User:ProteinBoxBot/PBB Log Wiki 10-21-07 debug run A

Log page index: User:ProteinBoxBot/PBB_Log_Index

• INFO: Beginning work on ADIPOQ... {October 21, 2007 11:45:32 AM PDT}
• SEARCH REDIRECT: Control Box Found: Adiponectin {October 21, 2007 11:46:43 AM PDT}
• UPLOAD: Added new Image to wikiCreated new protein page: Adiponectin {October 21, 2007 11:46:58 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:47:05 AM PDT}
• SKIP SUMMARY: SKIPPING Summary, No Errors. {October 21, 2007 11:47:05 AM PDT}
• UPDATE CITATIONS: Updating Citations, No Errors. {October 21, 2007 11:47:05 AM PDT}
• UPDATED: Updated protein page: Adiponectin {October 21, 2007 11:47:12 AM PDT}

• INFO: Beginning work on ARNTL... {October 21, 2007 11:33:30 AM PDT}
• SEARCH REDIRECT: Control Box Found: ARNTL {October 21, 2007 11:34:30 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:34:36 AM PDT}
• SKIP SUMMARY: Skipping Summary, No Errors. {October 21, 2007 11:34:36 AM PDT}
• SKIP CITATIONS: Skipping Citations, No Errors. {October 21, 2007 11:34:36 AM PDT}
• UPDATED: Warning while updating page: Could not find citation box. {October 21, 2007 11:35:01 AM PDT}
• UPDATED: Updated protein page (with warnings): ARNTL {October 21, 2007 11:35:01 AM PDT}

 <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->

{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = no
| update_citations = yes
}}
<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Aryl hydrocarbon receptor nuclear translocator-like
| HGNCid = 701
| Symbol = ARNTL
| AltSymbols =; BMAL1; BMAL1c; JAP3; MGC47515; MOP3; PASD3; TIC
| OMIM = 602550
| ECnumber =
| Homologene = 910
| MGIid = 1096381
| GeneAtlas_image1 = PBB_GE_ARNTL_210971_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_ARNTL_209824_s_at_tn.png
<!-- The Following entry is a time stamp of the last bot update.  It is typically hidden data -->
| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0004871 |text = signal transducer activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007623 |text = circadian rhythm}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 406
| Hs_Ensembl = ENSG00000133794
| Hs_RefseqProtein = NP_001025443
| Hs_RefseqmRNA = NM_001030272
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 11
| Hs_GenLoc_start = 13255921
| Hs_GenLoc_end = 13365345
| Hs_Uniprot = O00327
| Mm_EntrezGene = 11865
| Mm_Ensembl = ENSMUSG00000055116
| Mm_RefseqmRNA = NM_007489
| Mm_RefseqProtein = NP_031515
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 7
| Mm_GenLoc_start = 112998646
| Mm_GenLoc_end = 113105303
| Mm_Uniprot = Q3UHZ2
}}
}}
Aryl hydrocarbon receptor nuclear translocator-like, also known as ARNTL, Bmal1, or Mop3, is a gene.
The protein encoded by this gene is a basic-helix-loop-helix PAS (bHLH-PAS) domain containing protein that forms a heterodimer with a second bHLH-PAS protein, CLOCK, or its ortholog, Npas2. This complex binds to E-box response elements<ref name="pmid9576906">{{cite journal |author=Hogenesch JB, Gu YZ, Jain S, Bradfield CA |title=The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue=10 |pages=5474–9 |year=1998 |pmid=9576906 |doi=}}</ref> in  promoter regions of many genes including two families of repressor proteins, the Per genes<ref name="pmid9616112">{{cite journal |author=Gekakis N, Staknis D, Nguyen HB, et al |title=Role of the CLOCK protein in the mammalian circadian mechanism |journal=Science |volume=280 |issue=5369 |pages=1564–9 |year=1998 |pmid=9616112 |doi=}}</ref> (Per1, Per2, Per3) and the Cryptochromes<ref name="pmid10428031">{{cite journal |author=Kume K, Zylka MJ, Sriram S, et al |title=mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop |journal=Cell |volume=98 |issue=2 |pages=193–205 |year=1999 |pmid=10428031 |doi=}}</ref><ref name="pmid10531061">{{cite journal |author=Griffin EA, Staknis D, Weitz CJ |title=Light-independent role of CRY1 and CRY2 in the mammalian circadian clock |journal=Science |volume=286 |issue=5440 |pages=768–71 |year=1999 |pmid=10531061 |doi=}}</ref> (Cry1 and Cry2).  These repressor proteins are translated, and bind in a complex with casein kinase one epsilon<ref name="pmid10775102">{{cite journal |author=Lowrey PL, Shimomura K, Antoch MP, et al |title=Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau |journal=Science |volume=288 |issue=5465 |pages=483–92 |year=2000 |pmid=10775102 |doi=}}</ref> (Csnk1e) and delta (Csnk1d).  Next, the entire complex translocates to the nucleus, where it interacts with the Arntl/Clock heterodimer to inhibit its transactivation.  This hypothesis is supported by the observation that point mutants in the Arntl or Clock render them resistant to interaction and repression by Cryptochromes<ref name="pmid16474406">{{cite journal |author=Sato TK, Yamada RG, Ukai H, et al |title=Feedback repression is required for mammalian circadian clock function |journal=Nat. Genet. |volume=38 |issue=3 |pages=312–9 |year=2006 |pmid=16474406 |doi=10.1038/ng1745}}</ref>.  Transcription of Period and Cryptochrome genes, therefore, is inhibited, the protein levels of Period and Cryptochrome genes drop, and eventually repression is relieved to allow their transcription to build up again.  This  process occurs with a period length of approximately 24 hours.
Three transcript variants encoding two different isoforms have been found for this gene.<ref name="pmid9144434">{{cite journal |author=Ikeda M, Nomura M |title=cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS protein (BMAL1) and identification of alternatively spliced variants with alternative translation initiation site usage |journal=Biochem. Biophys. Res. Commun. |volume=233 |issue=1 |pages=258–64 |year=1997 |pmid=9144434 |doi=10.1006/bbrc.1997.6371}}</ref>  The importance of these transcript variants is unknown.
Arntl (or Bmal1 or Mop3) is the only component of the mammalian circadian clock whose sole deletion  in a mouse model generates arrhythmicity.<ref name="pmid11163178">{{cite journal |author=Bunger MK, Wilsbacher LD, Moran SM, et al |title=Mop3 is an essential component of the master circadian pacemaker in mammals |journal=Cell |volume=103 |issue=7 |pages=1009–17 |year=2000 |pmid=11163178 |doi=}}</ref>  In addition to defects in the clock, these Arntl null-mice also have reproductive problems<ref name="pmid16940279">{{cite journal |author=Boden MJ, Kennaway DJ |title=Circadian rhythms and reproduction |journal=Reproduction |volume=132 |issue=3 |pages=379–92 |year=2006 |pmid=16940279 |doi=10.1530/rep.1.00614}}</ref>, are small in stature, age quickly<ref name="pmid17369106">{{cite journal |author=Kondratov RV |title=A role of the circadian system and circadian proteins in aging |journal=Ageing Res. Rev. |volume=6 |issue=1 |pages=12–27 |year=2007 |pmid=17369106 |doi=10.1016/j.arr.2007.02.003}}</ref>, and have progressive arthropathy<ref name="pmid15739187">{{cite journal |author=Bunger MK, Walisser JA, Sullivan R, et al |title=Progressive arthropathy in mice with a targeted disruption of the Mop3/Bmal-1 locus |journal=Genesis |volume=41 |issue=3 |pages=122–32 |year=2005 |pmid=15739187 |doi=10.1002/gene.20102}}</ref> that results in having less overall locomotor activity than wild type mice.  Recent phenotyping data suggests that this gene<ref name="pmid15523558">{{cite journal |author=Rudic RD, McNamara P, Curtis AM, et al |title=BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis |journal=PLoS Biol. |volume=2 |issue=11 |pages=e377 |year=2004 |pmid=15523558 |doi=10.1371/journal.pbio.0020377}}</ref> and its partner Clock<ref name="pmid15845877">{{cite journal |author=Turek FW, Joshu C, Kohsaka A, et al |title=Obesity and metabolic syndrome in circadian Clock mutant mice |journal=Science |volume=308 |issue=5724 |pages=1043–5 |year=2005 |pmid=15845877 |doi=10.1126/science.1108750}}</ref> also play a role in regulation of glucose homeostasis and metabolism.  Finally, Arntl, Npas2, and Per2 have been associated with seasonal affective disorder in humans<ref name="pmid17457720">{{cite journal |author=Partonen T, Treutlein J, Alpman A, et al |title=Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter depression |journal=Ann. Med. |volume=39 |issue=3 |pages=229–38 |year=2007 |pmid=17457720 |doi=10.1080/07853890701278795}}</ref>.
Arntl transcription is circadian and reciprocally regulated by NR1D1<ref name="pmid12150932">{{cite journal |author=Preitner N, Damiola F, Lopez-Molina L, et al |title=The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator |journal=Cell |volume=110 |issue=2 |pages=251–60 |year=2002 |pmid=12150932 |doi=}}</ref> (Rev-erb-alpha) and RORA<ref name="pmid15312651">{{cite journal |author=Sato TK, Panda S, Miraglia LJ, et al |title=A functional genomics strategy reveals Rora as a component of the mammalian circadian clock |journal=Neuron |volume=43 |issue=4 |pages=527–37 |year=2004 |pmid=15312651 |doi=10.1016/j.neuron.2004.07.018}}</ref>, which establishes a second interlocking loop<ref name="pmid10807566">{{cite journal |author=Shearman LP, Sriram S, Weaver DR, et al |title=Interacting molecular loops in the mammalian circadian clock |journal=Science |volume=288 |issue=5468 |pages=1013–9 |year=2000 |pmid=10807566 |doi=}}</ref> in the mammalian circadian clock.

{{reflist|2}}

{{protein-stub}}

• INFO: Beginning work on CRY1... {October 21, 2007 11:35:01 AM PDT}
• SEARCH REDIRECT: Control Box Found: CRY1 {October 21, 2007 11:35:31 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:35:34 AM PDT}
• UPDATE SUMMARY: Updating Summary, No Errors. {October 21, 2007 11:35:34 AM PDT}
• SKIP CITATIONS: Skipping Citations, No Errors. {October 21, 2007 11:35:34 AM PDT}
• UPDATED: Warning while updating page: Could not find citation box. {October 21, 2007 11:35:46 AM PDT}
• UPDATED: Updated protein page (with warnings): CRY1 {October 21, 2007 11:35:46 AM PDT}

 <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->

{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}
<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Cryptochrome 1 (photolyase-like)
| HGNCid = 2384
| Symbol = CRY1
| AltSymbols =; PHLL1
| OMIM = 601933
| ECnumber =
| Homologene = 7042
| MGIid = 1270841
| GeneAtlas_image1 = PBB_GE_CRY1_209674_at_tn.png
<!-- 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:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0003913 |text = DNA photolyase activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0008020 |text = G-protein coupled photoreceptor activity}} {{GNF_GO|id=GO:0016829 |text = lyase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005739 |text = mitochondrion}}
| Process = {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007601 |text = visual perception}} {{GNF_GO|id=GO:0007623 |text = circadian rhythm}} {{GNF_GO|id=GO:0018298 |text = protein-chromophore linkage}} {{GNF_GO|id=GO:0050896 |text = response to stimulus}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 1407
| Hs_Ensembl = ENSG00000008405
| Hs_RefseqProtein = NP_004066
| Hs_RefseqmRNA = NM_004075
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 12
| Hs_GenLoc_start = 105909289
| Hs_GenLoc_end = 106011737
| Hs_Uniprot = Q16526
| Mm_EntrezGene = 12952
| Mm_Ensembl = ENSMUSG00000020038
| Mm_RefseqmRNA = NM_007771
| Mm_RefseqProtein = NP_031797
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 10
| Mm_GenLoc_start = 84561499
| Mm_GenLoc_end = 84614853
| Mm_Uniprot = P97784
}}
}}
Cryptochrome 1 (photolyase-like), also known as CRY1, is a human gene.
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text =
}}
{{protein-stub}}

• INFO: Beginning work on CRY2... {October 21, 2007 11:35:46 AM PDT}
• SEARCH REDIRECT: Control Box Found: CRY2 {October 21, 2007 11:36:15 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:36:18 AM PDT}
• UPDATE SUMMARY: Updating Summary, No Errors. {October 21, 2007 11:36:18 AM PDT}
• SKIP CITATIONS: Skipping Citations, No Errors. {October 21, 2007 11:36:18 AM PDT}
• UPDATED: Warning while updating page: Could not find citation box. {October 21, 2007 11:36:28 AM PDT}
• UPDATED: Updated protein page (with warnings): CRY2 {October 21, 2007 11:36:28 AM PDT}

 <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->

{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Cryptochrome 2 (photolyase-like)
| HGNCid = 2385
| Symbol = CRY2
| AltSymbols =; FLJ10332; HCRY2; KIAA0658; PHLL2
| OMIM = 603732
| ECnumber =
| Homologene = 56466
| MGIid = 1270859
| GeneAtlas_image1 = PBB_GE_CRY2_212695_at_tn.png
<!-- 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:0003913 |text = DNA photolyase activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0018298 |text = protein-chromophore linkage}} {{GNF_GO|id=GO:0048511 |text = rhythmic process}} {{GNF_GO|id=GO:0050896 |text = response to stimulus}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 1408
| Hs_Ensembl = ENSG00000121671
| Hs_RefseqProtein = NP_066940
| Hs_RefseqmRNA = NM_021117
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 11
| Hs_GenLoc_start = 45825605
| Hs_GenLoc_end = 45861372
| Hs_Uniprot = Q49AN0
| Mm_EntrezGene = 12953
| Mm_Ensembl = ENSMUSG00000068742
| Mm_RefseqmRNA = XM_994658
| Mm_RefseqProtein = XP_999752
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 2
| Mm_GenLoc_start = 92204485
| Mm_GenLoc_end = 92234867
| Mm_Uniprot = Q99JJ1
}}
}}
Cryptochrome 2 (photolyase-like), also known as CRY2, is a human gene.
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text =
}}
{{protein-stub}}

• INFO: Beginning work on CSNK1E... {October 21, 2007 11:36:28 AM PDT}
• SEARCH REDIRECT: Control Box Found: CSNK1E {October 21, 2007 11:37:13 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:37:27 AM PDT}
• UPDATE SUMMARY: Updating Summary, No Errors. {October 21, 2007 11:37:27 AM PDT}
• SKIP CITATIONS: Skipping Citations, No Errors. {October 21, 2007 11:37:27 AM PDT}
• UPDATED: Warning while updating page: Could not find citation box. {October 21, 2007 11:37:33 AM PDT}
• UPDATED: Updated protein page (with warnings): CSNK1E {October 21, 2007 11:37:33 AM PDT}

 <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->

{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}
<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_CSNK1E_image.jpg
| image_source = PDB rendering based on 1cki.
| PDB = {{PDB2|1cki}}, {{PDB2|1ckj}}
| Name = Casein kinase 1, epsilon
| HGNCid = 2453
| Symbol = CSNK1E
| AltSymbols =; HCKIE; MGC10398
| OMIM = 600863
| ECnumber =
| Homologene = 37548
| MGIid = 1351660
| GeneAtlas_image1 = PBB_GE_CSNK1E_202332_at_tn.png
<!-- 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:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0004681 |text = casein kinase I activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component =
| Process = {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 1454
| Hs_Ensembl = ENSG00000100181
| Hs_RefseqProtein = NP_001885
| Hs_RefseqmRNA = NM_001894
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 22
| Hs_GenLoc_start = 37017870
| Hs_GenLoc_end = 37124473
| Hs_Uniprot = P49674
| Mm_EntrezGene = 27373
| Mm_Ensembl = ENSMUSG00000022433
| Mm_RefseqmRNA = NM_013767
| Mm_RefseqProtein = NP_038795
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 15
| Mm_GenLoc_start = 79245107
| Mm_GenLoc_end = 79266120
| Mm_Uniprot = Q8CBH9
}}
}}
Casein kinase 1, epsilon, also known as CSNK1E, is a human gene.
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = The protein encoded by this gene is a serine/threonine protein kinase and a member of the casein kinase I protein family, whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein is found in the cytoplasm as a monomer and can phosphorylate a variety of proteins, including itself. This protein has been shown to phosphorylate period, a circadian rhythm protein. Two transcript variants encoding the same protein have been found for this gene.<ref>{{cite web | title = Entrez Gene: CSNK1E casein kinase 1, epsilon| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1454| accessdate = }}</ref>
}}

{{reflist}}

{{protein-stub}}

• INFO: Beginning work on FAS... {October 21, 2007 11:31:51 AM PDT}
• SEARCH REDIRECT: Control Box Found: Fas receptor {October 21, 2007 11:33:18 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:33:20 AM PDT}
• SKIP SUMMARY: SKIPPING Summary, No Errors. {October 21, 2007 11:33:20 AM PDT}
• UPDATE CITATIONS: Updating Citations, No Errors. {October 21, 2007 11:33:20 AM PDT}
• UPDATED: Updated protein page: Fas receptor {October 21, 2007 11:33:30 AM PDT}

• INFO: Beginning work on HBA1... {October 21, 2007 11:37:33 AM PDT}
• SEARCH REDIRECT: Control Box Found: HBA1 {October 21, 2007 11:38:17 AM PDT}
• UPLOAD: Added new Image to wikiCreated new protein page: HBA1 {October 21, 2007 11:38:32 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:38:39 AM PDT}
• UPDATE SUMMARY: Updating Summary, No Errors. {October 21, 2007 11:38:39 AM PDT}
• UPDATE CITATIONS: Updating Citations, No Errors. {October 21, 2007 11:38:39 AM PDT}
• UPDATED: Updated protein page: HBA1 {October 21, 2007 11:38:52 AM PDT}

• INFO: Beginning work on MTHFR... {October 21, 2007 11:38:52 AM PDT}
• SEARCH REDIRECT: Control Box Found: Methylenetetrahydrofolate reductase {October 21, 2007 11:40:51 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:40:52 AM PDT}
• SKIP SUMMARY: SKIPPING Summary, No Errors. {October 21, 2007 11:40:52 AM PDT}
• UPDATE CITATIONS: Updating Citations, No Errors. {October 21, 2007 11:40:52 AM PDT}
• UPDATED: Updated protein page: Methylenetetrahydrofolate reductase {October 21, 2007 11:41:03 AM PDT}

• INFO: Beginning work on NR1D2... {October 21, 2007 11:47:12 AM PDT}
• SEARCH REDIRECT: Control Box Found: NR1D2 {October 21, 2007 11:47:51 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:47:55 AM PDT}
• UPDATE SUMMARY: Updating Summary, No Errors. {October 21, 2007 11:47:55 AM PDT}
• SKIP CITATIONS: Skipping Citations, No Errors. {October 21, 2007 11:47:55 AM PDT}
• UPDATED: Warning while updating page: Could not find citation box. {October 21, 2007 11:48:02 AM PDT}
• UPDATED: Updated protein page (with warnings): NR1D2 {October 21, 2007 11:48:02 AM PDT}

 <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->

{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}
<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_NR1D2_image.jpg
| image_source = PDB rendering based on 1a6y.
| PDB = {{PDB2|1a6y}}, {{PDB2|1ga5}}, {{PDB2|1hlz}}
| Name = Nuclear receptor subfamily 1, group D, member 2
| HGNCid = 7963
| Symbol = NR1D2
| AltSymbols =; HZF2; BD73; EAR-1r; Hs.37288; RVR
| OMIM = 602304
| ECnumber =
| Homologene = 3763
| MGIid = 2449205
| GeneAtlas_image1 = PBB_GE_NR1D2_209750_at_tn.png
<!-- The Following entry is a time stamp of the last bot update.  It is typically hidden data -->
| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0003707 |text = steroid hormone receptor activity}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0043565 |text = sequence-specific DNA binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 9975
| Hs_Ensembl = ENSG00000174738
| Hs_RefseqProtein = XP_001130839
| Hs_RefseqmRNA = XM_001130839
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 3
| Hs_GenLoc_start = 23961810
| Hs_GenLoc_end = 23996240
| Hs_Uniprot = Q14995
| Mm_EntrezGene = 353187
| Mm_Ensembl = ENSMUSG00000021775
| Mm_RefseqmRNA = NM_011584
| Mm_RefseqProtein = NP_035714
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 14
| Mm_GenLoc_start = 16997124
| Mm_GenLoc_end = 17032066
| Mm_Uniprot = Q4VAB7
}}
}}
Nuclear receptor subfamily 1, group D, member 2, also known as NR1D2, is a human gene.
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text =
}}
{{protein-stub}}

• INFO: Beginning work on PER1... {October 21, 2007 11:41:03 AM PDT}
• SEARCH REDIRECT: Control Box Found: PER1 {October 21, 2007 11:41:20 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:41:22 AM PDT}
• UPDATE SUMMARY: Updating Summary, No Errors. {October 21, 2007 11:41:22 AM PDT}
• SKIP CITATIONS: Skipping Citations, No Errors. {October 21, 2007 11:41:22 AM PDT}
• UPDATED: Warning while updating page: Could not find citation box. {October 21, 2007 11:41:36 AM PDT}
• UPDATED: Updated protein page (with warnings): PER1 {October 21, 2007 11:41:36 AM PDT}

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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Period homolog 1 (Drosophila)
| HGNCid = 8845
| Symbol = PER1
| AltSymbols =; MGC88021; PER; RIGUI; hPER
| OMIM = 602260
| ECnumber =
| Homologene = 1966
| MGIid = 1098283
| GeneAtlas_image1 = PBB_GE_PER1_36829_at_tn.png
| GeneAtlas_image2 = PBB_GE_PER1_202861_at_tn.png
<!-- The Following entry is a time stamp of the last bot update.  It is typically hidden data -->
| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0009649 |text = entrainment of circadian clock}} {{GNF_GO|id=GO:0016481 |text = negative regulation of transcription}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 5187
| Hs_Ensembl = ENSG00000179094
| Hs_RefseqProtein = NP_002607
| Hs_RefseqmRNA = NM_002616
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 17
| Hs_GenLoc_start = 7984534
| Hs_GenLoc_end = 7996427
| Hs_Uniprot = O15534
| Mm_EntrezGene = 18626
| Mm_Ensembl = ENSMUSG00000020893
| Mm_RefseqmRNA = NM_011065
| Mm_RefseqProtein = NP_035195
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 11
| Mm_GenLoc_start = 68915129
| Mm_GenLoc_end = 68926158
| Mm_Uniprot = Q3U378
}}
}}
Period homolog 1 (Drosophila), also known as PER1, is a human gene.
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. Circadian expression in the suprachiasmatic nucleus continues in constant darkness, and a shift in the light/dark cycle evokes a proportional shift of gene expression in the suprachiasmatic nucleus. The specific function of this gene is not yet known. Alternative splicing has been observed in this gene; however, these variants have not been fully described.<ref>{{cite web | title = Entrez Gene: PER1 period homolog 1 (Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5187| accessdate = }}</ref>
}}

{{reflist}}

{{protein-stub}}

• INFO: Beginning work on PTEN... {October 21, 2007 11:41:36 AM PDT}
• SEARCH REDIRECT: Control Box Found: PTEN (gene) {October 21, 2007 11:41:59 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:42:00 AM PDT}
• SKIP SUMMARY: Skipping Summary, No Errors. {October 21, 2007 11:42:00 AM PDT}
• SKIP CITATIONS: Skipping Citations, No Errors. {October 21, 2007 11:42:00 AM PDT}
• UPDATED: Warning while updating page: Could not find citation box. {October 21, 2007 11:42:06 AM PDT}
• UPDATED: Updated protein page (with warnings): PTEN (gene) {October 21, 2007 11:42:06 AM PDT}

 <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->

{{PBB_Controls
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| require_manual_inspection = no
| update_protein_box = yes
| update_summary = no
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = Pten.jpg
| image_source = PTEN structure (PDB entry 1D5R visualized using PyMOL)
| PDB = {{PDB2|1d5r}}
| Name = Phosphatase and tensin homolog (mutated in multiple advanced cancers 1)
| HGNCid = 9588
| Symbol = PTEN
| AltSymbols =; BZS; MGC11227; MHAM; MMAC1; PTEN1; TEP1
| OMIM = 601728
| ECnumber =
| Homologene = 265
| MGIid = 109583
<!-- The Following entry is a time stamp of the last bot update.  It is typically hidden data -->
| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0004438 |text = phosphatidylinositol-3-phosphatase activity}} {{GNF_GO|id=GO:0004722 |text = protein serine/threonine phosphatase activity}} {{GNF_GO|id=GO:0004725 |text = protein tyrosine phosphatase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008138 |text = protein tyrosine/serine/threonine phosphatase activity}} {{GNF_GO|id=GO:0008289 |text = lipid binding}} {{GNF_GO|id=GO:0016314 |text = phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}} {{GNF_GO|id=GO:0030165 |text = PDZ domain binding}} {{GNF_GO|id=GO:0051717 |text = inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity}} {{GNF_GO|id=GO:0051800 |text = phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0000079 |text = regulation of cyclin-dependent protein kinase activity}} {{GNF_GO|id=GO:0006470 |text = protein amino acid dephosphorylation}} {{GNF_GO|id=GO:0006629 |text = lipid metabolic process}} {{GNF_GO|id=GO:0006917 |text = induction of apoptosis}} {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0007417 |text = central nervous system development}} {{GNF_GO|id=GO:0007507 |text = heart development}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0008285 |text = negative regulation of cell proliferation}} {{GNF_GO|id=GO:0016477 |text = cell migration}} {{GNF_GO|id=GO:0030336 |text = negative regulation of cell migration}} {{GNF_GO|id=GO:0031647 |text = regulation of protein stability}} {{GNF_GO|id=GO:0043066 |text = negative regulation of apoptosis}} {{GNF_GO|id=GO:0045786 |text = negative regulation of progression through cell cycle}} {{GNF_GO|id=GO:0046855 |text = inositol phosphate dephosphorylation}} {{GNF_GO|id=GO:0046856 |text = phosphoinositide dephosphorylation}} {{GNF_GO|id=GO:0051895 |text = negative regulation of focal adhesion formation}} {{GNF_GO|id=GO:0051898 |text = negative regulation of protein kinase B signaling cascade}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 5728
| Hs_Ensembl =
| Hs_RefseqProtein = NP_000305
| Hs_RefseqmRNA = NM_000314
| Hs_GenLoc_db =
| Hs_GenLoc_chr =
| Hs_GenLoc_start =
| Hs_GenLoc_end =
| Hs_Uniprot =
| Mm_EntrezGene = 19211
| Mm_Ensembl = ENSMUSG00000013663
| Mm_RefseqmRNA = NM_008960
| Mm_RefseqProtein = NP_032986
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 19
| Mm_GenLoc_start = 32823574
| Mm_GenLoc_end = 32892157
| Mm_Uniprot = Q3UFB0
}}
}}
PTEN (Phosphatase and Tensin homolog) gene is a human gene that acts as a tumor suppressor gene, which means that the protein encoded by this gene helps regulate the cycle of cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way. Mutations of this gene cause multiple advanced cancers.
The corresponding PTEN protein is found in almost all tissues in the body. The PTEN protein modifies lipids (fats) in cells by removing phosphate groups (clusters of one phosphorous and three oxygen atoms), making the PTEN protein a type of enzyme called a phosphatase. More specifically it is a phosphodiesterase and an inhibitor of the phospho-AKT pathway by removing the 3' phosphate group of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P<sub>3</sub>).
The structure of PTEN (solved by X-ray crystallography) reveals that it consists of a phosphatase domain, and a C2 domain: the phosphatase domain contains the active site which carries out the enzymatic function of the protein, whilst the C2 domain allows PTEN to bind to the phospholipid membrane so it is able to de-phosphorylate (PtdIns (3,4,5)P<sub>3</sub>)
When the PTEN enzyme is functioning properly, it acts as part of a chemical pathway that signals cells to stop dividing and causes cells to undergo programmed cell death (apoptosis) when necessary. These functions prevent uncontrolled cell growth that can lead to the formation of tumors. There is also evidence that the protein made by the PTEN gene may play a role in cell movement (migration) and sticking (adhesion) of cells to surrounding tissues.
PTEN is one of the most commonly lost tumour suppressors in human cancer. During tumor development, mutations and deletions of PTEN occur that inactivate its enzymatic activity leading to increased cell proliferation and reduced cell death. Frequent genetic inactivation of PTEN occurs in glioblastoma, endometrial cancer, prostate cancer, and reduced expression is found in many other tumor types such as lung and breast cancer.

PTEN mutation also causes a variety of inherited predispositions to cancer.

Cowden syndrome: Researchers have found more than 70 mutations in the PTEN gene in people with Cowden syndrome. These mutations can be changes in a small number of base pairs or, in some cases, deletions of a large number of base pairs. Most of these mutations cause the PTEN gene to make a protein that does not function properly or does not work at all. The defective protein is unable to stop cell division or signal abnormal cells to die, which can lead to tumor growth, particularly in the breast, thyroid or uterus.

Other disorders: Mutations in the PTEN gene cause several other disorders that, like Cowden syndrome, are characterized by the development of noncancerous tumors called hamartomas. These disorders include Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome. Together, the disorders caused by PTEN mutations are called PTEN hamartoma tumor syndromes, or PHTS. Mutations responsible for these syndromes cause the resulting protein to be nonfunctional or absent. The defective protein allows the cell to divide in an uncontrolled way and prevents damaged cells from dying, which can lead to the growth of tumors.

{{refbegin|2}}

• {{cite journal | author=Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R | title=PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. | journal=Science | year=1997 | pages=1943-1947 | volume=275 | issue=5308 | id=PMID 9072974}}
• {{cite journal | author=Simpson L, Parsons R | title=PTEN: life as a tumor suppressor

| journal=Exp Cell Res | year=2001 | pages=29-41 | volume=264 | issue=1 | id=PMID 11237521}}

• {{cite journal | author=Chu EC, Tarnawski AS | title=PTEN regulatory functions in tumor suppression and cell biology | journal=Med Sci Monit | year=2004 | pages=RA235-41 | volume=10 | issue=10 | id=PMID 15448614}}
• {{cite journal | author=Eng C | title=PTEN: one gene, many syndromes | journal=Hum Mutat | year=2003 | pages=183-98 | volume=22 | issue=3 | id=PMID 12938083}}
• {{cite journal | author=Hamada K, Sasaki T, Koni PA, Natsui M, Kishimoto H, Sasaki J, Yajima N, Horie Y, Hasegawa G, Naito M, Miyazaki J, Suda T, Itoh H, Nakao K, Mak TW, Nakano T, Suzuki A | title=The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis | journal=Genes Dev | year=2005 | pages=2054–65 | volume=19 | issue=17 | id=PMID 16107612}}
• {{cite journal | author=Leslie NR, Downes CP | title=PTEN function: how normal cells control it and tumour cells lose it | journal=Biochem J | year=2004 | pages=1–11 | volume=382 | issue=Pt 1 | id=PMID 15193142}}
• {{cite journal | author=Pilarski R, Eng C | title=Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome | journal=J Med Genet | year=2004 | pages=323-6 | volume=41 | issue=5 | id=PMID 15121767}}
• {{cite journal | author=Sansal I, Sellers WR | title=The biology and clinical relevance of the PTEN tumor suppressor pathway | journal=J Clin Oncol | year=2004 | pages=2954–63 | volume=22 | issue=14 | id=PMID 15254063}}
• {{cite journal | author=Waite KA, Eng C | title=Protean PTEN: form and function | journal=Am J Hum Genet | year=2002 | pages=829-44 | volume=70 | issue=4 | id=PMID 11875759}}
• {{cite journal | author=Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C | title=Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway | journal=Am J Hum Genet | year=2003 | pages=404-11 | volume=73 | issue=2 | id=PMID 12844284}}

{{refend}}

• [http://macromoleculeinsights.com/pten.php The PTEN Protein]
• [http://www.genecards.org/cgi-bin/carddisp?PTEN GeneCard]
• {{UMichOPM|protein|pdbid|1d5r}}
• {{MeshName|PTEN+Protein}}

{{Phosphatases}}

{{Tumor suppressor genes}}

Category:Tumor suppressor genes

Category:Peripheral membrane proteins

Category:EC 3.1.3

fr:PTEN (gène)

pl:PTEN

fi:PTEN

• INFO: Beginning work on SNCA... {October 21, 2007 11:42:06 AM PDT}
• SEARCH REDIRECT: Control Box Found: Alpha-synuclein {October 21, 2007 11:43:07 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:43:09 AM PDT}
• SKIP SUMMARY: SKIPPING Summary, No Errors. {October 21, 2007 11:43:09 AM PDT}
• UPDATE CITATIONS: Updating Citations, No Errors. {October 21, 2007 11:43:09 AM PDT}
• UPDATED: Warning while updating page: Could not find summary box. {October 21, 2007 11:43:19 AM PDT}
• UPDATED: Updated protein page (with warnings): Alpha-synuclein {October 21, 2007 11:43:19 AM PDT}

 <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->

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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_SNCA_image.jpg
| image_source = PDB rendering based on 1xq8.
| PDB = {{PDB2|1xq8}}
| Name = Synuclein, alpha (non A4 component of amyloid precursor)
| HGNCid = 11138
| Symbol = SNCA
| AltSymbols =; PD1; MGC110988; NACP; PARK1; PARK4
| OMIM = 163890
| ECnumber =
| Homologene = 293
| MGIid = 1277151
| GeneAtlas_image1 = PBB_GE_SNCA_204466_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_SNCA_204467_s_at_tn.png
<!-- The Following entry is a time stamp of the last bot update.  It is typically hidden data -->
| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0042802 |text = identical protein binding}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0019717 |text = synaptosome}}
| Process = {{GNF_GO|id=GO:0001956 |text = positive regulation of neurotransmitter secretion}} {{GNF_GO|id=GO:0001963 |text = synaptic transmission, dopaminergic}} {{GNF_GO|id=GO:0006644 |text = phospholipid metabolic process}} {{GNF_GO|id=GO:0006916 |text = anti-apoptosis}} {{GNF_GO|id=GO:0007417 |text = central nervous system development}} {{GNF_GO|id=GO:0040012 |text = regulation of locomotion}} {{GNF_GO|id=GO:0042416 |text = dopamine biosynthetic process}} {{GNF_GO|id=GO:0042493 |text = response to drug}} {{GNF_GO|id=GO:0048169 |text = regulation of long-term neuronal synaptic plasticity}} {{GNF_GO|id=GO:0048489 |text = synaptic vesicle transport}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 6622
| Hs_Ensembl = ENSG00000145335
| Hs_RefseqProtein = NP_000336
| Hs_RefseqmRNA = NM_000345
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 4
| Hs_GenLoc_start = 90866479
| Hs_GenLoc_end = 90978470
| Hs_Uniprot = P37840
| Mm_EntrezGene = 20617
| Mm_Ensembl = ENSMUSG00000025889
| Mm_RefseqmRNA = NM_001042451
| Mm_RefseqProtein = NP_001035916
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 6
| Mm_GenLoc_start = 60661224
| Mm_GenLoc_end = 60759433
| Mm_Uniprot = Q3U130
}}
}}
Alpha-synuclein is a synuclein protein of unknown function primarily found in neural tissue, where it is seen mainly in presynaptic terminals. It is predominantly expressed in the neocortex, hippocampus, striatum, thalamus, and cerebellum.  It is predominantly neuronal protein, but can also be found in glial cells.
Recent evidence suggests that alpha-synuclein functions as a molecular chaperone in the formation of SNARE complexes.
Alpha-synuclein is specifically upregulated in a discrete population of presynaptic terminals of the songbird brain during a period of song-acquisition-related synaptic rearrangement.<ref>George JM, Jin H, Woods WS, Clayton DF. (1995) Chracterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron 15:361-372. PMID 7646890</ref>
Normally an unstructured soluble protein, alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.  Alpha-synuclein is the primary structural component of Lewy body fibrils.  In addition, an alpha-synuclein fragment, known as the non-Abeta component (NAC), is found in amyloid plaques in Alzheimer's disease.
In rare cases of familial forms of Parkinson's disease there is a mutation in the gene coding for alpha-synuclein.  Three point mutations have been identified thus far: A53T, A30P and E46K.  In addition, triplication of the gene appears to be the cause of Parkinson's disease in another lineage.
Antibodies against alpha-synuclein have replaced antibodies against ubiquitin as the gold standard for immunostaining of Lewy bodies.

Synuclein

{{reflist}}

{{refbegin|2}}

• {{cite journal |author=Polymeropoulos M, Lavedan C, Leroy E et al |title=Mutation in the alpha-synuclein gene identified in families with Parkinson's disease |journal=Science |volume=276 |issue=5321 |pages=2045-7 |year=1997 |pmid=9197268}}

• {{cite journal |author=Neumann M, Kahle P, Giasson B et al |title=Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies |journal=J. Clin. Invest. |volume=110 |issue=10 |pages=1429-39 |year=2002 |pmid=12438441}}

• Sandra Blakeslee: In Folding Proteins, Clues to Many Diseases. In: The New York Times, May 27 2002

• {{cite journal |author=George JM |title=The synucleins |journal=Genome Biology |volume=3 |issue=1 |pages=reviews3002.1-3002.6 |year=2001 |pmid=11806835}}

{{PBB_Further_reading

| citations =

• {{cite journal | author=Lavedan C |title=The synuclein family. |journal=Genome Res. |volume=8 |issue= 9 |pages= 871-80 |year= 1998 |pmid= 9750188 |doi= }}
• {{cite journal | author=Ozawa T, Wakabayashi K, Oyanagi K |title=[Recent progress in the research of multiple system atrophy with special references to alpha-synuclein and suprachiasmatic nucleus] |journal=No To Shinkei |volume=54 |issue= 2 |pages= 111-7 |year= 2002 |pmid= 11889756 |doi= }}
• {{cite journal | author=Cole NB, Murphy DD |title=The cell biology of alpha-synuclein: a sticky problem? |journal=Neuromolecular Med. |volume=1 |issue= 2 |pages= 95-109 |year= 2002 |pmid= 12025860 |doi= }}
• {{cite journal | author=Iwatsubo T |title=[alpha-synuclein and Parkinson's disease] |journal=Seikagaku |volume=74 |issue= 6 |pages= 477-82 |year= 2002 |pmid= 12138709 |doi= }}
• {{cite journal | author=Trojanowski JQ, Lee VM |title=Parkinson's disease and related synucleinopathies are a new class of nervous system amyloidoses. |journal=Neurotoxicology |volume=23 |issue= 4-5 |pages= 457-60 |year= 2002 |pmid= 12428717 |doi= }}
• {{cite journal | author=Alves da Costa C |title=Recent advances on alpha-synuclein cell biology: functions and dysfunctions. |journal=Curr. Mol. Med. |volume=3 |issue= 1 |pages= 17-24 |year= 2003 |pmid= 12558071 |doi= }}
• {{cite journal | author=Di Rosa G, Puzzo D, Sant'Angelo A, et al. |title=Alpha-synuclein: between synaptic function and dysfunction. |journal=Histol. Histopathol. |volume=18 |issue= 4 |pages= 1257-66 |year= 2004 |pmid= 12973692 |doi= }}
• {{cite journal | author=Baptista MJ, Cookson MR, Miller DW |title=Parkin and alpha-synuclein: opponent actions in the pathogenesis of Parkinson's disease. |journal=The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry |volume=10 |issue= 1 |pages= 63-72 |year= 2004 |pmid= 14987449 |doi= 10.1177/1073858403260392 }}
• {{cite journal | author=Kim S, Seo JH, Suh YH |title=Alpha-synuclein, Parkinson's disease, and Alzheimer's disease. |journal=Parkinsonism Relat. Disord. |volume=10 Suppl 1 |issue= |pages= S9-13 |year= 2004 |pmid= 15109581 |doi= 10.1016/j.parkreldis.2003.11.005 }}
• {{cite journal | author=Sidhu A, Wersinger C, Vernier P |title=alpha-Synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson's disease. |journal=FEBS Lett. |volume=565 |issue= 1-3 |pages= 1-5 |year= 2004 |pmid= 15135042 |doi= 10.1016/j.febslet.2004.03.063 }}
• {{cite journal | author=Vekrellis K, Rideout HJ, Stefanis L |title=Neurobiology of alpha-synuclein. |journal=Mol. Neurobiol. |volume=30 |issue= 1 |pages= 1-21 |year= 2004 |pmid= 15247485 |doi= }}
• {{cite journal | author=Chiba-Falek O, Nussbaum RL |title=Regulation of alpha-synuclein expression: implications for Parkinson's disease. |journal=Cold Spring Harb. Symp. Quant. Biol. |volume=68 |issue= |pages= 409-15 |year= 2004 |pmid= 15338643 |doi= }}
• {{cite journal | author=Pankratz N, Foroud T |title=Genetics of Parkinson disease. |journal=NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics |volume=1 |issue= 2 |pages= 235-42 |year= 2005 |pmid= 15717024 |doi= }}
• {{cite journal | author=Singleton AB |title=Altered alpha-synuclein homeostasis causing Parkinson's disease: the potential roles of dardarin. |journal=Trends Neurosci. |volume=28 |issue= 8 |pages= 416-21 |year= 2005 |pmid= 15955578 |doi= 10.1016/j.tins.2005.05.009 }}
• {{cite journal | author=Lee HG, Zhu X, Takeda A, et al. |title=Emerging evidence for the neuroprotective role of alpha-synuclein. |journal=Exp. Neurol. |volume=200 |issue= 1 |pages= 1-7 |year= 2006 |pmid= 16780837 |doi= 10.1016/j.expneurol.2006.04.024 }}
• {{cite journal | author=Giorgi FS, Bandettini di Poggio A, Battaglia G, et al. |title=A short overview on the role of alpha-synuclein and proteasome in experimental models of Parkinson's disease. |journal=J. Neural Transm. Suppl. |volume= |issue= 70 |pages= 105-9 |year= 2006 |pmid= 17017516 |doi= }}

}}

{{refend}}

• {{MeshName|alpha-Synuclein}}

Category:Peripheral membrane proteins

de:Alpha-Synuclein

• INFO: Beginning work on SP1... {October 21, 2007 11:43:19 AM PDT}
• SEARCH REDIRECT: Control Box Found: Sp1 {October 21, 2007 11:44:18 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:44:21 AM PDT}
• SKIP SUMMARY: SKIPPING Summary, No Errors. {October 21, 2007 11:44:21 AM PDT}
• UPDATE CITATIONS: Updating Citations, No Errors. {October 21, 2007 11:44:21 AM PDT}
• UPDATED: Updated protein page: Sp1 {October 21, 2007 11:44:30 AM PDT}

• INFO: Beginning work on STAT3... {October 21, 2007 11:44:30 AM PDT}
• SEARCH REDIRECT: Control Box Found: STAT3 {October 21, 2007 11:45:17 AM PDT}
• UPDATE PROTEIN BOX: Updating Protein Box, No errors. {October 21, 2007 11:45:17 AM PDT}
• SKIP SUMMARY: SKIPPING Summary, No Errors. {October 21, 2007 11:45:17 AM PDT}
• UPDATE CITATIONS: Updating Citations, No Errors. {October 21, 2007 11:45:17 AM PDT}
• UPDATED: Warning while updating page: Could not find summary box. {October 21, 2007 11:45:32 AM PDT}
• UPDATED: Updated protein page (with warnings): STAT3 {October 21, 2007 11:45:32 AM PDT}

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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = stat3_structure.png
| image_source = PDB rendering based on 1bg1.
| PDB = {{PDB2|1bg1}}
| Name = Signal transducer and activator of transcription 3 (acute-phase response factor)
| HGNCid = 11364
| Symbol = STAT3
| AltSymbols =; APRF; FLJ20882; MGC16063
| OMIM = 102582
| ECnumber =
| Homologene = 7960
| MGIid = 103038
| GeneAtlas_image1 = PBB_GE_STAT3_208991_at_tn.png
| GeneAtlas_image2 = PBB_GE_STAT3_208992_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_STAT3_gnf1h01250_at_tn.png
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| DateOfBotUpdate = ~~~~~
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0005062 |text = hematopoietin/interferon-class (D200-domain) cytokine receptor signal transducer activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}} {{GNF_GO|id=GO:0008134 |text = transcription factor binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0000122 |text = negative regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0006928 |text = cell motility}} {{GNF_GO|id=GO:0006953 |text = acute-phase response}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007242 |text = intracellular signaling cascade}} {{GNF_GO|id=GO:0007259 |text = JAK-STAT cascade}} {{GNF_GO|id=GO:0007399 |text = nervous system development}} {{GNF_GO|id=GO:0019221 |text = cytokine and chemokine mediated signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 6774
| Hs_Ensembl = ENSG00000168610
| Hs_RefseqProtein = NP_003141
| Hs_RefseqmRNA = NM_003150
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 17
| Hs_GenLoc_start = 37718869
| Hs_GenLoc_end = 37794039
| Hs_Uniprot = P40763
| Mm_EntrezGene = 20848
| Mm_Ensembl = ENSMUSG00000004040
| Mm_RefseqmRNA = XM_001005155
| Mm_RefseqProtein = XP_001005155
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 11
| Mm_GenLoc_start = 100701188
| Mm_GenLoc_end = 100755630
| Mm_Uniprot = Q8CFJ6
}}
}}
STAT3 is tyrosine-phosphorylated and activated by a number of kinases. The binding of IL-6 family cytokines (including IL-6, oncostatin M and leukemia inhibitory factor) to the gp130 receptor triggers STAT3 phosphorylation by JAK2. EGF-R and certain other receptor tyrosine kinases, such as c-MET phosphorylate STAT3 in response to their ligands.<ref>{{cite online journal|author=Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB and Chin YE | year=2004 | title=Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells | journal=Mol Cell Biol | volume=24 | issue=21 | pages=9390-9400 | id=15485908}}</ref> STAT3 is also a target of the c-src non-receptor tyrosine kinase.<ref>{{cite online journal| author=Silva CM | year=2004 | title=Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis | journal=Oncogene | volume=23 | issue=48 | pages=8017-8023 | id=15489919}}</ref>
STAT3-deficient mouse embryos can not develop beyond embryonic day 7 (E7.0), when gastrulation initiates.<ref>{{cite online journal| author=Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T and Akira S | year=1997 | title=Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality | journal=PNAS | volume=94 | issue=8 | pages=3801-3084 | id=9108058}}</ref> It appears that at these early stages of development, STAT3 activation is required for self-renewal of embryonic stem cells (ESCs). Indeed, LIF, which is supplied to ESC cultures to maintain their undifferentiated state, can be omitted if STAT3 is activated through some other means.<ref>{{cite online journal| author=Matsuda T, Nakamura T, Nakao K, Arai T, Katsuki M, Heike T and Yokota T | year=1999 | title=STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells | journal=EMBO J | volume=18 | issue=15 | pages=4261-4269 | id=10428964}}</ref>
Constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis.<ref name="Klampfer">{{cite online journal| author=Klampfer L | year=2006 | title=Signal transducers and activators of transcription (STATs): Novel targets of chemopreventive and chemotherapeutic drugs | journal=Curr Cancer Drug Targets | volume=6 | issue=2 | pages=107-121 | id=16529541}}</ref><ref>{{cite online journal| author=Alvarez JV, Greulich H, Sellers WR, Meyerson M and Frank DA | year=2006 | title=Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor | journal=Cancer Res | volume=66 | issue=6 | pages=3162-3168 | id=16540667}}</ref><ref>{{cite online journal| author=Yin W, Cheepala S, Roberts JN, Syson-Chan K, Digiovanni J and Clifford JL | year=2006 | title=Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions | journal=Mol Cancer | volume=5 | issue=1 | article=15 | id=16603078}}</ref><ref>{{cite online journal| author=Kusaba T, Nakayama T, Yamazumi K, Yakata Y, Yoshizaki A, Inoue K, Nagayasu T and Sekine I | year=2006 | title=Activation of STAT3 is a marker of poor prognosis in human colorectal cancer | journal=Oncol Rep | volume=15 | issue=6 | pages=1445-1451 | id=16685378}}</ref> It has anti-apoptotic as well as proliferative effects.<ref name="Klampfer" />

{{Reflist|2}}

{{refbegin | 2}}

{{PBB_Further_reading

| citations =

• {{cite journal | author=Hoey T, Grusby MJ |title=STATs as mediators of cytokine-induced responses. |journal=Adv. Immunol. |volume=71 |issue= |pages= 145-62 |year= 1999 |pmid= 9917912 |doi= }}
• {{cite journal | author=Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW |title=Signaling through the JAK/STAT pathway, recent advances and future challenges. |journal=Gene |volume=285 |issue= 1-2 |pages= 1-24 |year= 2002 |pmid= 12039028 |doi= }}
• {{cite journal | author=Joseph AM, Kumar M, Mitra D |title=Nef: "necessary and enforcing factor" in HIV infection. |journal=Curr. HIV Res. |volume=3 |issue= 1 |pages= 87-94 |year= 2005 |pmid= 15638726 |doi= }}
• {{cite journal | author=Inghirami G, Chiarle R, Simmons WJ, et al. |title=New and old functions of STAT3: a pivotal target for individualized treatment of cancer. |journal=Cell Cycle |volume=4 |issue= 9 |pages= 1131-3 |year= 2006 |pmid= 16082218 |doi= }}
• {{cite journal | author=Leeman RJ, Lui VW, Grandis JR |title=STAT3 as a therapeutic target in head and neck cancer. |journal=Expert opinion on biological therapy |volume=6 |issue= 3 |pages= 231-41 |year= 2006 |pmid= 16503733 |doi= 10.1517/14712598.6.3.231 }}
• {{cite journal | author=Aggarwal BB, Sethi G, Ahn KS, et al. |title=Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. |journal=Ann. N. Y. Acad. Sci. |volume=1091 |issue= |pages= 151-69 |year= 2007 |pmid= 17341611 |doi= 10.1196/annals.1378.063 }}

}}

{{refend}}

{{Transcription factors}}

{{Adaptor proteins}}

Category:Gene expression

Category:Immune system

Category:Proteins

Category:Transcription factors

Category:Signal transduction

end log.