cd07765

KRAB (Kruppel-associated box) domain -A box

CDD entry
Member databaseCDD
CDD typedomain
Short nameKRAB_A-box
SetKRAB_A-box

Description

The KRAB domain is a transcription repression module, found in a subgroup of the zinc finger proteins (ZFPs) of the C2H2 family, KRAB-ZFPs. KRAB-ZFPs comprise the largest group of transcriptional regulators in mammals, and are only found in tetrapods. These proteins have been shown to play important roles in cell differentiation and organ development, and in regulating viral replication and transcription. A KRAB domain may consist of an A-box, or of an A-box plus either a B-box, a divergent B-box (b), or a C-box. Only the A-box is included in this model. The A-box is needed for repression, the B- and C- boxes are not. KRAB-ZFPs have one or two KRAB domains at their amino-terminal end, and multiple C2H2 zinc finger motifs at their C-termini. Some KRAB-ZFPs also contain a SCAN domain which mediates homo- and hetero-oligomerization. The KRAB domain is a protein-protein interaction module which represses transcription through recruiting corepressors. A key mechanism appears to be the following: KRAB-AFPs tethered to DNA recruit, via their KRAB domain, the repressor KAP1 (KRAB-associated protein-1, also known as transcription intermediary factor 1 beta , KRAB-A interacting protein , and tripartite motif protein 28). The KAP1/ KRAB-AFP complex in turn recruits the heterochromatin protein 1 (HP1) family, and other chromatin modulating proteins, leading to transcriptional repression through heterochromatin formation.
[23, 6, 12, 4, 17, 8, 27, 21, 24, 15, 16, 14, 19, 9, 20, 10, 22, 5, 1, 25, 7, 2, 11, 26, 18, 3, 13]

References

1.KRAB zinc finger proteins: an analysis of the molecular mechanisms governing their increase in numbers and complexity during evolution. Looman C, Abrink M, Mark C, Hellman L. Mol. Biol. Evol. 19, 2118-30, (2002). View articlePMID: 12446804

2.ZNF307, a novel zinc finger gene suppresses p53 and p21 pathway. Li J, Wang Y, Fan X, Mo X, Wang Z, Li Y, Yin Z, Deng Y, Luo N, Zhu C, Liu M, Ma Q, Ocorr K, Yuan W, Wu X. Biochem. Biophys. Res. Commun. 363, 895-900, (2007). View articlePMID: 17910948

3.Identification and characterization of human ZNF274 cDNA, which encodes a novel kruppel-type zinc-finger protein having nucleolar targeting ability. Yano K, Ueki N, Oda T, Seki N, Masuho Y, Muramatsu M. Genomics 65, 75-80, (2000). PMID: 10777669

4.KRAB zinc finger proteins and nuclear receptors: a possible cross-talk. Losson R. Biol. Chem. 378, 579-81, (1997). PMID: 9278136

5.A novel member of the RING finger family, KRIP-1, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins. Kim SS, Chen YM, O'Leary E, Witzgall R, Vidal M, Bonventre JV. Proc. Natl. Acad. Sci. U.S.A. 93, 15299-304, (1996). View articlePMID: 8986806

6.Meisetz and the birth of the KRAB motif. Birtle Z, Ponting CP. Bioinformatics 22, 2841-5, (2006). View articlePMID: 17032681

7.A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, Ferguson-Smith AC. Dev. Cell 15, 547-57, (2008). View articlePMID: 18854139

8.KRAB: a partner for SRY action on chromatin. Oh HJ, Lau YF. Mol. Cell. Endocrinol. 247, 47-52, (2006). View articlePMID: 16414182

9.MZF6D, a novel KRAB zinc-finger gene expressed exclusively in meiotic male germ cells. Looman C, Mark C, Abrink M, Hellman L. DNA Cell Biol. 22, 489-96, (2003). View articlePMID: 14565865

10.Conserved KRAB protein domain identified upstream from the zinc finger region of Kox 8. Thiesen HJ, Bellefroid E, Revelant O, Martial JA. Nucleic Acids Res. 19, 3996, (1991). View articlePMID: 1861988

11.Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cells. Akagi T, Usuda M, Matsuda T, Ko MS, Niwa H, Asano M, Koide H, Yokota T. Biochem Biophys Res Commun 331, 23-30, (2005). PMID: 15845352

12.Lineage-specific expansion of KRAB zinc-finger transcription factor genes: implications for the evolution of vertebrate regulatory networks. Hamilton AT, Huntley S, Kim J, Branscomb E, Stubbs L. Cold Spring Harb. Symp. Quant. Biol. 68, 131-40, (2003). View articlePMID: 15338611

13.KRAB can repress lentivirus proviral transcription independently of integration site. Bulliard Y, Wiznerowicz M, Barde I, Trono D. J Biol Chem 281, 35742-6, (2006). PMID: 16997916

14.A novel Kruppel-Associated Box identified in a panel of mammalian zinc finger proteins. Looman C, Hellman L, Abrink M. Mamm. Genome 15, 35-40, (2004). View articlePMID: 14727140

15.KRAB zinc-finger proteins localise to novel KAP1-containing foci that are adjacent to PML nuclear bodies. Briers S, Crawford C, Bickmore WA, Sutherland HG. J. Cell. Sci. 122, 937-46, (2009). View articlePMID: 19258395

16.Regulation of episomal gene expression by KRAB/KAP1-mediated histone modifications. Barde I, Laurenti E, Verp S, Groner AC, Towne C, Padrun V, Aebischer P, Trumpp A, Trono D. J. Virol. 83, 5574-80, (2009). View articlePMID: 19279087

17.All in the family: the BTB/POZ, KRAB, and SCAN domains. Collins T, Stone JR, Williams AJ. Mol. Cell. Biol. 21, 3609-15, (2001). View articlePMID: 11340155

18.Association of ZNF74 gene genotypes with age-at-onset of schizophrenia. Takase K, Ohtsuki T, Migita O, Toru M, Inada T, Yamakawa-Kobayashi K, Arinami T. Schizophr Res 52, 161-5, (2001). PMID: 11705709

19.Comparative analysis of KRAB zinc finger proteins in rodents and man: evidence for several evolutionarily distinct subfamilies of KRAB zinc finger genes. Mark C, Abrink M, Hellman L. DNA Cell Biol. 18, 381-96, (1999). View articlePMID: 10360839

20.The transcriptional repressor K-RBP modulates RTA-mediated transactivation and lytic replication of Kaposi's sarcoma-associated herpesvirus. Yang Z, Wood C. J. Virol. 81, 6294-306, (2007). View articlePMID: 17409159

21.The KRAB zinc finger gene ZNF74 encodes an RNA-binding protein tightly associated with the nuclear matrix. Grondin B, Bazinet M, Aubry M. J. Biol. Chem. 271, 15458-67, (1996). View articlePMID: 8663113

22.KAP-1, a novel corepressor for the highly conserved KRAB repression domain. Friedman JR, Fredericks WJ, Jensen DE, Speicher DW, Huang XP, Neilson EG, Rauscher FJ 3rd. Genes Dev. 10, 2067-78, (1996). View articlePMID: 8769649

23.KRAB-containing zinc-finger repressor proteins. Urrutia R. Genome Biol. 4, 231, (2003). View articlePMID: 14519192

24.The Kruppel-associated box repressor domain can trigger de novo promoter methylation during mouse early embryogenesis. Wiznerowicz M, Jakobsson J, Szulc J, Liao S, Quazzola A, Beermann F, Aebischer P, Trono D. J. Biol. Chem. 282, 34535-41, (2007). View articlePMID: 17893143

25.A KRAB domain zinc finger protein in imprinting and disease. Hirasawa R, Feil R. Dev. Cell 15, 487-8, (2008). View articlePMID: 18854130

26.Characterization of ZNF333, a novel double KRAB domain containing zinc finger gene on human chromosome 19p13.1. Tian Y, Breedveld GJ, Huang S, Oostra BA, Heutink P, Lo WH. Biochim Biophys Acta 1577, 121-5, (2002). PMID: 12151103

27.Alternative promoter usage and splicing of ZNF74 multifinger gene produce protein isoforms with a different repressor activity and nuclear partitioning. Cote F, Boisvert FM, Grondin B, Bazinet M, Goodyer CG, Bazett-Jones DP, Aubry M. DNA Cell Biol. 20, 159-73, (2001). View articlePMID: 11313019

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