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:NF2

Protein Summary

Gene summary

Gene name: NF2
ASpdb.0 ID: 4771
	Gene
Gene symbol	NF2
Gene ID	4771
Gene name	NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor
Synonyms	ACN\|BANF\|SCH\|SWNV\|merlin-1
Cytomap	22q12.2
Type of gene	protein-coding
Description	merlinbilateral acoustic neurofibromatosismoesin-ezrin-radixin likemoesin-ezrin-radixin-like proteinmoesin-ezrin-radizin-like proteinneurofibromin 2 (bilateral acoustic neuroma)neurofibromin-2schwannomerlinschwannomin
Modification date	20240407
UniProtAcc	P35240

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

Partner	Gene	GO ID	GO term	PubMed ID
Gene	NF2	GO:0005634	nucleus	10401006\|20178741
Gene	NF2	GO:0005730	nucleolus	9537418
Gene	NF2	GO:0005737	cytoplasm	9537418
Gene	NF2	GO:0005769	early endosome	10861283
Gene	NF2	GO:0005829	cytosol	-
Gene	NF2	GO:0005886	plasma membrane	10401006
Gene	NF2	GO:0008285	negative regulation of cell population proliferation	12444102\|20178741
Gene	NF2	GO:0022408	negative regulation of cell-cell adhesion	17210637
Gene	NF2	GO:0042532	negative regulation of tyrosine phosphorylation of STAT protein	12444102
Gene	NF2	GO:0046426	negative regulation of receptor signaling pathway via JAK-STAT	12444102
Gene	NF2	GO:0048471	perinuclear region of cytoplasm	17210637

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
P35240-1	P35240-1_6cds_A.pdb	6CDS	X-ray	2.62	A	15	339

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
P35240	NF2	P35240-1	P35240-10	595	220	39	121	Deletion	none	none	38	38
P35240	NF2	P35240-1	P35240-10	595	220	150	225	Deletion	none	none	66	66
P35240	NF2	P35240-1	P35240-10	595	220	334	379	Substitution	MERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEE	GQRGRSAEAGPAGSTRGGAKSQAEAPGDCHQAHVPAHEPNSSTVAS	175	220
P35240	NF2	P35240-1	P35240-10	595	220	380	595	Deletion	none	none	220	220
P35240	NF2	P35240-1	P35240-2	595	620	580	595	Substitution	LTLQSAKSRVAFFEEL	SSPRQKTYLHLSPQSRLFPGTLYVVMLYVVMVLPSVILTRA	580	620
P35240	NF2	P35240-1	P35240-3	595	590	580	590	Substitution	LTLQSAKSRVA	PQAQGRRPICI	580	590
P35240	NF2	P35240-1	P35240-3	595	590	591	595	Deletion	none	none	590	590
P35240	NF2	P35240-1	P35240-4	595	507	39	121	Deletion	none	none	38	38
P35240	NF2	P35240-1	P35240-4	595	507	580	590	Substitution	LTLQSAKSRVA	PQAQGRRPICI	497	507
P35240	NF2	P35240-1	P35240-4	595	507	591	595	Deletion	none	none	507	507
P35240	NF2	P35240-1	P35240-5	595	549	81	121	Deletion	none	none	80	80
P35240	NF2	P35240-1	P35240-5	595	549	580	590	Substitution	LTLQSAKSRVA	PQAQGRRPICI	539	549
P35240	NF2	P35240-1	P35240-5	595	549	591	595	Deletion	none	none	549	549
P35240	NF2	P35240-1	P35240-6	595	548	39	80	Deletion	none	none	38	38
P35240	NF2	P35240-1	P35240-6	595	548	580	590	Substitution	LTLQSAKSRVA	PQAQGRRPICI	538	548
P35240	NF2	P35240-1	P35240-6	595	548	591	595	Deletion	none	none	548	548
P35240	NF2	P35240-1	P35240-7	595	259	259	259	Substitution	N	R	259	259
P35240	NF2	P35240-1	P35240-7	595	259	260	595	Deletion	none	none	259	259
P35240	NF2	P35240-1	P35240-8	595	561	335	363	Deletion	none	none	334	334
P35240	NF2	P35240-1	P35240-8	595	561	580	590	Substitution	LTLQSAKSRVA	PQAQGRRPICI	551	561
P35240	NF2	P35240-1	P35240-8	595	561	591	595	Deletion	none	none	561	561
P35240	NF2	P35240-1	P35240-9	595	165	150	579	Deletion	none	none	149	149

Multiple sequence alignment of our canonical and alternatively spliced NF2

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of NF2

UniProt-id	ENSG	ENST	ENSP
P35240-1	ENSG00000186575.19	ENST00000338641.10	ENSP00000344666.5
P35240-10	ENSG00000186575.19	ENST00000432151.5	ENSP00000395885.1
P35240-3	ENSG00000186575.19	ENST00000397789.3	ENSP00000380891.3
P35240-3	ENSG00000186575.19	ENST00000403999.7	ENSP00000384797.3
P35240-3	ENSG00000186575.19	ENST00000672461.1	ENSP00000500919.1
P35240-3	ENSG00000186575.19	ENST00000672896.1	ENSP00000500117.1
P35240-4	ENSG00000186575.19	ENST00000334961.11	ENSP00000335652.7
P35240-4	ENSG00000186575.19	ENST00000353887.8	ENSP00000340626.4
P35240-5	ENSG00000186575.19	ENST00000361452.8	ENSP00000354897.4
P35240-6	ENSG00000186575.19	ENST00000361676.8	ENSP00000355183.4
P35240-8	ENSG00000186575.19	ENST00000403435.5	ENSP00000384029.1
P35240-9	ENSG00000186575.19	ENST00000413209.6	ENSP00000409921.2

UniProt-id	NM ID	NP ID
P35240-1	NM_000268.3	NP_000259.1
P35240-3	NM_016418.5	NP_057502.2
P35240-3	NM_181825.2	NP_861546.1
P35240-3	NM_181832.2	NP_861970.1
P35240-4	NM_181830.2	NP_861968.1
P35240-4	NM_181831.2	NP_861969.1
P35240-5	NM_181829.2	NP_861967.1
P35240-6	NM_181828.2	NP_861966.1
P35240-9	NM_181833.2	NP_861971.1

Amino acid sequences of our canonical and alternatively spliced NF2

accession_id	Protein sequence
P35240-1	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKKVLDHDVSKEE PVTFHFLAKFYPENAEEELVQEITQHLFFLQVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMT PEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKE FTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRL LQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKE ADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPLPPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLN
P35240-10	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEVKKQILDEKIYCPPEASVLLASYAVQAKNKKGTELLLGVDALGLHIYDPENR LTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRKADSLEVQQMKAQAREEKARKQGQRGRS
P35240-2	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKKVLDHDVSKEE PVTFHFLAKFYPENAEEELVQEITQHLFFLQVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMT PEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKE FTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRL LQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKE ADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPLPPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLN
P35240-3	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKKVLDHDVSKEE PVTFHFLAKFYPENAEEELVQEITQHLFFLQVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMT PEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKE FTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRL LQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKE ADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPLPPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLN
P35240-4	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRV INLYQMTPEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRN ISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTR DELERRLLQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEE SERRAKEADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPLPPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSK
P35240-5	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKKVKKQILDEKI YCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMTPEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNY FAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRR KADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQK AAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPL PPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDILHNENSDRGGSSKHNTIKKPQ
P35240-6	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEVLDHDVSKEEPVTFHFLAKFYPENAEEELVQEITQHLFFLQVKKQILDEKIY CPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMTPEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYF AIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRK ADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKA AEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPLP PDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDILHNENSDRGGSSKHNTIKKPQA
P35240-7	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKKVLDHDVSKEE PVTFHFLAKFYPENAEEELVQEITQHLFFLQVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMT
P35240-8	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKKVLDHDVSKEE PVTFHFLAKFYPENAEEELVQEITQHLFFLQVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMT PEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKE FTIKPLDKKIDVFKFNSSKLRVNKLILQLCIGNHDLFMRRRKADSLEVQQMKAQAREEKARKQMKEEATMANEALMRSEETADLLAEKAQ ITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIATKP TYPPMNPIPAPLPPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDILHNENSDRG
P35240-9	MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVAWLKMDKKVLDHDVSKEE

Protein Functional Features

Main function of this protein. (from UniProt)

NF2 (go to UniProt):P35240

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
P35240	Domain	22	311	Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00084	Type=Deletion;Start=39;End=121
P35240	Domain	22	311	Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00084	Type=Deletion;Start=150;End=225
P35240	Domain	22	311	Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00084	Type=Deletion;Start=39;End=121
P35240	Domain	22	311	Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00084	Type=Deletion;Start=81;End=121
P35240	Domain	22	311	Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00084	Type=Deletion;Start=39;End=80
P35240	Domain	22	311	Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00084	Type=Substitution;Start=259;End=259
P35240	Domain	22	311	Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00084	Type=Deletion;Start=260;End=595
P35240	Domain	22	311	Note=FERM;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00084	Type=Deletion;Start=150;End=579

Gene Isoform Structures and Expression Levels for NF2

Gene structures of our canonical and alternative spliced genes of NF2
* 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 P35240-1

3D view using mol* of P35240-10

3D view using mol* of P35240-2

3D view using mol* of P35240-3

3D view using mol* of P35240-4

3D view using mol* of P35240-5

3D view using mol* of P35240-6

3D view using mol* of P35240-7

3D view using mol* of P35240-8

3D view using mol* of P35240-9

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 P35240-1

pLDDT distribution across the protein length of P35240-10

pLDDT distribution across the protein length of P35240-2

pLDDT distribution across the protein length of P35240-3

pLDDT distribution across the protein length of P35240-4

pLDDT distribution across the protein length of P35240-5

pLDDT distribution across the protein length of P35240-6

pLDDT distribution across the protein length of P35240-7

pLDDT distribution across the protein length of P35240-8

pLDDT distribution across the protein length of P35240-9

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 P35240-1

Ramachandran plot of P35240-2

Ramachandran plot of P35240-3

Ramachandran plot of P35240-5

Ramachandran plot of P35240-6

Ramachandran plot of P35240-7

Ramachandran plot of P35240-8

Ramachandran plot of P35240-9

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
P35240-1	1.064	126	1.1	581.385	0.532	0.749	0.951	0.848	0.887	0.956	0.969	134,136,137,140,144,191,194,195,196,198,206,209,21 0,212,213,214,215,528,531,532,534,535,536,538,539, 540,543,562,566,567,571,572
P35240-10	1.02	232	1.071	912.38	0.632	0.665	0.853	0.663	0.823	0.805	1.499	28,29,31,33,35,36,37,40,43,44,46,48,49,50,52,55,56 ,57,58,59,60,61,62,74,76,77,78,85,90,140,143,144,1 47,150,151,153,154,155,156,158,159,162,163,165,166 ,167
P35240-2	1.028	247	1.076	918.211	0.603	0.68	0.828	0.747	0.834	0.896	1.117	134,136,137,140,144,187,190,191,194,195,198,206,20 9,210,212,213,214,215,242,244,248,250,251,252,255, 257,531,532,534,535,536,538,539,540,541,542,543,54 5,561,562,564,565,566,568,570,571,572,573,574,576, 577
P35240-3	1.041	179	1.002	408.17	0.481	0.76	1.002	0.69	1.209	0.571	1.273	58,60,61,101,102,103,104,107,108,110,209,212,213,2 14,215,217,218,237,238,239,306,309,310,311,312,313 ,314,315,318,321,322,572,573,574,575,577,578
P35240-4	1.035	302	1.073	1174.089	0.528	0.707	0.901	0.69	0.894	0.772	1.093	51,53,54,57,61,108,111,112,115,123,126,127,129,130 ,131,132,154,156,159,161,165,167,168,169,172,174,1 76,177,224,228,445,448,449,451,452,453,455,456,457 ,460,478,479,481,482,483,484,485,487,488,489,490,4 91,492,493,494,495,497,498,499,500,502,503,504,505
P35240-5	1.038	260	1.075	778.61	0.566	0.714	0.871	0.521	0.9	0.579	1.188	93,95,96,103,146,149,150,153,154,157,165,168,169,1 72,173,174,483,486,487,490,491,492,493,494,495,497 ,498,499,500,501,502,503,504,521,522,524,525,526,5 28,529,530,531,532,533,534,535,536,544
P35240-6	1.033	419	1.067	1405.271	0.552	0.715	0.917	0.806	0.928	0.868	1.121	29,54,55,56,58,59,60,61,62,65,66,67,68,69,72,75,76 ,79,92,94,95,98,102,149,152,153,156,164,167,168,17 0,171,172,173,175,176,178,194,195,196,197,200,202, 203,206,208,209,210,212,213,215,217,261,264,265,26 7,268,269,270,271,272,273,276,279,280,486,489,490, 492,493,494,496,497,498,501,519,520,522,523,524,52 5,526,528,529,530,531,532,533,534,535,536
P35240-7	0.959	152	0.986	472.311	0.681	0.631	0.826	0.309	1.02	0.303	0.914	27,28,29,65,66,67,72,74,86,87,89,91,92,93,95,97,98 ,99,100,101,121,124,125,130,131,216,218,219,220,22 1,222,236,237,238,249
P35240-8	1.084	142	1.128	402.682	0.46	0.762	0.95	0.694	0.824	0.842	1.276	134,136,137,210,213,214,215,499,500,503,504,506,50 7,510,511,514,533,536,537,538,541,542,543,544,545
P35240-9	1.018	89	1.114	220.206	0.681	0.611	0.788	1.681	0.427	3.94	1.646	109,115,118,119,120,122,123,126,127,129,131,132,13 3,138,141,142,144,145,148,149,152,153

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 P35240-1_P35240-1_6cds_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 P35240-1_6cds_A_P35240-10.pdb

3D view using mol* of P35240-1_6cds_A_P35240-2.pdb

3D view using mol* of P35240-1_6cds_A_P35240-3.pdb

3D view using mol* of P35240-1_6cds_A_P35240-4.pdb

3D view using mol* of P35240-1_6cds_A_P35240-5.pdb

3D view using mol* of P35240-1_6cds_A_P35240-6.pdb

3D view using mol* of P35240-1_6cds_A_P35240-7.pdb

3D view using mol* of P35240-1_6cds_A_P35240-8.pdb

3D view using mol* of P35240-1_6cds_A_P35240-9.pdb

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

3D view using mol* of P35240-1_P35240-10.pdb

3D view using mol* of P35240-1_P35240-2.pdb

3D view using mol* of P35240-1_P35240-3.pdb

3D view using mol* of P35240-1_P35240-4.pdb

3D view using mol* of P35240-1_P35240-5.pdb

3D view using mol* of P35240-1_P35240-6.pdb

3D view using mol* of P35240-1_P35240-7.pdb

3D view using mol* of P35240-1_P35240-8.pdb

3D view using mol* of P35240-1_P35240-9.pdb

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

./stats/secondary_structure/figure/P35240-1_vs_P35240-10.png

./stats/secondary_structure/figure/P35240-1_vs_P35240-2.png

./stats/secondary_structure/figure/P35240-1_vs_P35240-3.png

./stats/secondary_structure/figure/P35240-1_vs_P35240-4.png

./stats/secondary_structure/figure/P35240-1_vs_P35240-5.png

./stats/secondary_structure/figure/P35240-1_vs_P35240-6.png

./stats/secondary_structure/figure/P35240-1_vs_P35240-7.png

./stats/secondary_structure/figure/P35240-1_vs_P35240-8.png

./stats/secondary_structure/figure/P35240-1_vs_P35240-9.png

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

./stats/relative_asa/P35240-1_vs_P35240-10.png

./stats/relative_asa/P35240-1_vs_P35240-2.png

./stats/relative_asa/P35240-1_vs_P35240-3.png

./stats/relative_asa/P35240-1_vs_P35240-4.png

./stats/relative_asa/P35240-1_vs_P35240-5.png

./stats/relative_asa/P35240-1_vs_P35240-6.png

./stats/relative_asa/P35240-1_vs_P35240-7.png

./stats/relative_asa/P35240-1_vs_P35240-8.png

./stats/relative_asa/P35240-1_vs_P35240-9.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 NF2

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession

Gene name

DrugBank ID

Drug name

Drug group

Actions

Related Diseases to NF2

Previous studies relating to the alternative splicing of NF2 and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
NF2	8012353	Exon scanning for mutation of the NF2 gene in schwannomas.	Family studies and tumor analyses have combined to indicate that neurofibromatosis 2 (NF2), a disorder characterized by multiple benign tumors of the nervous system, and sporadic non-inherited forms of the same tumor types are both caused by inactivation of a tumor suppressor gene located in 22q12. Recently, the gene encoding merlin, a novel member of a family of cytoskeleton-associated proteins, was identified as the NF2 tumor suppressor. To facilitate the search for merlin mutations, we have defined the exon-intron boundaries for all 17 NF2 exons, including one subject to alternative splicing. We have developed polymerase chain reaction assays to amplify each exon from genomic DNA, and used these assays to perform single-strand conformation polymorphism analysis of DNA from 30 sporadic and eight NF2-derived schwannomas, the hallmark tumor type in this disorder. Of a maximum of 60 alleles scanned, 32 showed mutations affecting expression of the merlin protein. Thirty of these mutations are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal splicing, while two are missense mutations. Thus, inactivation of merlin is a common feature underlying both inherited and sporadic forms of schwannoma.	D009442	Neurilemmoma
NF2	8069299	Alternative splicing of the NF2 gene and its mutation analysis of breast and colorectal cancers.	To investigate a potential role of NF2, the gene responsible for hereditary bilateral acoustic neurinomas, during carcinogenesis of non-neurogenic tissues, we screened somatic mutations of NF2 in 55 breast cancers and 44 colorectal carcinomas by an RNase protection assay coupled with the reverse-transcriptase polymerase chain reaction (RT-PCR). By screening the entire coding region of the gene in these tumors, we detected missense mutations in the exon encoding the alpha-helical domain of the NF2 product in two colorectal carcinomas. No mutations were detected in any of the breast cancers. Our results suggested that inactivation of the NF2 gene was associated with carcinogenesis in some, but not the majority of, colorectal tumors. In the course of these analyses, we found various alternatively-spliced forms of NF2 transcript. These variants showed no specificity among the tissues examined except for one that resulted from alternative splicing at the 3'-region; this form was more abundantly expressed in skeletal and cardiac muscles than in other tissues.	D001943	Breast Neoplasms
NF2	8069299	Alternative splicing of the NF2 gene and its mutation analysis of breast and colorectal cancers.	To investigate a potential role of NF2, the gene responsible for hereditary bilateral acoustic neurinomas, during carcinogenesis of non-neurogenic tissues, we screened somatic mutations of NF2 in 55 breast cancers and 44 colorectal carcinomas by an RNase protection assay coupled with the reverse-transcriptase polymerase chain reaction (RT-PCR). By screening the entire coding region of the gene in these tumors, we detected missense mutations in the exon encoding the alpha-helical domain of the NF2 product in two colorectal carcinomas. No mutations were detected in any of the breast cancers. Our results suggested that inactivation of the NF2 gene was associated with carcinogenesis in some, but not the majority of, colorectal tumors. In the course of these analyses, we found various alternatively-spliced forms of NF2 transcript. These variants showed no specificity among the tissues examined except for one that resulted from alternative splicing at the 3'-region; this form was more abundantly expressed in skeletal and cardiac muscles than in other tissues.	D015179	Colorectal Neoplasms
NF2	11827459	Multiple transcription initiation sites, alternative splicing, and differential polyadenylation contribute to the complexity of human neurofibromatosis 2 transcripts.	Northern blot analysis has shown that the human neurofibromatosis type 2 (NF2) cDNA hybridizes to multiple RNA species. To examine whether these hybridizing RNA species represent NF2 transcripts, we cloned the complete NF2 cDNA by a combination of techniques: 5' and 3' rapid amplification of cDNA ends, RT-PCR, and searching and sequencing the NF2-related cDNA clones from the IMAGE consortium. We showed that human NF2 transcripts initiate at multiple positions. Analogous to those reported previously, NF2 transcripts undergo alternative splicing in the coding exons. We isolated eight alternatively spliced NF2 cDNA isoforms, including one that contains a new exon termed exon 2', which potentially could encode proteins of different sizes. We assembled the overlapping cDNA fragments, and the longest NF2 cDNA, containing all 17 exons, consists of 6067 nucleotides, which is consistent with the size of the major RNA species hybridized to the NF2 probe. The cDNA has a 425-nucleotide 5' untranslated region upstream from the ATG start codon, and a long 3' untranslated region of 3869 nucleotides. We also isolated two shorter NF2 cDNAs that were terminated by different polyadenylation signal sequences, which indicates that differential usage of multiple polyadenylation sites also contributes to the complexity of human NF2 transcripts. By reference to the transcription initiation site mapped, we analyzed the 5' flanking sequence of the human NF2 gene. Transient transfection analysis in human 293 kidney, SK-N-AS neuroblastoma, and NT2/D1 teratocarcinoma cells with NF2 promoter-luciferase chimeric constructs revealed a core promoter region extending 400 base pairs from the major transcription initiation site. Although multiple regions are required for full promoter activity, a site-directed mutagenesis experiment identified a GC-rich sequence (position -58 to -46), which could be bound by transcription factor Sp1, as a positive cis-acting regulatory element. Cotransfection studies in Drosophila melanogaster SL2 cells showed that Sp1 could activate the NF2 promoter through the GC-rich sequence.	D016518	Neurofibromatosis 2
NF2	22355270	Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma.	Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.	D043171	Chromosomal Instability
NF2	22355270	Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma.	Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.	D018450	Disease Progression
NF2	22355270	Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma.	Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.	D008577	Meningeal Neoplasms
NF2	22355270	Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma.	Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.	D008579	Meningioma

Clinically important variants in NF2

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance