Protein: Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (HP1 alpha-interacting protein) (HP1-BP38 protein) (Heterochromatin protein 2) (X-linked nuclear protein) (Q61687)
Organism: Mus musculus (Mouse)
Function: Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells probably implying recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according is required for its transcriptional repression in embryonic stem cells. Acts as negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (By similarity).
Subcellular location: Nucleus. Chromosome, telomere. Nucleus, PML body {ECO:0000250}. Note=Associated with pericentromeric heterochromatin during interphase and mitosis, probably by interacting with CBX5/HP1 alpha. Colocalizes with histone H3.3, DAXX, HIRA and ASF1A at PML-nuclear bodies (By similarity). In embryonic stem cells localized to telomeres; localization is reduced after 12 d of induction of cell differentiation. Colocalizes with cohesin (SMC1 and SMC3) and MECP2 at the maternal H19 ICR and the Gtl2/Dlk1 imprinted cluster in the brain. {ECO:0000250}.
Interaction partners:
- Death domain-associated protein 6
- Histone H3.3
- DNA repair protein RAD52 homolog
- Methyl-CpG-binding protein 2
- Nuclear autoantigen Sp-100
- DNA repair protein RAD51 homolog 1
- Cellular tumor antigen p53
- DNA
- DNA repair and recombination protein RAD54B
- Histone H3.2
Sequence:
MTAEPMSGNKLSTLVQKLHDFLAHSSEESEETCSSPRLVMNQSTDKICGSGLNSDMMENNKEEGASTSEKSRSSGSSRSKRKPSIVTKYVESDDEKPTDENVNEKAATENSENDITMQSLPKGTVIVQPEPVLNEDKDDFKGPEFRSRSKMKADNLKKRGEDGLHGIVSCTACGQQVNHFQKDSIYRHPSLKVLICKNCFKYYMSDDISRDSDGMDEQCRWCAEGGNLICCDFCHNAFCKKCILRNLGRKELSTIMDENNQWYCYICQPEPLLDLVTACNSVFENLEQLLQQNKKKIKVDSEKTSKVCDQTSKFSPKKSSSSCNGEEKKLEESCSGSVSSTYSHSALSVPKEMIKKTTKLIETTSNMNSSYIKFLKQAADNSEMTSAMKLCQLKSFKSVLDDIKKAHLALEEDLNSEIQALDDVHKEKNTKDLKSTDAKSETKLGKGEKSYSTEKREFLKLDARSSVKAIDGEEQRAHKSTSGEHKGSGRKDGSQYEPTNTPEDLDMDIVSVPSSVPEDIFDSLESAMEVQSSADYQGDGNSGTEPELESSSVKLNVSSKDSRGNIKSKVTAKVRKELFVKLTPVSLSNSPIKGVDCQEVSQEKNGRKSSGVARSSEKCRPREEISDHENNVTILLEDSDLRRSPRVKTTPLRRQTESNPAMSNSDEESNGTMKEKQKMSGPIRKKDKRNSADCATDNPKPHKVPKAKQPVIGDQNSDSDEMLAVLKEASQMGHSSSSDTDINEPQMNHKGKTGKDDNGKRKRKNSTSGSDFDTKKGKSTETSIISKKKRQNYSESSNYDSELEREIKTMSRIGAARKSVPEKKEEDSSEDEKQGKKVVDNGGHERAKTTQEGSSADDTGDTEGRQGGSCSIAGGSIEKVRSGVEFREMLCKPGVSSDGAEKPSVKEENVNSPEDKRVSKTKEKTKHLRSRQSRKGKGGSSDGTDRFPKKEQSDESSEGEKKQSRQRPGTKGKKAPDLKGETLKREQEWDSSSDGTERLPEEEEIGPFSKGIKQSKTDTAGGEKKGKKWKDKSCEKKEELSDSVDKLPGKGDSCDSSEDKKTRNRVSLREKKRFSLPAKSPGKRPECSSSDTEKSLKGQCCDSTEKRPKRIDLRERRNSSSKRNTKEVKSASSSSDAEGSSEDNKKQKKQRTSAKKKTGNTKEKKRNSLRATPKRKQVDITSSSSDIGDDDQNSAGEESSDEQKIKPVTENLVLPSHTGFCQSSGDEALSKSVPATVDDDDDDNDPENRIAKKMLLEEIKANLSSDEDGSSDDEPDGGGKKRIGKQSEESPADDGELRREQLAVNQVNSESDSDSEESKKPRYRHRLLRHKLTLSDGESGEEKPTKPKEHKEAKGRNRRKVSSEDSEDTDFQESGVSEEVSESEDEQRPRTRSAKKAELEENQRSYKQKKKRRRIKVQEDSSSENKSHSEEDKKEGDEEDEEDEDEDEEDENDDSKSPGKGRKKIRKILKDDKLRTETQNALKEEEERRKRIAEREREREKLREVIEIEDASPTKCPITTKLVLDENEETKEPLVQVHRNMVIKLKPHQVDGVQFMWDCCCESVEKTKKSPGSGCILAHCMGLGKTLQVVSFLHTVLLCDKLDFSTALVVCPLNTALNWMNEFEKWQEGLNDNEKLEVSELATVKRPQERSYMLQRWQEDGGVMIIGYEMYRNLAQGRNVKSRKLKDIFNKALVDPGPDFVVCDEGHILKNEASAVSKAMNSIKSRRRIILTGTPLQNNLIEYHCMVNFIKENLLGSIKEFRNRFINPIQNGQCADSTMVDVRVMKKRAHILYEMLAGCVQRKDYTALTKFLPPKHEYVLAVRMTAIQCKLYQYYLDHLTGVGNSTEGGRGKAGAKLFQDFQMLSRIWTHPWCLQLDYISKENKGYFDEDSMDEFIASDSDETSKSLSSDEKKKPKGKKGKKDSSSSGSGSDNDVEVIKVWNSRSRGGGDGNVDDTGNNPSVSLKLDESKTTSTSNPSSPAPDWYKDFVTDTDAEVLEHSGKMVLLFEILRMAEEIGDKVLVFSQSLISLDLIEDFLELASREKTEDKEKPLIYKGEGKWIRNIDYYRLDGSTNAQSRKKWAEEFNDETNVRGRLFIISTKAGSLGINLVAANRVIIFDASWNPSYDIQSIFRVYRFGQTKPVYVYRFLAQGTMEDKIYDRQVTKQSLSFRVVDQQQVERHFTMNELTELYTFEPDLLDDPNSEKKKKRDTPMLPKDTILAELLQIHKEHIVGYHEHDSLLDHKEEEELTEEERKAAWAEYEAEKKGLTMRFNIPTGTNLPPVTFTSQTPYIPFNLGALSAMSNQQLEDLINQGREKVVEATNSMTAVRIQPLEDIISTVWKENMNLSEAQVQALALSRQASQELDVKRREAIYNDVLTKQQMLINCVQRILMNRRLQQQYTQQQQQQLTYQQATLSHLMMPKPPNLIMTPSNYQQIDMRGMYQSVAGGMQPPPLQRAPPPTVRSKNPGPSPGKSM