ID STIL_HUMAN Reviewed; 1287 AA. AC Q15468; Q5T0C5; Q68CN9; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 09-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 167. DE RecName: Full=SCL-interrupting locus protein; DE AltName: Full=TAL-1-interrupting locus protein; GN Name=STIL; Synonyms=SIL; 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), CHROMOSOMAL REARRANGEMENT, AND RP TISSUE SPECIFICITY. RC TISSUE=Bone marrow; RX PubMed=1922059; DOI=10.1128/mcb.11.11.5462-5469.1991; RA Aplan P.D., Lombardi D.P., Kirsch I.R.; RT "Structural characterization of SIL, a gene frequently disrupted in T-cell RT acute lymphoblastic leukemia."; RL Mol. Cell. Biol. 11:5462-5469(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), AND RP VARIANTS VAL-86 AND ARG-1012. RX PubMed=12438740; DOI=10.1159/000064057; RA Karkera J.D., Izraeli S., Roessler E., Dutra A., Kirsch I.R., Muenke M.; RT "The genomic structure, chromosomal localization, and analysis of SIL as a RT candidate gene for holoprosencephaly."; RL Cytogenet. Genome Res. 97:62-67(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS VAL-86 AND RP ARG-984. RC TISSUE=Uterus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [6] RP CHROMOSOMAL REARRANGEMENT. RX PubMed=2209547; DOI=10.1002/j.1460-2075.1990.tb07535.x; RA Brown L., Cheng J.-T., Chen Q., Siciliano M.J., Crist W., Buchanan G., RA Baer R.; RT "Site-specific recombination of the tal-1 gene is a common occurrence in RT human T cell leukemia."; RL EMBO J. 9:3343-3351(1990). RN [7] RP CHROMOSOMAL REARRANGEMENT. RX PubMed=2255914; DOI=10.1126/science.2255914; RA Aplan P.D., Lombardi D.P., Ginsberg A.M., Cossman J., Bertness V.L., RA Kirsch I.R.; RT "Disruption of the human SCL locus by 'illegitimate' V-(D)-J recombinase RT activity."; RL Science 250:1426-1429(1990). RN [8] RP CHROMOSOMAL REARRANGEMENT. RX PubMed=1311214; RA Aplan P.D., Lombardi D.P., Reaman G.H., Sather H.N., Hammond G.D., RA Kirsch I.R.; RT "Involvement of the putative hematopoietic transcription factor SCL in T- RT cell acute lymphoblastic leukemia."; RL Blood 79:1327-1333(1992). RN [9] RP FUNCTION, AND INDUCTION. RX PubMed=9372240; RA Izraeli S., Colaizzo-Anas T., Bertness V.L., Mani K., Aplan P.D., RA Kirsch I.R.; RT "Expression of the SIL gene is correlated with growth induction and RT cellular proliferation."; RL Cell Growth Differ. 8:1171-1179(1997). RN [10] RP CHROMOSOMAL REARRANGEMENT. RX PubMed=11390401; DOI=10.1074/jbc.m103797200; RA Raghavan S.C., Kirsch I.R., Lieber M.R.; RT "Analysis of the V(D)J recombination efficiency at lymphoid chromosomal RT translocation breakpoints."; RL J. Biol. Chem. 276:29126-29133(2001). RN [11] RP CHROMOSOMAL REARRANGEMENT. RX PubMed=12681356; DOI=10.1016/s0145-2126(02)00260-6; RA Curry J.D., Smith M.T.; RT "Measurement of SIL-TAL1 fusion gene transcripts associated with human T- RT cell lymphocytic leukemia by real-time reverse transcriptase-PCR."; RL Leuk. Res. 27:575-582(2003). RN [12] RP CHROMOSOMAL REARRANGEMENT. RX PubMed=14504110; DOI=10.1182/blood-2003-05-1495; RA Cave H., Suciu S., Preudhomme C., Poppe B., Robert A., Uyttebroeck A., RA Malet M., Boutard P., Benoit Y., Mauvieux L., Lutz P., Mechinaud F., RA Grardel N., Mazingue F., Dupont M., Margueritte G., Pages M.-P., RA Bertrand Y., Plouvier E., Brunie G., Bastard C., Plantaz D., RA Vande Velde I., Hagemeijer A., Speleman F., Lessard M., Otten J., RA Vilmer E., Dastugue N.; RT "Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of RT HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: RT results of EORTC studies 58881 and 58951."; RL Blood 103:442-450(2004). RN [13] RP TISSUE SPECIFICITY. RX PubMed=15107824; DOI=10.1038/sj.onc.1207685; RA Erez A., Perelman M., Hewitt S.M., Cojacaru G., Goldberg I., Shahar I., RA Yaron P., Muler I., Campaner S., Amariglio N., Rechavi G., Kirsch I.R., RA Krupsky M., Kaminski N., Izraeli S.; RT "Sil overexpression in lung cancer characterizes tumors with increased RT mitotic activity."; RL Oncogene 23:5371-5377(2004). RN [14] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=16024801; DOI=10.1128/mcb.25.15.6660-6672.2005; RA Campaner S., Kaldis P., Izraeli S., Kirsch I.R.; RT "Sil phosphorylation in a Pin1 binding domain affects the duration of the RT spindle checkpoint."; RL Mol. Cell. Biol. 25:6660-6672(2005). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-753, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [16] RP INVOLVEMENT IN MCPH7. RX PubMed=19215732; DOI=10.1016/j.ajhg.2009.01.017; RA Kumar A., Girimaji S.C., Duvvari M.R., Blanton S.H.; RT "Mutations in STIL, encoding a pericentriolar and centrosomal protein, RT cause primary microcephaly."; RL Am. J. Hum. Genet. 84:286-290(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1135, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [18] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH CENPJ, FORMATION RP OF A COMPLEX WITH CENPJ AND SASS6, AND UBIQUITINATION. RX PubMed=22020124; DOI=10.1038/emboj.2011.378; RA Tang C.J., Lin S.Y., Hsu W.B., Lin Y.N., Wu C.T., Lin Y.C., Chang C.W., RA Wu K.S., Tang T.K.; RT "The human microcephaly protein STIL interacts with CPAP and is required RT for procentriole formation."; RL EMBO J. 30:4790-4804(2011). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395; SER-779 AND SER-1135, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP SUBCELLULAR LOCATION, AND INTERACTION WITH RBM14 AND CENPJ. RX PubMed=25385835; DOI=10.15252/embj.201488979; RA Shiratsuchi G., Takaoka K., Ashikawa T., Hamada H., Kitagawa D.; RT "RBM14 prevents assembly of centriolar protein complexes and maintains RT mitotic spindle integrity."; RL EMBO J. 34:97-114(2015). RN [22] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-64 AND ARG-67, AND RP INTERACTION WITH CEP85. RX PubMed=29712910; DOI=10.1038/s41467-018-04122-x; RA Liu Y., Gupta G.D., Barnabas D.D., Agircan F.G., Mehmood S., Wu D., RA Coyaud E., Johnson C.M., McLaughlin S.H., Andreeva A., Freund S.M.V., RA Robinson C.V., Cheung S.W.T., Raught B., Pelletier L., van Breugel M.; RT "Direct binding of CEP85 to STIL ensures robust PLK4 activation and RT efficient centriole assembly."; RL Nat. Commun. 9:1731-1731(2018). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CEP85. RX PubMed=32107292; DOI=10.1242/jcs.238352; RA Liu Y., Kim J., Philip R., Sridhar V., Chandrashekhar M., Moffat J., RA van Breugel M., Pelletier L.; RT "Direct interaction between CEP85 and STIL mediates PLK4-driven directed RT cell migration."; RL J. Cell Sci. 133:0-0(2020). RN [24] RP VARIANT MCPH7 TRP-798. RX PubMed=22989186; DOI=10.1111/j.1399-0004.2012.01949.x; RA Papari E., Bastami M., Farhadi A., Abedini S.S., Hosseini M., Bahman I., RA Mohseni M., Garshasbi M., Moheb L.A., Behjati F., Kahrizi K., Ropers H.H., RA Najmabadi H.; RT "Investigation of primary microcephaly in Bushehr province of Iran: novel RT STIL and ASPM mutations."; RL Clin. Genet. 83:488-490(2013). CC -!- FUNCTION: Immediate-early gene. Plays an important role in embryonic CC development as well as in cellular growth and proliferation; its long- CC term silencing affects cell survival and cell cycle distribution as CC well as decreases CDK1 activity correlated with reduced phosphorylation CC of CDK1. Plays a role as a positive regulator of the sonic hedgehog CC pathway, acting downstream of PTCH1 (PubMed:16024801, PubMed:9372240). CC Plays an important role in the regulation of centriole duplication. CC Required for the onset of procentriole formation and proper mitotic CC progression. During procentriole formation, is essential for the CC correct loading of SASS6 and CENPJ to the base of the procentriole to CC initiate procentriole assembly (PubMed:22020124). In complex with STIL CC acts as a modulator of PLK4-driven cytoskeletal rearrangements and CC directional cell motility (PubMed:32107292, PubMed:29712910). CC {ECO:0000269|PubMed:16024801, ECO:0000269|PubMed:22020124, CC ECO:0000269|PubMed:29712910, ECO:0000269|PubMed:32107292, CC ECO:0000269|PubMed:9372240}. CC -!- SUBUNIT: Homodimer (PubMed:22020124). Interacts with PIN1 via its WW CC domain. This interaction is dependent on STIL mitotic phosphorylation CC (By similarity). Interacts with CENPJ (PubMed:22020124, CC PubMed:25385835). Interacts with RBM14 and this interaction interferes CC with the interaction of STIL with CENPJ (PubMed:25385835). Forms a CC complex with CENPJ and SASS6 (PubMed:22020124). Interacts (via N- CC terminus) with CEP85; this interaction is essential for efficient CC centriolar targeting of STIL and subsequent PLK4 activation CC (PubMed:29712910). {ECO:0000250|UniProtKB:Q60988, CC ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:25385835, CC ECO:0000269|PubMed:29712910}. CC -!- INTERACTION: CC Q15468; Q9HC77: CENPJ; NbExp=15; IntAct=EBI-7488405, EBI-946194; CC Q15468; O00444: PLK4; NbExp=11; IntAct=EBI-7488405, EBI-746202; CC Q15468; Q6UVJ0: SASS6; NbExp=4; IntAct=EBI-7488405, EBI-1570153; CC Q15468; Q15468: STIL; NbExp=4; IntAct=EBI-7488405, EBI-7488405; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q60988}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome, centriole {ECO:0000269|PubMed:22020124, CC ECO:0000269|PubMed:25385835, ECO:0000269|PubMed:29712910}. Cytoplasm, CC cell cortex {ECO:0000269|PubMed:32107292}. Note=Localizes at the CC leading edge. {ECO:0000269|PubMed:32107292}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q15468-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15468-2; Sequence=VSP_022301; CC -!- TISSUE SPECIFICITY: Expressed in all hematopoietic tissues and cell CC lines. Highly expressed in a variety of tumors characterized by CC increased mitotic activity with highest expression in lung cancer. CC {ECO:0000269|PubMed:15107824, ECO:0000269|PubMed:1922059}. CC -!- INDUCTION: Down-regulated when cell proliferation ceased. Accumulates CC during G2 phase and falls at completion of the cell cycle. CC {ECO:0000269|PubMed:9372240}. CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:22020124}. CC -!- PTM: Phosphorylated following the activation of the mitotic checkpoint. CC {ECO:0000269|PubMed:16024801}. CC -!- DISEASE: Note=A chromosomal aberration involving STIL may be a cause of CC some T-cell acute lymphoblastic leukemias (T-ALL). A deletion at 1p32 CC between STIL and TAL1 genes leads to STIL/TAL1 fusion mRNA with STIL CC exon 1 splicing to TAL1 exon 3. As both STIL exon 1 and TAL1 exon 3 are CC 5'-untranslated exons, STIL/TAL1 fusion mRNA predicts a full-length CC TAL1 protein under the control of the STIL promoter, leading to CC inappropriate TAL1 expression. In childhood T-cell malignancies (T- CC ALL), a type of defect such as STIL/TAL1 fusion is associated with a CC good prognosis. In cultured lymphocytes from healthy adults, STIL/TAL1 CC fusion mRNA may be detected after 7 days of culture. CC {ECO:0000269|PubMed:11390401, ECO:0000269|PubMed:12681356, CC ECO:0000269|PubMed:1311214, ECO:0000269|PubMed:14504110, CC ECO:0000269|PubMed:1922059, ECO:0000269|PubMed:2209547, CC ECO:0000269|PubMed:2255914}. CC -!- DISEASE: Microcephaly 7, primary, autosomal recessive (MCPH7) CC [MIM:612703]: A disease defined as a head circumference more than 3 CC standard deviations below the age-related mean. Brain weight is CC markedly reduced and the cerebral cortex is disproportionately small. CC Despite this marked reduction in size, the gyral pattern is relatively CC well preserved, with no major abnormality in cortical architecture. CC Affected individuals are mentally retarded. Primary microcephaly is CC further defined by the absence of other syndromic features or CC significant neurological deficits due to degenerative brain disorder. CC {ECO:0000269|PubMed:19215732, ECO:0000269|PubMed:22989186}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/524/SIL"; 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; M74558; AAA60550.1; -; mRNA. DR EMBL; AF349657; AAK51418.1; -; Genomic_DNA. DR EMBL; AF349642; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349643; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349645; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349647; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349649; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349651; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349653; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349656; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349655; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349654; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349652; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349650; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349648; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349646; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; AF349644; AAK51418.1; JOINED; Genomic_DNA. DR EMBL; CR749851; CAH18699.1; -; mRNA. DR EMBL; AL513322; CAI13468.1; -; Genomic_DNA. DR EMBL; AL135960; CAI13468.1; JOINED; Genomic_DNA. DR EMBL; AL135960; CAI19733.1; -; Genomic_DNA. DR EMBL; AL513322; CAI19733.1; JOINED; Genomic_DNA. DR EMBL; BC126223; AAI26224.1; -; mRNA. DR CCDS; CCDS41329.1; -. [Q15468-2] DR CCDS; CCDS548.1; -. [Q15468-1] DR PIR; A41685; A41685. DR RefSeq; NP_001041631.1; NM_001048166.1. [Q15468-2] DR RefSeq; NP_001269865.1; NM_001282936.1. [Q15468-1] DR RefSeq; NP_001269866.1; NM_001282937.1. DR RefSeq; NP_001269867.1; NM_001282938.1. DR RefSeq; NP_001269868.1; NM_001282939.1. DR RefSeq; NP_003026.2; NM_003035.2. [Q15468-1] DR RefSeq; XP_006710897.1; XM_006710834.3. [Q15468-2] DR RefSeq; XP_011540293.1; XM_011541991.2. [Q15468-2] DR RefSeq; XP_011540294.1; XM_011541992.2. [Q15468-2] DR PDB; 4YYP; X-ray; 2.60 A; B=720-751. DR PDB; 5LHW; X-ray; 0.91 A; A=726-750. DR PDB; 5LHZ; X-ray; 2.51 A; D/E/F=726-750. DR PDB; 8OYK; X-ray; 1.65 A; A=718-749. DR PDB; 8OYL; X-ray; 1.67 A; A/B/C/D/E/F=718-749. DR PDBsum; 4YYP; -. DR PDBsum; 5LHW; -. DR PDBsum; 5LHZ; -. DR PDBsum; 8OYK; -. DR PDBsum; 8OYL; -. DR AlphaFoldDB; Q15468; -. DR SMR; Q15468; -. DR BioGRID; 112382; 187. DR ComplexPortal; CPX-1159; CPAP-STIL complex. DR DIP; DIP-60580N; -. DR IntAct; Q15468; 88. DR MINT; Q15468; -. DR STRING; 9606.ENSP00000360944; -. DR iPTMnet; Q15468; -. DR PhosphoSitePlus; Q15468; -. DR BioMuta; STIL; -. DR DMDM; 122070597; -. DR EPD; Q15468; -. DR jPOST; Q15468; -. DR MassIVE; Q15468; -. DR MaxQB; Q15468; -. DR PaxDb; 9606-ENSP00000360944; -. DR PeptideAtlas; Q15468; -. DR ProteomicsDB; 60604; -. [Q15468-1] DR ProteomicsDB; 60605; -. [Q15468-2] DR Pumba; Q15468; -. DR Antibodypedia; 53510; 122 antibodies from 18 providers. DR DNASU; 6491; -. DR Ensembl; ENST00000360380.7; ENSP00000353544.3; ENSG00000123473.17. [Q15468-1] DR Ensembl; ENST00000371877.8; ENSP00000360944.3; ENSG00000123473.17. [Q15468-2] DR GeneID; 6491; -. DR KEGG; hsa:6491; -. DR MANE-Select; ENST00000371877.8; ENSP00000360944.3; NM_001048166.1; NP_001041631.1. [Q15468-2] DR UCSC; uc001crd.2; human. [Q15468-1] DR AGR; HGNC:10879; -. DR CTD; 6491; -. DR DisGeNET; 6491; -. DR GeneCards; STIL; -. DR HGNC; HGNC:10879; STIL. DR HPA; ENSG00000123473; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; STIL; -. DR MIM; 181590; gene. DR MIM; 612703; phenotype. DR neXtProt; NX_Q15468; -. DR OpenTargets; ENSG00000123473; -. DR Orphanet; 93925; Alobar holoprosencephaly. DR Orphanet; 2512; Autosomal recessive primary microcephaly. DR Orphanet; 93924; Lobar holoprosencephaly. DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR Orphanet; 220386; Semilobar holoprosencephaly. DR Orphanet; 280195; Septopreoptic holoprosencephaly. DR PharmGKB; PA35780; -. DR VEuPathDB; HostDB:ENSG00000123473; -. DR eggNOG; ENOG502QVJ5; Eukaryota. DR GeneTree; ENSGT00390000007310; -. DR InParanoid; Q15468; -. DR OMA; CKCGYLT; -. DR OrthoDB; 2912266at2759; -. DR PhylomeDB; Q15468; -. DR TreeFam; TF331178; -. DR PathwayCommons; Q15468; -. DR SignaLink; Q15468; -. DR SIGNOR; Q15468; -. DR BioGRID-ORCS; 6491; 479 hits in 1155 CRISPR screens. DR ChiTaRS; STIL; human. DR GeneWiki; STIL; -. DR GenomeRNAi; 6491; -. DR Pharos; Q15468; Tbio. DR PRO; PR:Q15468; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q15468; Protein. DR Bgee; ENSG00000123473; Expressed in secondary oocyte and 160 other cell types or tissues. DR ExpressionAtlas; Q15468; baseline and differential. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0120099; C:procentriole replication complex; IPI:ComplexPortal. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0051298; P:centrosome duplication; IDA:MGI. DR GO; GO:0007368; P:determination of left/right symmetry; ISS:BHF-UCL. DR GO; GO:0000578; P:embryonic axis specification; ISS:BHF-UCL. DR GO; GO:0033504; P:floor plate development; ISS:BHF-UCL. DR GO; GO:0030900; P:forebrain development; ISS:BHF-UCL. DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL. DR GO; GO:0001701; P:in utero embryonic development; ISS:BHF-UCL. DR GO; GO:0007052; P:mitotic spindle organization; IMP:MGI. DR GO; GO:0035264; P:multicellular organism growth; ISS:BHF-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL. DR GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL. DR GO; GO:0021915; P:neural tube development; ISS:BHF-UCL. DR GO; GO:0030903; P:notochord development; ISS:BHF-UCL. DR GO; GO:0046601; P:positive regulation of centriole replication; IDA:ComplexPortal. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IDA:ComplexPortal. DR GO; GO:1905832; P:positive regulation of spindle assembly; NAS:ComplexPortal. DR GO; GO:0071539; P:protein localization to centrosome; IMP:MGI. DR GO; GO:0046599; P:regulation of centriole replication; IMP:UniProtKB. DR GO; GO:0060236; P:regulation of mitotic spindle organization; NAS:ComplexPortal. DR GO; GO:0007224; P:smoothened signaling pathway; ISS:BHF-UCL. DR InterPro; IPR026123; Sil. DR PANTHER; PTHR15128:SF0; SCL-INTERRUPTING LOCUS PROTEIN; 1. DR PANTHER; PTHR15128; TAL1 SCL INTERRUPTING LOCUS; 1. DR Pfam; PF15253; STIL_N; 1. DR Genevisible; Q15468; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Chromosomal rearrangement; KW Cytoplasm; Cytoskeleton; Developmental protein; Disease variant; KW Intellectual disability; Phosphoprotein; Primary microcephaly; KW Proto-oncogene; Reference proteome; Ubl conjugation. FT CHAIN 1..1287 FT /note="SCL-interrupting locus protein" FT /id="PRO_0000271332" FT REGION 1..1018 FT /note="Interaction with RBM14" FT /evidence="ECO:0000269|PubMed:25385835" FT REGION 231..781 FT /note="Interaction with CENPJ" FT /evidence="ECO:0000269|PubMed:22020124, FT ECO:0000269|PubMed:25385835" FT REGION 378..417 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 508..533 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 584..779 FT /note="PIN1-binding" FT /evidence="ECO:0000250" FT COMPBIAS 387..405 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 518..533 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 395 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 753 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 779 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1135 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 872 FT /note="N -> NS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_022301" FT VARIANT 86 FT /note="A -> V (in dbSNP:rs3125630)" FT /evidence="ECO:0000269|PubMed:12438740, FT ECO:0000269|PubMed:17974005" FT /id="VAR_029870" FT VARIANT 798 FT /note="L -> W (in MCPH7; dbSNP:rs398122976)" FT /evidence="ECO:0000269|PubMed:22989186" FT /id="VAR_072404" FT VARIANT 984 FT /note="H -> R (in dbSNP:rs13376679)" FT /evidence="ECO:0000269|PubMed:17974005" FT /id="VAR_029871" FT VARIANT 1012 FT /note="P -> R" FT /evidence="ECO:0000269|PubMed:12438740" FT /id="VAR_029872" FT VARIANT 1145 FT /note="A -> V (in dbSNP:rs3766317)" FT /id="VAR_051386" FT MUTAGEN 64 FT /note="L->A: Reduced centriole localization; when FT associated with 67-A. Does not fully rescue the centriole FT duplication defect in STIL depleted cells." FT /evidence="ECO:0000269|PubMed:29712910" FT MUTAGEN 67 FT /note="R->A: Reduced centriole localization; when FT associated with 64-A. Does not fully rescue the centriole FT duplication defect in STIL depleted cells." FT /evidence="ECO:0000269|PubMed:29712910" FT CONFLICT 70..71 FT /note="KQ -> NE (in Ref. 1; AAA60550 and 2; AAK51418)" FT /evidence="ECO:0000305" FT HELIX 726..746 FT /evidence="ECO:0007829|PDB:5LHW" SQ SEQUENCE 1287 AA; 142955 MW; 7F15BEDA8717659C CRC64; MEPIYPFARP QMNTRFPSSR MVPFHFPPSK CALWNPTPTG DFIYLHLSYY RNPKLVVTEK TIRLAYRHAK QNKKNSSCFL LGSLTADEDE EGVTLTVDRF DPGREVPECL EITPTASLPG DFLIPCKVHT QELCSREMIV HSVDDFSSAL KALQCHICSK DSLDCGKLLS LRVHITSRES LDSVEFDLHW AAVTLANNFK CTPVKPIPII PTALARNLSS NLNISQVQGT YKYGYLTMDE TRKLLLLLES DPKVYSLPLV GIWLSGITHI YSPQVWACCL RYIFNSSVQE RVFSESGNFI IVLYSMTHKE PEFYECFPCD GKIPDFRFQL LTSKETLHLF KNVEPPDKNP IRCELSAESQ NAETEFFSKA SKNFSIKRSS QKLSSGKMPI HDHDSGVEDE DFSPRPIPSP HPVSQKISKI QPSVPELSLV LDGNFIESNP LPTPLEMVNN ENPPLINHLE HLKPLQPQLY DEKHSPEVEA GEPSLRGIPN QLNQDKPALL RHCKVRQPPA YKKGNPHTRN SIKPSSHNGP SHDIFEKLQT VSAGNVQNEE YPIRPSTLNS RQSSLAPQSQ PHDFVFSPHN SGRPMELQIP TPPLPSYCST NVCRCCQHHS HIQYSPLNSW QGANTVGSIQ DVQSEALQKH SLFHPSGCPA LYCNAFCSSS SPIALRPQGD MGSCSPHSNI EPSPVARPPS HMDLCNPQPC TVCMHTPKTE SDNGMMGLSP DAYRFLTEQD RQLRLLQAQI QRLLEAQSLM PCSPKTTAVE DTVQAGRQME LVSVEAQSSP GLHMRKGVSI AVSTGASLFW NAAGEDQEPD SQMKQDDTKI SSEDMNFSVD INNEVTSLPG SASSLKAVDI PSFEESNIAV EEEFNQPLSV SNSSLVVRKE PDVPVFFPSG QLAESVSMCL QTGPTGGASN NSETSEEPKI EHVMQPLLHQ PSDNQKIYQD LLGQVNHLLN SSSKETEQPS TKAVIISHEC TRTQNVYHTK KKTHHSRLVD KDCVLNATLK QLRSLGVKID SPTKVKKNAH NVDHASVLAC ISPEAVISGL NCMSFANVGM SGLSPNGVDL SMEANAIALK YLNENQLSQL SVTRSNQNNC DPFSLLHINT DRSTVGLSLI SPNNMSFATK KYMKRYGLLQ SSDNSEDEEE PPDNADSKSE YLLNQNLRSI PEQLGGQKEP SKNDHEIINC SNCESVGTNA DTPVLRNITN EVLQTKAKQQ LTEKPAFLVK NLKPSPAVNL RTGKAEFTQH PEKENEGDIT IFPESLQPSE TLKQMNSMNS VGTFLDVKRL RQLPKLF //