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SGOL1 (shugoshin-like 1 (S. pombe))

Identity

Other namesNY-BR-85
SGO
Sgo1
HGNC (Hugo) SGOL1
LocusID (NCBI) 151648
Location 3p24.3
Location_base_pair Starts at 20209936 and ends at 20227698 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Telomeric to ZNF385D (zinc finger protein 385D); centromeric to KAT2B (lysine acetyltransferase 2B).
Note The Sgo1 gene was identified in fission yeast as a factor protecting centromeric Rec8 from degradation during meiosis I, and human Sgo1 homolog, SGOL1, was identified as a homologue of yeast Sgo1 on databases (Kitajima et al., 2004).

DNA/RNA

 
  Figure 1. Scheme of SGOL1 transcript variants. Exon numbers are shown at the top. Red and yellow boxes indicate exons of CDS and UTR, respectively.
Description The SGOL1 gene is composed of 9 exons and spans 25698 bases.
Transcription Transcript variant A2 (NM_001012410) has the longest coding sequence and encodes a protein comprised of 561 aa. Transcript variant A1 (NM_001012409) lacks exon 9 and encodes a protein comprised of 527 aa. Typically, "SGOL1" corresponds to type A1 or A2. Transcript variant B2 (NM_001012412) lacks a large proportion of exon 6 and encodes a protein comprised of 309 aa. Transcript B1 (NM_001012411) lacks exon 9 in addition to a large proportion of exon 6 and encodes a protein comprised of 275 aa. Transcript C2 (NM_138484) skips exon 6 and encodes a protein comprised of 292 aa. Transcript C1 (NM_001012413) lacks exon 9 in addition to exon 6 and encodes a protein comprised of 258 aa. Transcript D1 (NM_001199257) lacks exon 7 and exon 8 in addition to a large proportion of exon 6 and encodes a protein comprised of 215 aa. Transcript P1 (AB567656) lacks exon 3, resulting in leading to a stop codon within exon 4, and encodes a protein comprised of 59 aa. Furthermore, several transcript variants that have an alternate 5' UTR exon are also stored in databases (NM_001199251, NM_001199253, NM_001199255, NM_001199252, NM_001199254 and NM_001199256).
Pseudogene There are two pseudogenes on chromosome 1 (PGOHUM00000244068) and chromosome 7 (PGOHUM00000232695).

Protein

 
  Figure 2. Green, black and red boxes represent an N-terminal conserved coiled-coil region, a P-V-I motif and a C-terminal conserved basic region, respectively. Indicated numbers mean the exon numbers shown at Fig.1. SGOL1-interacting proteins are shown at the bottom.
Description SGOL1 protein (type A2) is a 64.2 kDa protein and has an N-terminal coiled-coil region, a P-V-I motif and a C-terminal conserved basic region. The N-terminal coiled-coil regions are required for the interaction with PP2A (Yamagishi et al., 2008) and the chromosomal passenger complex (CPC) (Tsukahara et al., 2010) at centromere. The P-V-I motif and the C-terminal basic region of SGOL1 are required for the interaction with HP1 (heterochromatin protein 1) and phosphorylated histone H2A at centromere, respectively (Yamagishi et al., 2008; Kawashima et al., 2010).
Expression Serum antibodies against NY-BR-85, which encodes SGOL1, are detected in breast cancer patients, and the expression of NY-BR-85 mRNA was detected in several tissues, including thymus and testis (Scanlan et al., 2001). Expression of SGOL1 was also detected in the extraction of HeLa cells (Salic et al., 2004; Kitajima et al., 2005) and various human leukemia cell lines (Yang et al., 2013), while the expression of SGOL1 was downregulated in the colorectal cancers (Iwaizumi et al., 2009).
Localisation Nucleus. During prophase and metaphase, SGOL1 localizes to the inner centromere (Salic et al., 2004; Kitajima et al., 2005).
Function SGOL1 is a crucial factor to protect centromeric cohesin during mitosis and to maintain genomic stability in human cells. SGOL1-knockdown caused severe mitotic arrest and precocious separation of centromeric cohesion in HeLa cells (Salic et al., 2004; Kitajima et al., 2006) and HCT116 cells, resulting in chromosomal instability (Iwaizumi et al., 2009; Kahyo et al., 2011). In addition, SGOL1 was needed for the kinetochore localization of PLK1 and CENP-F in HeLa cells (Salic et al., 2004; Pouwels et al., 2007). Several short isoforms of SGOL1 showed aberrant cell phenotypes including unstable chromatid cohesion (Suzuki et al., 2006; Kahyo et al., 2011). These results suggest that the short isoforms of SGOL1 function as a negative factor to native SGOL1, and that abundant expression of the SGOL1 short isoforms can be responsible for chromosomal instability.
Homology The coiled-coil and basic regions of shugoshin or shugoshin-like proteins are highly conserved between different species (Kitajima et al., 2004). SGOL2, a paralogue of SGOL1, was required for the PP2A-mediated protection of cohesin and the MCAK-mediated chromosome congression in HeLa cells (Tanno et al., 2010).

Mutations

Somatic Losses of heterozygosity at several polymorphic markers in SGOL1 locus (c.416+39_42delGAAA, c.504A>T and c.1461C>T) were detected in 31.2 % of human colorectal cancers (Iwaizumi et al., 2009).

Implicated in

Entity Breast cancer
Note NY-BR-85 is a serologically defined breast cancer antigen (Scanlan et al., 2001). NY-BR-86 was overexpressed in 90% of breast cancers.
  
Entity Colorectal cancer
Note The expression of SGOL1 was significantly downregulated in the colorectal cancer tissue in comparison with the paired normal mucosa, and the tumors in the SGOL1-downregulated group tended to be located on the left side of the large bowel, especially in the rectum, rather than in the other regions of the large bowel (Iwaizumi et al., 2009). The mRNA of the shortest isoform SGOL1-P1, the overexpression of which caused unstable chromatid cohesion in HCT116 cells, was detected specifically in colorectal cancer tissues (Kahyo et al., 2011).
Oncogenesis While Sgo1 homozygous mutant mice (Sgo1-/-) showed embryonic lethality, Sgo1 heterozygous mice (Sgo1+/-) showed an increase in formation of colonic aberrant crypt foci and accelerated development of colon tumors after exposure to azoxymethane, a colon carcinogen (Yamada et al., 2012).
  
Entity Hematological malignancies
Note SGOL1 was aberrantly expressed in various human leukemia cell lines and freshly isolated leukemia cells. SGOL1-knockdown suppressed the cell proliferation in several leukemia cell lines (Yang et al., 2013).
  

External links

Nomenclature
HGNC (Hugo)SGOL1   25088
Cards
AtlasSGOL1ID50710ch3p24
Entrez_Gene (NCBI)SGOL1  151648  shugoshin-like 1 (S. pombe)
GeneCards (Weizmann)SGOL1
Ensembl hg19 (Hinxton)ENSG00000129810 [Gene_View]  chr3:20209936-20227698 [Contig_View]  SGOL1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000129810 [Gene_View]  chr3:20209936-20227698 [Contig_View]  SGOL1 [Vega]
ICGC DataPortalENSG00000129810
cBioPortalSGOL1
AceView (NCBI)SGOL1
Genatlas (Paris)SGOL1
WikiGenes151648
SOURCE (Princeton)SGOL1
Genomic and cartography
GoldenPath hg19 (UCSC)SGOL1  -     chr3:20209936-20227698 -  3p24.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SGOL1  -     3p24.3   [Description]    (hg38-Dec_2013)
EnsemblSGOL1 - 3p24.3 [CytoView hg19]  SGOL1 - 3p24.3 [CytoView hg38]
Mapping of homologs : NCBISGOL1 [Mapview hg19]  SGOL1 [Mapview hg38]
OMIM609168   
Gene and transcription
Genbank (Entrez)AB187577 AB187578 AB187579 AB187580 AB187581
RefSeq transcript (Entrez)NM_001012409 NM_001012410 NM_001012411 NM_001012412 NM_001012413 NM_001199251 NM_001199252 NM_001199253 NM_001199254 NM_001199255 NM_001199256 NM_001199257 NM_138484
RefSeq genomic (Entrez)AC_000135 NC_000003 NC_018914 NT_022517 NW_001838877 NW_004929309
Consensus coding sequences : CCDS (NCBI)SGOL1
Cluster EST : UnigeneHs.105153 [ NCBI ]
CGAP (NCI)Hs.105153
Alternative Splicing : Fast-db (Paris)GSHG0021571
Alternative Splicing GalleryENSG00000129810
Gene ExpressionSGOL1 [ NCBI-GEO ]     SGOL1 [ SEEK ]   SGOL1 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ5FBB7 (Uniprot)
NextProtQ5FBB7  [Medical]
With graphics : InterProQ5FBB7
Splice isoforms : SwissVarQ5FBB7 (Swissvar)
Domains : Interpro (EBI)Shugoshin_C    Shugoshin_N   
Related proteins : CluSTrQ5FBB7
Domain families : Pfam (Sanger)Shugoshin_C (PF07557)    Shugoshin_N (PF07558)   
Domain families : Pfam (NCBI)pfam07557    pfam07558   
DMDM Disease mutations151648
Blocks (Seattle)Q5FBB7
PDB (SRS)3FGA    3Q6S    4A0I   
PDB (PDBSum)3FGA    3Q6S    4A0I   
PDB (IMB)3FGA    3Q6S    4A0I   
PDB (RSDB)3FGA    3Q6S    4A0I   
Human Protein AtlasENSG00000129810
Peptide AtlasQ5FBB7
HPRD12377
IPIIPI00554824   IPI00554467   IPI00103154   IPI00554450   IPI00554496   IPI00097163   IPI00555687   IPI00926073   
Protein Interaction databases
DIP (DOE-UCLA)Q5FBB7
IntAct (EBI)Q5FBB7
FunCoupENSG00000129810
BioGRIDSGOL1
IntegromeDBSGOL1
STRING (EMBL)SGOL1
Ontologies - Pathways
QuickGOQ5FBB7
Ontology : AmiGOmitotic cell cycle  chromosome, centromeric region  kinetochore  kinetochore  condensed chromosome kinetochore  condensed chromosome, centromeric region  condensed nuclear chromosome, centromeric region  spindle pole  protein binding  nucleus  nucleolus  cytoplasm  centrosome  cytosol  chromosome segregation  mitotic nuclear division  attachment of spindle microtubules to kinetochore  centriole-centriole cohesion  centriole-centriole cohesion  kinase binding  mitotic cohesin complex  meiotic chromosome segregation  
Ontology : EGO-EBImitotic cell cycle  chromosome, centromeric region  kinetochore  kinetochore  condensed chromosome kinetochore  condensed chromosome, centromeric region  condensed nuclear chromosome, centromeric region  spindle pole  protein binding  nucleus  nucleolus  cytoplasm  centrosome  cytosol  chromosome segregation  mitotic nuclear division  attachment of spindle microtubules to kinetochore  centriole-centriole cohesion  centriole-centriole cohesion  kinase binding  mitotic cohesin complex  meiotic chromosome segregation  
Pathways : KEGGOocyte meiosis   
REACTOMEQ5FBB7 [protein]
REACTOME PathwaysREACT_115566 Cell Cycle [pathway]
REACTOME PathwaysREACT_21300 Mitotic M-M/G1 phases [pathway]
Protein Interaction DatabaseSGOL1
DoCM (Curated mutations)SGOL1
Wikipedia pathwaysSGOL1
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerSGOL1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SGOL1
dbVarSGOL1
ClinVarSGOL1
1000_GenomesSGOL1 
Exome Variant ServerSGOL1
SNP (GeneSNP Utah)SGOL1
SNP : HGBaseSGOL1
Genetic variants : HAPMAPSGOL1
Genomic VariantsSGOL1  SGOL1 [DGVbeta]
Mutations
ICGC Data PortalENSG00000129810 
Somatic Mutations in Cancer : COSMICSGOL1 
CONAN: Copy Number AnalysisSGOL1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)3:20209936-20227698
Mutations and Diseases : HGMDSGOL1
OMIM609168   
MedgenSGOL1
NextProtQ5FBB7 [Medical]
GENETestsSGOL1
Disease Genetic AssociationSGOL1
Huge Navigator SGOL1 [HugePedia]  SGOL1 [HugeCancerGEM]
snp3D : Map Gene to Disease151648
DGIdb (Drug Gene Interaction db)SGOL1
General knowledge
Homologs : HomoloGeneSGOL1
Homology/Alignments : Family Browser (UCSC)SGOL1
Phylogenetic Trees/Animal Genes : TreeFamSGOL1
Chemical/Protein Interactions : CTD151648
Chemical/Pharm GKB GenePA134988556
Clinical trialSGOL1
Cancer Resource (Charite)ENSG00000129810
Other databases
Probes
Litterature
PubMed46 Pubmed reference(s) in Entrez
CoreMineSGOL1
GoPubMedSGOL1
iHOPSGOL1

Bibliography

Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression.
Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jager D, Chen YT, Mackay A, O'Hare MJ, Old LJ.
Cancer Immun. 2001 Mar 30;1:4.
PMID 12747765
 
The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis.
Kitajima TS, Kawashima SA, Watanabe Y.
Nature. 2004 Feb 5;427(6974):510-7. Epub 2004 Jan 18.
PMID 14730319
 
Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis.
Salic A, Waters JC, Mitchison TJ.
Cell. 2004 Sep 3;118(5):567-78.
PMID 15339662
 
Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization.
Kitajima TS, Hauf S, Ohsugi M, Yamamoto T, Watanabe Y.
Curr Biol. 2005 Feb 22;15(4):353-9.
PMID 15723797
 
Shugoshin collaborates with protein phosphatase 2A to protect cohesin.
Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y.
Nature. 2006 May 4;441(7089):46-52. Epub 2006 Mar 15.
PMID 16541025
 
Human Shugoshin mediates kinetochore-driven formation of kinetochore microtubules.
Suzuki H, Akiyama N, Tsuji M, Ohashi T, Saito S, Eto Y.
Cell Cycle. 2006 May;5(10):1094-101. Epub 2006 May 15.
PMID 16687935
 
Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1.
Pouwels J, Kukkonen AM, Lan W, Daum JR, Gorbsky GJ, Stukenberg T, Kallio MJ.
Cell Cycle. 2007 Jul 1;6(13):1579-85. Epub 2007 May 16.
PMID 17617734
 
Heterochromatin links to centromeric protection by recruiting shugoshin.
Yamagishi Y, Sakuno T, Shimura M, Watanabe Y.
Nature. 2008 Sep 11;455(7210):251-5. doi: 10.1038/nature07217.
PMID 18716626
 
Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer.
Iwaizumi M, Shinmura K, Mori H, Yamada H, Suzuki M, Kitayama Y, Igarashi H, Nakamura T, Suzuki H, Watanabe Y, Hishida A, Ikuma M, Sugimura H.
Gut. 2009 Feb;58(2):249-60. doi: 10.1136/gut.2008.149468. Epub 2008 Jul 17.
PMID 18635744
 
Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin.
Kawashima SA, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y.
Science. 2010 Jan 8;327(5962):172-7. doi: 10.1126/science.1180189. Epub 2009 Nov 19.
PMID 19965387
 
Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres.
Tanno Y, Kitajima TS, Honda T, Ando Y, Ishiguro K, Watanabe Y.
Genes Dev. 2010 Oct 1;24(19):2169-79. doi: 10.1101/gad.1945310.
PMID 20889715
 
Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation.
Tsukahara T, Tanno Y, Watanabe Y.
Nature. 2010 Oct 7;467(7316):719-23. doi: 10.1038/nature09390. Epub 2010 Aug 25.
PMID 20739936
 
A novel tumor-derived SGOL1 variant causes abnormal mitosis and unstable chromatid cohesion.
Kahyo T, Iwaizumi M, Shinmura K, Matsuura S, Nakamura T, Watanabe Y, Yamada H, Sugimura H.
Oncogene. 2011 Nov 3;30(44):4453-63. doi: 10.1038/onc.2011.152. Epub 2011 May 2.
PMID 21532624
 
Haploinsufficiency of SGO1 results in deregulated centrosome dynamics, enhanced chromosomal instability and colon tumorigenesis.
Yamada HY, Yao Y, Wang X, Zhang Y, Huang Y, Dai W, Rao CV.
Cell Cycle. 2012 Feb 1;11(3):479-88. doi: 10.4161/cc.11.3.18994. Epub 2012 Feb 1.
PMID 22262168
 
A novel treatment strategy targeting shugoshin 1 in hematological malignancies.
Yang J, Ikezoe T, Nishioka C, Yokoyama A.
Leuk Res. 2013 Jan;37(1):76-82. doi: 10.1016/j.leukres.2012.10.002. Epub 2012 Oct 24.
PMID 23102702
 
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Contributor(s)

Written04-2013Tomoaki Kahyo, Haruhiko Sugimura
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Citation

This paper should be referenced as such :
Kahyo, T ; Sugimura, H. SGOL1 (shugoshin-like 1 (S
pombe))
Atlas Genet Cytogenet Oncol Haematol. 2013;17(11):746-748.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/SGOL1ID50710ch3p24.html

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indexed on : Sat Dec 20 15:42:49 CET 2014

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