AiPD: Autoinhibited Protein Database

Q3B7N1

Gene name	CHD1L
Protein name	Chromodomain-helicase-DNA-binding protein 1-like
Names	EC 3.6.4.-
Species	Bos taurus (Bovine)
KEGG Pathway	bta:524787
EC number	3.6.4.-: Acting on ATP; involved in cellular and subcellular movement
Protein Class

Descriptions

Oncogenic chromatin remodeler ALC1 (ALC1, also known as CHD1L) is an ATP-dependent chromatin remodeler that relaxes the chromatin and plays an important role in the poly(ADP-ribose) polymerase 1-mediated DNA repair pathway. The macro domain of ALC1 binds to lobe 2 of the ATPase motor, sequestering two elements for nucleosome recognition. Autoinhibition by macro domain interactions stabilizes the ATPase lobe, impacting DNA damage repair. The cancer-related mutations of several basic residues on the macro domain disrupt the autoinhibition of ALC1, compromising its function in cells. Upon DNA damage, the interaction between the macro domain and PAR chains in PARP1 can also release the autoinhibition of ALC1 and target the remodeler to the sites of DNA damage. Furthermore, the histone H4 tails of nucleosome and other nucleosomal epitopes often provide the combinational cues to target and regulate chromatin remodelers, leading to the activation of ALC1 in cells.

Autoinhibitory domains (AIDs)

704-897 (Macro domain) SS

Target domain	350-515 (Lobe 2 of ATPase motor domain)
Relief mechanism	Ligand binding, Partner binding, Others
Assay

AID

704-897 (Macro domain)

Target domain

350-515 (Lobe 2 of ATPase motor domain)

Relief mechanism

Ligand binding (Interaction with histone H4 tails of nucleosome and other nucleosomal epitopes), Partner binding (Interaction between macro domain and PAR chains in PARP1 upon DNA damage), Others (Cancer-related mutations at Arg857 and Arg860)

Assay

Accessory elements

No accessory elements

References

Lehmann LC et al. (2017) "Mechanistic Insights into Autoinhibition of the Oncogenic Chromatin Remodeler ALC1", Molecular cell, 68, 847-859.e7

Wang L et al. (2021) "Structural basis of ALC1/CHD1L autoinhibition and the mechanism of activation by the nucleosome", Nature communications, 12, 4057

Autoinhibited structure

Activated structure

1 structures for Q3B7N1

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q3B7N1-F1	Predicted				AlphaFoldDB

No variants for Q3B7N1

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
No variants for Q3B7N1

No associated diseases with Q3B7N1

6 regional properties for Q3B7N1

Type	Name	Position	InterPro Accession
domain	AAA+ ATPase domain	252 - 399	IPR003593-1
domain	AAA+ ATPase domain	535 - 671	IPR003593-2
domain	ATPase, AAA-type, core	256 - 396	IPR003959-1
domain	ATPase, AAA-type, core	539 - 668	IPR003959-2
domain	CDC48, domain 2	111 - 183	IPR004201
domain	AAA ATPase, AAA+ lid domain	423 - 461	IPR041569

Functions

		Description
EC Number	3.6.4.-	Acting on ATP; involved in cellular and subcellular movement
Subcellular Localization	Nucleus Chromosome	Localizes at sites of DNA damage; recruited by histones H2B and H3 poly-ADP-ribosylated on 'Ser-6' and 'Ser-10', respectively (H2BS6ADPr and H3S10ADPr) by PARP1 or PARP2
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

2 GO annotations of cellular component

Name	Definition
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
site of double-strand break	A region of a chromosome at which a DNA double-strand break has occurred. DNA damage signaling and repair proteins accumulate at the lesion to respond to the damage and repair the DNA to form a continuous DNA helix.

8 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
ATP hydrolysis activity	Catalysis of the reaction
ATP-dependent chromatin remodeler activity	An activity, driven by ATP hydrolysis, that modulates the contacts between histones and DNA, resulting in a change in chromosome architecture within the nucleosomal array, leading to chromatin remodeling.
DNA helicase activity	Unwinding of a DNA helix, driven by ATP hydrolysis.
histone reader activity	A chromatin adaptor that recognizes specific forms of histones, either modified by a post-translational modification, or the unmodified form. Histone readers have roles in many processes, including in centromere function or in modulating the accessibility of cis-regulatory regions to the transcription machinery.
nucleosome binding	Binding to a nucleosome, a complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures.
nucleotide binding	Binding to a nucleotide, any compound consisting of a nucleoside that is esterified with (ortho)phosphate or an oligophosphate at any hydroxyl group on the ribose or deoxyribose.
poly-ADP-D-ribose modification-dependent protein binding	Binding to a protein upon poly-ADP-ribosylation of the target protein.

3 GO annotations of biological process

Name	Definition
chromatin remodeling	A dynamic process of chromatin reorganization resulting in changes to chromatin structure. These changes allow DNA metabolic processes such as transcriptional regulation, DNA recombination, DNA repair, and DNA replication.
DNA damage response	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
DNA repair	The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway.

13 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q24368	Iswi	Chromatin-remodeling complex ATPase chain Iswi	Drosophila melanogaster (Fruit fly)	SS
O60264	SMARCA5	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5	Homo sapiens (Human)	EV
P28370	SMARCA1	Probable global transcription activator SNF2L1	Homo sapiens (Human)	SS
Q9NRZ9	HELLS	Lymphoid-specific helicase	Homo sapiens (Human)	PR
Q86WJ1	CHD1L	Chromodomain-helicase-DNA-binding protein 1-like	Homo sapiens (Human)	EV
Q60848	Hells	Lymphocyte-specific helicase	Mus musculus (Mouse)	PR
Q91ZW3	Smarca5	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5	Mus musculus (Mouse)	SS
Q6PGB8	Smarca1	Probable global transcription activator SNF2L1	Mus musculus (Mouse)	SS
Q9CXF7	Chd1l	Chromodomain-helicase-DNA-binding protein 1-like	Mus musculus (Mouse)	SS
Q7G8Y3	Os01g0367900	Probable chromatin-remodeling complex ATPase chain	Oryza sativa subsp japonica (Rice)	PR
P41877	isw-1	Chromatin-remodeling complex ATPase chain isw-1	Caenorhabditis elegans	SS
Q8RWY3	CHR11	ISWI chromatin-remodeling complex ATPase CHR11	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9XFH4	DDM1	ATP-dependent DNA helicase DDM1	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MERVGAATPE	GDMPGFLLAL	QSKSRAEAPR	ARVQEQDLRQ	WGLTGIHLRP	YQLQGVNWLA
70	80	90	100	110	120
QCFHCQNGCI	LGDEMGLGKT	CQTIALFIYL	AGRLNDEGPF	LILCPLSVLS	NWKEEMERFA
130	140	150	160	170	180
PGLSCVTYAG	DKDKRACLQQ	DLKQESRFHV	LLTTYEICLK	DASFLKSFPW	SVLVVDEAHR
190	200	210	220	230	240
LKNQSSLLHK	TLSEFSVVFS	LLLTGTPIQN	SLQELYSLLS	FVEPDLFSKE	QVEDFVQRYQ
250	260	270	280	290	300
DIEKESESAS	ELYKLLQPFL	LRRVKAEVAT	ELPRKTEVVI	YHGMSALQKK	YYKAILMKDL
310	320	330	340	350	360
DAFENETAKK	VKLQNVLSQL	RKCVDHPYLF	DGVEPEPFEI	GDHLIEASGK	LHLLDKLLAF
370	380	390	400	410	420
LYSKGHRVLL	FSQMTQMLDI	LQDYLDYRGY	SYERVDGSVR	GEERHLAIKN	FGQQPIFTFL
430	440	450	460	470	480
LSTRAGGVGM	NLTAADTVIF	FDSDFNPQND	LQAAARAHRI	GQNKSVKVIR	LIGRDTVEEI
490	500	510	520	530	540
VYRKAASKLQ	LTNTIIEGGH	FTLGAQKPAA	DADLQLSEIL	KFGLDKLLSS	EGSTMHEIDL
550	560	570	580	590	600
KSILGETEDG	HWVSDALPTA	EEGSREPEEG	KNHMYLFEGK	DYSKEPSKED	RESFEQLVNL
610	620	630	640	650	660
QKTLLEKTSQ	EGRLLRNKGS	VPIPGLVEGS	TKRKRILSPE	ELEDRRKRRQ	EAAAKRKRLL
670	680	690	700	710	720
EEKRKKKEEA	EHKKKMAWWE	SNNYQSFCLP	SEESEPEDGE	DESSAQLEYE	DPDSTSIRYV
730	740	750	760	770	780
SGDVTHPQAG	AEDAVIVHCV	DDSGRWGRGG	LFTALETRSA	EPRKRYELAG	KMKDLSLGGV
790	800	810	820	830	840
LLFPIDDKES	RNEGQDLLAL	IVAQHRDRAN	VLSGIKMAAL	EEALKKIFLA	AKKRKASVHL
850	860	870	880	890
PRIGHATKGF	NWYGTERLIR	KHLASRGIPT	YIYYFPRSKA	AILHLQASSS	SSGQLVS