Modomics - A Database of RNA Modifications

ID Card:

Full name:	Double-stranded RNA-specific adenosine deaminase
Synonym:	ADAR1
GI:	313104303
UniProt:	P55265
Structures:	\| 1QBJ \| 1QGP \| 1XMK \| 2ACJ \| 2GXB \| 2L54 \| 2MDR \| 3F21 \| 3F22 \| 3F23 \| 3IRQ \| 3IRR \| 5ZU1 \| 5ZUO \| 5ZUP \| 7C0I \|
Alpha Fold Predicted Structure:	AF-P55265-F1
Enzyme type:	deaminase

PDB Structures:

1QBJ

Structure Description:

Title:	CRYSTAL STRUCTURE OF THE ZALPHA Z-DNA COMPLEX
Classification:	HYDROLASE/DNA
Technique:	X-Ray Diffraction
Resolution:	2.1
R value free:	0.265
R value observed:	0.227
R value work:	0.227

Abstract of the PDB Structure's related Publication:

The editing enzyme double-stranded RNA adenosine deaminase includes a DNA binding domain, Zalpha, which is specific for left-handed Z-DNA. The 2.1 angstrom crystal structure of Zalpha complexed to DNA reveals that the substrate is in the left-handed Z conformation. The contacts between Zalpha and Z-DNA are made primarily with the "zigzag" sugar-phosphate backbone, which provides a basis for the specificity for the Z conformation. A single base contact is observed to guanine in the syn conformation, characteristic of Z-DNA. Intriguingly, the helix-turn-helix motif, frequently used to recognize B-DNA, is used by Zalpha to contact Z-DNA.

Download RCSB-PDB Structures:

Pdb Files	1QBJ.pdb 1QGP.pdb 1XMK.pdb 2ACJ.pdb 2GXB.pdb 2L54.pdb 2MDR.pdb 3F21.pdb 3F22.pdb 3F23.pdb 3IRQ.pdb 3IRR.pdb 5ZU1.pdb 5ZUO.pdb 5ZUP.pdb 7C0I.pdb
Pdbx/mmCIF Files	1QBJ.cif 1QGP.cif 1XMK.cif 2ACJ.cif 2GXB.cif 2L54.cif 2MDR.cif 3F21.cif 3F22.cif 3F23.cif 3IRQ.cif 3IRR.cif 5ZU1.cif 5ZUO.cif 5ZUP.cif 7C0I.cif

Protein sequence:

MNPRQGYSLSGYYTHPFQGYEHRQLRYQQPGPGSSPSSFLLKQIEFLKGQLPEAPVIGKQTPSLPPSLPGLRPRFPVLLASSTRGRQVDIRGVPRGVHLRSQGLQRGFQHPSPRGRSLPQRGVDCLSSHFQELSIYQDQEQRILKFLEELGEGKATTAHDLSGKLGTPKKEINRVLYSLAKKGKLQKEAGTPPLWKIAVSTQAWNQHSGVVRPDGHSQGAPNSDPSLEPEDRNSTSVSEDLLEPFIAVSAQAWNQHSGVVRPDSHSQGSPNSDPGLEPEDSNSTSALEDPLEFLDMAEIKEKICDYLFNVSDSSALNLAKNIGLTKARDINAVLIDMERQGDVYRQGTTPPIWHLTDKKRERMQIKRNTNSVPETAPAAIPETKRNAEFLTCNIPTSNASNNMVTTEKVENGQEPVIKLENRQEARPEPARLKPPVHYNGPSKAGYVDFENGQWATDDIPDDLNSIRAAPGEFRAIMEMPSFYSHGLPRCSPYKKLTECQLKNPISGLLEYAQFASQTCEFNMIEQSGPPHEPRFKFQVVINGREFPPAEAGSKKVAKQDAAMKAMTILLEEAKAKDSGKSEESSHYSTEKESEKTAESQTPTPSATSFFSGKSPVTTLLECMHKLGNSCEFRLLSKEGPAHEPKFQYCVAVGAQTFPSVSAPSKKVAKQMAAEEAMKALHGEATNSMASDNQPEGMISESLDNLESMMPNKVRKIGELVRYLNTNPVGGLLEYARSHGFAAEFKLVDQSGPPHEPKFVYQAKVGGRWFPAVCAHSKKQGKQEAADAALRVLIGENEKAERMGFTELPLTGSTFHDQIAMLSHRCFNTLTNSFQPSLLGRKILAAIIMKKDSEDMGVVVSLGTGNRCVKGDSLSLKGETVNDCHAEIISRRGFIRFLYSELMKYNSQTAKDSIFEPAKGGEKLQIKKTVSFHLYISTAPCGDGALFDKSCSDRAMESTESRHYPVFENPKQGKLRTKVENGEGTIPVESSDIVPTWDGIRLGERLRTMSCSDKILRWNVLGLQGALLTHFLQPIYLKSVTLGYLFSQGHLTRAICCRVTRDGSAFEDGLRHPFIVNHPKVGRVSIYDSKRQSGKTKETSVNWCLADGYDLEILDGTRGTVDGPRNELSRVSKKNIFLLFKKLCSFRYRRDLLRLSYGEAKKAARDYETAKNYFKKGLKDMGYGNWISKPQEEKNFYLCPV

Comments:

Double-stranded RNA-specific adenosine deaminase enzymes (DSRAD) belong to the Adenosine deaminase acting on RNA (ADAR) gene family. Being an highly conserved group of enzymes they share a conserved domain architecture consisting of a variable number of N-terminal dsRNA binding domains (dsRBDs) and a C-terminal catalytic deaminase domain (Savva et al. 2012 ). ADAR is responsible for three modification along BLCAP mRNA that change the encoded protein, downstream of translation (Savva et al. 2012 ). These modifications bring to 8 possible BLCAP isoforms, with an amino acid switch from Y to C, Q to R, and K to R. The distribution of serotonin (5HT)2C receptor (5HT_2CR) in the brain suggests specific roles in normal physiology and in disease development such as in the case of, obesity, anxiety, epilepsy, sleep disorders, and motor dysfunction when dysregulated. 5HT_2CR's mRNA secondary structure differences between human, mouse, and rat transcripts suggest that ADAR does not have an intrinsic ability to recognize consensus sequences within its substrates. ADAR and ADARB1 edit AUA, AAU, and AUU codons in 5HT_2CR that translate for Isoleucine 156 (I156), Asparagine 158 (N158), and I 160 (I160), along the translated protein. Editing sites in 5HT_2CR are A, B, C, C', and D, placed in the first and third, first and second, and first coding positions of the three editing codons, respectively. A, B, C, C', and D are in the 466, 468, 472, 473, and 478 nucleotide positions, respectively. Thirtytwo editing-derived permutations are virtually possible. Nevertheless, only two editing profiles have been experimentally observed, among which is the unedited profile. In the partially edited profile, A and D sites are edited by ADAR and ADARB1, respectively. In the fully edited profile also B, C, and C' sites are edited by both of the two active ADAR isoforms. It appears that a cross-talk between ADAR isoforms exists and influences the modification profile of the intra-exonic region of the 5HT_2CR, determined by the relative expression of ADAR and ADARB1. Therefore, an interplay between the two enzymes on the shared editing sites is tempting to be inferred. (Werry et al. 2008 ) α3 subunit of the GABA_A receptor is an editing substrate for either ADAR and ADARB1. Editing of the third codon position of AUA codon triggers the I:M amino acid change, in the translated protein. Given the increasing editing extent that starts at birth and becomes close to 100% in the adult brain, it has been suggested that editing of Gabra-3 mRNA is important for normal brain development ( Ohlson et al. 2007).

Search:

Reaction	Substrate	SubstrateType	Position	(Anti)Codon	Modified (Anti)Codon	Amino Acid Change	Transcript Name	Transcript Region	Cellular Localization	References
A:I	RNA	pre-mRNA	5	TAT	TIT	Y:C	BLCAP	protein-coding region	Nucleus	19908260
A:I	RNA	pre-mRNA	14	CAG	CIG	Q:R	BLCAP	protein-coding region	Nucleus	19908260
A:I	RNA	pre-mRNA	44	AAG	AIG	K:R	BLCAP	protein-coding region	Nucleus	19908260
A:I	RNA	pre-mRNA	466	AUA	IUA	I:V	HTR2C	protein-coding region	Nucleus	18554725
A:I	RNA	pre.mRNA	468	IUA	IUI	V:V	HTR2C	protein-coding region	Nucleus	18554725
A:I	RNA	pre-mRNA	472-473	AAU	IIU	N:G	HTR2C	protein-coding region	Nucleus	18554725
A:I	RNA	pre-mRNA	15	AUA	AUI	I:M	GABA-3	protein-coding region	Nucleus	17369310


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Showing 1 to 7 of 7 entries

Alpha Fold Predicted Structure:

Downloading... [556792/1118578]

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Protein sequence:

M N P R Q G Y S L S G Y Y T H P F Q G Y E H R Q L R Y Q Q P G P G S S P S S F L L K Q I E F L K G Q L P E A P V I G K Q T P S L P P S L P G L R P R F P V L L A S S T R G R Q V D I R G V P R G V H L R S Q G L Q R G F Q H P S P R G R S L P Q R G V D C L S S H F Q E L S I Y Q D Q E Q R I L K F L E E L G E G K A T T A H D L S G K L G T P K K E I N R V L Y S L A K K G K L Q K E A G T P P L W K I A V S T Q A W N Q H S G V V R P D G H S Q G A P N S D P S L E P E D R N S T S V S E D L L E P F I A V S A Q A W N Q H S G V V R P D S H S Q G S P N S D P G L E P E D S N S T S A L E D P L E F L D M A E I K E K I C D Y L F N V S D S S A L N L A K N I G L T K A R D I N A V L I D M E R Q G D V Y R Q G T T P P I W H L T D K K R E R M Q I K R N T N S V P E T A P A A I P E T K R N A E F L T C N I P T S N A S N N M V T T E K V E N G Q E P V I K L E N R Q E A R P E P A R L K P P V H Y N G P S K A G Y V D F E N G Q W A T D D I P D D L N S I R A A P G E F R A I M E M P S F Y S H G L P R C S P Y K K L T E C Q L K N P I S G L L E Y A Q F A S Q T C E F N M I E Q S G P P H E P R F K F Q V V I N G R E F P P A E A G S K K V A K Q D A A M K A M T I L L E E A K A K D S G K S E E S S H Y S T E K E S E K T A E S Q T P T P S A T S F F S G K S P V T T L L E C M H K L G N S C E F R L L S K E G P A H E P K F Q Y C V A V G A Q T F P S V S A P S K K V A K Q M A A E E A M K A L H G E A T N S M A S D N Q P E G M I S E S L D N L E S M M P N K V R K I G E L V R Y L N T N P V G G L L E Y A R S H G F A A E F K L V D Q S G P P H E P K F V Y Q A K V G G R W F P A V C A H S K K Q G K Q E A A D A A L R V L I G E N E K A E R M G F T E L P L T G S T F H D Q I A M L S H R C F N T L T N S F Q P S L L G R K I L A A I I M K K D S E D M G V V V S L G T G N R C V K G D S L S L K G E T V N D C H A E I I S R R G F I R F L Y S E L M K Y N S Q T A K D S I F E P A K G G E K L Q I K K T V S F H L Y I S T A P C G D G A L F D K S C S D R A M E S T E S R H Y P V F E N P K Q G K L R T K V E N G E G T I P V E S S D I V P T W D G I R L G E R L R T M S C S D K I L R W N V L G L Q G A L L T H F L Q P I Y L K S V T L G Y L F S Q G H L T R A I C C R V T R D G S A F E D G L R H P F I V N H P K V G R V S I Y D S K R Q S G K T K E T S V N W C L A D G Y D L E I L D G T R G T V D G P R N E L S R V S K K N I F L L F K K L C S F R Y R R D L L R L S Y G E A K K A A R D Y E T A K N Y F K K G L K D M G Y G N W I S K P Q E E K N F Y L C P V

Secondary Structure Alphabet

G: 3-turn helix (3₁₀helix)
H: α-helix
I: 𝝅-helix (5 - turn helix)
T: Hydrogen Bonded Turn
B: β-sheet
S: Bend
C: Coil (residues not present in any of the above conformations)
N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files	AF-P55265-F1.pdb
Alpha Fold Pdbx/mmCIF Files	AF-P55265-F1.cif
DSSP Secondary Structures	P55265.dssp

Diseases connected to this enzyme:

Search:

Description	Reaction	Disease Name
A general decrease in editing activity of the human BLCAP transcript in cancerous tissues	A:I	Astrocytoma
A general decrease in editing activity of the human BLCAP transcript in cancerous tissues	A:I	Colorectal cancer
A general decrease in editing activity of the human BLCAP transcript in cancerous tissues	A:I	Bladder cancer
ADAR1 expression is higher in tumor tissues compared to patient-matched normal breast tissues. Silencing of ADAR1 decreases cell proliferation	A:I	Breast cancer
ADAR1 gene amplification is oncogenic in lung cancer and can enhance cell growth and invasion	A:I	Lung cancer
Alu-dependent A-to-I RNA editing increases in rheumatoid arthritis. Cathepsin S and TNF receptor-associated factors 1,2,3 and 5 are among the hyper-edited transcripts	A:I	Rheumatoid Arthritis
Alzheimer disease is correlated with a reduction of A to I RNA editing	A:I	Alzheimer
An increase in RNA editing on AZIN1 neutralizes a key inhibitor of the polyamine synthesis pathway, thereby promoting proliferation in vitro and tumor initiation in vivo. AZIN1 editing is associated with liver cirrhosis	A:I	Hepatocellular carcinoma
Deregulation GLI1 RNA editing is correlated to multiple myeloma	A:I	Myeloma
Mutations of the ADAR may impair its tertiary structure, entailing its defective activity, and are linked to the onset of DSH.	A:I	Dyschromatosis Symmetrica Hereditaria
Overexpression of ADAR1 contributes to the alterations in RNA editing patterns, including the editing on FLNB. Moreover, the editing of AZIN1 is responsible for the ADAR1-induced malignant phenotype during ESCC progression	A:I	Hepatocellular carcinoma
The overexpression of ADAR inhibits GBM cell line proliferation	A:I	Glioblastoma
The two edited forms of BLCAP fail to inhibit STAT3 phosphorylation. A-to-I RNA editing drives anti-tumorigenic BLCAP into a loss-of-function state that might facilitate the events leading to cervical cancer initiation, and progression	A:I	Cervical cancer
Two hyper-edited sites (Q103R and K96R) on CDK13 are more abundant in HCC tumor tissues and are associated with poor prognosis in HCC patients	A:I	Hepatocellular carcinoma
Upregulation of ADAR1 p-150 isoform, in the blastic crisis of CML, may be related to the activation of inflammatory pathways. An inflammatory mediator-driven isoform switch, which favors ADAR1 p150 expression, drives the expansion of malignant progenitors and contributes to CML progression.	A:I	Chronic Myeloid Leukemia


A general decrease in editing activity of the human BLCAP transcript in cancerous tissues
A general decrease in editing activity of the human BLCAP transcript in cancerous tissues
A general decrease in editing activity of the human BLCAP transcript in cancerous tissues
ADAR1 expression is higher in tumor tissues compared to patient-matched normal breast tissues. Silencing of ADAR1 decreases cell proliferation
ADAR1 gene amplification is oncogenic in lung cancer and can enhance cell growth and invasion
Alu-dependent A-to-I RNA editing increases in rheumatoid arthritis. Cathepsin S and TNF receptor-associated factors 1,2,3 and 5 are among the hyper-edited transcripts
Alzheimer disease is correlated with a reduction of A to I RNA editing
An increase in RNA editing on AZIN1 neutralizes a key inhibitor of the polyamine synthesis pathway, thereby promoting proliferation in vitro and tumor initiation in vivo. AZIN1 editing is associated with liver cirrhosis
Deregulation GLI1 RNA editing is correlated to multiple myeloma
Mutations of the ADAR may impair its tertiary structure, entailing its defective activity, and are linked to the onset of DSH.
Overexpression of ADAR1 contributes to the alterations in RNA editing patterns, including the editing on FLNB. Moreover, the editing of AZIN1 is responsible for the ADAR1-induced malignant phenotype during ESCC progression
The overexpression of ADAR inhibits GBM cell line proliferation
The two edited forms of BLCAP fail to inhibit STAT3 phosphorylation. A-to-I RNA editing drives anti-tumorigenic BLCAP into a loss-of-function state that might facilitate the events leading to cervical cancer initiation, and progression
Two hyper-edited sites (Q103R and K96R) on CDK13 are more abundant in HCC tumor tissues and are associated with poor prognosis in HCC patients
Upregulation of ADAR1 p-150 isoform, in the blastic crisis of CML, may be related to the activation of inflammatory pathways. An inflammatory mediator-driven isoform switch, which favors ADAR1 p150 expression, drives the expansion of malignant progenitors and contributes to CML progression.

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Publications:

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