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[edit] Quick Protein List - Date: 20:14, 9 August 2007 (UTC)
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AKT1
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<!-- BOT: PROTEIN BOX UPDATE = YES - This protein box is automatically updated by protein box bot. Change the update option to NO to have the bot skip updating this protein box -->
{{GNF_Protein_box
| image = PBB_Protein_AKT1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1h10.
| PDB = {{PDB2|1h10}}, {{PDB2|1unp}}, {{PDB2|1unq}}, {{PDB2|1unr}}, {{PDB2|2uvm}}
| Name = v-akt murine thymoma viral oncogene homolog 1
| HGNCid = 391
| Symbol = AKT1
| AltSymbols =; AKT; MGC99656; PKB; PRKBA; RAC; RAC-ALPHA
| OMIM = 164730
| ECnumber =
| Homologene = 3785
| MGIid = 87986
| GeneAtlas_image =
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| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0000060 |text = protein import into nucleus, translocation}} {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004672 |text = protein kinase activity}} {{GNF_GO|id=GO:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0005351 |text = sugar:hydrogen ion symporter activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005819 |text = spindle}} {{GNF_GO|id=GO:0005975 |text = carbohydrate metabolic process}} {{GNF_GO|id=GO:0005978 |text = glycogen biosynthetic process}} {{GNF_GO|id=GO:0006006 |text = glucose metabolic process}} {{GNF_GO|id=GO:0006417 |text = regulation of translation}} {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0006809 |text = nitric oxide biosynthetic process}} {{GNF_GO|id=GO:0006810 |text = transport}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007281 |text = germ cell development}} {{GNF_GO|id=GO:0008286 |text = insulin receptor signaling pathway}} {{GNF_GO|id=GO:0008637 |text = apoptotic mitochondrial changes}} {{GNF_GO|id=GO:0009408 |text = response to heat}} {{GNF_GO|id=GO:0009725 |text = response to hormone stimulus}} {{GNF_GO|id=GO:0015758 |text = glucose transport}} {{GNF_GO|id=GO:0016567 |text = protein ubiquitination}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0030027 |text = lamellipodium}} {{GNF_GO|id=GO:0030163 |text = protein catabolic process}} {{GNF_GO|id=GO:0042640 |text = anagen}} {{GNF_GO|id=GO:0042802 |text = identical protein binding}} {{GNF_GO|id=GO:0045884 |text = regulation of survival gene product activity}} {{GNF_GO|id=GO:0046777 |text = protein amino acid autophosphorylation}} {{GNF_GO|id=GO:0048009 |text = insulin-like growth factor receptor signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 207
| Hs_Ensembl = ENSG00000142208
| Hs_RefseqProtein = NP_001014431
| Hs_RefseqmRNA = NM_001014431
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 14
| Hs_GenLoc_start = 104306734
| Hs_GenLoc_end = 104333125
| Hs_Uniprot = P31749
| Mm_EntrezGene = 11651
| Mm_Ensembl = ENSMUSG00000001729
| Mm_RefseqmRNA = NM_009652
| Mm_RefseqProtein = NP_033782
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 12
| Mm_GenLoc_start = 113101636
| Mm_GenLoc_end = 113122084
| Mm_Uniprot =
}}
}}
<!-- BOT: SUMMARY BEGIN UPDATE = YES - This summary is automatically updated by protein box bot. Change the update option to NO to have the bot skip updating this summary -->
==Summary==
The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Multiple alternatively spliced transcript variants have been found for this gene.
<!-- BOT: SUMMARY END -->
APOE
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:05:31 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:05:31 PM PDT}
- INSPECTION: Manual Inspection Required for this protein: User:JonSDSUGrad/Sandbox/TEST2_APOE {August 9, 2007 1:05:31 PM PDT}
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{{GNF_Protein_box
| image = PBB_Protein_APOE_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1b68.
| PDB = {{PDB2|1b68}}, {{PDB2|1bz4}}, {{PDB2|1ea8}}, {{PDB2|1gs9}}, {{PDB2|1h7i}}, {{PDB2|1le2}}, {{PDB2|1le4}}, {{PDB2|1lpe}}, {{PDB2|1nfn}}, {{PDB2|1nfo}}, {{PDB2|1or2}}, {{PDB2|1or3}}
| Name = apolipoprotein E
| HGNCid = 613
| Symbol = APOE
| AltSymbols =; AD2; MGC1571; apoprotein
| OMIM = 107741
| ECnumber =
| Homologene = 30951
| MGIid = 88057
| GeneAtlas_image =
<!-- The Following entry is a time stamp of the last bot update. It is typically hidden data -->
| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0000302 |text = response to reactive oxygen species}} {{GNF_GO|id=GO:0001540 |text = beta-amyloid binding}} {{GNF_GO|id=GO:0005319 |text = lipid transporter activity}} {{GNF_GO|id=GO:0005543 |text = phospholipid binding}} {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0006707 |text = cholesterol catabolic process}} {{GNF_GO|id=GO:0006869 |text = lipid transport}} {{GNF_GO|id=GO:0006874 |text = cellular calcium ion homeostasis}} {{GNF_GO|id=GO:0006917 |text = induction of apoptosis}} {{GNF_GO|id=GO:0007010 |text = cytoskeleton organization and biogenesis}} {{GNF_GO|id=GO:0007271 |text = synaptic transmission, cholinergic}} {{GNF_GO|id=GO:0007611 |text = learning and/or memory}} {{GNF_GO|id=GO:0008015 |text = circulation}} {{GNF_GO|id=GO:0008034 |text = lipoprotein binding}} {{GNF_GO|id=GO:0008201 |text = heparin binding}} {{GNF_GO|id=GO:0016209 |text = antioxidant activity}} {{GNF_GO|id=GO:0030516 |text = regulation of axon extension}} {{GNF_GO|id=GO:0042157 |text = lipoprotein metabolic process}} {{GNF_GO|id=GO:0042311 |text = vasodilation}} {{GNF_GO|id=GO:0042627 |text = chylomicron}} {{GNF_GO|id=GO:0042632 |text = cholesterol homeostasis}} {{GNF_GO|id=GO:0046907 |text = intracellular transport}} {{GNF_GO|id=GO:0048156 |text = tau protein binding}} {{GNF_GO|id=GO:0048168 |text = regulation of neuronal synaptic plasticity}} {{GNF_GO|id=GO:0050749 |text = apolipoprotein E receptor binding}} {{GNF_GO|id=GO:0051262 |text = protein tetramerization}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 348
| Hs_Ensembl = ENSG00000130203
| Hs_RefseqProtein = NP_000032
| Hs_RefseqmRNA = NM_000041
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 19
| Hs_GenLoc_start = 50100879
| Hs_GenLoc_end = 50104489
| Hs_Uniprot = P02649
| Mm_EntrezGene = 11816
| Mm_Ensembl = ENSMUSG00000002985
| Mm_RefseqmRNA = NM_009696
| Mm_RefseqProtein = NP_033826
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 7
| Mm_GenLoc_start = 18854795
| Mm_GenLoc_end = 18857574
| Mm_Uniprot =
}}
}}
<!-- BOT: SUMMARY BEGIN UPDATE = YES - This summary is automatically updated by protein box bot. Change the update option to NO to have the bot skip updating this summary -->
==Summary==
Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by receptor-mediated endocytosis in the liver. Apolipoprotein E, a main apoprotein of the chylomicron, binds to a specific receptor on liver cells and peripheral cells. ApoE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. The APOE gene is mapped to chromosome 19 in a cluster with APOC1 and APOC2. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants.
<!-- BOT: SUMMARY END -->
APP
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:05:34 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:05:34 PM PDT}
AR
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:05:50 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:05:50 PM PDT}
BCL2
- NO JOB: Aborted upload due to both updates being turned off. No errors. {August 9, 2007 1:06:16 PM PDT}
- NO JOB: Location: User:JonSDSUGrad/Sandbox/TEST2_BCL2 {August 9, 2007 1:06:16 PM PDT}
BRCA1
- UPDATE SUMMARY: Updating Summary Only. {August 9, 2007 1:06:22 PM PDT}
- INSPECTION: Manual Inspection Required for this protein: User:JonSDSUGrad/Sandbox/TEST2_BRCA1 {August 9, 2007 1:06:22 PM PDT}
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{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = breast cancer 1
| HGNCid = 1100
| Symbol = BRCA1
| AltSymbols =; BRCAI; BRCC1; IRIS; PSCP; RNF53
| OMIM = 113705
| ECnumber =
| Homologene = 5276
| MGIid = 104537
| GeneAtlas_image =
<!-- The Following entry is a time stamp of the last bot update. It is typically hidden data -->
| DateOfBotUpdate = 23:21, 24 July 2007 (UTC)
| Function = {{GNF_GO|id=GO:0000075 |text = cell cycle checkpoint}} {{GNF_GO|id=GO:0000151 |text = ubiquitin ligase complex}} {{GNF_GO|id=GO:0000793 |text = condensed chromosome}} {{GNF_GO|id=GO:0003674 |text = molecular_function}} {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0003684 |text = damaged DNA binding}} {{GNF_GO|id=GO:0003713 |text = transcription coactivator activity}} {{GNF_GO|id=GO:0004842 |text = ubiquitin-protein ligase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005575 |text = cellular_component}} {{GNF_GO|id=GO:0005622 |text = intracellular}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0006260 |text = DNA replication}} {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006357 |text = regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0006359 |text = regulation of transcription from RNA polymerase III promoter}} {{GNF_GO|id=GO:0006633 |text = fatty acid biosynthetic process}} {{GNF_GO|id=GO:0006978 |text = DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator}} {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0007059 |text = chromosome segregation}} {{GNF_GO|id=GO:0007098 |text = centrosome cycle}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0008274 |text = gamma-tubulin ring complex}} {{GNF_GO|id=GO:0008630 |text = DNA damage response, signal transduction resulting in induction of apoptosis}} {{GNF_GO|id=GO:0009048 |text = dosage compensation, by inactivation of X chromosome}} {{GNF_GO|id=GO:0015631 |text = tubulin binding}} {{GNF_GO|id=GO:0016481 |text = negative regulation of transcription}} {{GNF_GO|id=GO:0016567 |text = protein ubiquitination}} {{GNF_GO|id=GO:0019899 |text = enzyme binding}} {{GNF_GO|id=GO:0030521 |text = androgen receptor signaling pathway}} {{GNF_GO|id=GO:0031398 |text = positive regulation of protein ubiquitination}} {{GNF_GO|id=GO:0031436 |text = BRCA1-BARD1 complex}} {{GNF_GO|id=GO:0042127 |text = regulation of cell proliferation}} {{GNF_GO|id=GO:0042981 |text = regulation of apoptosis}} {{GNF_GO|id=GO:0045717 |text = negative regulation of fatty acid biosynthetic process}} {{GNF_GO|id=GO:0045739 |text = positive regulation of DNA repair}} {{GNF_GO|id=GO:0045786 |text = negative regulation of progression through cell cycle}} {{GNF_GO|id=GO:0045893 |text = positive regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0046600 |text = negative regulation of centriole replication}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}} {{GNF_GO|id=GO:0050681 |text = androgen receptor binding}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 672
| Hs_Ensembl = ENSG00000012048
| Hs_RefseqProtein = NP_009225
| Hs_RefseqmRNA = NM_007294
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 17
| Hs_GenLoc_start = 38449840
| Hs_GenLoc_end = 38530994
| Hs_Uniprot = P38398
| Mm_EntrezGene = 12189
| Mm_Ensembl = ENSMUSG00000017146
| Mm_RefseqmRNA = NM_009764
| Mm_RefseqProtein = NP_033894
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 11
| Mm_GenLoc_start = 101305657
| Mm_GenLoc_end = 101367902
| Mm_Uniprot = P48754
}}
}}
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==Summary==
This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability and acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as BASC for BRCA1-associated genome surveillance complex. This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complex. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants have been described for this gene but only some have had their full-length natures identified.
<!-- BOT: SUMMARY END -->
CASP3
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:06:25 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:06:25 PM PDT}
CDKN1A
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:06:44 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:06:44 PM PDT}
CDKN2A
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:06:58 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:06:58 PM PDT}
CTNNB1
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:07:13 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:07:13 PM PDT}
EGFR
- NO JOB: Both updates are turned off with errors. {August 9, 2007 1:07:32 PM PDT}
- BAD FORMAT: There is a problem with the BOT commands on this page. Invoking a Mandantory Inspection. {August 9, 2007 1:07:32 PM PDT}
- INSPECTION: Manual Inspection Required for this protein: User:JonSDSUGrad/Sandbox/TEST2_EGFR {August 9, 2007 1:07:32 PM PDT}
{{Protein
|Name=Epidermal growth factor receptor
|image=EGFR_structure.png
|caption=The extracellular domain of EGFR in a complex with EGF {{PDB|1NQL}}
|Symbol=EGFR
|AltSymbols=ERBB1
|HGNCid=3236
|Chromosome=7
|Arm=p
|Band=12
|LocusSupplementaryData=
|ECnumber=2.7.1.112
|OMIM=131550
|EntrezGene=1956
|RefSeq=NM_005228
|UniProt=P00533
}}
{{otheruses4|a cell suface receptor|estimated measure of kidney function (eGFR)|Glomerular filtration rate}}
The '''epidermal growth factor receptor''' (EGFR; ErbB-1; HER1 in humans) is the [[Cell membrane|cell-surface]] [[receptor (biochemistry)|receptor]] for members of the [[epidermal growth factor]] family (EGF-family) of [[extracellular]] protein [[ligand (biochemistry)|ligands]]. The epidermal growth factor receptor is a member of the [[ErbB]] family of receptors, a subfamily of four closely related [[receptor tyrosine kinase]]s: EGFR (ErbB-1), [[HER2/neu|HER2/c-neu]] (ErbB-2), [[Her 3]] (ErbB-3) and [[Her 4]] (ErbB-4). Mutations affecting EGFR expression or activity could result in [[cancer]].
==Function==
EGFR (epidermal growth factor receptor) exists on the cell surface and is activated by binding of its specific [[ligand]]s, including [[epidermal growth factor]] and [[TGF alpha|transforming growth factor α]] (TGFα) (note, a full list of the ligands able to activate EGFR and other members of the ErbB family is given in the [[ErbB#Kinase activation|ErbB]] article). ErbB2 has no known direct activating ligand, and may be in an activated state constitutively.
Upon activation by its growth factor ligands, EGFR undergoes a transition from an inactive monomeric form to an active homodimer - although there is some evidence that preformed inactive dimers may also exist before ligand binding. In addition to forming homodimers after ligand binding, EGFR may pair with another member of the ErbB receptor family, such as ErbB2/Her2/neu, to create an activated heterodimer. There is also evidence to suggest that clusters of activated EGFRs form, although it remains unclear whether this clustering is important for activation itself or occurs subsequent to activation of individual dimers.
[[Image:EGF Receptor.jpg|left|thumb|Diagram of the EGF receptor highlighting important domains]]
EGFR dimerization stimulates its intrinsic intracellular protein-tyrosine kinase activity. As a result, [[protein kinase#regulation|autophosphorylation]] of five [[tyrosine]] (Y) residues in the C-terminal [[Protein domains|domain]] of EGFR occurs. These are Y992, Y1045, Y1068, Y1148 and Y1173 as shown in the diagram to the left. This autophosphorylation elicits downstream activation and signaling by several other proteins that associate with the phosphorylated tyrosines through their own phosphotyrosine-binding [[SH2 domain]]s. These downstream signaling proteins initiate several [[signal transduction]] cascades, principally the [[MAPK/ERK pathway|MAPK]], [[AKT|Akt]] and [[JNK]] pathways, leading to [[DNA replication|DNA synthesis]] and cell proliferation{{ref_N|1|a}}. Such proteins modulate phenotypes such as [[cell migration]], [[adhesion]], and [[Cell growth|proliferation]]. The kinase domain of EGFR can also cross-phosphorylate tyrosine residues of other receptors it is aggregated with, and can itself be activated in that manner.
==Clinical applications==
[[Mutation]]s that lead to EGFR overexpression (known as upregulation) or overactivity have been associated with a number of [[cancer]]s, including [[lung cancer]] and [[glioblastoma multiforme]]. In this latter case a more or less specific mutation of EGFR, called EGFRvIII is often met with [http://www.healthvalue.net/egfreceptor.html].
Mutations involving EGFR could lead to its constant activation which could result in uncontrolled cell division – a predisposition for [[cancer]]{{ref_N|2|a}} . Consequently, mutations of EGFR have been identified in several types of cancer, and it is the target of an expanding class of anticancer therapies.
The identification of EGFR as an [[oncogene]] has led to the development of anticancer therapeutics directed against EGFR, including [[gefitinib]]{{ref_N|3|a}} and [[erlotinib]] for lung cancer, and [[cetuximab]] for [[colon cancer]].
Many therapeutic approaches are aimed at the EGFR [http://www.healthvalue.net/EGFR-engl.html]. [[Cetuximab]] and [[panitumumab]] are examples of [[monoclonal antibodies|monoclonal antibody]] [[Enzyme inhibitor|inhibitors]]. However the former is of the IgG1 type, the latter of the IgG2 type; consequences on antibody dependent cellular cytotoxicity can be quite different [http://www.healthvalue.net/IgG1_IgG2.html]. Other monoclonals in clinical development are zalutumumab, nimotuzumab, matuzumab. Gefitinib, erlotinib and lapatinib (the latter still in clinical trials) are examples of small molecule [[kinase]] inhibitors. The monoclonal antibodies block the extracellular ligand binding domain. With the binding site blocked, signal molecules can no longer attach there and activate the tyrosine kinase. Another method is using small molecules to inhibit the EGFR tyrosine kinase, which is on the cytoplasmic side of the receptor. Without kinase activity, EGFR is unable to activate itself, which is a prerequisite for binding of downstream adaptor proteins. Ostensibly by halting the signaling cascade in cells that rely on this pathway for growth, tumor proliferation and migration is diminished.
In July 2007 it was discovered that the blood clotting protein Fibrinogen inhibits EGFR, thereby blocking regrowth of injured neuronal cells in the spine. [http://www.eurekalert.org/pub_releases/2007-07/uoc--bcp070307.php]
<!-- Image with unknown copyright status removed: [[Image:Egfr inhibitor diagram.jpg]] -->
==References==
#{{note_N|1|a}} A comprehensive pathway map of epidermal growth factor receptor signaling. ''[[Molecular Systems Biology]] doi:10.1038/msb4100014, 2005 May'' [http://www.nature.com/msb/journal/v1/n1/full/msb4100014.html]
#{{note_N|2|a}} [[Image:Free text.png]] Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. ''[[N Engl J Med]] 2004 May 20; 350(21): 2129-39. PMID 15118073'' [http://content.nejm.org/cgi/content/full/350/21/2129 Free text]
#{{note_N|3|a}} EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. ''[[Science (journal)|Science]] 2004 Jun 4; 304(5676): 1497-500. PMID 15118125''
==External links==
* {{cite journal |author=Herbst R |title=Review of epidermal growth factor receptor biology |journal=Int J Radiat Oncol Biol Phys |volume=59 |issue=2 Suppl |pages=21-6 |year=2004 |id=PMID 15142631}}
* {{MeshName|Epidermal+Growth+Factor+Receptor}}
* [http://www.eurekalert.org/pub_releases/2007-07/uoc--bcp070307.php Fibrinogen, a blood-clotting protein, found to inhibit EGFR] Explains lack of healing in spinal injuries.
{{Receptor tyrosine kinases}}
{{Oncogenes}}
{{Growth factor receptors}}
[[Category:Tyrosine kinase receptors]]
[[Category:Oncogenes]]
[[de:EGF-Rezeptor]]
[[fr:Récepteur à l'EGF]]
[[ja:上皮æˆ�é•·å› å�å�—容体]]
[[fi:Epidermaalisen kasvutekijän reseptori]]
****** Appended Protein Page ******
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<!-- BOT: PROTEIN BOX UPDATE = YES - This protein box is automatically updated by protein box bot. Change the update option to NO to have the bot skip updating this protein box -->
{{GNF_Protein_box
| image = PBB_Protein_EGFR_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1ivo.
| PDB = {{PDB2|1ivo}}, {{PDB2|1m14}}, {{PDB2|1m17}}, {{PDB2|1mox}}, {{PDB2|1nql}}, {{PDB2|1xkk}}, {{PDB2|1yy9}}, {{PDB2|1z9i}}, {{PDB2|2gs2}}, {{PDB2|2gs6}}, {{PDB2|2gs7}}, {{PDB2|2itn}}, {{PDB2|2ito}}, {{PDB2|2itp}}, {{PDB2|2itq}}, {{PDB2|2itt}}, {{PDB2|2itu}}, {{PDB2|2itv}}, {{PDB2|2itw}}, {{PDB2|2itx}}, {{PDB2|2ity}}, {{PDB2|2itz}}, {{PDB2|2j5e}}, {{PDB2|2j5f}}, {{PDB2|2j6m}}
| Name = epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog
| HGNCid = 3236
| Symbol = EGFR
| AltSymbols =; ERBB; ERBB1; mENA
| OMIM = 131550
| ECnumber =
| Homologene = 74545
| MGIid = 95294
| GeneAtlas_image =
<!-- The Following entry is a time stamp of the last bot update. It is typically hidden data -->
| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0001503 |text = ossification}} {{GNF_GO|id=GO:0003690 |text = double-stranded DNA binding}} {{GNF_GO|id=GO:0004710 |text = MAP/ERK kinase kinase activity}} {{GNF_GO|id=GO:0004888 |text = transmembrane receptor activity}} {{GNF_GO|id=GO:0005006 |text = epidermal growth factor receptor activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} {{GNF_GO|id=GO:0005622 |text = intracellular}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005768 |text = endosome}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0006950 |text = response to stress}} {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0007166 |text = cell surface receptor linked signal transduction}} {{GNF_GO|id=GO:0007173 |text = epidermal growth factor receptor signaling pathway}} {{GNF_GO|id=GO:0007202 |text = phospholipase C activation}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}} {{GNF_GO|id=GO:0016323 |text = basolateral plasma membrane}} {{GNF_GO|id=GO:0016337 |text = cell-cell adhesion}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0030122 |text = AP-2 adaptor complex}} {{GNF_GO|id=GO:0030139 |text = endocytic vesicle}} {{GNF_GO|id=GO:0030235 |text = nitric-oxide synthase regulator activity}} {{GNF_GO|id=GO:0030335 |text = positive regulation of cell migration}} {{GNF_GO|id=GO:0042327 |text = positive regulation of phosphorylation}} {{GNF_GO|id=GO:0042802 |text = identical protein binding}} {{GNF_GO|id=GO:0043006 |text = calcium-dependent phospholipase A2 activation}} {{GNF_GO|id=GO:0043406 |text = positive regulation of MAPK activity}} {{GNF_GO|id=GO:0045429 |text = positive regulation of nitric oxide biosynthetic process}} {{GNF_GO|id=GO:0045786 |text = negative regulation of progression through cell cycle}} {{GNF_GO|id=GO:0046777 |text = protein amino acid autophosphorylation}} {{GNF_GO|id=GO:0046982 |text = protein heterodimerization activity}} {{GNF_GO|id=GO:0050679 |text = positive regulation of epithelial cell proliferation}} {{GNF_GO|id=GO:0050730 |text = regulation of peptidyl-tyrosine phosphorylation}} {{GNF_GO|id=GO:0050999 |text = regulation of nitric-oxide synthase activity}} {{GNF_GO|id=GO:0051015 |text = actin filament binding}} {{GNF_GO|id=GO:0051205 |text = protein insertion into membrane}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 1956
| Hs_Ensembl = ENSG00000146648
| Hs_RefseqProtein = NP_005219
| Hs_RefseqmRNA = NM_005228
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 7
| Hs_GenLoc_start = 55054219
| Hs_GenLoc_end = 55242524
| Hs_Uniprot = P00533
| Mm_EntrezGene = 13649
| Mm_Ensembl = ENSMUSG00000020122
| Mm_RefseqmRNA = NM_007912
| Mm_RefseqProtein = NP_031938
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 11
| Mm_GenLoc_start = 16652206
| Mm_GenLoc_end = 16813912
| Mm_Uniprot =
}}
}}
<!-- BOT: SUMMARY BEGIN UPDATE = YES - This summary is automatically updated by protein box bot. Change the update option to NO to have the bot skip updating this summary -->
<!-- No Summary Available -->
<!-- BOT: SUMMARY END -->
ERBB2
- REDIRECT: Protein Redirected to: HER2 {August 9, 2007 1:07:32 PM PDT}
- NO JOB: Both updates are turned off with errors. {August 9, 2007 1:07:40 PM PDT}
- BAD FORMAT: There is a problem with the BOT commands on this page. Invoking a Mandantory Inspection. {August 9, 2007 1:07:40 PM PDT}
- INSPECTION: Manual Inspection Required for this protein: User:JonSDSUGrad/Sandbox/TEST2_HER2 {August 9, 2007 1:07:40 PM PDT}
{{protein
| Name = HER2/neu
| caption = Ribbon diagram of [[trastuzumab]] (in blue) bound to the extracellular domain of HER2/neu (in orange). From {{PDB|1N8Z}}.
| image = Trastuzumab Fab-HER2 complex 1N8Z.png
| width =
| HGNCid = 3430
| Symbol = ERBB2
| AltSymbols = NGL
| EntrezGene = 2064
| OMIM = 164870
| RefSeq = NM_001005862
| UniProt = P04626
| PDB =
| ECnumber =
| Chromosome = 17
| Arm = q
| Band = 11.2
| LocusSupplementaryData = -q12
}}
'''HER2/neu''' (also known as ErbB-2, {{gene|ERBB2}}) is a member of the [[ErbB]] protein family, more commonly known as the [[ErbB|epidermal growth factor receptor family]]. HER2/neu is notable for its role in the [[pathogenesis]] of [[breast cancer]] and as a target of treatment. It is a cell membrane surface-bound [[receptor tyrosine kinase]] and is normally involved in the [[signal transduction]] pathways leading to cell growth and differentiation. HER2 is thought to be an [[orphan receptor]], with none of the EGF family of ligands able to activate it. However, ErbB receptors dimerise on ligand binding, and HER2 is the preferential dimerisation partner of other members of the ErbB family.<ref name="Olayioye_2001">{{cite journal |author=Olayioye MA|title=Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members|journal= Breast Cancer Res |volume= 3 |issue= 6 |pages= 385-389 |year= 2001|doi= 10.1186/bcr327 |pmid= 11737890}}</ref> The ''HER2'' gene is a [[proto-oncogene]] located at the long arm of human chromosome 17(17q11.2-q12).
Approximately 25-30 percent of breast cancers have an amplification of the ''HER2/neu'' gene or overexpression of its protein product. Overexpression of this receptor in breast cancer is associated with increased disease recurrence and worse prognosis. Because of its prognostic role as well as its ability to predict response to [[trastuzumab]] (see below), breast tumors are routinely checked for overexpression of HER2/neu. Overexpression also occurs in other cancer such as ovarian cancer and stomach cancer.
The [[oncogene]] ''neu'' is so-named because it was derived from a [[neuroglioblastoma]] cell line in rat. HER2 is named because it has similar structure to human [[epidermal growth factor receptor]], or HER1. ErbB2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR. Gene cloning showed that ''neu'', HER2, and ErbB2 were the same.
Clinically, HER2/neu is important as the target of the monoclonal [[antibody]] [[trastuzumab]] (marketed as Herceptin). Trastuzumab is only effective in breast cancer where the HER2/neu receptor is overexpressed.
HER2 is co-localized, and thus most of the time co-amplified with the gene [[GRB7]], which is as well a proto-oncogene (active in e.g. breast cancer, testicular germ cell tumor, gastric cancer, and esophageal cancer).
The HER2 gene overexpression can be suppressed by the amplification of other genes and the use of the drug [[Herceptin]]. Research is currently being conducted to discover which disregulated genes may have this desired effect. Another monoclonal antibody, pertuzumab [http://www.healthvalue.net/EGFR-engl.html], which inhibits dimerization of HER2 and HER3 receptors, is in advanced clinical trials.
== References ==
<references/>
== External links ==
* [http://www.aacr.org/home/public--media/for-the-media/fact-sheets/cancer-concepts/her2.aspx AACR Cancer Concepts Factsheet on HER2]
* [http://logikbase.com/website/techprofile.cfm?licid=1027 Her2/neu Vaccine Protects Against Tumor Growth ]
* [http://logikbase.com/website/techprofile.cfm?licid=618 Chimeric molecules and Methods of Use]
* {{MeshName|Receptor,+erbB-2}}
{{genetics-stub}}
{{Receptor tyrosine kinases}}
{{Oncogenes}}
{{Tumor markers}}
[[Category:Tyrosine kinase receptors]]
[[de:HER2/neu]]
[[fr:HER2]]
[[ja:HER2]]
[[vi:HER-2/neu]]
****** Appended Protein Page ******
<!-- BOT: MANUAL_INSPECTION_REQUIRED = NO - change this option to YES to have the protein box bot require an operator inspection before updating occurs. -->
<!-- BOT: PROTEIN BOX UPDATE = YES - This protein box is automatically updated by protein box bot. Change the update option to NO to have the bot skip updating this protein box -->
{{GNF_Protein_box
| image = PBB_Protein_ERBB2_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1n8z.
| PDB = {{PDB2|1n8z}}, {{PDB2|1s78}}, {{PDB2|2a91}}
| Name = v-erb-b2 erythroblastic leukemia viral oncogene homolog 2
| HGNCid = 3430
| Symbol = ERBB2
| AltSymbols =; HER-2; HER-2/neu; HER2; NEU; NGL; TKR1; c-erb B2
| OMIM = 164870
| ECnumber =
| Homologene = 3273
| MGIid = 95410
| GeneAtlas_image =
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| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004713 |text = protein-tyrosine kinase activity}} {{GNF_GO|id=GO:0004715 |text = non-membrane spanning protein tyrosine kinase activity}} {{GNF_GO|id=GO:0004716 |text = receptor signaling protein tyrosine kinase activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0005006 |text = epidermal growth factor receptor activity}} {{GNF_GO|id=GO:0005506 |text = iron ion binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0006118 |text = electron transport}} {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007169 |text = transmembrane receptor protein tyrosine kinase signaling pathway}} {{GNF_GO|id=GO:0007422 |text = peripheral nervous system development}} {{GNF_GO|id=GO:0007507 |text = heart development}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0009055 |text = electron carrier activity}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}} {{GNF_GO|id=GO:0016324 |text = apical plasma membrane}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0030879 |text = mammary gland development}} {{GNF_GO|id=GO:0042552 |text = myelination}} {{GNF_GO|id=GO:0042802 |text = identical protein binding}} {{GNF_GO|id=GO:0043125 |text = ErbB-3 class receptor binding}} {{GNF_GO|id=GO:0043406 |text = positive regulation of MAPK activity}} {{GNF_GO|id=GO:0045765 |text = regulation of angiogenesis}} {{GNF_GO|id=GO:0046982 |text = protein heterodimerization activity}} {{GNF_GO|id=GO:0048015 |text = phosphoinositide-mediated signaling}} {{GNF_GO|id=GO:0050679 |text = positive regulation of epithelial cell proliferation}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 2064
| Hs_Ensembl = ENSG00000141736
| Hs_RefseqProtein = NP_004439
| Hs_RefseqmRNA = NM_004448
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 17
| Hs_GenLoc_start = 35104766
| Hs_GenLoc_end = 35138441
| Hs_Uniprot = P04626
| Mm_EntrezGene = 13866
| Mm_Ensembl = ENSMUSG00000062312
| Mm_RefseqmRNA = NM_001003817
| Mm_RefseqProtein = NP_001003817
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 11
| Mm_GenLoc_start = 98228574
| Mm_GenLoc_end = 98253806
| Mm_Uniprot =
}}
}}
<!-- BOT: SUMMARY BEGIN UPDATE = YES - This summary is automatically updated by protein box bot. Change the update option to NO to have the bot skip updating this summary -->
==Summary==
This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.
<!-- BOT: SUMMARY END -->
ESR1
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:07:46 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:07:46 PM PDT}
HIF1A
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:08:01 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:08:01 PM PDT}
HLA-B
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:08:17 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:08:17 PM PDT}
IGF1
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:08:31 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:08:31 PM PDT}
IL10
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:09:34 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:09:34 PM PDT}
IL1B
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:08:46 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:08:46 PM PDT}
IL6
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:09:01 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:09:01 PM PDT}
IL8
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:09:16 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:09:16 PM PDT}
ITGB1
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:09:56 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:09:56 PM PDT}
MAPK1
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:11:09 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:11:09 PM PDT}
MMP9
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:10:10 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:10:10 PM PDT}
NFKB1
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:10:24 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:10:24 PM PDT}
PPARG
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:10:39 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:10:39 PM PDT}
PRKCA
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:10:53 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:10:53 PM PDT}
PTGS2
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:11:26 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:11:26 PM PDT}
RB1
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:11:40 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:11:40 PM PDT}
SRC
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:11:55 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:11:55 PM PDT}
TGFB1
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:12:10 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:12:10 PM PDT}
TNF
TP53
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:12:44 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:12:44 PM PDT}
VEGFA
- UPDATE PROTEIN BOX: Updating Protein Box, No errors. {August 9, 2007 1:13:00 PM PDT}
- UPDATE SUMMARY: Updating Summary, No Errors. {August 9, 2007 1:13:00 PM PDT}
end log.
