CASC5: Difference between revisions

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Latest revision as of 03:37, 11 November 2017

CASC5 is a protein that is encoded by the CASC5 gene in humans.^[1]^[2]^[3]^[4]

Function

CASC5 is part of the kinetochore. It is involved in microtubule attachment to chromosome centromeres and in the activation of the spindle checkpoint during mitosis. The CASC5 gene is upregulated in the areas of cell proliferation surrounding the ventricles during fetal brain development.^[5]

Interactions

CASC5 has been shown to interact with MIS12,^[6]^[7] BUB1, BUBR1 and ZWINT-1.^[5]

Polymorphisms

Homozygous polymorphisms in the CASC5 gene have been seen in patients with autosomal recessive primary microcephaly (MCPH). The mutation resulted in the skipping of exon 18 transcription, causing a frameshift and the production of a truncated protein. This truncation inhibits the binding ability of MIS12.^[5]

References

↑ Hayette S, Tigaud I, Vanier A, Martel S, Corbo L, Charrin C, Beillard E, Deleage G, Magaud JP, Rimokh R (Oct 2000). "AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14)". Oncogene. 19 (38): 4446–50. doi:10.1038/sj.onc.1203789. PMID 10980622.
↑ Wei G, Takimoto M, Yoshida I, Mao PZ, Koya RC, Miura T, Kuzumaki N (Jun 2000). "Chromosomal assignment of a novel human gene D40". Nucleic Acids Symp Ser (42): 71–2. PMID 10780384.
↑ Cheeseman IM, Hori T, Fukagawa T, Desai A (Feb 2008). "KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates". Mol Biol Cell. 19 (2): 587–94. doi:10.1091/mbc.E07-10-1051. PMC 2230600. PMID 18045986.
↑ "Entrez Gene: CASC5 cancer susceptibility candidate 5".
↑ ^5.0 ^5.1 ^5.2 Genin A; et al. (Dec 2012). "Kinetochore KMN network gene CASC5 mutated in primary microcephaly". Hum Mol Genet. 21 (24): 5306–17. doi:10.1093/hmg/dds386.
↑ Cheeseman, Iain M; Niessen Sherry; Anderson Scott; Hyndman Francie; Yates John R; Oegema Karen; Desai Arshad (Sep 2004). "A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension". Genes Dev. United States. 18 (18): 2255–68. doi:10.1101/gad.1234104. ISSN 0890-9369. PMC 517519. PMID 15371340.
↑ Obuse, Chikashi; Iwasaki Osamu; Kiyomitsu Tomomi; Goshima Gohta; Toyoda Yusuke; Yanagida Mitsuhiro (Nov 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nat. Cell Biol. England. 6 (11): 1135–41. doi:10.1038/ncb1187. ISSN 1465-7392. PMID 15502821.

External links

Human CASC5 genome location and CASC5 gene details page in the UCSC Genome Browser.

Ray ME, Su YA, Meltzer PS, Trent JM (1996). "Isolation and characterization of genes associated with chromosome-6 mediated tumor suppression in human malignant melanoma". Oncogene. 12 (12): 2527–33. PMID 8700511.
Nagase T, Kikuno R, Nakayama M, et al. (2001). "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (4): 273–81. doi:10.1093/dnares/7.4.271. PMID 10997877.
Takimoto M, Wei G, Dosaka-Akita H, et al. (2002). "Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers". Br. J. Cancer. 86 (11): 1757–62. doi:10.1038/sj.bjc.6600328. PMC 2375411. PMID 12087463.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Chinwalla V, Chien A, Odero M, et al. (2003). "A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15". Oncogene. 22 (9): 1400–10. doi:10.1038/sj.onc.1206273. PMID 12618766.
Kuefer MU, Chinwalla V, Zeleznik-Le NJ, et al. (2003). "Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14)". Oncogene. 22 (9): 1418–24. doi:10.1038/sj.onc.1206272. PMID 12618768.
Cheeseman IM, Niessen S, Anderson S, et al. (2004). "A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension". Genes Dev. 18 (18): 2255–68. doi:10.1101/gad.1234104. PMC 517519. PMID 15371340.
Obuse C, Iwasaki O, Kiyomitsu T, et al. (2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nat. Cell Biol. 6 (11): 1135–41. doi:10.1038/ncb1187. PMID 15502821.
Sasao T, Itoh N, Takano H, et al. (2005). "The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa". Reproduction. 128 (6): 709–16. doi:10.1530/rep.1.00312. PMID 15579588.
Nousiainen M, Silljé HH, Sauer G, et al. (2006). "Phosphoproteome analysis of the human mitotic spindle". Proc. Natl. Acad. Sci. U.S.A. 103 (14): 5391–6. doi:10.1073/pnas.0507066103. PMC 1459365. PMID 16565220.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.

This article on a gene on human chromosome 15 is a stub. You can help Wikipedia by expanding it.

[pmid10980622-1] Hayette S, Tigaud I, Vanier A, Martel S, Corbo L, Charrin C, Beillard E, Deleage G, Magaud JP, Rimokh R (Oct 2000). "AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14)". Oncogene. 19 (38): 4446–50. doi:10.1038/sj.onc.1203789. PMID 10980622.

[pmid10780384-2] Wei G, Takimoto M, Yoshida I, Mao PZ, Koya RC, Miura T, Kuzumaki N (Jun 2000). "Chromosomal assignment of a novel human gene D40". Nucleic Acids Symp Ser (42): 71–2. PMID 10780384.

[pmid18045986-3] Cheeseman IM, Hori T, Fukagawa T, Desai A (Feb 2008). "KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates". Mol Biol Cell. 19 (2): 587–94. doi:10.1091/mbc.E07-10-1051. PMC 2230600. PMID 18045986.

[entrez-4] "Entrez Gene: CASC5 cancer susceptibility candidate 5".

[Genin_2012-5] 5.0 ^5.1 ^5.2 Genin A; et al. (Dec 2012). "Kinetochore KMN network gene CASC5 mutated in primary microcephaly". Hum Mol Genet. 21 (24): 5306–17. doi:10.1093/hmg/dds386.

[pmid15371340-6] Cheeseman, Iain M; Niessen Sherry; Anderson Scott; Hyndman Francie; Yates John R; Oegema Karen; Desai Arshad (Sep 2004). "A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension". Genes Dev. United States. 18 (18): 2255–68. doi:10.1101/gad.1234104. ISSN 0890-9369. PMC 517519. PMID 15371340.

[pmid15502821-7] Obuse, Chikashi; Iwasaki Osamu; Kiyomitsu Tomomi; Goshima Gohta; Toyoda Yusuke; Yanagida Mitsuhiro (Nov 2004). "A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1". Nat. Cell Biol. England. 6 (11): 1135–41. doi:10.1038/ncb1187. ISSN 1465-7392. PMID 15502821.

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@@ Line 1: / Line 1: @@
-<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
+{{Infobox_gene}}
-{{PBB_Controls
+'''CASC5''' is a [[protein]] that is encoded by the ''CASC5'' [[gene]] in humans.<ref name="pmid10980622">{{cite journal | vauthors = Hayette S, Tigaud I, Vanier A, Martel S, Corbo L, Charrin C, Beillard E, Deleage G, Magaud JP, Rimokh R | title = AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14) | journal = Oncogene | volume = 19 | issue = 38 | pages = 4446–50 |date=Oct 2000 | pmid = 10980622 | pmc =  | doi = 10.1038/sj.onc.1203789 }}</ref><ref name="pmid10780384">{{cite journal | vauthors = Wei G, Takimoto M, Yoshida I, Mao PZ, Koya RC, Miura T, Kuzumaki N | title = Chromosomal assignment of a novel human gene D40 | journal = Nucleic Acids Symp Ser | volume =  | issue = 42 | pages = 71–2 |date=Jun 2000 | pmid = 10780384 | pmc =  | doi =  }}</ref><ref name="pmid18045986">{{cite journal | vauthors = Cheeseman IM, Hori T, Fukagawa T, Desai A | title = KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates | journal = Mol Biol Cell | volume = 19 | issue = 2 | pages = 587–94 |date=Feb 2008 | pmid = 18045986 | pmc = 2230600 | doi = 10.1091/mbc.E07-10-1051 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CASC5 cancer susceptibility candidate 5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57082| accessdate = }}</ref>
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- | image =
- | image_source =
- | PDB =
- | Name = Cancer susceptibility candidate 5
- | HGNCid = 24054
- | Symbol = CASC5
- | AltSymbols =; AF15Q14; D40; KIAA1570
- | OMIM = 609173
- | ECnumber =
- | Homologene = 44890
- | MGIid = 1923714
- | Function = {{GNF_GO|id=GO:0005515 |text = protein binding}}
-  | Component = {{GNF_GO|id=GO:0001669 |text = acrosome}} {{GNF_GO|id=GO:0005634 |text = nucleus}}
- | Process = {{GNF_GO|id=GO:0001675 |text = acrosome formation}}
-  | Orthologs = {{GNF_Ortholog_box
-    | Hs_EntrezGene = 57082
-    | Hs_Ensembl = ENSG00000137812
-    | Hs_RefseqProtein = NP_653091
-    | Hs_RefseqmRNA = NM_144508
-    | Hs_GenLoc_db =
-    | Hs_GenLoc_chr = 15
-    | Hs_GenLoc_start = 38673755
-    | Hs_GenLoc_end = 38734467
-    | Hs_Uniprot = Q8NG31
-    | Mm_EntrezGene = 76464
-    | Mm_Ensembl =
-    | Mm_RefseqmRNA = XM_001005065
-    | Mm_RefseqProtein = XP_001005065
-    | Mm_GenLoc_db =
-    | Mm_GenLoc_chr =
-    | Mm_GenLoc_start =
-    | Mm_GenLoc_end =
-    | Mm_Uniprot =
-  }}
-}}
-'''Cancer susceptibility candidate 5''', also known as '''CASC5''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CASC5 cancer susceptibility candidate 5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57082| accessdate = }}</ref>
 <!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
 {{PBB_Summary
@@ Line 52: / Line 6: @@
 | summary_text =
 }}
+==Function==
+CASC5 is part of the [[kinetochore]]. It is involved in [[microtubule]] attachment to chromosome centromeres and in the activation of the [[spindle checkpoint]] during mitosis. The ''CASC5'' gene is [[upregulated]] in the areas of cell proliferation surrounding the ventricles during fetal brain development.<ref name="Genin 2012">{{cite journal | title=Kinetochore KMN network gene CASC5 mutated in primary microcephaly. | author=Genin A | journal=Hum Mol Genet |date=Dec 2012 | volume=21 | issue=24 | pages=5306–17 | doi=10.1093/hmg/dds386|display-authors=etal}}</ref>
+==Interactions==
+CASC5 has been shown to [[Protein-protein interaction|interact]] with [[MIS12]],<ref name=pmid15371340>{{cite journal |last=Cheeseman |first=Iain M |author2=Niessen Sherry|author3=Anderson Scott|author4=Hyndman Francie|author5=Yates John R|author6=Oegema Karen|author7=Desai Arshad |date=Sep 2004 |title=A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension |journal=Genes Dev. |volume=18 |issue=18 |pages=2255–68 |publisher= |location = United States| issn = 0890-9369| pmid = 15371340 |doi = 10.1101/gad.1234104 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=517519 }}</ref><ref name=pmid15502821>{{cite journal |last=Obuse |first=Chikashi |author2=Iwasaki Osamu|author3=Kiyomitsu Tomomi|author4=Goshima Gohta|author5=Toyoda Yusuke|author6=Yanagida Mitsuhiro |date=Nov 2004 |title=A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1 |journal=Nat. Cell Biol. |volume=6 |issue=11 |pages=1135–41 |publisher= |location = England| issn = 1465-7392| pmid = 15502821 |doi = 10.1038/ncb1187 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref> [[BUB1]], BUBR1 and [[ZWINT|ZWINT-1]].<ref name="Genin 2012"/>
+==Polymorphisms==
+Homozygous [[single nucleotide polymorphisms|polymorphisms]] in the ''CASC5'' gene have been seen in patients with autosomal recessive primary [[microcephaly]] (MCPH). The mutation resulted in the skipping of exon 18 [[Transcription (genetics)|transcription]], causing a [[frameshift]] and the production of a truncated protein. This truncation inhibits the binding ability of MIS12.<ref name="Genin 2012"/>
 ==References==
-{{reflist|2}}
+{{reflist|30em}}
+==External links==
+* {{UCSC gene info|CASC5}}
 ==Further reading==
 {{refbegin | 2}}
 {{PBB_Further_reading
 | citations =
-*{{cite journal  | author=Ray ME, Su YA, Meltzer PS, Trent JM |title=Isolation and characterization of genes associated with chromosome-6 mediated tumor suppression in human malignant melanoma. |journal=Oncogene |volume=12 |issue= 12 |pages= 2527-33 |year= 1996 |pmid= 8700511 |doi=  }}
+*{{cite journal  | vauthors=Ray ME, Su YA, Meltzer PS, Trent JM |title=Isolation and characterization of genes associated with chromosome-6 mediated tumor suppression in human malignant melanoma. |journal=Oncogene |volume=12 |issue= 12 |pages= 2527–33 |year= 1996 |pmid= 8700511 |doi=  }}
-*{{cite journal  | author=Wei G, Takimoto M, Yoshida I, ''et al.'' |title=Chromosomal assignment of a novel human gene D40. |journal=Nucleic Acids Symp. Ser. |volume= |issue= 42 |pages= 71-2 |year= 2000 |pmid= 10780384 |doi=  }}
+*{{cite journal  | vauthors=Nagase T, Kikuno R, Nakayama M |title=Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. |journal=DNA Res. |volume=7 |issue= 4 |pages= 273–81 |year= 2001 |pmid= 10997877 |doi=  10.1093/dnares/7.4.271|display-authors=etal}}
-*{{cite journal  | author=Hayette S, Tigaud I, Vanier A, ''et al.'' |title=AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14). |journal=Oncogene |volume=19 |issue= 38 |pages= 4446-50 |year= 2000 |pmid= 10980622 |doi= 10.1038/sj.onc.1203789 }}
+*{{cite journal  | vauthors=Takimoto M, Wei G, Dosaka-Akita H |title=Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers. |journal=Br. J. Cancer |volume=86 |issue= 11 |pages= 1757–62 |year= 2002 |pmid= 12087463 |doi= 10.1038/sj.bjc.6600328  | pmc=2375411 |display-authors=etal}}
-*{{cite journal  | author=Nagase T, Kikuno R, Nakayama M, ''et al.'' |title=Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. |journal=DNA Res. |volume=7 |issue= 4 |pages= 273-81 |year= 2001 |pmid= 10997877 |doi=  }}
+*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |display-authors=etal}}
-*{{cite journal  | author=Takimoto M, Wei G, Dosaka-Akita H, ''et al.'' |title=Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers. |journal=Br. J. Cancer |volume=86 |issue= 11 |pages= 1757-62 |year= 2002 |pmid= 12087463 |doi= 10.1038/sj.bjc.6600328 }}
+*{{cite journal  | vauthors=Chinwalla V, Chien A, Odero M |title=A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15. |journal=Oncogene |volume=22 |issue= 9 |pages= 1400–10 |year= 2003 |pmid= 12618766 |doi= 10.1038/sj.onc.1206273 |display-authors=etal}}
-*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
+*{{cite journal  | vauthors=Kuefer MU, Chinwalla V, Zeleznik-Le NJ |title=Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14). |journal=Oncogene |volume=22 |issue= 9 |pages= 1418–24 |year= 2003 |pmid= 12618768 |doi= 10.1038/sj.onc.1206272 |display-authors=etal}}
-*{{cite journal  | author=Chinwalla V, Chien A, Odero M, ''et al.'' |title=A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15. |journal=Oncogene |volume=22 |issue= 9 |pages= 1400-10 |year= 2003 |pmid= 12618766 |doi= 10.1038/sj.onc.1206273 }}
+*{{cite journal  | vauthors=Cheeseman IM, Niessen S, Anderson S |title=A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension. |journal=Genes Dev. |volume=18 |issue= 18 |pages= 2255–68 |year= 2004 |pmid= 15371340 |doi= 10.1101/gad.1234104  | pmc=517519 |display-authors=etal}}
-*{{cite journal  | author=Kuefer MU, Chinwalla V, Zeleznik-Le NJ, ''et al.'' |title=Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14). |journal=Oncogene |volume=22 |issue= 9 |pages= 1418-24 |year= 2003 |pmid= 12618768 |doi= 10.1038/sj.onc.1206272 }}
+*{{cite journal  | vauthors=Obuse C, Iwasaki O, Kiyomitsu T |title=A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. |journal=Nat. Cell Biol. |volume=6 |issue= 11 |pages= 1135–41 |year= 2004 |pmid= 15502821 |doi= 10.1038/ncb1187 |display-authors=etal}}
-*{{cite journal  | author=Cheeseman IM, Niessen S, Anderson S, ''et al.'' |title=A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension. |journal=Genes Dev. |volume=18 |issue= 18 |pages= 2255-68 |year= 2004 |pmid= 15371340 |doi= 10.1101/gad.1234104 }}
+*{{cite journal  | vauthors=Sasao T, Itoh N, Takano H |title=The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa. |journal=Reproduction |volume=128 |issue= 6 |pages= 709–16 |year= 2005 |pmid= 15579588 |doi= 10.1530/rep.1.00312 |display-authors=etal}}
-*{{cite journal  | author=Obuse C, Iwasaki O, Kiyomitsu T, ''et al.'' |title=A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. |journal=Nat. Cell Biol. |volume=6 |issue= 11 |pages= 1135-41 |year= 2004 |pmid= 15502821 |doi= 10.1038/ncb1187 }}
+*{{cite journal  | vauthors=Nousiainen M, Silljé HH, Sauer G |title=Phosphoproteome analysis of the human mitotic spindle. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue= 14 |pages= 5391–6 |year= 2006 |pmid= 16565220 |doi= 10.1073/pnas.0507066103  | pmc=1459365 |display-authors=etal}}
-*{{cite journal  | author=Sasao T, Itoh N, Takano H, ''et al.'' |title=The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa. |journal=Reproduction |volume=128 |issue= 6 |pages= 709-16 |year= 2005 |pmid= 15579588 |doi= 10.1530/rep.1.00312 }}
+*{{cite journal  | vauthors=Olsen JV, Blagoev B, Gnad F |title=Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. |journal=Cell |volume=127 |issue= 3 |pages= 635–48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 |display-authors=etal}}
-*{{cite journal  | author=Nousiainen M, Silljé HH, Sauer G, ''et al.'' |title=Phosphoproteome analysis of the human mitotic spindle. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue= 14 |pages= 5391-6 |year= 2006 |pmid= 16565220 |doi= 10.1073/pnas.0507066103 }}
-*{{cite journal  | author=Olsen JV, Blagoev B, Gnad F, ''et al.'' |title=Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. |journal=Cell |volume=127 |issue= 3 |pages= 635-48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 }}
 }}
 {{refend}}
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