ID SRRT_MOUSE Reviewed; 875 AA. AC Q99MR6; Q3UD04; Q5D042; Q8VEE6; Q99MR4; Q99MR5; Q99MR7; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 07-OCT-2020, entry version 141. DE RecName: Full=Serrate RNA effector molecule homolog; DE AltName: Full=Arsenite-resistance protein 2; GN Name=Srrt; Synonyms=Ars2, Asr2; 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 [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS A; B; RP C AND D). RC STRAIN=129/Sv; RX PubMed=11239002; DOI=10.1093/nar/29.6.1352; RA Wilson M.D., Riemer C., Martindale D.W., Schnupf P., Boright A.P., RA Cheung T.L., Hardy D.M., Schwartz S., Scherer S.W., Tsui L.-C., Miller W., RA Koop B.F.; RT "Comparative analysis of the gene-dense ACHE/TFR2 region on human RT chromosome 7q22 with the orthologous region on mouse chromosome 5."; RL Nucleic Acids Res. 29:1352-1365(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D). RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Kidney, and Mammary tumor; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 477-875 (ISOFORM C). RC STRAIN=C57BL/6J; TISSUE=Bone marrow; 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 [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-543, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [5] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=18086880; DOI=10.1128/mcb.01565-07; RA Wilson M.D., Wang D., Wagner R., Breyssens H., Gertsenstein M., Lobe C., RA Lu X., Nagy A., Burke R.D., Koop B.F., Howard P.L.; RT "ARS2 is a conserved eukaryotic gene essential for early mammalian RT development."; RL Mol. Cell. Biol. 28:1503-1514(2008). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, INTERACTION RP WITH NCBP1 AND DROSHA, AND DISRUPTION PHENOTYPE. RX PubMed=19632182; DOI=10.1016/j.cell.2009.04.046; RA Gruber J.J., Zatechka D.S., Sabin L.R., Yong J., Lum J.J., Kong M., RA Zong W.-X., Zhang Z., Lau C.-K., Rawlings J., Cherry S., Ihle J.N., RA Dreyfuss G., Thompson C.B.; RT "Ars2 links the nuclear cap-binding complex to RNA interference and cell RT proliferation."; RL Cell 138:328-339(2009). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-543, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-543, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, RC 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 [9] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=22198669; DOI=10.1038/nature10712; RA Andreu-Agullo C., Maurin T., Thompson C.B., Lai E.C.; RT "Ars2 maintains neural stem-cell identity through direct transcriptional RT activation of Sox2."; RL Nature 481:195-198(2012). CC -!- FUNCTION: Acts as a mediator between the cap-binding complex (CBC) and CC the primary microRNAs (miRNAs) processing machinery during cell CC proliferation. Contributes to the stability and delivery of capped CC primary miRNA transcripts to the primary miRNA processing complex CC containing DGCR8 and DROSHA, thereby playing a role in RNA-mediated CC gene silencing (RNAi) by miRNAs. Binds capped RNAs (m7GpppG-capped CC RNA); however interaction is probably mediated via its interaction with CC NCBP1/CBP80 component of the CBC complex. Involved in cell cycle CC progression at S phase. Does not directly confer arsenite resistance CC but rather modulates arsenic sensitivity. Independently of its activity CC on miRNAs, necessary and sufficient to promote neural stem cell self- CC renewal. Does so by directly binding SOX2 promoter and positively CC regulating its transcription. {ECO:0000269|PubMed:19632182, CC ECO:0000269|PubMed:22198669}. CC -!- SUBUNIT: Interacts with CASP8AP2 and ERBB4 (By similarity). Interacts CC with NCBP1/CBP80 and DROSHA (PubMed:19632182). Interacts with LUZP4 (By CC similarity). Interacts with NCBP2/CBP20 and NCBP3 (By similarity). CC Interacts with MTREX (By similarity). {ECO:0000250|UniProtKB:Q9BXP5, CC ECO:0000269|PubMed:19632182}. CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Cytoplasm. CC Note=Predominantly nuclear. Shuttles between the nucleus and the CC cytoplasm in a CRM1-dependent way. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=A; CC IsoId=Q99MR6-1; Sequence=Displayed; CC Name=B; CC IsoId=Q99MR6-2; Sequence=VSP_000325; CC Name=C; CC IsoId=Q99MR6-3; Sequence=VSP_000325, VSP_000326; CC Name=D; CC IsoId=Q99MR6-4; Sequence=VSP_000326; CC -!- TISSUE SPECIFICITY: Widely expressed, with a preference for CC proliferating cells. Highly expressed in hematopoietic tissues and CC reduced or absent expression in parenchymal organs like liver and CC kidney. In the brain, expressed in the subventricular zone by niche CC astrocytes, ependymal cells and neural stem cells. In this cerebral CC context, expressed in slowly dividing cells. CC {ECO:0000269|PubMed:18086880, ECO:0000269|PubMed:19632182, CC ECO:0000269|PubMed:22198669}. CC -!- INDUCTION: Upon cell proliferation. {ECO:0000269|PubMed:19632182}. CC -!- DISRUPTION PHENOTYPE: Death around the time of implantation. Deletion CC in adults leads to proliferative arrest and bone marrow hypoplasia CC whereas parenchymal organs composed of nonproliferating cells are CC unaffected. {ECO:0000269|PubMed:18086880, ECO:0000269|PubMed:19632182}. CC -!- SIMILARITY: Belongs to the ARS2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH19117.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAE29458.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AF312033; AAK28817.1; -; Genomic_DNA. DR EMBL; AF312033; AAK28818.1; -; Genomic_DNA. DR EMBL; AF312033; AAK28819.1; -; Genomic_DNA. DR EMBL; AF312033; AAK28820.1; -; Genomic_DNA. DR EMBL; BC019117; AAH19117.1; ALT_INIT; mRNA. DR EMBL; BC066831; AAH66831.1; -; mRNA. DR EMBL; AK150310; BAE29458.1; ALT_INIT; mRNA. DR CCDS; CCDS39331.1; -. [Q99MR6-1] DR CCDS; CCDS80439.1; -. [Q99MR6-3] DR CCDS; CCDS80440.1; -. [Q99MR6-4] DR RefSeq; NP_001103379.1; NM_001109909.1. [Q99MR6-4] DR RefSeq; NP_001103380.1; NM_001109910.1. [Q99MR6-3] DR RefSeq; NP_113582.1; NM_031405.2. [Q99MR6-1] DR RefSeq; XP_006504692.1; XM_006504629.1. DR SMR; Q99MR6; -. DR BioGRID; 219965; 13. DR IntAct; Q99MR6; 2. DR MINT; Q99MR6; -. DR STRING; 10090.ENSMUSP00000043123; -. DR iPTMnet; Q99MR6; -. DR PhosphoSitePlus; Q99MR6; -. DR SwissPalm; Q99MR6; -. DR jPOST; Q99MR6; -. DR PaxDb; Q99MR6; -. DR PeptideAtlas; Q99MR6; -. DR PRIDE; Q99MR6; -. DR Antibodypedia; 30897; 135 antibodies. DR Ensembl; ENSMUST00000040873; ENSMUSP00000043123; ENSMUSG00000037364. [Q99MR6-1] DR Ensembl; ENSMUST00000197466; ENSMUSP00000142564; ENSMUSG00000037364. [Q99MR6-3] DR Ensembl; ENSMUST00000199243; ENSMUSP00000143232; ENSMUSG00000037364. [Q99MR6-4] DR GeneID; 83701; -. DR KEGG; mmu:83701; -. DR UCSC; uc009acb.2; mouse. [Q99MR6-1] DR UCSC; uc009acc.2; mouse. [Q99MR6-3] DR UCSC; uc012eew.1; mouse. [Q99MR6-4] DR CTD; 51593; -. DR MGI; MGI:1933527; Srrt. DR eggNOG; KOG2295; Eukaryota. DR GeneTree; ENSGT00390000005492; -. DR InParanoid; Q99MR6; -. DR OMA; FVCHVGV; -. DR OrthoDB; 525905at2759; -. DR PhylomeDB; Q99MR6; -. DR TreeFam; TF317609; -. DR Reactome; R-MMU-6807505; RNA polymerase II transcribes snRNA genes. DR Reactome; R-MMU-72163; mRNA Splicing - Major Pathway. DR BioGRID-ORCS; 83701; 5 hits in 19 CRISPR screens. DR ChiTaRS; Srrt; mouse. DR PRO; PR:Q99MR6; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; Q99MR6; protein. DR Bgee; ENSMUSG00000037364; Expressed in retinal neural layer and 62 other tissues. DR Genevisible; Q99MR6; MM. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0006397; P:mRNA processing; IEA:InterPro. DR GO; GO:0097150; P:neuronal stem cell population maintenance; IMP:UniProtKB. DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:CACAO. DR GO; GO:0031053; P:primary miRNA processing; IMP:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB. DR InterPro; IPR035979; RBD_domain_sf. DR InterPro; IPR039727; SE/Ars2. DR InterPro; IPR007042; SERRATE/Ars2_C. DR InterPro; IPR021933; SERRATE/Ars2_N. DR PANTHER; PTHR13165; PTHR13165; 2. DR Pfam; PF04959; ARS2; 1. DR Pfam; PF12066; SERRATE_Ars2_N; 1. DR SUPFAM; SSF54928; SSF54928; 1. PE 1: Evidence at protein level; KW Acetylation; Activator; Alternative splicing; Cytoplasm; Isopeptide bond; KW Methylation; Nucleus; Phosphoprotein; Reference proteome; KW RNA-mediated gene silencing; Transcription; Transcription regulation; KW Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT CHAIN 2..875 FT /note="Serrate RNA effector molecule homolog" FT /id="PRO_0000220966" FT COMPBIAS 10..82 FT /note="Arg-rich" FT COMPBIAS 258..401 FT /note="Glu-rich" FT COMPBIAS 759..827 FT /note="Pro-rich" FT MOD_RES 2 FT /note="N-acetylglycine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 4 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 8 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 67 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 74 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 136 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 492 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 539 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 543 FT /note="Phosphothreonine" FT /evidence="ECO:0000244|PubMed:15345747, FT ECO:0000244|PubMed:19131326, ECO:0000244|PubMed:21183079" FT MOD_RES 569 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 670 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 678 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 832 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 839 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT MOD_RES 849 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT CROSSLNK 150 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q9BXP5" FT VAR_SEQ 775..779 FT /note="ILPPG -> S (in isoform B and isoform C)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_000325" FT VAR_SEQ 809..815 FT /note="Missing (in isoform C and isoform D)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16141072" FT /id="VSP_000326" FT CONFLICT 567 FT /note="E -> G (in Ref. 3; BAE29458)" FT /evidence="ECO:0000305" SQ SEQUENCE 875 AA; 100452 MW; 9571445674452886 CRC64; MGDSDDEYDR RRRDKFRRER SDYDRSRERD ERRRGDDWND REWDRGRERR SRGEYRDYDR NRRERFSPPR HELSPPQKRM RRDWDEHSSD PYHSGYDMPY AGGGGGPTYG PPQPWGHPDV HIMQHHVLPI QARLGSIAEI DLGVPPPIMK SFKEFLLSLD DSVDETEAVK RYNDYKLDFR RQQMQDFFLA HKDEEWFRSK YHPDEVGKRR QEARGALQNR LKVFLSLMES GWFDNLLLDI DKADAIVKML DAAVIKMEGG TENDLRILEQ EEEEEQAGKT GEASKKEEAR AGPALGEGER KANDKDEKKE DGKQAENDSS NDDKTKKSEG DGDKEEKKEE AEKEAKKSKK RNRKQSGDDS FDEGSVSESE SESEGGQAEE EKEEAEEALK EKEKPKEEEK EKPKDAAGLE CKPRPLHKTC SLFMRNIAPN ISRAEIISLC KRYPGFMRVA LSEPQPERRF FRRGWVTFDR SVNIKEICWN LQNIRLRECE LSPGVNRDLT RRVRNINGIT QHKQIVRNDI KLAAKLIHTL DDRTQLWASE PGTPPVPTSL PSQNPILKNI TDYLIEEVSA EEEELLGSSG GPPPEEPPKE GNPAEINVER DEKLIKVLDK LLLYLRIVHS LDYYNTCEYP NEDEMPNRCG IIHVRGPMPP NRISHGEVLE WQKTFEEKLT PLLSVRESLS EEEAQKMGRK DPEQEVEKFV TSNTQELGKD KWLCPLSGKK FKGPEFVRKH IFNKHAEKIE EVKKEVAFFN NFLTDAKRPA LPEIKPAQPP GPAQILPPGL TPGLPYPHQT PQGLMPYGQP RPPILGYGAG AVRPAVPTGG PPYPHAPYGA GRGNYDAFRG QGGYPGKPRN RMVRGDPRAI VEYRDLDAPD DVDFF //