Reviewed, UniProtKB/Swiss-Prot P46100 (ATRX_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcriptional regulator ATRX
    EC=3.6.1.-
Alternative name(s):
    ATP-dependent helicase ATRX
    X-linked helicase II
    X-linked nuclear protein
      Short name=XNP
    Znf-HX

Gene names

Name:	ATRX
Synonyms:	RAD54L, XH2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2492 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Could be a global transcriptional regulator. Modifies gene expression by affecting chromatin. May be involved in brain development and facial morphogenesis.
Subunit structure	Probably binds EZH2. Binds annexin V in a calcium and phosphatidylcholine/phosphatidylserine-dependent manner By similarity. Interacts directly with CBX5 via the PxVxL motif.
Subcellular location	Nucleus. Note= Associated with pericentromeric heterochromatin during interphase and mitosis, probably by interacting with HP1.
Tissue specificity	Ubiquitous.
Domain	Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Defects in ATRX are the cause of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) [MIM:301040]. ATR-X is an X-linked disorder comprising severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions. Defects in ATRX are the cause of mental retardation syndromic X-linked with hypotonic facies syndrome type 1 (MRXSHF1) [MIM:309580]; also called Carpenter-Waziri syndrome (CWS), Juberg-Marsidi syndrome (JMS), Smith-Fineman-Myers syndrome type 1 (SFM1). 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. Defects in ATRX are a cause of alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:300448]. In this disorder, alpha-thalassemia occurs as an acquired abnormality in association with a multilineage myelodysplasia.
Sequence similarities	Belongs to the SNF2/RAD54 helicase family. Contains 1 GATA-type zinc finger. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. Contains 1 PHD-type zinc finger.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation Mental retardation
Domain	Zinc-finger
Ligand	ATP-binding DNA-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Helicase Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA methylation Traceable author statement. Source: ProtInc DNA recombination Ref.8 Traceable author statement. Source: ProtInc DNA repair Ref.8 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Ref.8 Traceable author statement. Source: ProtInc
Cellular component	nuclear heterochromatin Ref.10 Traceable author statement. Source: ProtInc
Molecular function	DNA helicase activity Ref.8 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	1	EBI-396461,EBI-77321

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 4 (identifier: P46100-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: P46100-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-204: Missing.

Isoform 2 (identifier: P46100-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-117: Missing.

Isoform 3 (identifier: P46100-4)

The sequence of this isoform differs from the canonical sequence as follows:
     124-161: Missing.

Isoform 5 (identifier: P46100-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-117: Missing.
     124-161: Missing.

Isoform 6 (identifier: P46100-6)

The sequence of this isoform differs from the canonical sequence as follows:
     124-162: Missing.
     573-601: Missing.
     1419-2492: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

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	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 2492	2492	Transcriptional regulator ATRX
Regions
	Domain	1581 – 1768	188	Helicase ATP-binding
	Domain	2025 – 2205	181	Helicase C-terminal
	Zinc finger	171 – 200	30	GATA-type; atypical
	Zinc finger	220 – 268	49	PHD-type
	Nucleotide binding	1594 – 1601	8	ATP Potential
	Motif	581 – 594	14	PxVxL motif
	Motif	1719 – 1722	4	DEGH box
	Compositional bias	745 – 750	6	Poly-Ser
	Compositional bias	1151 – 1156	6	Poly-Ser
	Compositional bias	1166 – 1169	4	Poly-Lys
	Compositional bias	1202 – 1206	5	Poly-Ser
	Compositional bias	1259 – 1266	8	Poly-Asp
	Compositional bias	1443 – 1466	24	Poly-Glu
	Compositional bias	1499 – 1502	4	Poly-Glu
	Compositional bias	1929 – 1939	11	Poly-Lys
	Compositional bias	1941 – 1948	8	Poly-Ser
	Compositional bias	2222 – 2225	4	Poly-Lys
	Compositional bias	2262 – 2265	4	Poly-Glu
	Compositional bias	2420 – 2425	6	Poly-Gln
Amino acid modifications
	Modified residue	34	1	Phosphoserine
	Modified residue	71	1	Phosphoserine
	Modified residue	74	1	Phosphoserine
	Modified residue	87	1	Phosphothreonine
	Modified residue	92	1	Phosphoserine By similarity
	Modified residue	634	1	Phosphoserine
	Modified residue	729	1	Phosphoserine
	Modified residue	731	1	Phosphoserine
	Modified residue	849	1	Phosphoserine
	Modified residue	850	1	Phosphoserine
	Modified residue	871	1	Phosphoserine
	Modified residue	1348	1	Phosphoserine
	Modified residue	1352	1	Phosphoserine
	Modified residue	1527	1	Phosphoserine
Natural variations
	Alternative sequence	1 – 204	204	Missing in isoform 1.
	Alternative sequence	1 – 117	117	Missing in isoform 2 and isoform 5.
	Alternative sequence	124 – 162	39	Missing in isoform 6.
	Alternative sequence	124 – 161	38	Missing in isoform 3 and isoform 5.
	Alternative sequence	573 – 601	29	Missing in isoform 6.
	Alternative sequence	1419 – 2492	1074	Missing in isoform 6.
	Natural variant	175	1	G → E in ATR-X.
	Natural variant	178 – 198	21	Missing in ATR-X.
	Natural variant	179	1	N → S in ATR-X.
	Natural variant	190	1	P → A in ATR-X.
	Natural variant	190	1	P → L in ATR-X.
	Natural variant	190	1	P → S in ATR-X.
	Natural variant	192	1	L → F in ATR-X.
	Natural variant	194	1	V → I in ATR-X.
	Natural variant	200	1	C → S in ATR-X.
	Natural variant	219	1	Q → P in ATR-X.
	Natural variant	220	1	C → R in ATR-X.
	Natural variant	220	1	C → Y in MRXSHF1.
	Natural variant	222	1	W → S in ATR-X.
	Natural variant	243	1	C → F in ATR-X.
	Natural variant	246	1	R → C in ATR-X.
	Natural variant	246	1	R → L in ATR-X.
	Natural variant	249	1	G → C in ATR-X.
	Natural variant	249	1	G → D in ATR-X.
	Natural variant	409	1	L → S in MRXSHF1.
	Natural variant	596	1	P → S: dbSNP rs1051678.
	Natural variant	740	1	G → E: dbSNP rs1051680.
	Natural variant	929	1	Q → E: dbSNP rs3088074.
	Natural variant	1538	1	V → G in ATR-X; could be a polymorphism.
	Natural variant	1552	1	V → F in ATR-X.
	Natural variant	1609	1	H → R in ATR-X.
	Natural variant	1614	1	C → R in ATR-X.
	Natural variant	1621	1	T → M in ATR-X.
	Natural variant	1645	1	L → S in ATR-X.
	Natural variant	1650	1	K → N in ATR-X.
	Natural variant	1713	1	P → S in ATR-X; without alpha-thalassemia.
	Natural variant	1742	1	R → K in ATR-X; atypical; patients presents spastic paraplegia at birth.
	Natural variant	1847	1	Y → C in ATR-X.
	Natural variant	1860	1	N → S Rare polymorphism.
	Natural variant	2035	1	D → V in ATR-X.
	Natural variant	2050	1	I → T in MRXSHF1; originally reported as Carpenter-Waziri syndrome.
	Natural variant	2084	1	Y → H in ATR-X.
	Natural variant	2131	1	R → Q in MRXSHF1; originally reported as Juberg-Marsidi syndrome.
	Natural variant	2163	1	Y → C in ATR-X.
	Natural variant	2271	1	R → G in MRXSHF1.
Experimental info
	Sequence conflict	879	1	A → R Ref.5
	Sequence conflict	1286	1	S → P Ref.4
	Sequence conflict	1625 – 1632	8	VCPLNTAL → GLSSSILAF Ref.5
	Sequence conflict	2259 – 2265	7	DHKEEEE → TTKKKKR Ref.5
	Sequence conflict	2280	1	A → G Ref.5
	Sequence conflict	2283	1	K → R Ref.5
	Sequence conflict	2284	1	V → G in AAB40698, AAB49970 and AAB49971. Ref.1
	Sequence conflict	2284	1	V → G Ref.3 Ref.5 Ref.8
	Sequence conflict	2403 – 2431	29	SCVQR…TYQQA → QLCSANTYEQKAPAAVQSAA TATNDLSTT Ref.5
	Sequence conflict	2436