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PROSITE documentation PDOC50806 [for PROSITE entry PS50806]

KRAB-related domain profile


This domain of about 63 amino acid residues is related to the KRAB domain (see <PDOC50805> and has been identified in the N-terminal ends of proteins belonging to the SSX family [1,2,3]. Proteins of the SSX family lack the C2H2-type zinc finger (see <PDOC00028>) which is invariably found in proteins containing the KRAB domain. The KRAB-related domains show greatest homology to the KRAB A subdomain and contain a high proportion of the amino acids which are usually conserved between the KRAB A subdomains of zinc finger proteins [1].

Although the KRAB-related domains of SSX1 and SSX2 contribute to the repressive activity of these proteins, transcriptional repression is mainly mediated by a region located in their C-terminus. Hence, unlike the KRAB domain, the KRAB-related domain is only a weak transcriptional repression domain. In addition the KRAB-related domain is unable to interact with the KAP-1/TIF1-β protein which appears to function as a universal corepressor for KRAB domain proteins [4].

Translocations which result in the fusion of the SYT gene to either of the closely related SSX1 or SSX2 genes are associated with synovial sarcomas [1]. The resulting SYT-SSX1/SSX2 proteins analyzed so far lack the KRAB-related domain and act as activators of transcription [4].

The profile we developed spans the complete KRAB-related domain.

Last update:

December 2001 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

KRAB_RELATED, PS50806; KRAB-related domain profile  (MATRIX)


1AuthorsCrew A.J., Clark J., Fisher C., Gill S., Grimer R., Chand A., Shipley J., Gusterson B.A., Cooper C.S.
TitleFusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma.
SourceEMBO J. 14:2333-2340(1995).
PubMed ID7539744

2Authorsde Leeuw B., Balemans M., Geurts van Kessel A.
SourceCytogenet. Cell Genet. 73:179-183(1996).

3AuthorsGure A.O., Tureci O., Sahin U., Tsang S., Scanlan M.J., Jager E., Knuth A., Pfreundschuh M., Old L.J., Chen Y.-T.
TitleSSX: a multigene family with several members transcribed in normal testis and human cancer.
SourceInt. J. Cancer 72:965-971(1997).
PubMed ID9378559

4AuthorsLim F.L., Soulez M., Koczan D., Thiesen H.-J., Knight J.C.
TitleA KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas.
SourceOncogene 17:2013-2018(1998).
PubMed ID9788446

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