Full text data of SEPT2
SEPT2
(DIFF6, KIAA0158, NEDD5)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Septin-2 (Neural precursor cell expressed developmentally down-regulated protein 5; NEDD-5)
Septin-2 (Neural precursor cell expressed developmentally down-regulated protein 5; NEDD-5)
UniProt
Q15019
ID SEPT2_HUMAN Reviewed; 361 AA.
AC Q15019; B4DGE8; Q14132; Q53QU3; Q8IUK9; Q96CB0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 1.
DT 22-JAN-2014, entry version 150.
DE RecName: Full=Septin-2;
DE AltName: Full=Neural precursor cell expressed developmentally down-regulated protein 5;
DE Short=NEDD-5;
GN Name=SEPT2; Synonyms=DIFF6, KIAA0158, NEDD5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV.
RT The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8697812;
RA Mori T., Miura K., Fujiwara T., Shin S., Inazawa J., Nakamura Y.;
RT "Isolation and mapping of a human gene (DIFF6) homologous to yeast
RT CDC3, CDC10, CDC11, and CDC12, and mouse Diff6.";
RL Cytogenet. Cell Genet. 73:224-227(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Hu G.;
RT "Human homolog of mouse Nedd5 mRNA.";
RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 51-66, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP PHOSPHORYLATION AT SER-218.
RX PubMed=15150837; DOI=10.1002/rcm.1453;
RA She Y.M., Huang Y.W., Zhang L., Trimble W.S.;
RT "Septin 2 phosphorylation: theoretical and mass spectrometric evidence
RT for the existence of a single phosphorylation site in vivo.";
RL Rapid Commun. Mass Spectrom. 18:1123-1130(2004).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=15915442; DOI=10.1002/path.1789;
RA Hall P.A., Jung K., Hillan K.J., Russell S.E.H.;
RT "Expression profiling the human septin gene family.";
RL J. Pathol. 206:269-278(2005).
RN [10]
RP INTERACTION WITH MAP4, AND COORDINATED EXPRESSION WITH SEPT2 AND
RP SEPT7.
RX PubMed=16093351; DOI=10.1091/mbc.E05-03-0267;
RA Kremer B.E., Haystead T., Macara I.G.;
RT "Mammalian septins regulate microtubule stability through interaction
RT with the microtubule-binding protein MAP4.";
RL Mol. Biol. Cell 16:4648-4659(2005).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15774761; DOI=10.1126/science.1106823;
RA Spiliotis E.T., Kinoshita M., Nelson W.J.;
RT "A mitotic septin scaffold required for mammalian chromosome
RT congression and segregation.";
RL Science 307:1781-1785(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
RP INTERACTION WITH SEPT6 AND SEPT7.
RX PubMed=16914550; DOI=10.1074/jbc.M605179200;
RA Low C., Macara I.G.;
RT "Structural analysis of septin 2, 6, and 7 complexes.";
RL J. Biol. Chem. 281:30697-30706(2006).
RN [14]
RP FUNCTION.
RX PubMed=17803907; DOI=10.1016/j.cell.2007.06.053;
RA Kremer B.E., Adang L.A., Macara I.G.;
RT "Septins regulate actin organization and cell-cycle arrest through
RT nuclear accumulation of NCK mediated by SOCS7.";
RL Cell 130:837-850(2007).
RN [15]
RP FUNCTION, AND COLOCALIZATION WITH POLYGLUTAMYLATED TUBULIN.
RX PubMed=18209106; DOI=10.1083/jcb.200710039;
RA Spiliotis E.T., Hunt S.J., Hu Q., Kinoshita M., Nelson W.J.;
RT "Epithelial polarity requires septin coupling of vesicle transport to
RT polyglutamylated microtubules.";
RL J. Cell Biol. 180:295-303(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [22]
RP PHOSPHORYLATION AT SER-218, MUTAGENESIS OF SER-218, AND TISSUE
RP SPECIFICITY.
RX PubMed=19165576; DOI=10.1007/s11010-008-0020-2;
RA Yu W., Ding X., Chen F., Liu M., Shen S., Gu X., Yu L.;
RT "The phosphorylation of SEPT2 on Ser218 by casein kinase 2 is
RT important to hepatoma carcinoma cell proliferation.";
RL Mol. Cell. Biochem. 325:61-67(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [24]
RP INTERACTION WITH SEPT9, AND ROLE IN BACTERIAL INFECTION.
RX PubMed=19145258; DOI=10.1371/journal.pone.0004196;
RA Mostowy S., Nam Tham T., Danckaert A., Guadagnini S.,
RA Boisson-Dupuis S., Pizarro-Cerda J., Cossart P.;
RT "Septins regulate bacterial entry into host cells.";
RL PLoS ONE 4:E4196-E4196(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-190, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 1-315 IN COMPLEXES WITH GTP,
RP ELECTRON MICROSCOPY, MUTAGENESIS OF PHE-156; TRP-260 AND HIS-270, AND
RP SUBUNIT.
RX PubMed=17637674; DOI=10.1038/nature06052;
RA Sirajuddin M., Farkasovsky M., Hauer F., Kuehlmann D., Macara I.G.,
RA Weyand M., Stark H., Wittinghofer A.;
RT "Structural insight into filament formation by mammalian septins.";
RL Nature 449:311-315(2007).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 21-320 IN COMPLEX WITH GDP,
RP AND SUBUNIT.
RG Structural genomics consortium (SGC);
RT "Human septin 2 in complex with GDP.";
RL Submitted (AUG-2007) to the PDB data bank.
CC -!- FUNCTION: Filament-forming cytoskeletal GTPase. Required for
CC normal organization of the actin cytoskeleton. Plays a role in the
CC biogenesis of polarized columnar-shaped epithelium by maintaining
CC polyglutamylated microtubules, thus facilitating efficient vesicle
CC transport, and by impeding MAP4 binding to tubulin. Required for
CC the progression through mitosis. Forms a scaffold at the midplane
CC of the mitotic splindle required to maintain CENPE localization at
CC kinetochores and consequently chromosome congression. During
CC anaphase, may be required for chromosome segregation and spindle
CC elongation. Plays a role in ciliogenesis and collective cell
CC movements. In cilia, required for the integrity of the diffusion
CC barrier at the base of the primary cilium that prevents diffusion
CC of transmembrane proteins between the cilia and plasma membranes:
CC probably acts by regulating the assembly of the tectonic-like
CC complex (also named B9 complex) by localizing TMEM231 protein. May
CC play a role in the internalization of 2 intracellular microbial
CC pathogens, Listeria monocytogenes and Shigella flexneri.
CC -!- SUBUNIT: Septins polymerize into heterooligomeric protein
CC complexes that form filaments, and associate with cellular
CC membranes, actin filaments and microtubules. GTPase activity is
CC required for filament formation. Filaments are assembled from
CC asymmetrical heterotrimers, composed of SEPT2, SEPT6 and SEPT7
CC that associate head-to-head to form a hexameric unit. Interaction
CC between SEPT2 and SEPT7 seems indirect. Interacts with SEPT5 (By
CC similarity). Interaction with SEPT4 not detected (By similarity).
CC Interacts with SEPT9. Interacts with MAP4.
CC -!- INTERACTION:
CC Q14141:SEPT6; NbExp=4; IntAct=EBI-741220, EBI-745901;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton.
CC Cytoplasm, cytoskeleton, spindle. Chromosome, centromere,
CC kinetochore. Cleavage furrow. Midbody. Cytoplasm, cell cortex.
CC Cell projection, cilium membrane (By similarity). Note=In
CC metaphase cells, localized within the microtubule spindle. At the
CC metaphase plate, in close apposition to the kinetochores of the
CC congressed chromosomes. In cells undergoing cytokinesis, localized
CC to the midbody, the ingressing cleavage furrow, and the central
CC spindle. During bacterial infection, displays a collar shape
CC structure next to actin at the pole of invading bacteria. In
CC epithelial cells, colocalizes with polyglutamylated tubulin around
CC the trans-Golgi network, as well as juxatnuclear and proximal
CC Golgi apparatus. Localizes at the base of the cilia near the
CC morphological distinction between the cilia and plasma membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15019-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15019-2; Sequence=VSP_038271;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed. Up-regulated in liver
CC cancer.
CC -!- MISCELLANEOUS: Coordinated expression with SEPT6 and SEPT7.
CC -!- SIMILARITY: Belongs to the septin family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY14718.1; Type=Erroneous gene model prediction;
CC Sequence=BAA09928.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SEPT2ID44125ch2q37.html";
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DR EMBL; D63878; BAA09928.2; ALT_INIT; mRNA.
DR EMBL; D28540; BAA05893.1; -; mRNA.
DR EMBL; AF038404; AAB92377.1; -; mRNA.
DR EMBL; AK294563; BAG57759.1; -; mRNA.
DR EMBL; AC005104; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104841; AAY14718.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC014455; AAH14455.1; -; mRNA.
DR EMBL; BC033559; AAH33559.1; -; mRNA.
DR RefSeq; NP_001008491.1; NM_001008491.2.
DR RefSeq; NP_001008492.1; NM_001008492.2.
DR RefSeq; NP_001269901.1; NM_001282972.1.
DR RefSeq; NP_001269902.1; NM_001282973.1.
DR RefSeq; NP_004395.1; NM_004404.4.
DR RefSeq; NP_006146.1; NM_006155.2.
DR RefSeq; XP_005247068.1; XM_005247011.1.
DR RefSeq; XP_005247069.1; XM_005247012.1.
DR RefSeq; XP_005247070.1; XM_005247013.1.
DR UniGene; Hs.721234; -.
DR PDB; 2QA5; X-ray; 3.40 A; A/B=1-315.
DR PDB; 2QAG; X-ray; 4.00 A; A=1-361.
DR PDB; 2QNR; X-ray; 2.60 A; A/B=22-320.
DR PDBsum; 2QA5; -.
DR PDBsum; 2QAG; -.
DR PDBsum; 2QNR; -.
DR ProteinModelPortal; Q15019; -.
DR SMR; Q15019; 34-305.
DR DIP; DIP-38220N; -.
DR IntAct; Q15019; 12.
DR MINT; MINT-1433588; -.
DR STRING; 9606.ENSP00000353157; -.
DR PhosphoSite; Q15019; -.
DR DMDM; 2500769; -.
DR OGP; Q15019; -.
DR PaxDb; Q15019; -.
DR PRIDE; Q15019; -.
DR DNASU; 4735; -.
DR Ensembl; ENST00000360051; ENSP00000353157; ENSG00000168385.
DR Ensembl; ENST00000391971; ENSP00000375832; ENSG00000168385.
DR Ensembl; ENST00000391973; ENSP00000375834; ENSG00000168385.
DR Ensembl; ENST00000401990; ENSP00000385109; ENSG00000168385.
DR Ensembl; ENST00000402092; ENSP00000385172; ENSG00000168385.
DR GeneID; 4735; -.
DR KEGG; hsa:4735; -.
DR UCSC; uc002wbc.3; human.
DR CTD; 4735; -.
DR GeneCards; GC02P242254; -.
DR HGNC; HGNC:7729; SEPT2.
DR HPA; CAB017190; -.
DR HPA; HPA018481; -.
DR MIM; 601506; gene.
DR neXtProt; NX_Q15019; -.
DR PharmGKB; PA31535; -.
DR eggNOG; COG5019; -.
DR HOGENOM; HOG000233586; -.
DR HOVERGEN; HBG065093; -.
DR KO; K16942; -.
DR OrthoDB; EOG79KPF0; -.
DR ChiTaRS; SEPT2; human.
DR EvolutionaryTrace; Q15019; -.
DR GeneWiki; SEPT2; -.
DR GenomeRNAi; 4735; -.
DR NextBio; 18256; -.
DR PRO; PR:Q15019; -.
DR ArrayExpress; Q15019; -.
DR Bgee; Q15019; -.
DR CleanEx; HS_SEPT2; -.
DR Genevestigator; Q15019; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0060170; C:cilium membrane; ISS:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0000777; C:condensed chromosome kinetochore; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0000145; C:exocyst; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0031105; C:septin complex; IEA:InterPro.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0030234; F:enzyme regulator activity; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0042384; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0002036; P:regulation of L-glutamate transport; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR InterPro; IPR000038; Cell_div_GTP-bd.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR016491; Septin.
DR InterPro; IPR008113; Septin2.
DR PANTHER; PTHR18884; PTHR18884; 1.
DR Pfam; PF00735; Septin; 1.
DR PIRSF; PIRSF006698; Septin; 1.
DR PRINTS; PR01740; SEPTIN2.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle;
KW Cell division; Cell membrane; Cell projection; Centromere; Chromosome;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW GTP-binding; Kinetochore; Membrane; Mitosis; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 361 Septin-2.
FT /FTId=PRO_0000173515.
FT NP_BIND 44 51 GTP.
FT NP_BIND 183 191 GTP.
FT REGION 260 270 Important for dimerization.
FT BINDING 78 78 GTP (By similarity).
FT BINDING 104 104 GTP; via amide nitrogen (By similarity).
FT BINDING 241 241 GTP; via amide nitrogen and carbonyl
FT oxygen.
FT BINDING 256 256 GTP.
FT SITE 156 156 Important for dimerization.
FT MOD_RES 17 17 Phosphotyrosine (By similarity).
FT MOD_RES 190 190 N6-acetyllysine.
FT MOD_RES 218 218 Phosphoserine.
FT VAR_SEQ 1 1 M -> MPWISEGRATRPCLRVPSARRGDEGLHQRDEASQKM
FT (in isoform 2).
FT /FTId=VSP_038271.
FT MUTAGEN 156 156 F->D: Loss of dimerization.
FT MUTAGEN 218 218 S->A: Loss of phosphorylation.
FT MUTAGEN 260 260 W->A: Loss of dimerization.
FT MUTAGEN 270 270 H->D: Loss of dimerization.
FT CONFLICT 69 69 P -> S (in Ref. 6; AAH14455).
FT CONFLICT 72 72 A -> AALNTRKTLLW (in Ref. 6; AAH33559).
FT CONFLICT 360 361 HV -> TCKVMCTYKKSEKTLSWIKKKTFQMHDPAVCFQSL
FT GGCHPHFNSTCA (in Ref. 2; BAA05893).
FT HELIX 23 34
FT STRAND 38 45
FT HELIX 50 58
FT STRAND 85 88
FT STRAND 95 102
FT HELIX 118 133
FT STRAND 148 153
FT STRAND 155 159
FT HELIX 162 171
FT TURN 172 174
FT STRAND 177 181
FT HELIX 184 186
FT HELIX 189 205
FT HELIX 225 232
FT STRAND 236 238
FT STRAND 243 245
FT STRAND 254 258
FT STRAND 261 264
FT TURN 268 270
FT HELIX 273 282
FT HELIX 284 293
FT HELIX 295 305
SQ SEQUENCE 361 AA; 41487 MW; 12CCBBE30806F92F CRC64;
MSKQQPTQFI NPETPGYVGF ANLPNQVHRK SVKKGFEFTL MVVGESGLGK STLINSLFLT
DLYPERVIPG AAEKIERTVQ IEASTVEIEE RGVKLRLTVV DTPGYGDAIN CRDCFKTIIS
YIDEQFERYL HDESGLNRRH IIDNRVHCCF YFISPFGHGL KPLDVAFMKA IHNKVNIVPV
IAKADTLTLK ERERLKKRIL DEIEEHNIKI YHLPDAESDE DEDFKEQTRL LKASIPFSVV
GSNQLIEAKG KKVRGRLYPW GVVEVENPEH NDFLKLRTML ITHMQDLQEV TQDLHYENFR
SERLKRGGRK VENEDMNKDQ ILLEKEAELR RMQEMIARMQ AQMQMQMQGG DGDGGALGHH
V
//
ID SEPT2_HUMAN Reviewed; 361 AA.
AC Q15019; B4DGE8; Q14132; Q53QU3; Q8IUK9; Q96CB0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 1.
DT 22-JAN-2014, entry version 150.
DE RecName: Full=Septin-2;
DE AltName: Full=Neural precursor cell expressed developmentally down-regulated protein 5;
DE Short=NEDD-5;
GN Name=SEPT2; Synonyms=DIFF6, KIAA0158, NEDD5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV.
RT The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8697812;
RA Mori T., Miura K., Fujiwara T., Shin S., Inazawa J., Nakamura Y.;
RT "Isolation and mapping of a human gene (DIFF6) homologous to yeast
RT CDC3, CDC10, CDC11, and CDC12, and mouse Diff6.";
RL Cytogenet. Cell Genet. 73:224-227(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Hu G.;
RT "Human homolog of mouse Nedd5 mRNA.";
RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 51-66, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP PHOSPHORYLATION AT SER-218.
RX PubMed=15150837; DOI=10.1002/rcm.1453;
RA She Y.M., Huang Y.W., Zhang L., Trimble W.S.;
RT "Septin 2 phosphorylation: theoretical and mass spectrometric evidence
RT for the existence of a single phosphorylation site in vivo.";
RL Rapid Commun. Mass Spectrom. 18:1123-1130(2004).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=15915442; DOI=10.1002/path.1789;
RA Hall P.A., Jung K., Hillan K.J., Russell S.E.H.;
RT "Expression profiling the human septin gene family.";
RL J. Pathol. 206:269-278(2005).
RN [10]
RP INTERACTION WITH MAP4, AND COORDINATED EXPRESSION WITH SEPT2 AND
RP SEPT7.
RX PubMed=16093351; DOI=10.1091/mbc.E05-03-0267;
RA Kremer B.E., Haystead T., Macara I.G.;
RT "Mammalian septins regulate microtubule stability through interaction
RT with the microtubule-binding protein MAP4.";
RL Mol. Biol. Cell 16:4648-4659(2005).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15774761; DOI=10.1126/science.1106823;
RA Spiliotis E.T., Kinoshita M., Nelson W.J.;
RT "A mitotic septin scaffold required for mammalian chromosome
RT congression and segregation.";
RL Science 307:1781-1785(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
RP INTERACTION WITH SEPT6 AND SEPT7.
RX PubMed=16914550; DOI=10.1074/jbc.M605179200;
RA Low C., Macara I.G.;
RT "Structural analysis of septin 2, 6, and 7 complexes.";
RL J. Biol. Chem. 281:30697-30706(2006).
RN [14]
RP FUNCTION.
RX PubMed=17803907; DOI=10.1016/j.cell.2007.06.053;
RA Kremer B.E., Adang L.A., Macara I.G.;
RT "Septins regulate actin organization and cell-cycle arrest through
RT nuclear accumulation of NCK mediated by SOCS7.";
RL Cell 130:837-850(2007).
RN [15]
RP FUNCTION, AND COLOCALIZATION WITH POLYGLUTAMYLATED TUBULIN.
RX PubMed=18209106; DOI=10.1083/jcb.200710039;
RA Spiliotis E.T., Hunt S.J., Hu Q., Kinoshita M., Nelson W.J.;
RT "Epithelial polarity requires septin coupling of vesicle transport to
RT polyglutamylated microtubules.";
RL J. Cell Biol. 180:295-303(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [22]
RP PHOSPHORYLATION AT SER-218, MUTAGENESIS OF SER-218, AND TISSUE
RP SPECIFICITY.
RX PubMed=19165576; DOI=10.1007/s11010-008-0020-2;
RA Yu W., Ding X., Chen F., Liu M., Shen S., Gu X., Yu L.;
RT "The phosphorylation of SEPT2 on Ser218 by casein kinase 2 is
RT important to hepatoma carcinoma cell proliferation.";
RL Mol. Cell. Biochem. 325:61-67(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [24]
RP INTERACTION WITH SEPT9, AND ROLE IN BACTERIAL INFECTION.
RX PubMed=19145258; DOI=10.1371/journal.pone.0004196;
RA Mostowy S., Nam Tham T., Danckaert A., Guadagnini S.,
RA Boisson-Dupuis S., Pizarro-Cerda J., Cossart P.;
RT "Septins regulate bacterial entry into host cells.";
RL PLoS ONE 4:E4196-E4196(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-190, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 1-315 IN COMPLEXES WITH GTP,
RP ELECTRON MICROSCOPY, MUTAGENESIS OF PHE-156; TRP-260 AND HIS-270, AND
RP SUBUNIT.
RX PubMed=17637674; DOI=10.1038/nature06052;
RA Sirajuddin M., Farkasovsky M., Hauer F., Kuehlmann D., Macara I.G.,
RA Weyand M., Stark H., Wittinghofer A.;
RT "Structural insight into filament formation by mammalian septins.";
RL Nature 449:311-315(2007).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 21-320 IN COMPLEX WITH GDP,
RP AND SUBUNIT.
RG Structural genomics consortium (SGC);
RT "Human septin 2 in complex with GDP.";
RL Submitted (AUG-2007) to the PDB data bank.
CC -!- FUNCTION: Filament-forming cytoskeletal GTPase. Required for
CC normal organization of the actin cytoskeleton. Plays a role in the
CC biogenesis of polarized columnar-shaped epithelium by maintaining
CC polyglutamylated microtubules, thus facilitating efficient vesicle
CC transport, and by impeding MAP4 binding to tubulin. Required for
CC the progression through mitosis. Forms a scaffold at the midplane
CC of the mitotic splindle required to maintain CENPE localization at
CC kinetochores and consequently chromosome congression. During
CC anaphase, may be required for chromosome segregation and spindle
CC elongation. Plays a role in ciliogenesis and collective cell
CC movements. In cilia, required for the integrity of the diffusion
CC barrier at the base of the primary cilium that prevents diffusion
CC of transmembrane proteins between the cilia and plasma membranes:
CC probably acts by regulating the assembly of the tectonic-like
CC complex (also named B9 complex) by localizing TMEM231 protein. May
CC play a role in the internalization of 2 intracellular microbial
CC pathogens, Listeria monocytogenes and Shigella flexneri.
CC -!- SUBUNIT: Septins polymerize into heterooligomeric protein
CC complexes that form filaments, and associate with cellular
CC membranes, actin filaments and microtubules. GTPase activity is
CC required for filament formation. Filaments are assembled from
CC asymmetrical heterotrimers, composed of SEPT2, SEPT6 and SEPT7
CC that associate head-to-head to form a hexameric unit. Interaction
CC between SEPT2 and SEPT7 seems indirect. Interacts with SEPT5 (By
CC similarity). Interaction with SEPT4 not detected (By similarity).
CC Interacts with SEPT9. Interacts with MAP4.
CC -!- INTERACTION:
CC Q14141:SEPT6; NbExp=4; IntAct=EBI-741220, EBI-745901;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton.
CC Cytoplasm, cytoskeleton, spindle. Chromosome, centromere,
CC kinetochore. Cleavage furrow. Midbody. Cytoplasm, cell cortex.
CC Cell projection, cilium membrane (By similarity). Note=In
CC metaphase cells, localized within the microtubule spindle. At the
CC metaphase plate, in close apposition to the kinetochores of the
CC congressed chromosomes. In cells undergoing cytokinesis, localized
CC to the midbody, the ingressing cleavage furrow, and the central
CC spindle. During bacterial infection, displays a collar shape
CC structure next to actin at the pole of invading bacteria. In
CC epithelial cells, colocalizes with polyglutamylated tubulin around
CC the trans-Golgi network, as well as juxatnuclear and proximal
CC Golgi apparatus. Localizes at the base of the cilia near the
CC morphological distinction between the cilia and plasma membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15019-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15019-2; Sequence=VSP_038271;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed. Up-regulated in liver
CC cancer.
CC -!- MISCELLANEOUS: Coordinated expression with SEPT6 and SEPT7.
CC -!- SIMILARITY: Belongs to the septin family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY14718.1; Type=Erroneous gene model prediction;
CC Sequence=BAA09928.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SEPT2ID44125ch2q37.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; D63878; BAA09928.2; ALT_INIT; mRNA.
DR EMBL; D28540; BAA05893.1; -; mRNA.
DR EMBL; AF038404; AAB92377.1; -; mRNA.
DR EMBL; AK294563; BAG57759.1; -; mRNA.
DR EMBL; AC005104; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104841; AAY14718.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC014455; AAH14455.1; -; mRNA.
DR EMBL; BC033559; AAH33559.1; -; mRNA.
DR RefSeq; NP_001008491.1; NM_001008491.2.
DR RefSeq; NP_001008492.1; NM_001008492.2.
DR RefSeq; NP_001269901.1; NM_001282972.1.
DR RefSeq; NP_001269902.1; NM_001282973.1.
DR RefSeq; NP_004395.1; NM_004404.4.
DR RefSeq; NP_006146.1; NM_006155.2.
DR RefSeq; XP_005247068.1; XM_005247011.1.
DR RefSeq; XP_005247069.1; XM_005247012.1.
DR RefSeq; XP_005247070.1; XM_005247013.1.
DR UniGene; Hs.721234; -.
DR PDB; 2QA5; X-ray; 3.40 A; A/B=1-315.
DR PDB; 2QAG; X-ray; 4.00 A; A=1-361.
DR PDB; 2QNR; X-ray; 2.60 A; A/B=22-320.
DR PDBsum; 2QA5; -.
DR PDBsum; 2QAG; -.
DR PDBsum; 2QNR; -.
DR ProteinModelPortal; Q15019; -.
DR SMR; Q15019; 34-305.
DR DIP; DIP-38220N; -.
DR IntAct; Q15019; 12.
DR MINT; MINT-1433588; -.
DR STRING; 9606.ENSP00000353157; -.
DR PhosphoSite; Q15019; -.
DR DMDM; 2500769; -.
DR OGP; Q15019; -.
DR PaxDb; Q15019; -.
DR PRIDE; Q15019; -.
DR DNASU; 4735; -.
DR Ensembl; ENST00000360051; ENSP00000353157; ENSG00000168385.
DR Ensembl; ENST00000391971; ENSP00000375832; ENSG00000168385.
DR Ensembl; ENST00000391973; ENSP00000375834; ENSG00000168385.
DR Ensembl; ENST00000401990; ENSP00000385109; ENSG00000168385.
DR Ensembl; ENST00000402092; ENSP00000385172; ENSG00000168385.
DR GeneID; 4735; -.
DR KEGG; hsa:4735; -.
DR UCSC; uc002wbc.3; human.
DR CTD; 4735; -.
DR GeneCards; GC02P242254; -.
DR HGNC; HGNC:7729; SEPT2.
DR HPA; CAB017190; -.
DR HPA; HPA018481; -.
DR MIM; 601506; gene.
DR neXtProt; NX_Q15019; -.
DR PharmGKB; PA31535; -.
DR eggNOG; COG5019; -.
DR HOGENOM; HOG000233586; -.
DR HOVERGEN; HBG065093; -.
DR KO; K16942; -.
DR OrthoDB; EOG79KPF0; -.
DR ChiTaRS; SEPT2; human.
DR EvolutionaryTrace; Q15019; -.
DR GeneWiki; SEPT2; -.
DR GenomeRNAi; 4735; -.
DR NextBio; 18256; -.
DR PRO; PR:Q15019; -.
DR ArrayExpress; Q15019; -.
DR Bgee; Q15019; -.
DR CleanEx; HS_SEPT2; -.
DR Genevestigator; Q15019; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0060170; C:cilium membrane; ISS:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0000777; C:condensed chromosome kinetochore; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0000145; C:exocyst; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0031105; C:septin complex; IEA:InterPro.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0030234; F:enzyme regulator activity; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0042384; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0002036; P:regulation of L-glutamate transport; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR InterPro; IPR000038; Cell_div_GTP-bd.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR016491; Septin.
DR InterPro; IPR008113; Septin2.
DR PANTHER; PTHR18884; PTHR18884; 1.
DR Pfam; PF00735; Septin; 1.
DR PIRSF; PIRSF006698; Septin; 1.
DR PRINTS; PR01740; SEPTIN2.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle;
KW Cell division; Cell membrane; Cell projection; Centromere; Chromosome;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW GTP-binding; Kinetochore; Membrane; Mitosis; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 361 Septin-2.
FT /FTId=PRO_0000173515.
FT NP_BIND 44 51 GTP.
FT NP_BIND 183 191 GTP.
FT REGION 260 270 Important for dimerization.
FT BINDING 78 78 GTP (By similarity).
FT BINDING 104 104 GTP; via amide nitrogen (By similarity).
FT BINDING 241 241 GTP; via amide nitrogen and carbonyl
FT oxygen.
FT BINDING 256 256 GTP.
FT SITE 156 156 Important for dimerization.
FT MOD_RES 17 17 Phosphotyrosine (By similarity).
FT MOD_RES 190 190 N6-acetyllysine.
FT MOD_RES 218 218 Phosphoserine.
FT VAR_SEQ 1 1 M -> MPWISEGRATRPCLRVPSARRGDEGLHQRDEASQKM
FT (in isoform 2).
FT /FTId=VSP_038271.
FT MUTAGEN 156 156 F->D: Loss of dimerization.
FT MUTAGEN 218 218 S->A: Loss of phosphorylation.
FT MUTAGEN 260 260 W->A: Loss of dimerization.
FT MUTAGEN 270 270 H->D: Loss of dimerization.
FT CONFLICT 69 69 P -> S (in Ref. 6; AAH14455).
FT CONFLICT 72 72 A -> AALNTRKTLLW (in Ref. 6; AAH33559).
FT CONFLICT 360 361 HV -> TCKVMCTYKKSEKTLSWIKKKTFQMHDPAVCFQSL
FT GGCHPHFNSTCA (in Ref. 2; BAA05893).
FT HELIX 23 34
FT STRAND 38 45
FT HELIX 50 58
FT STRAND 85 88
FT STRAND 95 102
FT HELIX 118 133
FT STRAND 148 153
FT STRAND 155 159
FT HELIX 162 171
FT TURN 172 174
FT STRAND 177 181
FT HELIX 184 186
FT HELIX 189 205
FT HELIX 225 232
FT STRAND 236 238
FT STRAND 243 245
FT STRAND 254 258
FT STRAND 261 264
FT TURN 268 270
FT HELIX 273 282
FT HELIX 284 293
FT HELIX 295 305
SQ SEQUENCE 361 AA; 41487 MW; 12CCBBE30806F92F CRC64;
MSKQQPTQFI NPETPGYVGF ANLPNQVHRK SVKKGFEFTL MVVGESGLGK STLINSLFLT
DLYPERVIPG AAEKIERTVQ IEASTVEIEE RGVKLRLTVV DTPGYGDAIN CRDCFKTIIS
YIDEQFERYL HDESGLNRRH IIDNRVHCCF YFISPFGHGL KPLDVAFMKA IHNKVNIVPV
IAKADTLTLK ERERLKKRIL DEIEEHNIKI YHLPDAESDE DEDFKEQTRL LKASIPFSVV
GSNQLIEAKG KKVRGRLYPW GVVEVENPEH NDFLKLRTML ITHMQDLQEV TQDLHYENFR
SERLKRGGRK VENEDMNKDQ ILLEKEAELR RMQEMIARMQ AQMQMQMQGG DGDGGALGHH
V
//
MIM
601506
*RECORD*
*FIELD* NO
601506
*FIELD* TI
*601506 SEPTIN 2; SEPT2
;;NEURAL PRECURSOR CELL EXPRESSED, DEVELOPMENTALLY DOWNREGULATED 5;
read moreNEDD5;;
DIFF6
*FIELD* TX
CLONING
Mori et al. (1996) isolated a human cDNA that encodes a protein
homologous to murine H5 and Diff6 and to yeast CDC10 (603151). The NEDD5
cDNA encodes a predicted protein of 406 amino acids. The deduced peptide
sequence contains conserved domains rich in basic residues, a motif of
the GTPase superfamily. Different poly(A) sites account for generation
of 2 transcripts. The major 3.5-kb transcript was expressed ubiquitously
in all human tissues examined, and a 2.0-kb alternative transcript
lacking any long AU-rich element in the 3-prime noncoding region was
expressed abundantly only in testis, heart, and skeletal muscle.
GENE FUNCTION
Low and Macara (2006) noted that specific combinations of septins can
hetero-oligomerize and form filaments in vitro and in vivo. Using
fluorescence resonance energy transfer, size exclusion chromatography,
and multi-angle light scattering analyses, they characterized the
complex formed by SEPT2, SEPT6 (300683), and SEPT7 (603151). SEPT6 and
SEPT7 interacted through a parallel coiled-coil domain, and SEPT2
interacted with SEPT6 through its C-terminal coiled-coil domain.
Kremer et al. (2007) showed that knockdown of SEPT2, SEPT6, and SEPT7 in
HeLa cells caused actin stress fibers to disintegrate and cells to lose
polarity. They found that these septins acted through SOCS7 (608788) to
restrict nuclear accumulation of NCK (NCK1; 600508). In the absence of
septin filaments, SOCS7 recruited NCK into the nucleus. Moreover,
depletion of NCK from the cytoplasm triggered dissolution of actin
stress fibers and loss of cell polarity. Kremer et al. (2007) also
showed that the association between septins, SOCS7, and NCK played a
role in the DNA damage checkpoint response. NCK entered the nucleus
following DNA damage and was required for ultraviolet (UV)-induced cell
cycle arrest. Furthermore, nuclear NCK was essential for activation of
p53 (TP53; 191170) in response to UV-induced DNA damage. Kremer et al.
(2007) concluded that septins, SOCS7, and NCK are part of a signaling
pathway that couples regulation of the DNA damage response to the
cytoskeleton.
Hu et al. (2010) demonstrated that ciliary membrane proteins are highly
mobile, but their diffusion is impeded at the base of the cilium by a
diffusion barrier. Sept2, a member of the septin family of guanosine
triphosphatases that form a diffusion barrier in budding yeast,
localized at the base of the ciliary membrane. Sept2 depletion resulted
in loss of ciliary membrane protein localization and Sonic hedgehog
(SHH; 600725) signal transduction, and inhibited ciliogenesis. Thus, Hu
et al. (2010) concluded that SEPT2 is a part of a diffusion barrier at
the base of the ciliary membrane and is essential for retaining
receptor-signaling pathways in the primary cilium. These experiments
used IMCD3 (mouse kidney inner medullary collecting duct) cells and
murine embryonic fibroblasts.
BIOCHEMICAL FEATURES
- Crystal Structure
Sirajuddin et al. (2007) presented the crystal structures of the human
SEPT2 G domain and the heterotrimeric human SEPT2-SEPT6-SEPT7 complex.
This structure revealed a universal bipolar polymer building block,
composed of an extended G domain, which forms oligomers and filaments by
conserved interactions between adjacent nucleotide-binding sites and/or
the amino- and carboxy-terminal extensions. Unexpectedly, x-ray
crystallography and electron microscopy showed that the predicted coiled
coils are not involved in or required for complex and/or filament
formation. The asymmetrical heterotrimers associate head-to-head to form
a hexameric unit that is nonpolarized along the filament axis but is
rotationally asymmetrical. Sirajuddin et al. (2007) concluded that the
architecture of septin filaments differs fundamentally from that of
other cytoskeletal structures.
MAPPING
By fluorescence in situ hybridization, Mori et al. (1996) mapped the
NEDD5 gene to 2q37.
*FIELD* RF
1. Hu, Q.; Milenkovic, L.; Jin, H.; Scott, M. P.; Nachury, M. V.;
Spiliotis, E. T.; Nelson, W. J.: A septin diffusion barrier at the
base of the primary cilium maintains ciliary membrane protein distribution. Science 329:
436-439, 2010.
2. Kremer, B. E.; Adang, L. A.; Macara, I. G.: Septins regulate actin
organization and cell-cycle arrest through nuclear accumulation of
NCK mediated by SOCS7. Cell 130: 837-850, 2007.
3. Low, C.; Macara, I. G.: Structural analysis of septin 2, 6, and
7 complexes. J. Biol. Chem. 281: 30697-30706, 2006.
4. Mori, T.; Miura, K.; Fujiwara, T.; Shin, S.; Inazawa, J.; Nakamura,
Y.: Isolation and mapping of a human gene (DIFF6) homologous to yeast
CDC3, CDC10, CDC11, and CDC12, and mouse Diff6. Cytogenet. Cell Genet. 73:
224-227, 1996.
5. Sirajuddin, M.; Farkasovsky, M.; Hauer, F.; Kuhlmann, D.; Macara,
I. G.; Weyand, M.; Stark, H.; Wittinghofer, A.: Structural insight
into filament formation by mammalian septins. Nature 449: 311-315,
2007.
*FIELD* CN
Ada Hamosh - updated: 9/1/2010
Patricia A. Hartz - updated: 2/7/2008
Ada Hamosh - updated: 1/10/2008
Paul J. Converse - updated: 10/30/2007
*FIELD* CD
Victor A. McKusick: 11/15/1996
*FIELD* ED
alopez: 09/01/2010
terry: 9/1/2010
mgross: 2/8/2008
terry: 2/7/2008
alopez: 1/28/2008
terry: 1/10/2008
mgross: 10/30/2007
carol: 10/1/2007
alopez: 11/8/1999
alopez: 10/15/1998
carol: 7/22/1998
mark: 11/17/1996
mark: 11/15/1996
*RECORD*
*FIELD* NO
601506
*FIELD* TI
*601506 SEPTIN 2; SEPT2
;;NEURAL PRECURSOR CELL EXPRESSED, DEVELOPMENTALLY DOWNREGULATED 5;
read moreNEDD5;;
DIFF6
*FIELD* TX
CLONING
Mori et al. (1996) isolated a human cDNA that encodes a protein
homologous to murine H5 and Diff6 and to yeast CDC10 (603151). The NEDD5
cDNA encodes a predicted protein of 406 amino acids. The deduced peptide
sequence contains conserved domains rich in basic residues, a motif of
the GTPase superfamily. Different poly(A) sites account for generation
of 2 transcripts. The major 3.5-kb transcript was expressed ubiquitously
in all human tissues examined, and a 2.0-kb alternative transcript
lacking any long AU-rich element in the 3-prime noncoding region was
expressed abundantly only in testis, heart, and skeletal muscle.
GENE FUNCTION
Low and Macara (2006) noted that specific combinations of septins can
hetero-oligomerize and form filaments in vitro and in vivo. Using
fluorescence resonance energy transfer, size exclusion chromatography,
and multi-angle light scattering analyses, they characterized the
complex formed by SEPT2, SEPT6 (300683), and SEPT7 (603151). SEPT6 and
SEPT7 interacted through a parallel coiled-coil domain, and SEPT2
interacted with SEPT6 through its C-terminal coiled-coil domain.
Kremer et al. (2007) showed that knockdown of SEPT2, SEPT6, and SEPT7 in
HeLa cells caused actin stress fibers to disintegrate and cells to lose
polarity. They found that these septins acted through SOCS7 (608788) to
restrict nuclear accumulation of NCK (NCK1; 600508). In the absence of
septin filaments, SOCS7 recruited NCK into the nucleus. Moreover,
depletion of NCK from the cytoplasm triggered dissolution of actin
stress fibers and loss of cell polarity. Kremer et al. (2007) also
showed that the association between septins, SOCS7, and NCK played a
role in the DNA damage checkpoint response. NCK entered the nucleus
following DNA damage and was required for ultraviolet (UV)-induced cell
cycle arrest. Furthermore, nuclear NCK was essential for activation of
p53 (TP53; 191170) in response to UV-induced DNA damage. Kremer et al.
(2007) concluded that septins, SOCS7, and NCK are part of a signaling
pathway that couples regulation of the DNA damage response to the
cytoskeleton.
Hu et al. (2010) demonstrated that ciliary membrane proteins are highly
mobile, but their diffusion is impeded at the base of the cilium by a
diffusion barrier. Sept2, a member of the septin family of guanosine
triphosphatases that form a diffusion barrier in budding yeast,
localized at the base of the ciliary membrane. Sept2 depletion resulted
in loss of ciliary membrane protein localization and Sonic hedgehog
(SHH; 600725) signal transduction, and inhibited ciliogenesis. Thus, Hu
et al. (2010) concluded that SEPT2 is a part of a diffusion barrier at
the base of the ciliary membrane and is essential for retaining
receptor-signaling pathways in the primary cilium. These experiments
used IMCD3 (mouse kidney inner medullary collecting duct) cells and
murine embryonic fibroblasts.
BIOCHEMICAL FEATURES
- Crystal Structure
Sirajuddin et al. (2007) presented the crystal structures of the human
SEPT2 G domain and the heterotrimeric human SEPT2-SEPT6-SEPT7 complex.
This structure revealed a universal bipolar polymer building block,
composed of an extended G domain, which forms oligomers and filaments by
conserved interactions between adjacent nucleotide-binding sites and/or
the amino- and carboxy-terminal extensions. Unexpectedly, x-ray
crystallography and electron microscopy showed that the predicted coiled
coils are not involved in or required for complex and/or filament
formation. The asymmetrical heterotrimers associate head-to-head to form
a hexameric unit that is nonpolarized along the filament axis but is
rotationally asymmetrical. Sirajuddin et al. (2007) concluded that the
architecture of septin filaments differs fundamentally from that of
other cytoskeletal structures.
MAPPING
By fluorescence in situ hybridization, Mori et al. (1996) mapped the
NEDD5 gene to 2q37.
*FIELD* RF
1. Hu, Q.; Milenkovic, L.; Jin, H.; Scott, M. P.; Nachury, M. V.;
Spiliotis, E. T.; Nelson, W. J.: A septin diffusion barrier at the
base of the primary cilium maintains ciliary membrane protein distribution. Science 329:
436-439, 2010.
2. Kremer, B. E.; Adang, L. A.; Macara, I. G.: Septins regulate actin
organization and cell-cycle arrest through nuclear accumulation of
NCK mediated by SOCS7. Cell 130: 837-850, 2007.
3. Low, C.; Macara, I. G.: Structural analysis of septin 2, 6, and
7 complexes. J. Biol. Chem. 281: 30697-30706, 2006.
4. Mori, T.; Miura, K.; Fujiwara, T.; Shin, S.; Inazawa, J.; Nakamura,
Y.: Isolation and mapping of a human gene (DIFF6) homologous to yeast
CDC3, CDC10, CDC11, and CDC12, and mouse Diff6. Cytogenet. Cell Genet. 73:
224-227, 1996.
5. Sirajuddin, M.; Farkasovsky, M.; Hauer, F.; Kuhlmann, D.; Macara,
I. G.; Weyand, M.; Stark, H.; Wittinghofer, A.: Structural insight
into filament formation by mammalian septins. Nature 449: 311-315,
2007.
*FIELD* CN
Ada Hamosh - updated: 9/1/2010
Patricia A. Hartz - updated: 2/7/2008
Ada Hamosh - updated: 1/10/2008
Paul J. Converse - updated: 10/30/2007
*FIELD* CD
Victor A. McKusick: 11/15/1996
*FIELD* ED
alopez: 09/01/2010
terry: 9/1/2010
mgross: 2/8/2008
terry: 2/7/2008
alopez: 1/28/2008
terry: 1/10/2008
mgross: 10/30/2007
carol: 10/1/2007
alopez: 11/8/1999
alopez: 10/15/1998
carol: 7/22/1998
mark: 11/17/1996
mark: 11/15/1996