Protein:TPR |
Protein Summary |
 Gene summary |
| Gene name: TPR | ASpdb.0 ID: 7175 | Gene | Gene symbol | TPR | Gene ID | 7175 |
| Gene name | translocated promoter region, nuclear basket protein |
| Synonyms | MRT79 |
| Cytomap | 1q31.1 |
| Type of gene | protein-coding |
| Description | nucleoprotein TPRNPC-associated intranuclear proteinmegatornuclear pore complex-associated protein TPRtranslocated promoter region (to activated MET oncogene)translocated promoter region proteintumor potentiating region |
| Modification date | 20240407 |
| UniProtAcc | P12270 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | TPR | GO:0000776 | kinetochore | 19273613 |
| Gene | TPR | GO:0000776 | kinetochore | 20133940 |
| Gene | TPR | GO:0003682 | chromatin binding | 17897941 |
| Gene | TPR | GO:0003729 | mRNA binding | 17897941 |
| Gene | TPR | GO:0005634 | nucleus | 15654337 |
| Gene | TPR | GO:0005635 | nuclear envelope | 17098863|24315095|24970816 |
| Gene | TPR | GO:0005643 | nuclear pore | 9828100|9864356|11514627|12802065 |
| Gene | TPR | GO:0005737 | cytoplasm | 11952838|12802065 |
| Gene | TPR | GO:0005868 | cytoplasmic dynein complex | 20133940 |
| Gene | TPR | GO:0006404 | RNA import into nucleus | 9864356 |
| Gene | TPR | GO:0006606 | protein import into nucleus | 9864356 |
| Gene | TPR | GO:0015631 | tubulin binding | 20133940 |
| Gene | TPR | GO:0017056 | structural constituent of nuclear pore | 22253824 |
| Gene | TPR | GO:0031072 | heat shock protein binding | 17897941 |
| Gene | TPR | GO:0031965 | nuclear membrane | 9024684|9828100|9864356|11514627|11839768|11952838|12802065|15229283|18794356|20407419|22253824 |
| Gene | TPR | GO:0031990 | mRNA export from nucleus in response to heat stress | 17897941 |
| Gene | TPR | GO:0034399 | nuclear periphery | 9024684|11514627|11839768|11952838|15229283|22401879 |
| Gene | TPR | GO:0034605 | cellular response to heat | 17897941 |
| Gene | TPR | GO:0042405 | nuclear inclusion body | 11514627|11839768 |
| Gene | TPR | GO:0042803 | protein homodimerization activity | 11514627|12802065 |
| Gene | TPR | GO:0044615 | nuclear pore nuclear basket | 9024684|11839768|15229283|18981471 |
| Gene | TPR | GO:0046832 | negative regulation of RNA export from nucleus | 22253824 |
| Gene | TPR | GO:0051019 | mitogen-activated protein kinase binding | 18794356 |
| Gene | TPR | GO:0070840 | dynein complex binding | 20133940 |
| Gene | TPR | GO:0070849 | response to epidermal growth factor | 18794356 |
| Gene | TPR | GO:0072686 | mitotic spindle | 20133940 |
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 |
| P12270-1 | P12270-1_5to5_A.pdb | 5TO5 | X-ray | 2.5 | A | 2 | 142 |
| 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 |
| P12270 | TPR | P12270-1 | P12270-2 | 2363 | 726 | 726 | 726 | Substitution | E | L | 726 | 726 |
| P12270 | TPR | P12270-1 | P12270-2 | 2363 | 726 | 727 | 2363 | Deletion | none | none | 726 | 726 |
| Multiple sequence alignment of our canonical and alternatively spliced TPR |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TPR |
| UniProt-id | ENSG | ENST | ENSP |
| P12270-1 | ENSG00000047410.14 | ENST00000367478.9 | ENSP00000356448.3 |
| P12270-2 | ENSG00000047410.14 | ENST00000613151.1 | ENSP00000483425.1 |
| UniProt-id | NM ID | NP ID |
| P12270-1 | NM_003292.2 | NP_003283.2 |
| Amino acid sequences of our canonical and alternatively spliced TPR |
| accession_id | Protein sequence |
| P12270-1 | MAAVLQQVLERTELNKLPKSVQNKLEKFLADQQSEIDGLKGRHEKFKVESEQQYFEIEKRLSHSQERLVNETRECQSLRLELEKLNNQLK ALTEKNKELEIAQDRNIAIQSQFTRTKEELEAEKRDLIRTNERLSQELEYLTEDVKRLNEKLKESNTTKGELQLKLDELQASDVSVKYRE KRLEQEKELLHSQNTWLNTELKTKTDELLALGREKGNEILELKCNLENKKEEVSRLEEQMNGLKTSNEHLQKHVEDLLTKLKEAKEQQAS MEEKFHNELNAHIKLSNLYKSAADDSEAKSNELTRAVEELHKLLKEAGEANKAIQDHLLEVEQSKDQMEKEMLEKIGRLEKELENANDLL SATKRKGAILSEEELAAMSPTAAAVAKIVKPGMKLTELYNAYVETQDQLLLEKLENKRINKYLDEIVKEVEAKAPILKRQREEYERAQKA VASLSVKLEQAMKEIQRLQEDTDKANKQSSVLERDNRRMEIQVKDLSQQIRVLLMELEEARGNHVIRDEEVSSADISSSSEVISQHLVSY RNIEELQQQNQRLLVALRELGETREREEQETTSSKITELQLKLESALTELEQLRKSRQHQMQLVDSIVRQRDMYRILLSQTTGVAIPLHA SSLDDVSLASTPKRPSTSQTVSTPAPVPVIESTEAIEAKAALKQLQEIFENYKKEKAENEKIQNEQLEKLQEQVTDLRSQNTKISTQLDF ASKRYEMLQDNVEGYRREITSLHERNQKLTATTQKQEQIINTMTQDLRGANEKLAVAEVRAENLKKEKEMLKLSEVRLSQQRESLLAEQR GQNLLLTNLQTIQGILERSETETKQRLSSQIEKLEHEISHLKKKLENEVEQRHTLTRNLDVQLLDTKRQLDTETNLHLNTKELLKNAQKE IATLKQHLSNMEVQVASQSSQRTGKGQPSNKEDVDDLVSQLRQTEEQVNDLKERLKTSTSNVEQYQAMVTSLEESLNKEKQVTEEVRKNI EVRLKESAEFQTQLEKKLMEVEKEKQELQDDKRRAIESMEQQLSELKKTLSSVQNEVQEALQRASTALSNEQQARRDCQEQAKIAVEAQN KYERELMLHAADVEALQAAKEQVSKMASVRQHLEETTQKAESQLLECKASWEERERMLKDEVSKCVCRCEDLEKQNRLLHDQIEKLSDKV VASVKEGVQGPLNVSLSEEGKSQEQILEILRFIRREKEIAETRFEVAQVESLRYRQRVELLERELQELQDSLNAEREKVQVTAKTMAQHE ELMKKTETMNVVMETNKMLREEKERLEQDLQQMQAKVRKLELDILPLQEANAELSEKSGMLQAEKKLLEEDVKRWKARNQHLVSQQKDPD TEEYRKLLSEKEVHTKRIQQLTEEIGRLKAEIARSNASLTNNQNLIQSLKEDLNKVRTEKETIQKDLDAKIIDIQEKVKTITQVKKIGRR YKTQYEELKAQQDKVMETSAQSSGDHQEQHVSVQEMQELKETLNQAETKSKSLESQVENLQKTLSEKETEARNLQEQTVQLQSELSRLRQ DLQDRTTQEEQLRQQITEKEEKTRKAIVAAKSKIAHLAGVKDQLTKENEELKQRNGALDQQKDELDVRITALKSQYEGRISRLERELREH QERHLEQRDEPQEPSNKVPEQQRQITLKTTPASGERGIASTSDPPTANIKPTPVVSTPSKVTAAAMAGNKSTPRASIRPMVTPATVTNPT TTPTATVMPTTQVESQEAMQSEGPVEHVPVFGSTSGSVRSTSPNVQPSISQPILTVQQQTQATAFVQPTQQSHPQIEPANQELSSNIVEV VQSSPVERPSTSTAVFGTVSATPSSSLPKRTREEEEDSTIEASDQVSDDTVEMPLPKKLKSVTPVGTEEEVMAEESTDGEVETQVYNQDS QDSIGEGVTQGDYTPMEDSEETSQSLQIDLGPLQSDQQTTTSSQDGQGKGDDVIVIDSDDEEEDDDENDGEHEDYEEDEEDDDDDEDDTG MGDEGEDSNEGTGSADGNDGYEADDAEGGDGTDPGTETEESMGGGEGNHRAADSQNSGEGNTGAAESSFSQEVSREQQPSSASERQAPRA PQSPRRPPHPLPPRLTIHAPPQELGPPVQRIQMTRRQSVGRGLQLTPGIGGMQQHFFDDEDRTVPSTPTLVVPHRTDGFAEAIHSPQVAG VPRFRFGPPEDMPQTSSSHSDLGQLASQGGLGMYETPLFLAHEEESGGRSVPTTPLQVAAPVTVFTESTTSDASEHASQSVPMVTTSTGT LSTTNETATGDDGDEVFVEAESEGISSEAGLEIDSQQEEEPVQASDESDLPSTSQDPPSSSSVDTSSSQPKPFRRVRLQTTLRQGVRGRQ |
| P12270-2 | MAAVLQQVLERTELNKLPKSVQNKLEKFLADQQSEIDGLKGRHEKFKVESEQQYFEIEKRLSHSQERLVNETRECQSLRLELEKLNNQLK ALTEKNKELEIAQDRNIAIQSQFTRTKEELEAEKRDLIRTNERLSQELEYLTEDVKRLNEKLKESNTTKGELQLKLDELQASDVSVKYRE KRLEQEKELLHSQNTWLNTELKTKTDELLALGREKGNEILELKCNLENKKEEVSRLEEQMNGLKTSNEHLQKHVEDLLTKLKEAKEQQAS MEEKFHNELNAHIKLSNLYKSAADDSEAKSNELTRAVEELHKLLKEAGEANKAIQDHLLEVEQSKDQMEKEMLEKIGRLEKELENANDLL SATKRKGAILSEEELAAMSPTAAAVAKIVKPGMKLTELYNAYVETQDQLLLEKLENKRINKYLDEIVKEVEAKAPILKRQREEYERAQKA VASLSVKLEQAMKEIQRLQEDTDKANKQSSVLERDNRRMEIQVKDLSQQIRVLLMELEEARGNHVIRDEEVSSADISSSSEVISQHLVSY RNIEELQQQNQRLLVALRELGETREREEQETTSSKITELQLKLESALTELEQLRKSRQHQMQLVDSIVRQRDMYRILLSQTTGVAIPLHA SSLDDVSLASTPKRPSTSQTVSTPAPVPVIESTEAIEAKAALKQLQEIFENYKKEKAENEKIQNEQLEKLQEQVTDLRSQNTKISTQLDF |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| TPR (go to UniProt):P12270 |
| 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 * 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 |
| P12270 | Region | 912 | 935 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Region | 1218 | 1320 | Note=Necessary for interaction with HSF1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17897941;Dbxref=PMID:17897941 | Type=Deletion;Start=727;End=2363 |
| P12270 | Region | 1454 | 1474 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Region | 1619 | 1674 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Region | 1803 | 2134 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Region | 1812 | 1867 | Note=Sufficient and essential for mediating its nuclear import | Type=Deletion;Start=727;End=2363 |
| P12270 | Region | 2227 | 2363 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Coiled coil | 661 | 1173 | Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=726;End=726 |
| P12270 | Coiled coil | 661 | 1173 | Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=727;End=2363 |
| P12270 | Coiled coil | 1215 | 1630 | Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 912 | 927 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 1619 | 1636 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 1637 | 1674 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 1803 | 1827 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 1880 | 1898 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 1905 | 1938 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 1945 | 1985 | Note=Acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 2000 | 2014 | Note=Acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 2030 | 2068 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 2071 | 2090 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 2227 | 2260 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
| P12270 | Compositional bias | 2296 | 2325 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=727;End=2363 |
Gene Isoform Structures and Expression Levels for TPR |
| Gene structures of our canonical and alternative spliced genes of TPR * 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. |
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| Expression levels of gene isoforms across TCGA. |
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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 P12270-1 |
| 3D view using mol* of P12270-2 |
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. |
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 P12270-1 |
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| Ramachandran plot of P12270-2 |
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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 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P12270-1_P12270-1_5to5_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 P12270-1_5to5_A_P12270-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P12270-1_P12270-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P12270-1_vs_P12270-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P12270-1_vs_P12270-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P12270 | Region | 1218 | 1320 | Note=Necessary for interaction with HSF1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17897941;Dbxref=PMID:17897941 | Type=Deletion;Start=727;End=2363 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to TPR |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to TPR |
| Previous studies relating to the alternative splicing of TPR and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| TPR | 1549355 | Nucleotide sequence analysis of human tpr cDNA clones. | In this study we have characterized cDNA clones corresponding to a gene, called tpr, that has been implicated in the activation of the met and raf proto-oncogenes. Sequencing of tpr clones isolated from an HT1080 human fibrosarcoma cell line cDNA library identified an open reading frame (ORF) of 726 amino acids. In addition we have established that alternative splicing can result in the deletion of a 30 bp sequence that spans the translation termination site of this ORF. This modification generates mRNAs encoding a tpr protein that has an extended C-terminal domain. The 726 amino acid tpr protein is predicted to have extensive regions of alpha-helix and has three stretches of a heptad repeat motif that is characteristic of proteins adopting a coiled-coil conformation. The tpr protein exhibits weak homology (28-39%) to the alpha-helical domains of several proteins including tropomyosin, spectrin, laminin B1, the Drosophila glued protein and the tail region of myosin heavy chain. | D014178 | Translocation, Genetic |
| TPR | 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 |
| TPR | 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 |
| TPR | 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 TPR |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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