ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

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	Protein Summary
	AS Summary
	Protein Functional Features
	Gene Isoform Structures and Expression Levels
	Protein Structures
	pLDDT Score Distribution
	Ramachandran Plot of Protein Structures
	Potential Active Site Information
	Protein Structure and Feature Comparision
	Protein-Protein Interaction
	Related Drugs
	Related Diseases
	Clinically Important Variants

Protein:BRD2

Protein Summary

Gene summary

Gene name: BRD2
ASpdb.0 ID: 6046
	Gene
Gene symbol	BRD2
Gene ID	6046
Gene name	bromodomain containing 2
Synonyms	BRD2-IT1\|D6S113E\|FSH\|FSHRG1\|FSRG1\|NAT\|O27.1.1\|RING3\|RNF3
Cytomap	6p21.32
Type of gene	protein-coding
Description	bromodomain-containing protein 2BRD2 intronic transcript 1female sterile homeotic-related gene 1really interesting new gene 3 protein
Modification date	20240403
UniProtAcc	P25440

Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Gene	BRD2	GO:0000785	chromatin	17848202\|20048151\|20709061
Gene	BRD2	GO:0003682	chromatin binding	18406326
Gene	BRD2	GO:0004674	protein serine/threonine kinase activity	8595877
Gene	BRD2	GO:0005634	nucleus	8595877\|25593309
Gene	BRD2	GO:0005654	nucleoplasm	-
Gene	BRD2	GO:0006357	regulation of transcription by RNA polymerase II	18406326\|28262505
Gene	BRD2	GO:0006468	protein phosphorylation	8595877
Gene	BRD2	GO:0016607	nuclear speck	-
Gene	BRD2	GO:0070577	lysine-acetylated histone binding	17848202\|18406326\|20048151\|20709061\|35410381
Gene	BRD2	GO:0071168	protein localization to chromatin	28262505
Gene	BRD2	GO:0140033	acetylation-dependent protein binding	28262505
Gene	BRD2	GO:0140588	chromatin looping	35410381
Gene	BRD2	GO:2000330	positive regulation of T-helper 17 cell lineage commitment	28262505

AS Summary

Information of the canonical protein with experimentally identified structure from PDB (2023).

UniProt Acc	File name	PDB ID	Method	Resolution	Chain	Start	End
P25440-1	P25440-1_6ulq_B.pdb	6ULQ	X-ray	2.7	B	65	191

ASpdb's canonical and alternatively spliced isoform information.

accession_id

gene_name

canonical_id

alternative_id

canonical_length

alternative_length

canonical_start

canonical_end

type

originalSEQ

variationSEQ

alternative_start

alternative_end

P25440

BRD2

P25440-1

P25440-2

801

836

615

Substitution

LQAGVQWRDLGLLQPPLLGFKRFSCLSLPSSQDYRL

615

650

P25440

BRD2

P25440-1

P25440-3

801

754

Deletion

none

P25440

BRD2

P25440-1

P25440-4

801

681

120

Deletion

none

Multiple sequence alignment of our canonical and alternatively spliced BRD2

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of BRD2

UniProt-id	ENSG	ENST	ENSP
P25440-1	ENSG00000204256.14	ENST00000374825.9	ENSP00000363958.4
P25440-1	ENSG00000204256.14	ENST00000374831.8	ENSP00000363964.4
P25440-1	ENSG00000234507.9	ENST00000383108.6	ENSP00000372588.2
P25440-1	ENSG00000215077.10	ENST00000399528.5	ENSP00000382444.1
P25440-1	ENSG00000215077.10	ENST00000399529.7	ENSP00000382445.3
P25440-1	ENSG00000234507.9	ENST00000438194.6	ENSP00000401791.2
P25440-1	ENSG00000204256.14	ENST00000449085.4	ENSP00000409145.3
P25440-1	ENSG00000235307.12	ENST00000549126.4	ENSP00000449380.2
P25440-1	ENSG00000235307.12	ENST00000552587.4	ENSP00000449609.1
P25440-1	ENSG00000204256.14	ENST00000678250.1	ENSP00000502900.1
P25440-2	ENSG00000204256.14	ENST00000395287.5	ENSP00000378702.1
P25440-2	ENSG00000215077.10	ENST00000399527.5	ENSP00000382443.1
P25440-2	ENSG00000234507.9	ENST00000442863.5	ENSP00000410994.1
P25440-2	ENSG00000235307.12	ENST00000448067.5	ENSP00000412885.1
P25440-3	ENSG00000235307.12	ENST00000436979.5	ENSP00000405634.1

UniProt-id	NM ID	NP ID
P25440-1	NM_001113182.2	NP_001106653.1
P25440-1	NM_005104.3	NP_005095.1
P25440-2	NM_001199455.1	NP_001186384.1
P25440-3	NM_001199456.1	NP_001186385.1
P25440-4	NM_001291986.1	NP_001278915.1

Amino acid sequences of our canonical and alternatively spliced BRD2

accession_id	Protein sequence
P25440-1	MLQNVTPHNKLPGEGNAGLLGLGPEAAAPGKRIRKPSLLYEGFESPTMASVPALQLTPANPPPPEVSNPKKPGRVTNQLQYLHKVVMKAL WKHQFAWPFRQPVDAVKLGLPDYHKIIKQPMDMGTIKRRLENNYYWAASECMQDFNTMFTNCYIYNKPTDDIVLMAQTLEKIFLQKVASM PQEEQELVVTIPKNSHKKGAKLAALQGSVTSAHQVPAVSSVSHTALYTPPPEIPTTVLNIPHPSVISSPLLKSLHSAGPPLLAVTAAPPA QPLAKKKGVKRKADTTTPTPTAILAPGSPASPPGSLEPKAARLPPMRRESGRPIKPPRKDLPDSQQQHQSSKKGKLSEQLKHCNGILKEL LSKKHAAYAWPFYKPVDASALGLHDYHDIIKHPMDLSTVKRKMENRDYRDAQEFAADVRLMFSNCYKYNPPDHDVVAMARKLQDVFEFRY AKMPDEPLEPGPLPVSTAMPPGLAKSSSESSSEESSSESSSEEEEEEDEEDEEEEESESSDSEEERAHRLAELQEQLRAVHEQLAALSQG PISKPKRKREKKEKKKKRKAEKHRGRAGADEDDKGPRAPRPPQPKKSKKASGSGGGSAALGPSGFGPSGGSGTKLPKKATKTAPPALPTG YDSEEEEESRPMSYDEKRQLSLDINKLPGEKLGRVVHIIQAREPSLRDSNPEEIEIDFETLKPSTLRELERYVLSCLRKKPRKPYTIKKP
P25440-2	MLQNVTPHNKLPGEGNAGLLGLGPEAAAPGKRIRKPSLLYEGFESPTMASVPALQLTPANPPPPEVSNPKKPGRVTNQLQYLHKVVMKAL WKHQFAWPFRQPVDAVKLGLPDYHKIIKQPMDMGTIKRRLENNYYWAASECMQDFNTMFTNCYIYNKPTDDIVLMAQTLEKIFLQKVASM PQEEQELVVTIPKNSHKKGAKLAALQGSVTSAHQVPAVSSVSHTALYTPPPEIPTTVLNIPHPSVISSPLLKSLHSAGPPLLAVTAAPPA QPLAKKKGVKRKADTTTPTPTAILAPGSPASPPGSLEPKAARLPPMRRESGRPIKPPRKDLPDSQQQHQSSKKGKLSEQLKHCNGILKEL LSKKHAAYAWPFYKPVDASALGLHDYHDIIKHPMDLSTVKRKMENRDYRDAQEFAADVRLMFSNCYKYNPPDHDVVAMARKLQDVFEFRY AKMPDEPLEPGPLPVSTAMPPGLAKSSSESSSEESSSESSSEEEEEEDEEDEEEEESESSDSEEERAHRLAELQEQLRAVHEQLAALSQG PISKPKRKREKKEKKKKRKAEKHRGRAGADEDDKGPRAPRPPQPKKSKKASGSGGGSAALGPSGFGPSGGSGTKLQAGVQWRDLGLLQPP LLGFKRFSCLSLPSSQDYRLPKKATKTAPPALPTGYDSEEEEESRPMSYDEKRQLSLDINKLPGEKLGRVVHIIQAREPSLRDSNPEEIE IDFETLKPSTLRELERYVLSCLRKKPRKPYTIKKPVGKTKEELALEKKRELEKRLQDVSGQLNSTKKPPKKANEKTESSSAQQVAVSRLS
P25440-3	MASVPALQLTPANPPPPEVSNPKKPGRVTNQLQYLHKVVMKALWKHQFAWPFRQPVDAVKLGLPDYHKIIKQPMDMGTIKRRLENNYYWA ASECMQDFNTMFTNCYIYNKPTDDIVLMAQTLEKIFLQKVASMPQEEQELVVTIPKNSHKKGAKLAALQGSVTSAHQVPAVSSVSHTALY TPPPEIPTTVLNIPHPSVISSPLLKSLHSAGPPLLAVTAAPPAQPLAKKKGVKRKADTTTPTPTAILAPGSPASPPGSLEPKAARLPPMR RESGRPIKPPRKDLPDSQQQHQSSKKGKLSEQLKHCNGILKELLSKKHAAYAWPFYKPVDASALGLHDYHDIIKHPMDLSTVKRKMENRD YRDAQEFAADVRLMFSNCYKYNPPDHDVVAMARKLQDVFEFRYAKMPDEPLEPGPLPVSTAMPPGLAKSSSESSSEESSSESSSEEEEEE DEEDEEEEESESSDSEEERAHRLAELQEQLRAVHEQLAALSQGPISKPKRKREKKEKKKKRKAEKHRGRAGADEDDKGPRAPRPPQPKKS KKASGSGGGSAALGPSGFGPSGGSGTKLPKKATKTAPPALPTGYDSEEEEESRPMSYDEKRQLSLDINKLPGEKLGRVVHIIQAREPSLR DSNPEEIEIDFETLKPSTLRELERYVLSCLRKKPRKPYTIKKPVGKTKEELALEKKRELEKRLQDVSGQLNSTKKPPKKANEKTESSSAQ
P25440-4	MDMGTIKRRLENNYYWAASECMQDFNTMFTNCYIYNKPTDDIVLMAQTLEKIFLQKVASMPQEEQELVVTIPKNSHKKGAKLAALQGSVT SAHQVPAVSSVSHTALYTPPPEIPTTVLNIPHPSVISSPLLKSLHSAGPPLLAVTAAPPAQPLAKKKGVKRKADTTTPTPTAILAPGSPA SPPGSLEPKAARLPPMRRESGRPIKPPRKDLPDSQQQHQSSKKGKLSEQLKHCNGILKELLSKKHAAYAWPFYKPVDASALGLHDYHDII KHPMDLSTVKRKMENRDYRDAQEFAADVRLMFSNCYKYNPPDHDVVAMARKLQDVFEFRYAKMPDEPLEPGPLPVSTAMPPGLAKSSSES SSEESSSESSSEEEEEEDEEDEEEEESESSDSEEERAHRLAELQEQLRAVHEQLAALSQGPISKPKRKREKKEKKKKRKAEKHRGRAGAD EDDKGPRAPRPPQPKKSKKASGSGGGSAALGPSGFGPSGGSGTKLPKKATKTAPPALPTGYDSEEEEESRPMSYDEKRQLSLDINKLPGE KLGRVVHIIQAREPSLRDSNPEEIEIDFETLKPSTLRELERYVLSCLRKKPRKPYTIKKPVGKTKEELALEKKRELEKRLQDVSGQLNST

Protein Functional Features

Main function of this protein. (from UniProt)

BRD2 (go to UniProt):P25440

Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained protein feature among the 13 regional features.

Accession_id	Subsection	Start	End	Funcitonal feature	Splicing information
P25440	Domain	91	163	Note=Bromo 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00035	Type=Deletion;Start=1;End=120
P25440	Region	53	73	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=1;End=120
P25440	Region	456	647	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=615;End=615

Gene Isoform Structures and Expression Levels for BRD2

Gene structures of our canonical and alternative spliced genes of BRD2
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Expression levels of gene isoforms across GTEx.

Expression levels of gene isoforms across TCGA.

Protein Structures

PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

3D view using mol* of P25440-1

3D view using mol* of P25440-2

3D view using mol* of P25440-3

3D view using mol* of P25440-4

pLDDT Score Distribution

pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

pLDDT distribution across the protein length of P25440-1

pLDDT distribution across the protein length of P25440-2

pLDDT distribution across the protein length of P25440-3

pLDDT distribution across the protein length of P25440-4

Ramachandran Plot of Protein Structures

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.

Ramachandran plot of P25440-1

Ramachandran plot of P25440-3

Potential Active Site Information

The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.

UniProt-id	Site score	Size	D score	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
P25440-1	1.056	96	1.089	202.027	0.47	0.756	1.059	1.199	0.877	1.367	1.03	370,371,372,374,375,376,377,381,383,386,390,393,39 4,395,421,424,425,428,429,433,435
P25440-2	1.049	95	1.042	224.665	0.428	0.799	1.113	1.007	1.085	0.928	0.462	97,98,99,101,102,103,104,108,110,113,117,120,121,1 22,148,151,152,155,156,162
P25440-3	1.014	84	1.02	197.225	0.472	0.787	1.11	1.191	0.963	1.237	0.694	323,324,325,327,328,329,330,334,336,339,346,347,34 8,374,377,378,381,382,388
P25440-4	1.051	97	1.081	215.747	0.481	0.754	1.05	1.391	0.91	1.528	0.73	250,251,252,254,255,256,257,261,263,266,270,273,27 4,275,301,304,305,308,309,313,315,318

Protein Structure and Feature Comparision

Protein Structure Comparision Using Template Modeling Scores (TM-score).

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)

3D view using mol* of P25440-1_P25440-1_6ulq_B.pdb

Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P25440-1_6ulq_B_P25440-2.pdb

3D view using mol* of P25440-1_6ulq_B_P25440-3.pdb

3D view using mol* of P25440-1_6ulq_B_P25440-4.pdb

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P25440-1_P25440-2.pdb

3D view using mol* of P25440-1_P25440-3.pdb

3D view using mol* of P25440-1_P25440-4.pdb

Protein Feature Comparison of the protein sequendary structures among the protiens.

./stats/secondary_structure/figure/P25440-1_vs_P25440-2.png

./stats/secondary_structure/figure/P25440-1_vs_P25440-3.png

./stats/secondary_structure/figure/P25440-1_vs_P25440-4.png

Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.

./stats/relative_asa/P25440-1_vs_P25440-2.png

./stats/relative_asa/P25440-1_vs_P25440-3.png

./stats/relative_asa/P25440-1_vs_P25440-4.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Interactors from STRING.

Gene name

Interactors

Related Drugs to BRD2

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession

Gene name

DrugBank ID

Drug name

Drug group

Actions

Related Diseases to BRD2

Previous studies relating to the alternative splicing of BRD2 and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
BRD2	24711643	Identifying biological pathways that underlie primordial short stature using network analysis.	Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M 'interactome', to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure.	D004392	Dwarfism
BRD2	24711643	Identifying biological pathways that underlie primordial short stature using network analysis.	Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M 'interactome', to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure.	D006130	Growth Disorders
BRD2	24711643	Identifying biological pathways that underlie primordial short stature using network analysis.	Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M 'interactome', to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure.	D009123	Muscle Hypotonia

Clinically important variants in BRD2

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance