Q15468 (STIL_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 88.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: SCL-interrupting locus protein Alternative name(s): TAL-1-interrupting locus protein | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1287 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1. Ref.9 Ref.14 |
| Subunit structure | Interacts with PIN1 via its WW domain. This interaction is dependent on STIL mitotic phosphorylation By similarity. |
| Subcellular location | |
| Tissue specificity | Expressed in all hematopoietic tissues and cell lines. Highly expressed in a variety of tumors characterized by increased mitotic activity with highest expression in lung cancer. Ref.1 Ref.13 |
| Induction | Down-regulated when cell proliferation ceased. Accumulates during G2 phase and falls at completion of the cell cycle. Ref.9 |
| Post-translational modification | Phosphorylated following the activation of the mitotic checkpoint. Ref.14 |
| Involvement in disease | A chromosomal aberration involving STIL may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). A deletion at 1p32 between STIL and TAL1 genes leads to STIL/TAL1 fusion mRNA with STIL exon 1 slicing to TAL1 exon 3. As both STIL exon 1 and TAL1 exon 3 are 5'-untranslated exons, STIL/TAL1 fusion mRNA predicts a full length TAL1 protein under the control of the STIL promoter, leading to inappropriate TAL1 expression. In childhood T-cell malignancies (T-ALL), a type of defect such as STIL/TAL1 fusion is associated with a good prognosis. In cultured lymphocytes from healthy adults, STIL/TAL1 fusion mRNA may be detected after 7 days of culture. Microcephaly, primary, 7 (MCPH7) [MIM:612703]: A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q15468-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q15468-2) The sequence of this isoform differs from the canonical sequence as follows: 872-872: N → NS | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1287 | 1287 | SCL-interrupting locus protein | PRO_0000271332 | |||||
Regions | |||||||||
| Region | 584 – 779 | 196 | PIN1-binding By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 753 | 1 | Phosphoserine Ref.15 | ||||||
| Modified residue | 1135 | 1 | Phosphoserine Ref.17 | ||||||
Natural variations | |||||||||
| Alternative sequence | 872 | 1 | N → NS in isoform 2. | VSP_022301 | |||||
| Natural variant | 86 | 1 | A → V. Ref.2 Ref.3 Corresponds to variant rs3125630 [ dbSNP | Ensembl ]. | VAR_029870 | |||||
| Natural variant | 984 | 1 | H → R. Ref.3 Corresponds to variant rs13376679 [ dbSNP | Ensembl ]. | VAR_029871 | |||||
| Natural variant | 1012 | 1 | P → R. Ref.2 | VAR_029872 | |||||
| Natural variant | 1145 | 1 | A → V. Corresponds to variant rs3766317 [ dbSNP | Ensembl ]. | VAR_051386 | |||||
Experimental info | |||||||||
| Sequence conflict | 70 – 71 | 2 | KQ → NE in AAA60550. Ref.1 | ||||||
| Sequence conflict | 70 – 71 | 2 | KQ → NE in AAK51418. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia." Aplan P.D., Lombardi D.P., Kirsch I.R. Mol. Cell. Biol. 11:5462-5469(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL REARRANGEMENT, TISSUE SPECIFICITY. Tissue: Bone marrow. |
| [2] | "The genomic structure, chromosomal localization, and analysis of SIL as a candidate gene for holoprosencephaly." Karkera J.D., Izraeli S., Roessler E., Dutra A., Kirsch I.R., Muenke M. Cytogenet. Genome Res. 97:62-67(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), VARIANTS VAL-86 AND ARG-1012. |
| [3] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS VAL-86 AND ARG-984. Tissue: Uterus. |
| [4] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [6] | "Site-specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia." Brown L., Cheng J.-T., Chen Q., Siciliano M.J., Crist W., Buchanan G., Baer R. EMBO J. 9:3343-3351(1990) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL REARRANGEMENT. |
| [7] | "Disruption of the human SCL locus by 'illegitimate' V-(D)-J recombinase activity." Aplan P.D., Lombardi D.P., Ginsberg A.M., Cossman J., Bertness V.L., Kirsch I.R. Science 250:1426-1429(1990) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL REARRANGEMENT. |
| [8] | "Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia." Aplan P.D., Lombardi D.P., Reaman G.H., Sather H.N., Hammond G.D., Kirsch I.R. Blood 79:1327-1333(1992) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL REARRANGEMENT. |
| [9] | "Expression of the SIL gene is correlated with growth induction and cellular proliferation." Izraeli S., Colaizzo-Anas T., Bertness V.L., Mani K., Aplan P.D., Kirsch I.R. Cell Growth Differ. 8:1171-1179(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION. |
| [10] | "Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints." Raghavan S.C., Kirsch I.R., Lieber M.R. J. Biol. Chem. 276:29126-29133(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL REARRANGEMENT. |
| [11] | "Measurement of SIL-TAL1 fusion gene transcripts associated with human T-cell lymphocytic leukemia by real-time reverse transcriptase-PCR." Curry J.D., Smith M.T. Leuk. Res. 27:575-582(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL REARRANGEMENT. |
| [12] | "Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951." Cave H., Suciu S., Preudhomme C., Poppe B., Robert A., Uyttebroeck A., Malet M., Boutard P., Benoit Y., Mauvieux L., Lutz P., Mechinaud F., Grardel N., Mazingue F., Dupont M., Margueritte G., Pages M.-P., Bertrand Y. Dastugue N.Blood 103:442-450(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL REARRANGEMENT. |
| [13] | "Sil overexpression in lung cancer characterizes tumors with increased mitotic activity." Erez A., Perelman M., Hewitt S.M., Cojacaru G., Goldberg I., Shahar I., Yaron P., Muler I., Campaner S., Amariglio N., Rechavi G., Kirsch I.R., Krupsky M., Kaminski N., Izraeli S. Oncogene 23:5371-5377(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [14] | "Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint." Campaner S., Kaldis P., Izraeli S., Kirsch I.R. Mol. Cell. Biol. 25:6660-6672(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION. |
| [15] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-753, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [16] | "Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly." Kumar A., Girimaji S.C., Duvvari M.R., Blanton S.H. Am. J. Hum. Genet. 84:286-290(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MCPH7. |
| [17] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1135, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | M74558 mRNA. Translation: AAA60550.1. AF349657 AF349644 Genomic DNA. Translation: AAK51418.1.CR749851 mRNA. Translation: CAH18699.1. AL513322, AL135960 Genomic DNA. Translation: CAI13468.1. AL135960, AL513322 Genomic DNA. Translation: CAI19733.1. BC126223 mRNA. Translation: AAI26224.1. |
| IPI | IPI00328131. IPI00745920. |
| PIR | A41685. |
| RefSeq | NP_001041631.1. NM_001048166.1. NP_003026.2. NM_003035.2. |
| UniGene | Hs.525198. |
3D structure databases | |
| ProteinModelPortal | Q15468. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | 9606.ENSP00000360944. |
PTM databases | |
| PhosphoSite | Q15468. |
Polymorphism databases | |
| DMDM | 122070597. |
Proteomic databases | |
| PaxDb | Q15468. |
| PRIDE | Q15468. |
Protocols and materials databases | |
| DNASU | 6491. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000243182; ENSP00000243182; ENSG00000123473. ENST00000337817; ENSP00000337367; ENSG00000123473. ENST00000360380; ENSP00000353544; ENSG00000123473. ENST00000371877; ENSP00000360944; ENSG00000123473. |
| GeneID | 6491. |
| KEGG | hsa:6491. |
| UCSC | uc001crc.1. human. uc001crd.1. human. |
Organism-specific databases | |
| CTD | 6491. |
| GeneCards | GC01M047715. |
| HGNC | HGNC:10879. STIL. |
| MIM | 181590. gene. 612703. phenotype. |
| neXtProt | NX_Q15468. |
| Orphanet | 2512. Autosomal recessive primary microcephaly. 99861. Precursor T-cell acute lymphoblastic leukemia. |
| PharmGKB | PA35780. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG39781. |
| HOGENOM | HOG000231284. |
| HOVERGEN | HBG079548. |
| KO | K16724. |
| OMA | ACISPEA. |
| OrthoDB | EOG447FT1. |
| PhylomeDB | Q15468. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | hedgehog_2pathway. Signaling events mediated by the Hedgehog family. |
Gene expression databases | |
| ArrayExpress | Q15468. |
| Bgee | Q15468. |
| CleanEx | HS_STIL. |
| Genevestigator | Q15468. |
Family and domain databases | |
| InterPro | IPR026123. Sil. [Graphical view] |
| PANTHER | PTHR15128. PTHR15128. 1 hit. |
| ProtoNet | Search... |
Other | |
| GenomeRNAi | 6491. |
| NextBio | 25225. |
| SOURCE | Search... |
Entry information
| Entry name | STIL_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q15468 Secondary accession number(s): Q5T0C5, Q68CN9 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |

Clusters with
