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:MAP3K7

Protein Summary

Gene summary

Gene name: MAP3K7
ASpdb.0 ID: 6885
	Gene
Gene symbol	MAP3K7
Gene ID	6885
Gene name	mitogen-activated protein kinase kinase kinase 7
Synonyms	CSCF\|FMD2\|MEKK7\|TAK1\|TGF1a
Cytomap	6q15
Type of gene	protein-coding
Description	mitogen-activated protein kinase kinase kinase 7TGF-beta activated kinase 1transforming growth factor-beta-activated kinase 1
Modification date	20240408
UniProtAcc	O43318

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

Partner	Gene	GO ID	GO term	PubMed ID
Gene	MAP3K7	GO:0000165	MAPK cascade	8663074\|11865055
Gene	MAP3K7	GO:0004674	protein serine/threonine kinase activity	10094049\|10702308\|11460167\|37832545
Gene	MAP3K7	GO:0004707	MAP kinase activity	11865055
Gene	MAP3K7	GO:0004709	MAP kinase kinase kinase activity	8663074\|9079627\|11460167
Gene	MAP3K7	GO:0005737	cytoplasm	12242293
Gene	MAP3K7	GO:0005829	cytosol	12242293
Gene	MAP3K7	GO:0005829	cytosol	-
Gene	MAP3K7	GO:0005886	plasma membrane	-
Gene	MAP3K7	GO:0006954	inflammatory response	34017102
Gene	MAP3K7	GO:0007249	canonical NF-kappaB signal transduction	10882101\|19675569\|34871740\|35952808
Gene	MAP3K7	GO:0007252	I-kappaB phosphorylation	11460167
Gene	MAP3K7	GO:0007254	JNK cascade	9079627
Gene	MAP3K7	GO:0034142	toll-like receptor 4 signaling pathway	25371197
Gene	MAP3K7	GO:0038066	p38MAPK cascade	11460167
Gene	MAP3K7	GO:0038172	interleukin-33-mediated signaling pathway	20532808
Gene	MAP3K7	GO:0038173	interleukin-17A-mediated signaling pathway	31376257
Gene	MAP3K7	GO:0042742	defense response to bacterium	11460167
Gene	MAP3K7	GO:0043123	positive regulation of canonical NF-kappaB signal transduction	11460167
Gene	MAP3K7	GO:0043507	positive regulation of JUN kinase activity	11460167
Gene	MAP3K7	GO:0051403	stress-activated MAPK cascade	9079627
Gene	MAP3K7	GO:0097110	scaffold protein binding	23776175
Gene	MAP3K7	GO:0140672	ATAC complex	18838386
Gene	MAP3K7	GO:1990450	linear polyubiquitin binding	35952808

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
O43318-1	O43318-1_2eva_A.pdb	2EVA	X-ray	2.0	A	31	303

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

O43318

MAP3K7

O43318-1

O43318-2

606

579

404

430

Deletion

none

403

O43318

MAP3K7

O43318-1

O43318-3

606

518

509

518

Substitution

PLAPCPNSKE

ARTSCRTGPG

509

518

O43318

MAP3K7

O43318-1

O43318-3

606

518

519

606

Deletion

none

518

O43318

MAP3K7

O43318-1

O43318-4

606

491

404

430

Deletion

none

403

O43318

MAP3K7

O43318-1

O43318-4

606

491

509

518

Substitution

PLAPCPNSKE

ARTSCRTGPG

482

491

O43318

MAP3K7

O43318-1

O43318-4

606

491

519

606

Deletion

none

491

Multiple sequence alignment of our canonical and alternatively spliced MAP3K7

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of MAP3K7

UniProt-id	ENSG	ENST	ENSP
O43318-1	ENSG00000135341.19	ENST00000369329.8	ENSP00000358335.3
O43318-2	ENSG00000135341.19	ENST00000369332.7	ENSP00000358338.3
O43318-2	ENSG00000135341.19	ENST00000700580.1	ENSP00000515074.1
O43318-3	ENSG00000135341.19	ENST00000369325.7	ENSP00000358331.3
O43318-4	ENSG00000135341.19	ENST00000369327.7	ENSP00000358333.3

UniProt-id	NM ID	NP ID
O43318-1	NM_145331.2	NP_663304.1
O43318-2	NM_003188.3	NP_003179.1
O43318-3	NM_145332.2	NP_663305.1
O43318-4	NM_145333.2	NP_663306.1

Amino acid sequences of our canonical and alternatively spliced MAP3K7

accession_id	Protein sequence
O43318-1	MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDVAIKQIESESERKAFIVELRQLSRVNHPNIV KLYGACLNPVCLVMEYAEGGSLYNVLHGAEPLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTAC DIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIMWAVHNGTRPPLIKNLPKPIESLMTRCWSKD PSQRPSMEEIVKIMTHLMRYFPGADEPLQYPCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQ SESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGNILDVPEIVISGNGQPRRRSIQDLTVTGTEP GQVSSRSSSPSVRMITTSGPTSEKPTRSHPWTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEI
O43318-2	MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDVAIKQIESESERKAFIVELRQLSRVNHPNIV KLYGACLNPVCLVMEYAEGGSLYNVLHGAEPLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTAC DIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIMWAVHNGTRPPLIKNLPKPIESLMTRCWSKD PSQRPSMEEIVKIMTHLMRYFPGADEPLQYPCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQ SESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTR SHPWTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEIALLLQRKQELVAELDQDEKDQQNTSRL
O43318-3	MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDVAIKQIESESERKAFIVELRQLSRVNHPNIV KLYGACLNPVCLVMEYAEGGSLYNVLHGAEPLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTAC DIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIMWAVHNGTRPPLIKNLPKPIESLMTRCWSKD PSQRPSMEEIVKIMTHLMRYFPGADEPLQYPCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQ SESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGNILDVPEIVISGNGQPRRRSIQDLTVTGTEP
O43318-4	MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDVAIKQIESESERKAFIVELRQLSRVNHPNIV KLYGACLNPVCLVMEYAEGGSLYNVLHGAEPLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTAC DIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIMWAVHNGTRPPLIKNLPKPIESLMTRCWSKD PSQRPSMEEIVKIMTHLMRYFPGADEPLQYPCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQ SESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTR

Protein Functional Features

Main function of this protein. (from UniProt)

MAP3K7 (go to UniProt):O43318

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

Gene Isoform Structures and Expression Levels for MAP3K7

Gene structures of our canonical and alternative spliced genes of MAP3K7
* 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 O43318-1

3D view using mol* of O43318-2

3D view using mol* of O43318-3

3D view using mol* of O43318-4

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 O43318-1

pLDDT distribution across the protein length of O43318-2

pLDDT distribution across the protein length of O43318-3

pLDDT distribution across the protein length of O43318-4

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 O43318-1

Ramachandran plot of O43318-3

Ramachandran plot of O43318-4

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
O43318-1	1.15	76	1.227	163.268	0.309	0.86	1.205	4.162	0.333	12.499	1.809	186,201,202,237,240,241,244,497,499,502,531,534,53 5,538
O43318-2	1.068	125	1.084	379.015	0.508	0.792	1.023	1.093	1.017	1.074	1.043	42,43,45,46,47,50,61,63,77,81,90,104,105,106,107,1 10,111,114,156,158,160,161,163,174,175,176,178,185 ,188,189,190,191,192
O43318-3	1.044	142	1.03	387.933	0.555	0.764	0.982	0.464	1.131	0.41	0.912	42,43,44,45,46,47,50,61,63,77,81,90,104,105,106,10 7,110,111,114,154,156,158,160,161,163,174,175,176, 177,178,179,180,181,184,185,188,189,190,191
O43318-4	1.082	108	1.131	271.313	0.534	0.75	0.949	1.055	0.796	1.326	0.528	42,43,44,45,46,50,61,63,77,81,90,104,106,107,110,1 11,114,158,160,161,163,174,175,176

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 O43318-1_O43318-1_2eva_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 O43318-1_2eva_A_O43318-2.pdb

3D view using mol* of O43318-1_2eva_A_O43318-3.pdb

3D view using mol* of O43318-1_2eva_A_O43318-4.pdb

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

3D view using mol* of O43318-1_O43318-2.pdb

3D view using mol* of O43318-1_O43318-3.pdb

3D view using mol* of O43318-1_O43318-4.pdb

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

./stats/secondary_structure/figure/O43318-1_vs_O43318-2.png

./stats/secondary_structure/figure/O43318-1_vs_O43318-3.png

./stats/secondary_structure/figure/O43318-1_vs_O43318-4.png

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

./stats/relative_asa/O43318-1_vs_O43318-2.png

./stats/relative_asa/O43318-1_vs_O43318-3.png

./stats/relative_asa/O43318-1_vs_O43318-4.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 MAP3K7

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession

Gene name

DrugBank ID

Drug name

Drug group

Actions

Related Diseases to MAP3K7

Previous studies relating to the alternative splicing of MAP3K7 and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
MAP3K7	21822258	Treatment with IL-17 prolongs the half-life of chemokine CXCL1 mRNA via the adaptor TRAF5 and the splicing-regulatory factor SF2 (ASF).	Interleukin 17 (IL-17) promotes the expression of chemokines and cytokines via the induction of gene transcription and post-transcriptional stabilization of mRNA. We show here that IL-17 enhanced the stability of chemokine CXCL1 mRNA and other mRNAs through a pathway that involved the adaptor Act1, the adaptors TRAF2 or TRAF5 and the splicing factor SF2 (also known as alternative splicing factor (ASF)). TRAF2 and TRAF5 were necessary for IL-17 to signal the stabilization of CXCL1 mRNA. Furthermore, IL-17 promoted the formation of complexes of TRAF5-TRAF2, Act1 and SF2 (ASF). Overexpression of SF2 (ASF) shortened the half-life of CXCL1 mRNA, whereas depletion of SF2 (ASF) prolonged it. SF2 (ASF) bound chemokine mRNA in unstimulated cells, whereas the SF2 (ASF)-mRNA interaction was much lower after stimulation with IL-17. Our findings define an IL-17-induced signaling pathway that links to the stabilization of selected mRNA species through Act1, TRAF2-TRAF5 and the RNA-binding protein SF2 (ASF).	D007249	Inflammation

Clinically important variants in MAP3K7

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance