Protein:PTPN6 |
Protein Summary |
 Gene summary |
| Gene name: PTPN6 | ASpdb.0 ID: 5777 | Gene | Gene symbol | PTPN6 | Gene ID | 5777 |
| Gene name | protein tyrosine phosphatase non-receptor type 6 |
| Synonyms | HCP|HCPH|HPTP1C|PTP-1C|SH-PTP1|SHP-1|SHP-1L|SHP1 |
| Cytomap | 12p13.31 |
| Type of gene | protein-coding |
| Description | tyrosine-protein phosphatase non-receptor type 6hematopoietic cell phosphatasehematopoietic cell protein-tyrosine phosphataseprotein-tyrosine phosphatase 1Cprotein-tyrosine phosphatase SHP-1 |
| Modification date | 20240403 |
| UniProtAcc | P29350 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | PTPN6 | GO:0005001 | transmembrane receptor protein tyrosine phosphatase activity | 11266449 |
| Gene | PTPN6 | GO:0005634 | nucleus | 19838216 |
| Gene | PTPN6 | GO:0005654 | nucleoplasm | - |
| Gene | PTPN6 | GO:0005730 | nucleolus | - |
| Gene | PTPN6 | GO:0005737 | cytoplasm | 10940933|19838216 |
| Gene | PTPN6 | GO:0006470 | protein dephosphorylation | 11266449 |
| Gene | PTPN6 | GO:0018108 | peptidyl-tyrosine phosphorylation | 9285411|18802077 |
| Gene | PTPN6 | GO:0030154 | cell differentiation | 11266449 |
| Gene | PTPN6 | GO:0070372 | regulation of ERK1 and ERK2 cascade | 11266449 |
| Gene | PTPN6 | GO:0106015 | negative regulation of inflammatory response to wounding | 27830702 |
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 |
| P29350-1 | P29350-1_3ps5_A.pdb | 3PS5 | X-ray | 3.1 | A | 1 | 529 |
| 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 |
| P29350 | PTPN6 | P29350-1 | P29350-2 | 595 | 556 | 1 | 39 | Deletion | none | none | 0 | 0 |
| P29350 | PTPN6 | P29350-1 | P29350-2 | 595 | 556 | 40 | 44 | Substitution | SLSVR | MLSRG | 1 | 5 |
| P29350 | PTPN6 | P29350-1 | P29350-3 | 595 | 597 | 1 | 3 | Substitution | MVR | MLSRG | 1 | 5 |
| P29350 | PTPN6 | P29350-1 | P29350-4 | 595 | 624 | 559 | 595 | Substitution | HKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRK | SLESSAGTVAASPVRRGGQRGLPVPGPPVLSPDLHQLPVLAPLHPAADTRRMCMRTCTLRTRGRRK | 559 | 624 |
| Multiple sequence alignment of our canonical and alternatively spliced PTPN6 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of PTPN6 |
| UniProt-id | ENSG | ENST | ENSP |
| P29350-1 | ENSG00000111679.17 | ENST00000318974.14 | ENSP00000326010.9 |
| P29350-3 | ENSG00000111679.17 | ENST00000399448.5 | ENSP00000382376.1 |
| P29350-4 | ENSG00000111679.17 | ENST00000456013.5 | ENSP00000391592.1 |
| UniProt-id | NM ID | NP ID |
| P29350-1 | NM_002831.5 | NP_002822.2 |
| P29350-3 | NM_080548.4 | NP_536858.1 |
| P29350-3 | XM_011520988.1 | XP_011519290.1 |
| P29350-4 | NM_080549.3 | NP_536859.1 |
| Amino acid sequences of our canonical and alternatively spliced PTPN6 |
| accession_id | Protein sequence |
| P29350-1 | MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQQGVLQDRD GTIIHLKYPLNCSDPTSERWYHGHMSGGQAETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGG LETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTAKAGFWEEFESLQKQEVKNLHQRLEGQRPEN KGKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNK CVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPII VHCSAGIGRTGTIIVIDMLMENISTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNIT |
| P29350-2 | MLSRGVGDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQQGVLQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQAETLLQAKGE PWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGGLETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVN AADIENRVLELNKKQESEDTAKAGFWEEFESLQKQEVKNLHQRLEGQRPENKGKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYIKN QLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNKCVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSP LDNGDLIREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDCDIDIQKTIQ MVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNITYPPAMKNAHAKASRTSSKHKEDVYENLHTKNKREEKVKK |
| P29350-3 | MLSRGWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQQGVLQD RDGTIIHLKYPLNCSDPTSERWYHGHMSGGQAETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTV GGLETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTAKAGFWEEFESLQKQEVKNLHQRLEGQRP ENKGKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGR NKCVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGP IIVHCSAGIGRTGTIIVIDMLMENISTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGN |
| P29350-4 | MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQQGVLQDRD GTIIHLKYPLNCSDPTSERWYHGHMSGGQAETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGG LETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTAKAGFWEEFESLQKQEVKNLHQRLEGQRPEN KGKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNK CVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPII VHCSAGIGRTGTIIVIDMLMENISTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNIT |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| PTPN6 (go to UniProt):P29350 |
| 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 |
| P29350 | Domain | 4 | 100 | Note=SH2 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00191 | Type=Deletion;Start=1;End=39 |
| P29350 | Domain | 4 | 100 | Note=SH2 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00191 | Type=Substitution;Start=40;End=44 |
| P29350 | Region | 535 | 595 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=559;End=595 |
| P29350 | Compositional bias | 554 | 589 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=559;End=595 |
Gene Isoform Structures and Expression Levels for PTPN6 |
| Gene structures of our canonical and alternative spliced genes of PTPN6 * 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 P29350-1 |
| 3D view using mol* of P29350-2 |
| 3D view using mol* of P29350-3 |
| 3D view using mol* of P29350-4 |
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 P29350-1 |
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| pLDDT distribution across the protein length of P29350-2 |
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| pLDDT distribution across the protein length of P29350-3 |
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| pLDDT distribution across the protein length of P29350-4 |
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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 P29350-1 |
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| Ramachandran plot of P29350-2 |
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| Ramachandran plot of P29350-4 |
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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 |
| P29350-1 | 0.998 | 371 | 1.032 | 1297.226 | 0.657 | 0.668 | 0.832 | 0.486 | 0.946 | 0.514 | 0.779 | 1,3,4,16,19,20,21,22,23,27,44,47,76,77,80,82,97,98 ,99,100,101,109,112,115,127,211,212,213,214,215,21 6,217,246,247,250,254,308,309,310,311,312,313,314, 315,316,317,318,319,320,427,430,431,434,437,438,44 0,441,443,444,446,447,448,468,469,470,471,472,473, 474,475,476,477,478,479,480,481,482,483,485,486,48 7,489,514,515,518,519,522,523,526,527,530 |
| P29350-2 | 1.026 | 175 | 1.051 | 687.029 | 0.662 | 0.721 | 0.868 | 0.482 | 0.986 | 0.489 | 0.514 | 32,33,34,37,59,60,62,63,65,66,70,72,73,74,75,76,84 ,88,98,99,100,103,104,105,173,174,175,176,177,178, 180,207,208,211,215,270,272,273,277,429,430,433,43 7,441,442,443,444,446,447,448,450,451 |
| P29350-3 | 1.038 | 267 | 1.012 | 1001.903 | 0.54 | 0.755 | 1.023 | 0.457 | 1.171 | 0.39 | 0.696 | 1,2,3,79,81,82,83,84,86,87,88,95,96,97,98,99,100,1 01,103,106,108,109,110,113,114,115,116,117,121,125 ,129,215,216,217,218,219,220,221,224,227,228,248,2 49,252,256,311,313,314,315,316,317,318,470,471,474 ,478,481,482,483,484,485,487,488,489,491 |
| P29350-4 | 1.022 | 180 | 1.047 | 801.591 | 0.646 | 0.716 | 0.901 | 0.529 | 0.99 | 0.534 | 0.709 | 1,2,3,22,26,73,77,79,80,82,95,96,97,98,99,100,109, 112,114,115,116,119,123,127,139,212,213,214,215,21 6,217,246,247,250,254,309,311,312,313,314,315,316, 468,469,472,476,477,480,481,482,483,485,486,487 |
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 P29350-1_P29350-1_3ps5_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 P29350-1_3ps5_A_P29350-2.pdb |
| 3D view using mol* of P29350-1_3ps5_A_P29350-3.pdb |
| 3D view using mol* of P29350-1_3ps5_A_P29350-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P29350-1_P29350-2.pdb |
| 3D view using mol* of P29350-1_P29350-3.pdb |
| 3D view using mol* of P29350-1_P29350-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P29350-1_vs_P29350-2.png |
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| ./stats/secondary_structure/figure/P29350-1_vs_P29350-3.png |
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| ./stats/secondary_structure/figure/P29350-1_vs_P29350-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P29350-1_vs_P29350-2.png |
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| ./stats/relative_asa/P29350-1_vs_P29350-3.png |
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| ./stats/relative_asa/P29350-1_vs_P29350-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to PTPN6 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P29350 | PTPN6 | DB01133 | Tiludronic acid | approved, investigational, vet_approved | inhibitor |
Related Diseases to PTPN6 |
| Previous studies relating to the alternative splicing of PTPN6 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| PTPN6 | 11001933 | RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. | The SH2 domain-containing tyrosine phosphatase PTPN6 (SHP-1, PTP1C, HCP) is a 68 kDa cytoplasmic protein primarily expressed in hematopoietic cell development, proliferation and receptor-mediated mitogenic signaling pathways. By means of direct dephosphorylation, it down-regulates a broad spectrum of growth-promoting receptors, including the Kit tyrosine kinase, activated to elicit a prominent cascade of intracellular events by stem cell factor binding. The pivotal contribution of PTPN6 in modulating myeloid cell signaling has been revealed by the finding that shp-1 mutation is responsible for the overexpansion and inappropriate activation of myelomonocytic populations in motheaten (me/me) and motheaten viable (me(v)/me(v)) mice. Association of PTPN6 with c-Kit and negative modulation of the myeloid leukocyte signal transduction pathways prompted us to examine the expression of the protein tyrosine phosphatase PTPN6 gene in CD34(+)/CD117(+) blasts from acute myeloid leukemia patients. We identified and cloned cDNAs representing novel PTPN6 mRNA species, derived from aberrant splicing within the N-SH2 domain leading to retention of intron 3. Sequence analysis of cDNA clones revealed multiple A-->G editing conversions. The editing of PTPN6 mRNA mainly occurred as an A-->G conversion of A(7866), which represents the putative branch site in IVS3 of PTPN6 mRNA. Evidence that editing of A(7866) abrogates splicing has been obtained in vitro by using an edited clone and its backward clone generated by site-directed mutagenesis. The level of the aberrant intron-retaining splice variant, evaluated by semi-quantitative RT-PCR, was lower in CD117(+)-AML bone marrow mononuclear cells at remission than at diagnosis, suggesting the involvement of post-transcriptional PTPN6 processing in leukemogenesis. | D000208 | Acute Disease |
| PTPN6 | 11001933 | RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. | The SH2 domain-containing tyrosine phosphatase PTPN6 (SHP-1, PTP1C, HCP) is a 68 kDa cytoplasmic protein primarily expressed in hematopoietic cell development, proliferation and receptor-mediated mitogenic signaling pathways. By means of direct dephosphorylation, it down-regulates a broad spectrum of growth-promoting receptors, including the Kit tyrosine kinase, activated to elicit a prominent cascade of intracellular events by stem cell factor binding. The pivotal contribution of PTPN6 in modulating myeloid cell signaling has been revealed by the finding that shp-1 mutation is responsible for the overexpansion and inappropriate activation of myelomonocytic populations in motheaten (me/me) and motheaten viable (me(v)/me(v)) mice. Association of PTPN6 with c-Kit and negative modulation of the myeloid leukocyte signal transduction pathways prompted us to examine the expression of the protein tyrosine phosphatase PTPN6 gene in CD34(+)/CD117(+) blasts from acute myeloid leukemia patients. We identified and cloned cDNAs representing novel PTPN6 mRNA species, derived from aberrant splicing within the N-SH2 domain leading to retention of intron 3. Sequence analysis of cDNA clones revealed multiple A-->G editing conversions. The editing of PTPN6 mRNA mainly occurred as an A-->G conversion of A(7866), which represents the putative branch site in IVS3 of PTPN6 mRNA. Evidence that editing of A(7866) abrogates splicing has been obtained in vitro by using an edited clone and its backward clone generated by site-directed mutagenesis. The level of the aberrant intron-retaining splice variant, evaluated by semi-quantitative RT-PCR, was lower in CD117(+)-AML bone marrow mononuclear cells at remission than at diagnosis, suggesting the involvement of post-transcriptional PTPN6 processing in leukemogenesis. | D007951 | Leukemia, Myeloid |
Clinically important variants in PTPN6 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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