InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ATRX

Summary

InnateDB Protein

IDBP-239148.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ATRX

Protein Name

alpha thalassemia/mental retardation syndrome X-linked

Synonyms

ATR2; JMS; MRXHF1; RAD54; RAD54L; SFM1; SHS; XH2; XNP; ZNF-HX;

Species

Homo sapiens

Ensembl Protein

ENSP00000378967

InnateDB Gene

IDBG-77514 (ATRX)

Protein Structure

UniProt Annotation

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 which probably implies recruitment of CBX5 to telomers. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according (PubMed:24500201) is not sufficient to decrease chromatin condensation at telomers nor to increase expression of telomeric RNA in fibroblasts. May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as negative regulator of chromatin incorporation of transcriptionally repressive histone H2AFY, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. 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. May be involved in brain development and facial morphogenesis. {ECO:0000269PubMed:12953102, ECO:0000269PubMed:14990586, ECO:0000269PubMed:20504901, ECO:0000269PubMed:20651253, ECO:0000269PubMed:21029860, ECO:0000269PubMed:22391447, ECO:0000269PubMed:22829774, ECO:0000269PubMed:24500201}.

Subcellular Localization

Nucleus. Chromosome, telomere. Nucleus, PML body. 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. Colocalizes with cohesin (SMC1 and SMC3) and MECP2 at the maternal H19 ICR (By similarity). {ECO:0000250}.

Disease Associations

Alpha-thalassemia mental retardation syndrome, X-linked (ATRX) [MIM:301040]: A disorder characterized by severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions. {ECO:0000269PubMed:10204841, ECO:0000269PubMed:10417298, ECO:0000269PubMed:10660327, ECO:0000269PubMed:10995512, ECO:0000269PubMed:12116232, ECO:0000269PubMed:16955409, ECO:0000269PubMed:7697714, ECO:0000269PubMed:8968741, ECO:0000269PubMed:9043863, ECO:0000269PubMed:9326931}. Note=The disease is caused by mutations affecting the gene represented in this entry.Mental retardation, X-linked, syndromic, with hypotonic facies 1 (MRXSHF1) [MIM:309580]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSHF1 is a syndromic mental retardation. Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects. {ECO:0000269PubMed:10398237, ECO:0000269PubMed:10751095, ECO:0000269PubMed:11050622, ECO:0000269PubMed:15565397, ECO:0000269PubMed:16222662, ECO:0000269PubMed:8630485}. Note=The disease is caused by mutations affecting the gene represented in this entry.Alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:300448]: A disorder characterized by hypochromic, microcytic red blood cells, hemoglobin H detected in peripheral blood, and multilineage myelodysplasia. {ECO:0000269PubMed:12858175}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 63 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	63 [view]
Protein-Protein	63 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003678	DNA helicase activity
GO:0004386	helicase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0015616	DNA translocase activity
GO:0035064	methylated histone binding
GO:0042393	histone binding
GO:0070087	chromo shadow domain binding

Biological Process

GO:0006200	ATP catabolic process
GO:0006281	DNA repair
GO:0006306	DNA methylation
GO:0006310	DNA recombination
GO:0006334	nucleosome assembly
GO:0006336	DNA replication-independent nucleosome assembly
GO:0006338	chromatin remodeling
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0010571	positive regulation of nuclear cell cycle DNA replication
GO:0030330	DNA damage response, signal transduction by p53 class mediator
GO:0031297	replication fork processing
GO:0032206	positive regulation of telomere maintenance
GO:0032508	DNA duplex unwinding
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0072711	cellular response to hydroxyurea
GO:1901581	negative regulation of telomeric RNA transcription from RNA pol II promoter

Cellular Component

GO:0005634	nucleus
GO:0005720	nuclear heterochromatin
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0016605	PML body
GO:0031933	telomeric heterochromatin
GO:0070603	SWI/SNF superfamily-type complex

Protein Structure and Domains

PDB ID

InterPro

IPR000330 SNF2-related
IPR001650 Helicase, C-terminal
IPR011011 Zinc finger, FYVE/PHD-type
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00176
PF00271

PRINTS

PIRSF

SMART

SM00490
SM00487

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P46100