; Q14562: DHX8; NbExp=2; IntAct=EBI-2557660, EBI-2511477;
CC Q9ULR0; P36957: DLST; NbExp=3; IntAct=EBI-2557660, EBI-351007;
CC Q9ULR0; Q8IYI6: EXOC8; NbExp=3; IntAct=EBI-2557660, EBI-742102;
CC Q9ULR0; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-2557660, EBI-6658203;
CC Q9ULR0; Q8N371-3: KDM8; NbExp=5; IntAct=EBI-2557660, EBI-12161375;
CC Q9ULR0; P25800: LMO1; NbExp=3; IntAct=EBI-2557660, EBI-8639312;
CC Q9ULR0; P25791-3: LMO2; NbExp=3; IntAct=EBI-2557660, EBI-11959475;
CC Q9ULR0; P40692: MLH1; NbExp=3; IntAct=EBI-2557660, EBI-744248;
CC Q9ULR0; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-2557660, EBI-1055945;
CC Q9ULR0; P37173: TGFBR2; NbExp=3; IntAct=EBI-2557660, EBI-296151;
CC Q9ULR0; Q8N131: TMEM123; NbExp=3; IntAct=EBI-2557660, EBI-749248;
CC Q9ULR0; Q9HCS7: XAB2; NbExp=7; IntAct=EBI-2557660, EBI-295232;
CC Q9ULR0-1; Q8N715: CCDC185; NbExp=3; IntAct=EBI-18398632, EBI-740814;
CC Q9ULR0-1; Q8IYI6: EXOC8; NbExp=3; IntAct=EBI-18398632, EBI-742102;
CC Q9ULR0-1; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-18398632, EBI-7225287;
CC Q9ULR0-1; O95363: FARS2; NbExp=3; IntAct=EBI-18398632, EBI-2513774;
CC Q9ULR0-1; Q9H4M3-2: FBXO44; NbExp=3; IntAct=EBI-18398632, EBI-12104696;
CC Q9ULR0-1; O43559: FRS3; NbExp=3; IntAct=EBI-18398632, EBI-725515;
CC Q9ULR0-1; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-18398632, EBI-726510;
CC Q9ULR0-1; Q9Y5B8: NME7; NbExp=3; IntAct=EBI-18398632, EBI-744782;
CC Q9ULR0-1; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-18398632, EBI-398874;
CC Q9ULR0-1; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-18398632, EBI-1504830;
CC Q9ULR0-1; Q5T7W7: TSTD2; NbExp=3; IntAct=EBI-18398632, EBI-8994397;
CC Q9ULR0-1; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-18398632, EBI-7353612;
CC Q9ULR0-1; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-18398632, EBI-6427977;
CC Q9ULR0-1; Q9UEG4: ZNF629; NbExp=3; IntAct=EBI-18398632, EBI-9977294;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11991638,
CC ECO:0000269|PubMed:25599396, ECO:0000269|PubMed:29301961}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=Q9ULR0-3; Sequence=Displayed;
CC Name=2; Synonyms=ISY1-RAB43;
CC IsoId=Q9ULR0-1; Sequence=VSP_039411;
CC Name=1;
CC IsoId=Q9ULR0-2; Sequence=VSP_039410;
CC -!- MISCELLANEOUS: [Isoform 2]: Based on a readthrough transcript which may
CC produce a ISY1-RAB43 fusion protein. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ISY1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86474.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB032986; BAA86474.1; ALT_INIT; mRNA.
DR EMBL; BC004442; AAH04442.1; -; mRNA.
DR EMBL; BC007409; AAH07409.1; -; mRNA.
DR EMBL; BC019849; AAH19849.1; -; mRNA.
DR CCDS; CCDS43149.1; -. [Q9ULR0-3]
DR CCDS; CCDS56277.1; -. [Q9ULR0-2]
DR RefSeq; NP_001186398.1; NM_001199469.1. [Q9ULR0-2]
DR RefSeq; NP_001191819.1; NM_001204890.1. [Q9ULR0-1]
DR RefSeq; NP_065752.1; NM_020701.3. [Q9ULR0-3]
DR PDB; 5YZG; EM; 4.10 A; y=1-285.
DR PDB; 6FF7; EM; 4.50 A; w=1-285.
DR PDB; 6ZYM; EM; 3.40 A; s=1-285.
DR PDB; 7A5P; EM; 5.00 A; s=1-285.
DR PDBsum; 5YZG; -.
DR PDBsum; 6FF7; -.
DR PDBsum; 6ZYM; -.
DR PDBsum; 7A5P; -.
DR AlphaFoldDB; Q9ULR0; -.
DR SMR; Q9ULR0; -.
DR BioGRID; 121531; 119.
DR BioGRID; 1529628; 35.
DR CORUM; Q9ULR0; -.
DR DIP; DIP-56636N; -.
DR IntAct; Q9ULR0; 68.
DR MINT; Q9ULR0; -.
DR STRING; 9606.ENSP00000411822; -.
DR iPTMnet; Q9ULR0; -.
DR PhosphoSitePlus; Q9ULR0; -.
DR BioMuta; ISY1; -.
DR DMDM; 300669687; -.
DR EPD; Q9ULR0; -.
DR jPOST; Q9ULR0; -.
DR MassIVE; Q9ULR0; -.
DR MaxQB; Q9ULR0; -.
DR PaxDb; Q9ULR0; -.
DR PeptideAtlas; Q9ULR0; -.
DR PRIDE; Q9ULR0; -.
DR ProteomicsDB; 85097; -. [Q9ULR0-3]
DR ProteomicsDB; 85098; -. [Q9ULR0-1]
DR ProteomicsDB; 85099; -. [Q9ULR0-2]
DR Antibodypedia; 34841; 46 antibodies from 14 providers.
DR DNASU; 57461; -.
DR Ensembl; ENST00000273541.12; ENSP00000273541.8; ENSG00000240682.10. [Q9ULR0-2]
DR Ensembl; ENST00000393295.8; ENSP00000376973.4; ENSG00000240682.10. [Q9ULR0-3]
DR GeneID; 100534599; -.
DR GeneID; 57461; -.
DR KEGG; hsa:100534599; -.
DR KEGG; hsa:57461; -.
DR MANE-Select; ENST00000393295.8; ENSP00000376973.4; NM_020701.4; NP_065752.1.
DR UCSC; uc003elp.3; human. [Q9ULR0-3]
DR CTD; 100534599; -.
DR CTD; 57461; -.
DR DisGeNET; 100534599; -.
DR GeneCards; ISY1; -.
DR HGNC; HGNC:29201; ISY1.
DR HPA; ENSG00000240682; Low tissue specificity.
DR MIM; 612764; gene.
DR neXtProt; NX_Q9ULR0; -.
DR OpenTargets; ENSG00000240682; -.
DR OpenTargets; ENSG00000261796; -.
DR PharmGKB; PA162392343; -.
DR VEuPathDB; HostDB:ENSG00000240682; -.
DR eggNOG; KOG3068; Eukaryota.
DR GeneTree; ENSGT00390000014109; -.
DR HOGENOM; CLU_043453_0_0_1; -.
DR InParanoid; Q9ULR0; -.
DR OMA; VNCLFTC; -.
DR OrthoDB; 1513531at2759; -.
DR PhylomeDB; Q9ULR0; -.
DR TreeFam; TF105841; -.
DR PathwayCommons; Q9ULR0; -.
DR Reactome; R-HSA-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-HSA-6781827; Transcription-Coupled Nucleotide Excision Repair (TC-NER).
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR SignaLink; Q9ULR0; -.
DR BioGRID-ORCS; 100534599; 169 hits in 610 CRISPR screens.
DR BioGRID-ORCS; 57461; 670 hits in 1003 CRISPR screens.
DR Pharos; Q9ULR0; Tdark.
DR PRO; PR:Q9ULR0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9ULR0; protein.
DR Bgee; ENSG00000240682; Expressed in calcaneal tendon and 184 other tissues.
DR ExpressionAtlas; Q9ULR0; baseline and differential.
DR Genevisible; Q9ULR0; HS.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0071014; C:post-mRNA release spliceosomal complex; IBA:GO_Central.
DR GO; GO:0071020; C:post-spliceosomal complex; IBA:GO_Central.
DR GO; GO:0000974; C:Prp19 complex; IBA:GO_Central.
DR GO; GO:0071006; C:U2-type catalytic step 1 spliceosome; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000350; P:generation of catalytic spliceosome for second transesterification step; IBA:GO_Central.
DR GO; GO:0000389; P:mRNA 3'-splice site recognition; IBA:GO_Central.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IDA:UniProtKB.
DR Gene3D; 1.10.287.660; -; 1.
DR InterPro; IPR029012; Helix_hairpin_bin_sf.
DR InterPro; IPR009360; Isy1.
DR InterPro; IPR037200; Isy1_sf.
DR PANTHER; PTHR13021; PTHR13021; 1.
DR Pfam; PF06246; Isy1; 1.
DR SUPFAM; SSF140102; SSF140102; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome; Spliceosome.
FT CHAIN 1..285
FT /note="Pre-mRNA-splicing factor ISY1 homolog"
FT /id="PRO_0000235813"
FT REGION 194..244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..228
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 127
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 247
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VAR_SEQ 140
FT /note="P -> RQVRWLMPVIPALWEAEAGGSQA (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039410"
FT VAR_SEQ 285
FT /note="Y -> CRSGTRPARSGSAPSPRATTAVPMGPSLPTTSPRGAPSCRCLTGLRM
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10574461"
FT /id="VSP_039411"
FT STRAND 4..7
FT /evidence="ECO:0007829|PDB:6ZYM"
FT HELIX 11..18
FT /evidence="ECO:0007829|PDB:6ZYM"
SQ SEQUENCE 285 AA; 32992 MW; AB43602EBCB51B2C CRC64;
MARNAEKAMT ALARFRQAQL EEGKVKERRP FLASECTELP KAEKWRRQII GEISKKVAQI
QNAGLGEFRI RDLNDEINKL LREKGHWEVR IKELGGPDYG KVGPKMLDHE GKEVPGNRGY
KYFGAAKDLP GVRELFEKEP LPPPRKTRAE LMKAIDFEYY GYLDEDDGVI VPLEQEYEKK
LRAELVEKWK AEREARLARG EKEEEEEEEE EINIYAVTEE ESDEEGSQEK GGDDSQQKFI
AHVPVPSQQE IEEALVRRKK MELLQKYASE TLQAQSEEAR RLLGY
