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:FCGR2B

Protein Summary

Gene summary

Gene name: FCGR2B
ASpdb.0 ID: 2213
	Gene
Gene symbol	FCGR2B
Gene ID	2213
Gene name	Fc gamma receptor IIb
Synonyms	CD32\|CD32B\|FCG2\|FCGR2\|FCGR2C\|FcGRIIB\|FcRII-c\|FcgammaRIIb\|IGFR2
Cytomap	1q23.3
Type of gene	protein-coding
Description	low affinity immunoglobulin gamma Fc region receptor II-bCDw32Fc fragment of IgG receptor IIbFc fragment of IgG, low affinity II, receptor for (CD32)Fc fragment of IgG, low affinity IIb, receptor (CD32)Fc fragment of IgG, low affinity IIb, receptor f
Modification date	20240310
UniProtAcc	P31994

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

Partner	Gene	GO ID	GO term	PubMed ID
Gene	FCGR2B	GO:0002252	immune effector process	2142460
Gene	FCGR2B	GO:0005886	plasma membrane	2142460\|23921129
Gene	FCGR2B	GO:0006898	receptor-mediated endocytosis	2142460
Gene	FCGR2B	GO:0006909	phagocytosis	2142460
Gene	FCGR2B	GO:0019772	low-affinity IgG receptor activity	2142460
Gene	FCGR2B	GO:0019864	IgG binding	2142460
Gene	FCGR2B	GO:0038094	Fc-gamma receptor signaling pathway	2142460

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
P31994-1	P31994-1_2fcb_A.pdb	2FCB	X-ray	1.74	A	46	217

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

P31994

FCGR2B

P31994-1

P31994-2

310

291

254

272

Deletion

none

253

P31994

FCGR2B

P31994-1

P31994-3

310

303

Deletion

none

P31994

FCGR2B

P31994-1

P31994-4

310

309

Deletion

none

P31994

FCGR2B

P31994-1

P31994-5

310

290

Deletion

none

P31994

FCGR2B

P31994-1

P31994-5

310

290

254

272

Deletion

none

252

Multiple sequence alignment of our canonical and alternatively spliced FCGR2B

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of FCGR2B

UniProt-id	ENSG	ENST	ENSP
P31994-1	ENSG00000072694.22	ENST00000358671.10	ENSP00000351497.5
P31994-2	ENSG00000072694.22	ENST00000236937.13	ENSP00000236937.9
P31994-3	ENSG00000072694.22	ENST00000367961.8	ENSP00000356938.4

UniProt-id	NM ID	NP ID
P31994-1	NM_004001.4	NP_003992.3
P31994-2	NM_001002274.2	NP_001002274.1
P31994-3	NM_001190828.1	NP_001177757.1
P31994-4	NM_001002275.2	NP_001002275.1
P31994-5	NM_001002273.2	NP_001002273.1

Amino acid sequences of our canonical and alternatively spliced FCGR2B

accession_id	Protein sequence
P31994-1	MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAAPPKAVLKLEPQWINVLQEDSVTLTCRGTHSPESDSIQWFHNGNL IPTHTQPSYRFKANNNDSGEYTCQTGQTSLSDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPN FSIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAAVVALIYCRKKRISALPGYPECREMGETLPE
P31994-2	MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAAPPKAVLKLEPQWINVLQEDSVTLTCRGTHSPESDSIQWFHNGNL IPTHTQPSYRFKANNNDSGEYTCQTGQTSLSDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPN FSIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAAVVALIYCRKKRISANPTNPDEADKVGAENT
P31994-3	MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAAPPKAVLKLEPQWINVLQEDSVTLTCRGTHSPESDSIQWFHNGNLIPTHTQP SYRFKANNNDSGEYTCQTGQTSLSDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPNFSIPQAN HSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAAVVALIYCRKKRISALPGYPECREMGETLPEKPANPTN
P31994-4	MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAPPKAVLKLEPQWINVLQEDSVTLTCRGTHSPESDSIQWFHNGNLI PTHTQPSYRFKANNNDSGEYTCQTGQTSLSDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPNF SIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAAVVALIYCRKKRISALPGYPECREMGETLPEK
P31994-5	MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAPPKAVLKLEPQWINVLQEDSVTLTCRGTHSPESDSIQWFHNGNLI PTHTQPSYRFKANNNDSGEYTCQTGQTSLSDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPNF SIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAAVVALIYCRKKRISANPTNPDEADKVGAENTI

Protein Functional Features

Main function of this protein. (from UniProt)

FCGR2B (go to UniProt):P31994

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
P31994	Topological domain	43	217	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=39;End=45
P31994	Topological domain	43	217	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=46;End=46
P31994	Topological domain	43	217	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=46;End=46
P31994	Topological domain	241	310	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=254;End=272
P31994	Topological domain	241	310	Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255	Type=Deletion;Start=254;End=272

Gene Isoform Structures and Expression Levels for FCGR2B

Gene structures of our canonical and alternative spliced genes of FCGR2B
* 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 P31994-1

3D view using mol* of P31994-2

3D view using mol* of P31994-3

3D view using mol* of P31994-4

3D view using mol* of P31994-5

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 P31994-1

pLDDT distribution across the protein length of P31994-2

pLDDT distribution across the protein length of P31994-3

pLDDT distribution across the protein length of P31994-4

pLDDT distribution across the protein length of P31994-5

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 P31994-1

Ramachandran plot of P31994-4

Ramachandran plot of P31994-5

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
P31994-1	0.747	60	0.704	117.306	0.695	0.567	0.77	0.14	1.117	0.125	0.576	54,55,56,58,61,65,66,67,68,136,151,152,153,154,157 ,158,159,160,177,179
P31994-2	0.705	36	0.597	75.803	0.538	0.696	1.033	0.558	1.179	0.474	0.826	54,56,58,61,64,65,66,67,102,136,151,153,157
P31994-3	0.751	60	0.719	125.195	0.71	0.573	0.74	0.279	1.083	0.257	0.453	49,51,54,57,58,59,95,129,144,145,146,147,150,151,1 52,153,170,172
P31994-4	0.728	46	0.628	80.262	0.586	0.644	0.98	0.497	1.215	0.409	0.715	69,70,71,72,73,74,75,76,77,78,79,81,96,114,116,117
P31994-5	0.789	31	0.836	140.287	0.696	0.623	0.864	1.954	0.188	10.372	7.953	25,28,29,32,33,36,233,234,237,238,241,242

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 P31994-1_P31994-1_2fcb_A.pdb

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

3D view using mol* of P31994-1_2fcb_A_P31994-2.pdb

3D view using mol* of P31994-1_2fcb_A_P31994-3.pdb

3D view using mol* of P31994-1_2fcb_A_P31994-4.pdb

3D view using mol* of P31994-1_2fcb_A_P31994-5.pdb

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

3D view using mol* of P31994-1_P31994-2.pdb

3D view using mol* of P31994-1_P31994-3.pdb

3D view using mol* of P31994-1_P31994-4.pdb

3D view using mol* of P31994-1_P31994-5.pdb

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

./stats/secondary_structure/figure/P31994-1_vs_P31994-2.png

./stats/secondary_structure/figure/P31994-1_vs_P31994-3.png

./stats/secondary_structure/figure/P31994-1_vs_P31994-4.png

./stats/secondary_structure/figure/P31994-1_vs_P31994-5.png

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

./stats/relative_asa/P31994-1_vs_P31994-2.png

./stats/relative_asa/P31994-1_vs_P31994-3.png

./stats/relative_asa/P31994-1_vs_P31994-4.png

./stats/relative_asa/P31994-1_vs_P31994-5.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 FCGR2B

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession	Gene name	DrugBank ID	Drug name	Drug group	Actions
P31994	FCGR2B	DB00112	Bevacizumab	approved, investigational
P31994	FCGR2B	DB00005	Etanercept	approved, investigational	ligand
P31994	FCGR2B	DB00081	Tositumomab	approved, investigational
P31994	FCGR2B	DB00028	Human immunoglobulin G	approved, investigational	antagonist
P31994	FCGR2B	DB00098	Antithymocyte immunoglobulin (rabbit)	approved
P31994	FCGR2B	DB00110	Palivizumab	approved, investigational
P31994	FCGR2B	DB00054	Abciximab	approved
P31994	FCGR2B	DB00111	Daclizumab	investigational, withdrawn
P31994	FCGR2B	DB11767	Sarilumab	approved, investigational	unknown
P31994	FCGR2B	DB00087	Alemtuzumab	approved, investigational	binder

Related Diseases to FCGR2B

Previous studies relating to the alternative splicing of FCGR2B and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
FCGR2B	15459183	CD72 polymorphisms associated with alternative splicing modify susceptibility to human systemic lupus erythematosus through epistatic interaction with FCGR2B.	We previously reported association of FCGR2B-Ile232Thr with systemic lupus erythematosus (SLE) in three Asian populations. Because polymorphism of CD72, another inhibitory receptor of B cells, was associated with murine SLE, we identified human CD72 polymorphisms, tested their association with SLE and examined genetic interaction with FCGR2B in the Japanese (160 SLE, 277 controls), Thais (87 SLE, 187 controls) and Caucasians (94 families containing SLE members). Four polymorphisms and six rare variations were detected. The former constituted two major haplotypes that contained one or two repeats of 13 nucleotides in intron 8 (designated as 1 and 2, respectively). Although association with susceptibility to SLE was not detected, the 1 allele was significantly associated with nephritis among the Japanese patients (P=0.024). RT-PCR identified a novel alternatively spliced (AS) transcript that was expressed at the protein level in COS-7 transfectants. The ratio of AS/common isoforms was strikingly increased in individuals with 2/2 genotype when compared with 1/1 (P=0.000038) or 1/2 (P=0.0085) genotypes. Using the two Asian cohorts, significant association of FCGR2B-232Thr/Thr with SLE was observed only in the presence of CD72-1/1 genotype (OR 4.63, 95% CI 1.47-14.6, P=0.009 versus FCGR2B-232Ile/Ile plus CD72-2/2). Minigene assays demonstrated that the 13-nucleotide repeat and 4 bp deletion within the same haplotype of intron 8 could regulate alternative splicing. The AS isoform lacks exon 8, and is deduced to contain 49 amino acid changes in the membrane-distal portion of the extracellular domain, where considerable amino acid changes are known in CD72(c) allele associated with murine SLE. These results indicated that the presence of CD72-2 allele decreases risk for human SLE conferred by FCGR2B-232Thr, possibly by increasing the AS isoform of CD72.	D020022	Genetic Predisposition to Disease

Clinically important variants in FCGR2B

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance