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Center for Computational Systems Medicine
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Protein Summary

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AS Summary

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Protein Functional Features

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Gene Isoform Structures and Expression Levels

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Protein Structures

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pLDDT Score Distribution

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Ramachandran Plot of Protein Structures

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Potential Active Site Information

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Protein Structure and Feature Comparision

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Protein-Protein Interaction

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Related Drugs

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Related Diseases

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Clinically Important Variants

Protein:TIE1

Protein Summary

check button Gene summary
Gene name: TIE1
ASpdb.0 ID: 7075
Gene
Gene symbol

TIE1

Gene ID

7075

Gene nametyrosine kinase with immunoglobulin like and EGF like domains 1
SynonymsJTK14|LMPHM11|TIE
Cytomap

1p34.2

Type of geneprotein-coding
Descriptiontyrosine-protein kinase receptor Tie-1tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 1
Modification date20240411
UniProtAcc

P35590


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID


AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
P35590-1P35590-1_5n06_A.pdb5N06X-ray2.5A643738

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
P35590TIE1P35590-1P35590-21138379348379SubstitutionDRIPQILNMASELEFNLETMPRINCAAAGNPFGWRDWVDTSTEKQNTDEGRFGGHVSAPVGAPG348379
P35590TIE1P35590-1P35590-211383793801138Deletionnonenone379379
P35590TIE1P35590-1P35590-31138317305317SubstitutionACAPGHFGADCRLVHQGHCGAREDHS305317
P35590TIE1P35590-1P35590-311383173181138Deletionnonenone317317

check buttonMultiple sequence alignment of our canonical and alternatively spliced TIE1

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TIE1
UniProt-idENSGENSTENSP
P35590-1ENSG00000066056.14ENST00000372476.8ENSP00000361554.3
P35590-2ENSG00000066056.14ENST00000538015.1ENSP00000440063.1

UniProt-idNM IDNP ID
P35590-1NM_005424.4NP_005415.1

check buttonAmino acid sequences of our canonical and alternatively spliced TIE1
accession_idProtein sequence
P35590-1MVWRVPPFLLPILFLASHVGAAVDLTLLANLRLTDPQRFFLTCVSGEAGAGRGSDAWGPPLLLEKDDRIVRTPPGPPLRLARNGSHQVTL
RGFSKPSDLVGVFSCVGGAGARRTRVIYVHNSPGAHLLPDKVTHTVNKGDTAVLSARVHKEKQTDVIWKSNGSYFYTLDWHEAQDGRFLL
QLPNVQPPSSGIYSATYLEASPLGSAFFRLIVRGCGAGRWGPGCTKECPGCLHGGVCHDHDGECVCPPGFTGTRCEQACREGRFGQSCQE
QCPGISGCRGLTFCLPDPYGCSCGSGWRGSQCQEACAPGHFGADCRLQCQCQNGGTCDRFSGCVCPSGWHGVHCEKSDRIPQILNMASEL
EFNLETMPRINCAAAGNPFPVRGSIELRKPDGTVLLSTKAIVEPEKTTAEFEVPRLVLADSGFWECRVSTSGGQDSRRFKVNVKVPPVPL
AAPRLLTKQSRQLVVSPLVSFSGDGPISTVRLHYRPQDSTMDWSTIVVDPSENVTLMNLRPKTGYSVRVQLSRPGEGGEGAWGPPTLMTT
DCPEPLLQPWLEGWHVEGTDRLRVSWSLPLVPGPLVGDGFLLRLWDGTRGQERRENVSSPQARTALLTGLTPGTHYQLDVQLYHCTLLGP
ASPPAHVLLPPSGPPAPRHLHAQALSDSEIQLTWKHPEALPGPISKYVVEVQVAGGAGDPLWIDVDRPEETSTIIRGLNASTRYLFRMRA
SIQGLGDWSNTVEESTLGNGLQAEGPVQESRAAEEGLDQQLILAVVGSVSATCLTILAALLTLVCIRRSCLHRRRTFTYQSGSGEETILQ
FSSGTLTLTRRPKLQPEPLSYPVLEWEDITFEDLIGEGNFGQVIRAMIKKDGLKMNAAIKMLKEYASENDHRDFAGELEVLCKLGHHPNI
INLLGACKNRGYLYIAIEYAPYGNLLDFLRKSRVLETDPAFAREHGTASTLSSRQLLRFASDAANGMQYLSEKQFIHRDLAARNVLVGEN
LASKIADFGLSRGEEVYVKKTMGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEQPRNCDD
P35590-2MVWRVPPFLLPILFLASHVGAAVDLTLLANLRLTDPQRFFLTCVSGEAGAGRGSDAWGPPLLLEKDDRIVRTPPGPPLRLARNGSHQVTL
RGFSKPSDLVGVFSCVGGAGARRTRVIYVHNSPGAHLLPDKVTHTVNKGDTAVLSARVHKEKQTDVIWKSNGSYFYTLDWHEAQDGRFLL
QLPNVQPPSSGIYSATYLEASPLGSAFFRLIVRGCGAGRWGPGCTKECPGCLHGGVCHDHDGECVCPPGFTGTRCEQACREGRFGQSCQE
QCPGISGCRGLTFCLPDPYGCSCGSGWRGSQCQEACAPGHFGADCRLQCQCQNGGTCDRFSGCVCPSGWHGVHCEKSGWRDWVDTSTEKQ
P35590-3MVWRVPPFLLPILFLASHVGAAVDLTLLANLRLTDPQRFFLTCVSGEAGAGRGSDAWGPPLLLEKDDRIVRTPPGPPLRLARNGSHQVTL
RGFSKPSDLVGVFSCVGGAGARRTRVIYVHNSPGAHLLPDKVTHTVNKGDTAVLSARVHKEKQTDVIWKSNGSYFYTLDWHEAQDGRFLL
QLPNVQPPSSGIYSATYLEASPLGSAFFRLIVRGCGAGRWGPGCTKECPGCLHGGVCHDHDGECVCPPGFTGTRCEQACREGRFGQSCQE

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
TIE1 (go to UniProt):P35590

check buttonRetention 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_idSubsectionStartEndFuncitonal featureSplicing information
P35590Topological domain22759Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Substitution;Start=348;End=379
P35590Topological domain22759Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=380;End=1138
P35590Topological domain22759Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Substitution;Start=305;End=317
P35590Topological domain22759Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=318;End=1138
P35590Transmembrane760784Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=380;End=1138
P35590Transmembrane760784Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=318;End=1138
P35590Topological domain7851138Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=380;End=1138
P35590Topological domain7851138Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=318;End=1138
P35590Domain305345Note=EGF-like 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00076Type=Substitution;Start=305;End=317
P35590Domain305345Note=EGF-like 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00076Type=Deletion;Start=318;End=1138
P35590Domain372426Note=Ig-like C2-type 2Type=Substitution;Start=348;End=379
P35590Domain372426Note=Ig-like C2-type 2Type=Deletion;Start=380;End=1138
P35590Domain372426Note=Ig-like C2-type 2Type=Deletion;Start=318;End=1138
P35590Domain446545Note=Fibronectin type-III 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316Type=Deletion;Start=380;End=1138
P35590Domain446545Note=Fibronectin type-III 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316Type=Deletion;Start=318;End=1138
P35590Domain548642Note=Fibronectin type-III 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316Type=Deletion;Start=380;End=1138
P35590Domain548642Note=Fibronectin type-III 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316Type=Deletion;Start=318;End=1138
P35590Domain646739Note=Fibronectin type-III 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316Type=Deletion;Start=380;End=1138
P35590Domain646739Note=Fibronectin type-III 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316Type=Deletion;Start=318;End=1138
P35590Domain8391118Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159Type=Deletion;Start=380;End=1138
P35590Domain8391118Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159Type=Deletion;Start=318;End=1138


Gene Isoform Structures and Expression Levels for TIE1

check buttonGene structures of our canonical and alternative spliced genes of TIE1
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of TIE1

check button Expression levels of gene isoforms across GTEx.
gtex expression

check button Expression levels of gene isoforms across TCGA.
tcga expression


Protein Structures

check button 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 P35590-1
3D view using mol* of P35590-2
3D view using mol* of P35590-3


pLDDT Score Distribution

check button 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 P35590-1
all structure
pLDDT distribution across the protein length of P35590-2
all structure
pLDDT distribution across the protein length of P35590-3
all structure


Ramachandran Plot of Protein Structures


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.
Ramachandran plot of P35590-1
all structure
Ramachandran plot of P35590-2
all structure

Potential Active Site Information


check button The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.
UniProt-idSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
P35590-11.0612281.076336.140.3670.7851.0280.7211.0290.7011.04530,31,32,33,34,39,118,119,120,121,122,123,128,129,
130,131,132,133,147,282,291,292,293,298,299,300,30
1,302,303,314,316
P35590-21.0612201.074368.0390.3590.7891.0530.8511.0420.8161.12931,33,34,39,99,118,119,120,121,123,128,129,130,131
,132,133,147,149,282,291,292,293,298,299,300,301,3
02,314,315,316
P35590-31.0392391.061556.6890.4940.7420.9770.70.9930.7051.16831,33,34,39,96,99,118,119,120,121,122,123,128,129,
130,131,132,133,134,135,147,233,247,248,250,282,28
9,290,291,292,293,294,295,296,297,298,299,300,301,
302,306,310

Protein Structure and Feature Comparision


check button Protein Structure Comparision Using Template Modeling Scores (TM-score).
all structure

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)
3D view using mol* of P35590-1_P35590-1_5n06_A.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P35590-1_5n06_A_P35590-2.pdb
3D view using mol* of P35590-1_5n06_A_P35590-3.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P35590-1_P35590-2.pdb
3D view using mol* of P35590-1_P35590-3.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/P35590-1_vs_P35590-2.png
all structure<
./stats/secondary_structure/figure/P35590-1_vs_P35590-3.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/P35590-1_vs_P35590-2.png
all structure<
./stats/relative_asa/P35590-1_vs_P35590-3.png
all structure<


Protein-Protein Interaction


check button Interactors from UniProt.
Accession_idSubsectionStartEndFuncitonal featureSplicing information


check button Interactors from STRING.
Gene nameInteractors


Related Drugs to TIE1


check button Drugs targeting this gene/protein.
(DrugBank)
UniProt accessionGene nameDrugBank IDDrug nameDrug groupActions
P35590TIE1DB12010Fostamatinibapproved, investigationalinhibitor

Related Diseases to TIE1


check button Previous studies relating to the alternative splicing of TIE1 and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term
TIE118593464Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis.Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF)--a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins--many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in an in vivo model of arthritis.D001172Arthritis, Rheumatoid
TIE118593464Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis.Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF)--a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins--many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in an in vivo model of arthritis.D004195Disease Models, Animal


Clinically important variants in TIE1


check button (ClinVar, 04/20/2024)
accession_iduniprot_idgene_nameTypeVariantClinical_significance