ID INT8_HUMAN Reviewed; 995 AA. AC Q75QN2; B2RN92; Q5RKZ3; Q6P1R5; Q7Z314; Q9NVS6; Q9NWY7; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 07-OCT-2020, entry version 141. DE RecName: Full=Integrator complex subunit 8; DE Short=Int8; DE AltName: Full=Protein kaonashi-1; GN Name=INTS8; Synonyms=C8orf52; 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 [MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Atsushi S., Asakawa S., Shimizu N.; RT "Novel gene with no significant domain."; RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, Testis, and Uterus; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 180-995 (ISOFORM 2). RC TISSUE=Rectum tumor; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 307-995 (ISOFORM 1). RC TISSUE=Carcinoma, and Teratocarcinoma; 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [6] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE INTEGRATOR RP COMPLEX. RX PubMed=16239144; DOI=10.1016/j.cell.2005.08.019; RA Baillat D., Hakimi M.-A., Naeaer A.M., Shilatifard A., Cooch N., RA Shiekhattar R.; RT "Integrator, a multiprotein mediator of small nuclear RNA processing, RT associates with the C-terminal repeat of RNA polymerase II."; RL Cell 123:265-276(2005). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-18, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP VARIANTS NEDCHS GLY-298 AND 973-GLU--LEU-975 DEL, CHARACTERIZATION OF RP VARIANTS NEDCHS GLY-298 AND 973-GLU--LEU-975 DEL, DEVELOPMENTAL STAGE, AND RP FUNCTION. RX PubMed=28542170; DOI=10.1371/journal.pgen.1006809; RA Oegema R., Baillat D., Schot R., van Unen L.M., Brooks A., Kia S.K., RA Hoogeboom A.J.M., Xia Z., Li W., Cesaroni M., Lequin M.H., RA van Slegtenhorst M., Dobyns W.B., de Coo I.F.M., Verheijen F.W., Kremer A., RA van der Spek P.J., Heijsman D., Wagner E.J., Fornerod M., Mancini G.M.S.; RT "Human mutations in integrator complex subunits link transcriptome RT integrity to brain development."; RL PLoS Genet. 13:e1006809-e1006809(2017). CC -!- FUNCTION: Component of the Integrator complex, a complex involved in CC the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'- CC box-dependent processing. The Integrator complex is associated with the CC C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) CC and is recruited to the U1 and U2 snRNAs genes. CC {ECO:0000269|PubMed:28542170}. CC -!- SUBUNIT: Belongs to the multiprotein complex Integrator, at least CC composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, CC INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12. CC {ECO:0000269|PubMed:16239144}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q75QN2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q75QN2-2; Sequence=VSP_021469; CC -!- DEVELOPMENTAL STAGE: Highly expressed in the brain in the ventricular CC and subventricular zones, caudal and lateral ganglionic eminences and CC cerebellar primordium at 16-21 postconceptional week. CC {ECO:0000269|PubMed:28542170}. CC -!- DISEASE: Neurodevelopmental disorder with cerebellar hypoplasia and CC spasticity (NEDCHS) [MIM:618572]: An autosomal recessive CC neurodevelopmental disorder characterized by global developmental CC delay, profound intellectual disability, seizures, absent speech, CC spasticity, facial and limb dysmorphism, and subtle structural brain CC abnormalities including cerebellar hypoplasia. CC {ECO:0000269|PubMed:28542170}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the Integrator subunit 8 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH50536.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA91238.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA91671.1; 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; AB161944; BAD10863.1; -; mRNA. DR EMBL; CH471060; EAW91726.1; -; Genomic_DNA. DR EMBL; BC050536; AAH50536.1; ALT_FRAME; mRNA. DR EMBL; BC064915; AAH64915.1; -; mRNA. DR EMBL; BC136754; AAI36755.1; -; mRNA. DR EMBL; BX538203; CAD98067.1; -; mRNA. DR EMBL; AK000537; BAA91238.1; ALT_INIT; mRNA. DR EMBL; AK001403; BAA91671.1; ALT_INIT; mRNA. DR EMBL; BK005731; DAA05731.1; -; mRNA. DR CCDS; CCDS34925.1; -. [Q75QN2-1] DR RefSeq; NP_060334.2; NM_017864.3. [Q75QN2-1] DR RefSeq; XP_016869108.1; XM_017013619.1. DR SMR; Q75QN2; -. DR BioGRID; 120788; 27. DR CORUM; Q75QN2; -. DR IntAct; Q75QN2; 11. DR MINT; Q75QN2; -. DR STRING; 9606.ENSP00000430338; -. DR iPTMnet; Q75QN2; -. DR PhosphoSitePlus; Q75QN2; -. DR BioMuta; INTS8; -. DR DMDM; 74712892; -. DR EPD; Q75QN2; -. DR jPOST; Q75QN2; -. DR MassIVE; Q75QN2; -. DR MaxQB; Q75QN2; -. DR PaxDb; Q75QN2; -. DR PeptideAtlas; Q75QN2; -. DR PRIDE; Q75QN2; -. DR ProteomicsDB; 68647; -. [Q75QN2-1] DR ProteomicsDB; 68648; -. [Q75QN2-2] DR Antibodypedia; 25892; 36 antibodies. DR Ensembl; ENST00000523731; ENSP00000430338; ENSG00000164941. [Q75QN2-1] DR GeneID; 55656; -. DR KEGG; hsa:55656; -. DR UCSC; uc003yhb.5; human. [Q75QN2-1] DR CTD; 55656; -. DR DisGeNET; 55656; -. DR EuPathDB; HostDB:ENSG00000164941.13; -. DR GeneCards; INTS8; -. DR HGNC; HGNC:26048; INTS8. DR HPA; ENSG00000164941; Low tissue specificity. DR MalaCards; INTS8; -. DR MIM; 611351; gene. DR MIM; 618572; phenotype. DR neXtProt; NX_Q75QN2; -. DR OpenTargets; ENSG00000164941; -. DR PharmGKB; PA142672371; -. DR eggNOG; ENOG502QQS8; Eukaryota. DR GeneTree; ENSGT00390000007597; -. DR HOGENOM; CLU_012129_0_0_1; -. DR InParanoid; Q75QN2; -. DR KO; K13145; -. DR OMA; KYRELDC; -. DR OrthoDB; 461829at2759; -. DR PhylomeDB; Q75QN2; -. DR TreeFam; TF324241; -. DR PathwayCommons; Q75QN2; -. DR Reactome; R-HSA-6807505; RNA polymerase II transcribes snRNA genes. DR SIGNOR; Q75QN2; -. DR BioGRID-ORCS; 55656; 665 hits in 874 CRISPR screens. DR ChiTaRS; INTS8; human. DR GeneWiki; INTS8; -. DR GenomeRNAi; 55656; -. DR Pharos; Q75QN2; Tdark. DR PRO; PR:Q75QN2; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q75QN2; protein. DR Bgee; ENSG00000164941; Expressed in secondary oocyte and 241 other tissues. DR ExpressionAtlas; Q75QN2; baseline and differential. DR Genevisible; Q75QN2; HS. DR GO; GO:0032039; C:integrator complex; IDA:HGNC-UCL. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0034472; P:snRNA 3'-end processing; IBA:GO_Central. DR GO; GO:0016180; P:snRNA processing; IDA:HGNC-UCL. DR GO; GO:0042795; P:snRNA transcription by RNA polymerase II; TAS:Reactome. DR InterPro; IPR038751; Int8. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR PANTHER; PTHR13350; PTHR13350; 1. DR SUPFAM; SSF48452; SSF48452; 1. PE 1: Evidence at protein level; KW Alternative splicing; Disease mutation; Mental retardation; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; TPR repeat. FT CHAIN 1..995 FT /note="Integrator complex subunit 8" FT /id="PRO_0000259553" FT REPEAT 250..288 FT /note="TPR 1" FT REPEAT 320..356 FT /note="TPR 2" FT REPEAT 570..603 FT /note="TPR 3" FT REPEAT 833..866 FT /note="TPR 4" FT MOD_RES 18 FT /note="Phosphothreonine" FT /evidence="ECO:0000244|PubMed:17081983" FT VAR_SEQ 879..895 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_021469" FT VARIANT 298 FT /note="D -> G (in NEDCHS; occurs in a splice site resulting FT in altered splicing and probable nonsense-mediated mRNA FT decay)" FT /evidence="ECO:0000269|PubMed:28542170" FT /id="VAR_083358" FT VARIANT 973..975 FT /note="Missing (in NEDCHS; alters the assembly of the FT Integrator complex)" FT /evidence="ECO:0000269|PubMed:28542170" FT /id="VAR_083359" FT CONFLICT 778 FT /note="V -> A (in Ref. 5; BAA91238)" FT /evidence="ECO:0000305" FT CONFLICT 832 FT /note="N -> S (in Ref. 4; CAD98067)" FT /evidence="ECO:0000305" SQ SEQUENCE 995 AA; 113088 MW; 24D06E11821BD4D5 CRC64; MSAEAADREA ATSSRPCTPP QTCWFEFLLE ESLLEKHLRK PCPDPAPVQL IVQFLEQASK PSVNEQNQVQ PPPDNKRNRI LKLLALKVAA HLKWDLDILE KSLSVPVLNM LLNELLCISK VPPGTKHVDM DLATLPPTTA MAVLLYNRWA IRTIVQSSFP VKQAKPGPPQ LSVMNQMQQE KELTENILKV LKEQAADSIL VLEAALKLNK DLYVHTMRTL DLLAMEPGMV NGETESSTAG LKVKTEEMQC QVCYDLGAAY FQQGSTNSAV YENAREKFFR TKELIAEIGS LSLHCTIDEK RLAGYCQACD VLVPSSDSTS QQLTPYSQVH ICLRSGNYQE VIQIFIEDNL TLSLPVQFRQ SVLRELFKKA QQGNEALDEI CFKVCACNTV RDILEGRTIS VQFNQLFLRP NKEKIDFLLE VCSRSVNLEK ASESLKGNMA AFLKNVCLGL EDLQYVFMIS SHELFITLLK DEERKLLVDQ MRKRSPRVNL CIKPVTSFYD IPASASVNIG QLEHQLILSV DPWRIRQILI ELHGMTSERQ FWTVSNKWEV PSVYSGVILG IKDNLTRDLV YILMAKGLHC STVKDFSHAK QLFAACLELV TEFSPKLRQV MLNEMLLLDI HTHEAGTGQA GERPPSDLIS RVRGYLEMRL PDIPLRQVIA EECVAFMLNW RENEYLTLQV PAFLLQSNPY VKLGQLLAAT CKELPGPKES RRTAKDLWEV VVQICSVSSQ HKRGNDGRVS LIKQRESTLG IMYRSELLSF IKKLREPLVL TIILSLFVKL HNVREDIVND ITAEHISIWP SSIPNLQSVD FEAVAITVKE LVRYTLSINP NNHSWLIIQA DIYFATNQYS AALHYYLQAG AVCSDFFNKA VPPDVYTDQV IKRMIKCCSL LNCHTQVAIL CQFLREIDYK TAFKSLQEQN SHDAMDSYYD YIWDVTILEY LTYLHHKRGE TDKRQIAIKA IGQTELNASN PEEVLQLAAQ RRKKKFLQAM AKLYF //