SSX2IP (synovial sarcoma, X breakpoint 2 interacting protein)

2012-03-01   Ghazala Khan , Barbara Guinn 

University of Bedfordshire, Division of Science, Park Square, Luton, Bedfordshire, UK (GK, BG); Cancer Sciences Unit, University of Southampton, Southampton, UK (BG); Department of Haematological Medicine, Kings College, London, UK (BG)

Identity

HGNC
LOCATION
1p22.3
LOCUSID
ALIAS
ADIP,hMsd1
FUSION GENES

DNA/RNA

Note

The SSX2IP gene is located on chromosome 1p22.3 (Entrez Gene).
Atlas Image
Location of SSX2IP gene on chromosome 1 and the surrounding region.

Description

SSX2IP includes over 46 kb and consists of 14 exons however the first one is not translated (de Bruijn et al., 2002).

Transcription

The gene contains 33 introns. 18 different mRNAs are produced; 17 spliced and 1 un-spliced form (Thierry-Mieg and Thierry-Mieg, 2006).

Pseudogene

A pseudogene of this gene is found on chromosome 3 (provided by RefSeq, Oct 2009 from Entrez Gene).

Proteins

Note

SSX2IP was discovered due to its interaction with SSX2 in a yeast two-hybrid system and believed to regulate the function of SSX2 in the testes and malignant cells (de Bruijn et al., 2002).
Atlas Image
Structural representation of SSX2IP protein in human, mouse and chicken showing the binding regions (Breslin et al., 2007).

Description

There are 3-4 coil coiled regions in each version of SSX2IP. Only human SSX2IP has a nuclear localisation signal (NLS).

Expression

Expression observed in various normal tissues, the highest being in the brain (de Bruijn et al., 2002). It is expressed less but significantly in kidney, testes, spinal cord, liver, heart, lung, pancreas, skeletal muscle, ovary, placenta, foetal liver and foetal brain (Breslin et al., 2007).

Localisation

SSX2IP co-localises with SSX2 to the nucleus and some fragments to the cytoplasm (de Bruijn et al., 2002). It has also been seen to localise on the surface of myeloid cell lines and primary AML (Denniss et al., 2007). ADIP co-localises with afadin at adherens junctions and in perinuclear regions (Asada et al., 2003).

Function

It has been suggested that SSX2IP regulates the function of SSX2 (de Bruijn et al., 2002). Rodent ADIP binds with F-actin binding proteins afadin and α-actinin and could therefore be involved in forming actin structure at cell-cell adherens junction as well as construction of actin bundle at nectin-based cell adhesion sites (Asada et al., 2003). Through its interaction with the actin-binding protein β-spectrin, ADIP may have a role in actin-dependent organization of the Golgi complex. ADIP binds β-cop, which is a subunit of the coatomer complex, proposing a role in vesicle trafficking (Asada et al., 2004).

Implicated in

Note
SSX2IP expression has been seen to be elevated in 33% of acute myeloid leukaemia patient samples at presentation (Guinn et al., 2005). Peak expression on the surface of myeloid leukaemia cells is during mitosis (Denniss et al., 2007). Patients with the t(15;17) translocation have increased levels of SSX2IP whereas expression is decreased in patients with the t(8;21) translocation (Guinn et al., 2008).
Prognosis
Patients with no chromosomal abnormalities showed improved survival rates with elevated expression of SSX2IP. High level of SSX2IP expression is associated with other positive prognostic markers such as days in remission and age at diagnosis (Guinn et al., 2009).
Cytogenetics
The t(15;17) translocation leads to PML-RARα product. Overexpression of PML during the cell cycle leads to G1 arrest in normal fibroblasts which cannot occur once PML attaches to RARα. Genes regulating cyclin dependent kinase activity are upregulated in correlation with overexpression of SSX2IP. The t(8;21) translocation generates the AML1-ETO fusion product. Cells with this gene product develop aneuploidy due to decreased regulation at the spindle checkpoint. Low levels of SSX2IP relate to reduced expression of CDC20, a substrate-targeting subunit of the anaphase-promoting complex (Guinn et al., 2008).

Bibliography

Pubmed IDLast YearTitleAuthors
153581832004Afadin- and alpha-actinin-binding protein ADIP directly binds beta'-COP, a subunit of the coatomer complex.Asada M et al
179045212007SSX2IP: an emerging role in cancer.Breslin A et al
176860612007The leukaemia-associated antigen, SSX2IP, is expressed during mitosis on the surface of myeloid leukaemia cells.Denniss FA et al
191794772009Elevated expression of the leukemia-associated antigen SSX2IP predicts survival in acute myeloid leukemia patients who lack detectable cytogenetic rearrangements.Guinn B et al
161126462005Humoral detection of leukaemia-associated antigens in presentation acute myeloid leukaemia.Guinn BA et al
180284842008SSX2IP expression in acute myeloid leukaemia: an association with mitotic spindle failure in t(8;21), and cell cycle in t(15;17) patients.Guinn BA et al
169258342006AceView: a comprehensive cDNA-supported gene and transcripts annotation.Thierry-Mieg D et al
120071892002The cancer-related protein SSX2 interacts with the human homologue of a Ras-like GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP.de Bruijn DR et al

Other Information

Locus ID:

NCBI: 117178
MIM: 608690
HGNC: 16509
Ensembl: ENSG00000117155

Variants:

dbSNP: 117178
ClinVar: 117178
TCGA: ENSG00000117155
COSMIC: SSX2IP

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000117155ENST00000342203Q9Y2D8
ENSG00000117155ENST00000422026C9JIX7
ENSG00000117155ENST00000437941Q9Y2D8
ENSG00000117155ENST00000476905S4R403
ENSG00000117155ENST00000481102Q9Y2D8
ENSG00000117155ENST00000603677S4R2Y6
ENSG00000117155ENST00000605755Q9Y2D8

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
Adherens junctionKEGGko04520
Adherens junctionKEGGhsa04520

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
243564492014The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary transition zone.29
120071892002The cancer-related protein SSX2 interacts with the human homologue of a Ras-like GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP.22
267516422016Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation.22
259266402015The Nectin-4/Afadin Protein Complex and Intercellular Membrane Pores Contribute to Rapid Spread of Measles Virus in Primary Human Airway Epithelia.18
258337122015Centriolar satellite- and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly.12
234523952013SSX2IP promotes metastasis and chemotherapeutic resistance of hepatocellular carcinoma.9
180284842008SSX2IP expression in acute myeloid leukaemia: an association with mitotic spindle failure in t(8;21), and cell cycle in t(15;17) patients.6
265457772015The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation.6
265682952016Afadin is localized at cell-cell contact sites in mesangial cells and regulates migratory polarity.2
318371712020Expression and prognostic utility of SSX2IP in patients with nasopharyngeal carcinoma.0

Citation

Ghazala Khan ; Barbara Guinn

SSX2IP (synovial sarcoma, X breakpoint 2 interacting protein)

Atlas Genet Cytogenet Oncol Haematol. 2012-03-01

Online version: http://atlasgeneticsoncology.org/gene/42407/ssx2ip