Full text data of NDE1
NDE1
(NUDE)
[Confidence: low (only semi-automatic identification from reviews)]
Nuclear distribution protein nudE homolog 1; NudE
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Nuclear distribution protein nudE homolog 1; NudE
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9NXR1
ID NDE1_HUMAN Reviewed; 346 AA.
AC Q9NXR1; Q49AQ2;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 13-JUN-2006, sequence version 2.
DT 22-JAN-2014, entry version 101.
DE RecName: Full=Nuclear distribution protein nudE homolog 1;
DE Short=NudE;
GN Name=NDE1; Synonyms=NUDE;
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 2).
RC TISSUE=Colon;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta, 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 [4]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=12556484; DOI=10.1128/MCB.23.4.1239-1250.2003;
RA Yan X., Li F., Liang Y., Shen Y., Zhao X., Huang Q., Zhu X.;
RT "Human Nudel and NudE as regulators of cytoplasmic dynein in poleward
RT protein transport along the mitotic spindle.";
RL Mol. Cell. Biol. 23:1239-1250(2003).
RN [5]
RP INTERACTION WITH DYNACTIN; TUBULIN GAMMA; PAFAH1B1; PCM1 AND PCNT.
RX PubMed=16291865; DOI=10.1091/mbc.E05-04-0360;
RA Guo J., Yang Z., Song W., Chen Q., Wang F., Zhang Q., Zhu X.;
RT "Nudel contributes to microtubule anchoring at the mother centriole
RT and is involved in both dynein-dependent and -independent centrosomal
RT protein assembly.";
RL Mol. Biol. Cell 17:680-689(2006).
RN [6]
RP INTERACTION WITH ZNF365, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND
RP MUTAGENESIS OF THR-191; THR-215; THR-228; THR-243; THR-246 AND
RP SER-282.
RX PubMed=16682949; DOI=10.1038/sj.onc.1209637;
RA Hirohashi Y., Wang Q., Liu Q., Li B., Du X., Zhang H., Furuuchi K.,
RA Masuda K., Sato N., Greene M.I.;
RT "Centrosomal proteins Nde1 and Su48 form a complex regulated by
RT phosphorylation.";
RL Oncogene 25:6048-6055(2006).
RN [7]
RP FUNCTION, INTERACTION WITH CENPF, AND SUBCELLULAR LOCATION.
RX PubMed=17600710; DOI=10.1016/j.cub.2007.05.077;
RA Vergnolle M.A.S., Taylor S.S.;
RT "Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor
RT complexes.";
RL Curr. Biol. 17:1173-1179(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211; THR-215; THR-228;
RP SER-231; SER-239; THR-243; THR-246 AND SER-282, AND MASS 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 [10]
RP PALMITOYLATION AT CYS-274 BY ZDHHC2; ZDHHC3 AND ZDHHC7.
RX PubMed=19927128; DOI=10.1038/emboj.2009.325;
RA Shmueli A., Segal M., Sapir T., Tsutsumi R., Noritake J., Bar A.,
RA Sapoznik S., Fukata Y., Orr I., Fukata M., Reiner O.;
RT "Ndel1 palmitoylation: a new mean to regulate cytoplasmic dynein
RT activity.";
RL EMBO J. 29:107-119(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-243; THR-246 AND
RP SER-282, AND MASS 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 [12]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN
RP LIS4.
RX PubMed=21529752; DOI=10.1016/j.ajhg.2011.03.019;
RA Bakircioglu M., Carvalho O.P., Khurshid M., Cox J.J., Tuysuz B.,
RA Barak T., Yilmaz S., Caglayan O., Dincer A., Nicholas A.K.,
RA Quarrell O., Springell K., Karbani G., Malik S., Gannon C.,
RA Sheridan E., Crosier M., Lisgo S.N., Lindsay S., Bilguvar K.,
RA Gergely F., Gunel M., Woods C.G.;
RT "The essential role of centrosomal NDE1 in human cerebral cortex
RT neurogenesis.";
RL Am. J. Hum. Genet. 88:523-535(2011).
RN [13]
RP INVOLVEMENT IN LIS4.
RX PubMed=21529751; DOI=10.1016/j.ajhg.2011.04.003;
RA Alkuraya F.S., Cai X., Emery C., Mochida G.H., Al-Dosari M.S.,
RA Felie J.M., Hill R.S., Barry B.J., Partlow J.N., Gascon G.G.,
RA Kentab A., Jan M., Shaheen R., Feng Y., Walsh C.A.;
RT "Human mutations in NDE1 cause extreme microcephaly with
RT lissencephaly.";
RL Am. J. Hum. Genet. 88:536-547(2011).
RN [14]
RP ERRATUM.
RA Alkuraya F.S., Cai X., Emery C., Mochida G.H., Al-Dosari M.S.,
RA Felie J.M., Hill R.S., Barry B.J., Partlow J.N., Gascon G.G.,
RA Kentab A., Jan M., Shaheen R., Feng Y., Walsh C.A.;
RL Am. J. Hum. Genet. 88:677-677(2011).
CC -!- FUNCTION: Required for centrosome duplication and formation and
CC function of the mitotic spindle. Essential for the development of
CC the cerebral cortex. May regulate the production of neurons by
CC controlling the orientation of the mitotic spindle during division
CC of cortical neuronal progenitors of the proliferative ventricular
CC zone of the brain. Orientation of the division plane perpendicular
CC to the layers of the cortex gives rise to two proliferative
CC neuronal progenitors whereas parallel orientation of the division
CC plane yields one proliferative neuronal progenitor and a post-
CC mitotic neuron. A premature shift towards a neuronal fate within
CC the progenitor population may result in an overall reduction in
CC the final number of neurons and an increase in the number of
CC neurons in the deeper layers of the cortex.
CC -!- SUBUNIT: Self-associates. Interacts with CNTRL, LIS1, dynein,
CC SLMAP and TCP1 (By similarity). Interacts with CENPF, dynactin,
CC tubulin gamma, PAFAH1B1, PCM1 and PCNT. Interacts with ZNF365.
CC -!- INTERACTION:
CC Q70YC5:ZNF365; NbExp=4; IntAct=EBI-941227, EBI-941182;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome.
CC Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton,
CC spindle. Cleavage furrow. Note=Localizes to the interphase and S
CC phase centrosome. During mitosis, partially associated with the
CC mitotic spindle. Concentrates at the plus ends of microtubules
CC coincident with kinetochores in metaphase and anaphase in a CENPF-
CC dependent manner. Also localizes to the cleavage furrow during
CC cytokinesis. manner. Also localizes to the cleavage furrow during
CC cytokinesis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NXR1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NXR1-2; Sequence=VSP_019305;
CC -!- TISSUE SPECIFICITY: Expressed in the neuroepithelium throughout
CC the developing brain, including the cerebral cortex and
CC cerebellum.
CC -!- PTM: Phosphorylated in mitosis. Phosphorylated in vitro by CDC2.
CC Phosphorylation at Thr-246 is essential for the G2/M transition
CC (By similarity).
CC -!- DISEASE: Lissencephaly 4 (LIS4) [MIM:614019]: A neurodevelopmental
CC disorder characterized by lissencephaly, severe brain atrophy,
CC extreme microcephaly, and profound mental retardation. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the nudE family.
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DR EMBL; AK000108; BAA90949.1; -; mRNA.
DR EMBL; AC026401; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF001548; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001421; AAH01421.1; -; mRNA.
DR EMBL; BC033900; AAH33900.1; -; mRNA.
DR RefSeq; NP_001137451.1; NM_001143979.1.
DR RefSeq; NP_060138.1; NM_017668.2.
DR RefSeq; XP_005255454.1; XM_005255397.1.
DR RefSeq; XP_005255455.1; XM_005255398.1.
DR UniGene; Hs.655378; -.
DR ProteinModelPortal; Q9NXR1; -.
DR SMR; Q9NXR1; 8-167.
DR IntAct; Q9NXR1; 7.
DR STRING; 9606.ENSP00000345892; -.
DR PhosphoSite; Q9NXR1; -.
DR DMDM; 108860813; -.
DR PaxDb; Q9NXR1; -.
DR PRIDE; Q9NXR1; -.
DR Ensembl; ENST00000342673; ENSP00000345892; ENSG00000072864.
DR Ensembl; ENST00000396353; ENSP00000379641; ENSG00000072864.
DR Ensembl; ENST00000396354; ENSP00000379642; ENSG00000072864.
DR Ensembl; ENST00000396355; ENSP00000379643; ENSG00000072864.
DR GeneID; 54820; -.
DR KEGG; hsa:54820; -.
DR UCSC; uc002ddt.1; human.
DR CTD; 54820; -.
DR GeneCards; GC16P015743; -.
DR HGNC; HGNC:17619; NDE1.
DR HPA; HPA018536; -.
DR HPA; HPA024075; -.
DR MIM; 609449; gene.
DR MIM; 614019; phenotype.
DR neXtProt; NX_Q9NXR1; -.
DR Orphanet; 2177; Hydranencephaly.
DR Orphanet; 1083; Microlissencephaly.
DR PharmGKB; PA128394673; -.
DR eggNOG; NOG240815; -.
DR HOGENOM; HOG000280681; -.
DR HOVERGEN; HBG082010; -.
DR KO; K16738; -.
DR OMA; EVQHSEG; -.
DR OrthoDB; EOG74R1R5; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR ChiTaRS; NDE1; human.
DR GeneWiki; NDE1; -.
DR GenomeRNAi; 54820; -.
DR NextBio; 57569; -.
DR PRO; PR:Q9NXR1; -.
DR ArrayExpress; Q9NXR1; -.
DR Bgee; Q9NXR1; -.
DR CleanEx; HS_NDE1; -.
DR Genevestigator; Q9NXR1; -.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0000777; C:condensed chromosome kinetochore; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0031616; C:spindle pole centrosome; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0051298; P:centrosome duplication; ISS:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IMP:UniProtKB.
DR GO; GO:0051303; P:establishment of chromosome localization; IMP:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0007020; P:microtubule nucleation; IEA:Ensembl.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0047496; P:vesicle transport along microtubule; IEA:Ensembl.
DR InterPro; IPR006964; NUDE_C.
DR Pfam; PF04880; NUDE_C; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Centromere;
KW Chromosome; Coiled coil; Complete proteome; Cytoplasm; Cytoskeleton;
KW Developmental protein; Differentiation; Kinetochore; Lipoprotein;
KW Lissencephaly; Microtubule; Mitosis; Neurogenesis; Palmitate;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 346 Nuclear distribution protein nudE homolog
FT 1.
FT /FTId=PRO_0000240202.
FT REGION 1 93 Self-association (By similarity).
FT REGION 88 156 Interaction with PAFAH1B1 (By
FT similarity).
FT REGION 167 290 Interaction with CENPF (By similarity).
FT COILED 18 188 Potential.
FT MOD_RES 211 211 Phosphoserine.
FT MOD_RES 215 215 Phosphothreonine.
FT MOD_RES 228 228 Phosphothreonine.
FT MOD_RES 231 231 Phosphoserine.
FT MOD_RES 239 239 Phosphoserine.
FT MOD_RES 243 243 Phosphothreonine.
FT MOD_RES 246 246 Phosphothreonine.
FT MOD_RES 282 282 Phosphoserine.
FT LIPID 274 274 S-palmitoyl cysteine; by ZDHHC2, ZDHHC3
FT and ZDHHC7.
FT VAR_SEQ 318 346 GKRLEFGKPPSHMSSSPLPSAQGVVKMLL -> DTSCRWLS
FT KSTTRSSSSC (in isoform 2).
FT /FTId=VSP_019305.
FT MUTAGEN 191 191 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-215; E-228; E-243; E-
FT 246 and E-282.
FT MUTAGEN 191 191 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-215; V-228; V-243; V-
FT 246 and A-282.
FT MUTAGEN 215 215 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-228; E-243; E-
FT 246 and E-282.
FT MUTAGEN 215 215 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-228; V-243; V-
FT 246 and A-282.
FT MUTAGEN 228 228 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-215; E-243; E-
FT 246 and E-282.
FT MUTAGEN 228 228 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-215; V-243; V-
FT 246 and A-282.
FT MUTAGEN 243 243 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-215; E-228; E-
FT 246 and E-282.
FT MUTAGEN 243 243 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-215; V-228; V-
FT 246 and A-282.
FT MUTAGEN 246 246 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-215; E-228; E-
FT 243 and E-282.
FT MUTAGEN 246 246 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-215; V-228; V-
FT 243 and A-282.
FT MUTAGEN 282 282 S->A: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-215; V-228; V-
FT 243 and V-246.
FT MUTAGEN 282 282 S->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-215; E-228; E-
FT 243 and E-246.
FT CONFLICT 191 191 T -> I (in Ref. 3; AAH33900).
SQ SEQUENCE 346 AA; 38808 MW; A681DEF652B5ACE5 CRC64;
MEDSGKTFSS EEEEANYWKD LAMTYKQRAE NTQEELREFQ EGSREYEAEL ETQLQQIETR
NRDLLSENNR LRMELETIKE KFEVQHSEGY RQISALEDDL AQTKAIKDQL QKYIRELEQA
NDDLERAKRA TIMSLEDFEQ RLNQAIERNA FLESELDEKE NLLESVQRLK DEARDLRQEL
AVQQKQEKPR TPMPSSVEAE RTDTAVQATG SVPSTPIAHR GPSSSLNTPG SFRRGLDDST
GGTPLTPAAR ISALNIVGDL LRKVGALESK LASCRNLVYD QSPNRTGGPA SGRSSKNRDG
GERRPSSTSV PLGDKGLGKR LEFGKPPSHM SSSPLPSAQG VVKMLL
//
ID NDE1_HUMAN Reviewed; 346 AA.
AC Q9NXR1; Q49AQ2;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 13-JUN-2006, sequence version 2.
DT 22-JAN-2014, entry version 101.
DE RecName: Full=Nuclear distribution protein nudE homolog 1;
DE Short=NudE;
GN Name=NDE1; Synonyms=NUDE;
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 2).
RC TISSUE=Colon;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta, 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 [4]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=12556484; DOI=10.1128/MCB.23.4.1239-1250.2003;
RA Yan X., Li F., Liang Y., Shen Y., Zhao X., Huang Q., Zhu X.;
RT "Human Nudel and NudE as regulators of cytoplasmic dynein in poleward
RT protein transport along the mitotic spindle.";
RL Mol. Cell. Biol. 23:1239-1250(2003).
RN [5]
RP INTERACTION WITH DYNACTIN; TUBULIN GAMMA; PAFAH1B1; PCM1 AND PCNT.
RX PubMed=16291865; DOI=10.1091/mbc.E05-04-0360;
RA Guo J., Yang Z., Song W., Chen Q., Wang F., Zhang Q., Zhu X.;
RT "Nudel contributes to microtubule anchoring at the mother centriole
RT and is involved in both dynein-dependent and -independent centrosomal
RT protein assembly.";
RL Mol. Biol. Cell 17:680-689(2006).
RN [6]
RP INTERACTION WITH ZNF365, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND
RP MUTAGENESIS OF THR-191; THR-215; THR-228; THR-243; THR-246 AND
RP SER-282.
RX PubMed=16682949; DOI=10.1038/sj.onc.1209637;
RA Hirohashi Y., Wang Q., Liu Q., Li B., Du X., Zhang H., Furuuchi K.,
RA Masuda K., Sato N., Greene M.I.;
RT "Centrosomal proteins Nde1 and Su48 form a complex regulated by
RT phosphorylation.";
RL Oncogene 25:6048-6055(2006).
RN [7]
RP FUNCTION, INTERACTION WITH CENPF, AND SUBCELLULAR LOCATION.
RX PubMed=17600710; DOI=10.1016/j.cub.2007.05.077;
RA Vergnolle M.A.S., Taylor S.S.;
RT "Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor
RT complexes.";
RL Curr. Biol. 17:1173-1179(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211; THR-215; THR-228;
RP SER-231; SER-239; THR-243; THR-246 AND SER-282, AND MASS 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 [10]
RP PALMITOYLATION AT CYS-274 BY ZDHHC2; ZDHHC3 AND ZDHHC7.
RX PubMed=19927128; DOI=10.1038/emboj.2009.325;
RA Shmueli A., Segal M., Sapir T., Tsutsumi R., Noritake J., Bar A.,
RA Sapoznik S., Fukata Y., Orr I., Fukata M., Reiner O.;
RT "Ndel1 palmitoylation: a new mean to regulate cytoplasmic dynein
RT activity.";
RL EMBO J. 29:107-119(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-243; THR-246 AND
RP SER-282, AND MASS 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 [12]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN
RP LIS4.
RX PubMed=21529752; DOI=10.1016/j.ajhg.2011.03.019;
RA Bakircioglu M., Carvalho O.P., Khurshid M., Cox J.J., Tuysuz B.,
RA Barak T., Yilmaz S., Caglayan O., Dincer A., Nicholas A.K.,
RA Quarrell O., Springell K., Karbani G., Malik S., Gannon C.,
RA Sheridan E., Crosier M., Lisgo S.N., Lindsay S., Bilguvar K.,
RA Gergely F., Gunel M., Woods C.G.;
RT "The essential role of centrosomal NDE1 in human cerebral cortex
RT neurogenesis.";
RL Am. J. Hum. Genet. 88:523-535(2011).
RN [13]
RP INVOLVEMENT IN LIS4.
RX PubMed=21529751; DOI=10.1016/j.ajhg.2011.04.003;
RA Alkuraya F.S., Cai X., Emery C., Mochida G.H., Al-Dosari M.S.,
RA Felie J.M., Hill R.S., Barry B.J., Partlow J.N., Gascon G.G.,
RA Kentab A., Jan M., Shaheen R., Feng Y., Walsh C.A.;
RT "Human mutations in NDE1 cause extreme microcephaly with
RT lissencephaly.";
RL Am. J. Hum. Genet. 88:536-547(2011).
RN [14]
RP ERRATUM.
RA Alkuraya F.S., Cai X., Emery C., Mochida G.H., Al-Dosari M.S.,
RA Felie J.M., Hill R.S., Barry B.J., Partlow J.N., Gascon G.G.,
RA Kentab A., Jan M., Shaheen R., Feng Y., Walsh C.A.;
RL Am. J. Hum. Genet. 88:677-677(2011).
CC -!- FUNCTION: Required for centrosome duplication and formation and
CC function of the mitotic spindle. Essential for the development of
CC the cerebral cortex. May regulate the production of neurons by
CC controlling the orientation of the mitotic spindle during division
CC of cortical neuronal progenitors of the proliferative ventricular
CC zone of the brain. Orientation of the division plane perpendicular
CC to the layers of the cortex gives rise to two proliferative
CC neuronal progenitors whereas parallel orientation of the division
CC plane yields one proliferative neuronal progenitor and a post-
CC mitotic neuron. A premature shift towards a neuronal fate within
CC the progenitor population may result in an overall reduction in
CC the final number of neurons and an increase in the number of
CC neurons in the deeper layers of the cortex.
CC -!- SUBUNIT: Self-associates. Interacts with CNTRL, LIS1, dynein,
CC SLMAP and TCP1 (By similarity). Interacts with CENPF, dynactin,
CC tubulin gamma, PAFAH1B1, PCM1 and PCNT. Interacts with ZNF365.
CC -!- INTERACTION:
CC Q70YC5:ZNF365; NbExp=4; IntAct=EBI-941227, EBI-941182;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome.
CC Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton,
CC spindle. Cleavage furrow. Note=Localizes to the interphase and S
CC phase centrosome. During mitosis, partially associated with the
CC mitotic spindle. Concentrates at the plus ends of microtubules
CC coincident with kinetochores in metaphase and anaphase in a CENPF-
CC dependent manner. Also localizes to the cleavage furrow during
CC cytokinesis. manner. Also localizes to the cleavage furrow during
CC cytokinesis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NXR1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NXR1-2; Sequence=VSP_019305;
CC -!- TISSUE SPECIFICITY: Expressed in the neuroepithelium throughout
CC the developing brain, including the cerebral cortex and
CC cerebellum.
CC -!- PTM: Phosphorylated in mitosis. Phosphorylated in vitro by CDC2.
CC Phosphorylation at Thr-246 is essential for the G2/M transition
CC (By similarity).
CC -!- DISEASE: Lissencephaly 4 (LIS4) [MIM:614019]: A neurodevelopmental
CC disorder characterized by lissencephaly, severe brain atrophy,
CC extreme microcephaly, and profound mental retardation. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the nudE family.
CC -----------------------------------------------------------------------
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DR EMBL; AK000108; BAA90949.1; -; mRNA.
DR EMBL; AC026401; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF001548; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001421; AAH01421.1; -; mRNA.
DR EMBL; BC033900; AAH33900.1; -; mRNA.
DR RefSeq; NP_001137451.1; NM_001143979.1.
DR RefSeq; NP_060138.1; NM_017668.2.
DR RefSeq; XP_005255454.1; XM_005255397.1.
DR RefSeq; XP_005255455.1; XM_005255398.1.
DR UniGene; Hs.655378; -.
DR ProteinModelPortal; Q9NXR1; -.
DR SMR; Q9NXR1; 8-167.
DR IntAct; Q9NXR1; 7.
DR STRING; 9606.ENSP00000345892; -.
DR PhosphoSite; Q9NXR1; -.
DR DMDM; 108860813; -.
DR PaxDb; Q9NXR1; -.
DR PRIDE; Q9NXR1; -.
DR Ensembl; ENST00000342673; ENSP00000345892; ENSG00000072864.
DR Ensembl; ENST00000396353; ENSP00000379641; ENSG00000072864.
DR Ensembl; ENST00000396354; ENSP00000379642; ENSG00000072864.
DR Ensembl; ENST00000396355; ENSP00000379643; ENSG00000072864.
DR GeneID; 54820; -.
DR KEGG; hsa:54820; -.
DR UCSC; uc002ddt.1; human.
DR CTD; 54820; -.
DR GeneCards; GC16P015743; -.
DR HGNC; HGNC:17619; NDE1.
DR HPA; HPA018536; -.
DR HPA; HPA024075; -.
DR MIM; 609449; gene.
DR MIM; 614019; phenotype.
DR neXtProt; NX_Q9NXR1; -.
DR Orphanet; 2177; Hydranencephaly.
DR Orphanet; 1083; Microlissencephaly.
DR PharmGKB; PA128394673; -.
DR eggNOG; NOG240815; -.
DR HOGENOM; HOG000280681; -.
DR HOVERGEN; HBG082010; -.
DR KO; K16738; -.
DR OMA; EVQHSEG; -.
DR OrthoDB; EOG74R1R5; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR ChiTaRS; NDE1; human.
DR GeneWiki; NDE1; -.
DR GenomeRNAi; 54820; -.
DR NextBio; 57569; -.
DR PRO; PR:Q9NXR1; -.
DR ArrayExpress; Q9NXR1; -.
DR Bgee; Q9NXR1; -.
DR CleanEx; HS_NDE1; -.
DR Genevestigator; Q9NXR1; -.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0000777; C:condensed chromosome kinetochore; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0031616; C:spindle pole centrosome; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0051298; P:centrosome duplication; ISS:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IMP:UniProtKB.
DR GO; GO:0051303; P:establishment of chromosome localization; IMP:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0007020; P:microtubule nucleation; IEA:Ensembl.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0047496; P:vesicle transport along microtubule; IEA:Ensembl.
DR InterPro; IPR006964; NUDE_C.
DR Pfam; PF04880; NUDE_C; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Centromere;
KW Chromosome; Coiled coil; Complete proteome; Cytoplasm; Cytoskeleton;
KW Developmental protein; Differentiation; Kinetochore; Lipoprotein;
KW Lissencephaly; Microtubule; Mitosis; Neurogenesis; Palmitate;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 346 Nuclear distribution protein nudE homolog
FT 1.
FT /FTId=PRO_0000240202.
FT REGION 1 93 Self-association (By similarity).
FT REGION 88 156 Interaction with PAFAH1B1 (By
FT similarity).
FT REGION 167 290 Interaction with CENPF (By similarity).
FT COILED 18 188 Potential.
FT MOD_RES 211 211 Phosphoserine.
FT MOD_RES 215 215 Phosphothreonine.
FT MOD_RES 228 228 Phosphothreonine.
FT MOD_RES 231 231 Phosphoserine.
FT MOD_RES 239 239 Phosphoserine.
FT MOD_RES 243 243 Phosphothreonine.
FT MOD_RES 246 246 Phosphothreonine.
FT MOD_RES 282 282 Phosphoserine.
FT LIPID 274 274 S-palmitoyl cysteine; by ZDHHC2, ZDHHC3
FT and ZDHHC7.
FT VAR_SEQ 318 346 GKRLEFGKPPSHMSSSPLPSAQGVVKMLL -> DTSCRWLS
FT KSTTRSSSSC (in isoform 2).
FT /FTId=VSP_019305.
FT MUTAGEN 191 191 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-215; E-228; E-243; E-
FT 246 and E-282.
FT MUTAGEN 191 191 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-215; V-228; V-243; V-
FT 246 and A-282.
FT MUTAGEN 215 215 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-228; E-243; E-
FT 246 and E-282.
FT MUTAGEN 215 215 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-228; V-243; V-
FT 246 and A-282.
FT MUTAGEN 228 228 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-215; E-243; E-
FT 246 and E-282.
FT MUTAGEN 228 228 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-215; V-243; V-
FT 246 and A-282.
FT MUTAGEN 243 243 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-215; E-228; E-
FT 246 and E-282.
FT MUTAGEN 243 243 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-215; V-228; V-
FT 246 and A-282.
FT MUTAGEN 246 246 T->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-215; E-228; E-
FT 243 and E-282.
FT MUTAGEN 246 246 T->V: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-215; V-228; V-
FT 243 and A-282.
FT MUTAGEN 282 282 S->A: Retained on spindle poles during
FT mitosis, no loss of phosphorylation in
FT vivo and increased ZNF365-binding; when
FT associated with V-191; V-215; V-228; V-
FT 243 and V-246.
FT MUTAGEN 282 282 S->E: Loss of centrosomal localization
FT and reduced ZNF365-binding; when
FT associated with E-191; E-215; E-228; E-
FT 243 and E-246.
FT CONFLICT 191 191 T -> I (in Ref. 3; AAH33900).
SQ SEQUENCE 346 AA; 38808 MW; A681DEF652B5ACE5 CRC64;
MEDSGKTFSS EEEEANYWKD LAMTYKQRAE NTQEELREFQ EGSREYEAEL ETQLQQIETR
NRDLLSENNR LRMELETIKE KFEVQHSEGY RQISALEDDL AQTKAIKDQL QKYIRELEQA
NDDLERAKRA TIMSLEDFEQ RLNQAIERNA FLESELDEKE NLLESVQRLK DEARDLRQEL
AVQQKQEKPR TPMPSSVEAE RTDTAVQATG SVPSTPIAHR GPSSSLNTPG SFRRGLDDST
GGTPLTPAAR ISALNIVGDL LRKVGALESK LASCRNLVYD QSPNRTGGPA SGRSSKNRDG
GERRPSSTSV PLGDKGLGKR LEFGKPPSHM SSSPLPSAQG VVKMLL
//
MIM
609449
*RECORD*
*FIELD* NO
609449
*FIELD* TI
*609449 NUDE, A. NIDULANS, HOMOLOG OF, 1; NDE1
;;NUDE;;
HOM-TES-87
*FIELD* TX
CLONING
read more
Using Lis1 (PAFAH1B1; 601545) as bait in a yeast 2-hybrid screen of a
rat liver cDNA library, Kitagawa et al. (2000) cloned rat Nude. The
deduced 344-amino acid protein contains an asp- and glu-rich N-terminal
half and a ser- and thr-rich C-terminal half. Rat Nude shares
significant homology with a fungal nuclear distribution protein, NudE,
and a Xenopus mitotic phosphoprotein, Mpp43. Northern blot analysis
detected a 2.4-kb Nude transcript in all rat tissues examined.
By subtractive hybridization to isolate testis-specific transcripts,
followed by serologic expression screening with antibodies from a
seminoma patient, Tureci et al. (2002) isolated NDE1, which they
designated HOM-TES-87. Northern blot analysis detected high expression
in testis, and RT-PCR detected NDE1 in other tissues.
By PCR of a placenta cDNA library, Yan et al. (2003) cloned human NUDE.
Western blot analysis detected NUDE at an apparent molecular mass of
about 40 kD in several human cell lines. Western blot analysis of mouse
tissues detected highest expression in brain, with much lower expression
in heart, skeletal muscle, and lung, and little to no expression in
other tissues examined.
Bakircioglu et al. (2011) found NDE1 expression in the apical
neuroepithelium throughout the developing human and mouse brain. NDE1
was strongly expressed in apical precursors in the ventricular zone and
in the newborn neuronal population of the human embryonic brain, but had
reduced expression in the subventricular zone. In the mouse brain, Nde1
localized to the centrosomes of all cells. In apical neuroepithelial
cells, expression of centrosomal Nde1 was greatest during interphase and
early mitosis and reduced during metaphase. In cultured cells, Nde1
colocalized with gamma-tubulin (TUBG1; 191135) at the centrosome and was
present in the cytoplasm, at the centrosome, and on the mitotic spindle.
GENE STRUCTURE
The NDE1 gene contains 9 exons, the last of which is entirely contained
in the neighboring MYH11 gene (160745) (Bakircioglu et al., 2011).
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NDE1
gene to chromosome 16 (TMAP SHGC-60785). Bakircioglu et al. (2011) noted
that the NDE1 gene maps to chromosome 16p13.
GENE FUNCTION
Kitagawa et al. (2000) found that rat Nude and the catalytic subunits of
Pafah (see PAFAH1B2; 602508) interacted with Pafah1b1 in a competitive
manner. They suggested that PAFAH1B1 functions in nuclear migration by
interacting with multiple intracellular proteins, including NUDE.
Yan et al. (2003) found that NUDE was phosphorylated in M phase of the
cell cycle in human cells. A fraction of NUDE bound strongly to
centrosomes in interphase and localized to mitotic spindles in early M
phase. ATP inhibitor assays indicated that NUDE bound cytoplasmic dynein
(see 600112) and migrated with it to spindle poles along microtubules.
Burdick et al. (2008) noted that NDE1 is a homolog of NDEL1 (607538) and
also binds to DISC1 (605210). NDE1 was expressed at constant levels in
the rat cerebral cortex from embryonic day (E) 14 to adulthood, whereas
NDEL1 expression showed a time-course increase peaking at postnatal day
7. Further studies with a ser704-to-cys (S704C) polymorphism in the
DISC1 gene showed that NDE1 bound stronger to ser704, while NDEL1 bound
stronger to cys704. The findings suggested an interaction of these 3
proteins, with possible competitive binding between NDEL1 and NDE1 for
DISC1.
Alkuraya et al. (2011) demonstrated the NDE1 is phosphorylated by CDK1
(116940) and that phosphorylation of NDE1 at thr246 in the C-terminal
domain is required for cells to progress through the G2/M phase of
mitosis.
MOLECULAR GENETICS
By linkage analysis followed by candidate gene sequencing, Bakircioglu
et al. (2011) identified 2 different homozygous truncating mutations in
the NDE1 gene (609449.0001 and 609449.0002, respectively) in affected
members of 3 consanguineous families with lissencephaly-4 (LIS4; 614019)
with extreme microcephaly. The disorder showed dual pathogenesis of
profound early prenatal failure of neuron production and later prenatal
deficiency of cortical lamination.
Alkuraya et al. (2011) independently identified 2 homozygous truncating
mutations in the NDE1 gene (609449.0001 and 609449.0003, respectively)
in affected members from 2 consanguineous Saudi Arabian families with
LIS4. Patient-derived lymphoblast cells showed spindle-structure
defects, including tripolar spindles, misaligned mitotic chromosomes,
nuclear fragmentation, and abnormal microtubule organizations,
supporting an essential role for NDE1 in normal mitotic spindle
function, neuronal proliferation, and human cerebral cortical
neurogenesis.
ANIMAL MODEL
Feng and Walsh (2004) found that Nde1-null mice were viable, but they
showed a small-brain phenotype. At 6 to 8 weeks of age, the brains of
Nde1-null mice were one-third smaller than their wildtype or
heterozygous counterparts. The size reduction predominantly affected the
cerebral cortex, while other brain structures, including the
hippocampus, midbrain, and cerebellum, appeared normal or were only
slightly reduced in size. Cortical lamination was mostly preserved, but
the mutant cortex had fewer neurons and thin superficial cortical layers
II to IV. Bromodeoxyuridine birthdating revealed retarded and modestly
disorganized neuronal migration. More dramatic defects were found in
mitotic progression, mitotic orientation, and chromosome localization in
cortical progenitors. The small cerebral cortex of Nde1-null mice
appeared to reflect both reduced progenitor cell division and altered
neuronal cell fates. In vitro analysis demonstrated that Nde1 was
essential for centrosome duplication and mitotic spindle assembly. Feng
and Walsh (2004) concluded that mitotic spindle function and orientation
are essential for normal cortical development.
Interaction between Nde1 and Lis1 is critical in the development of the
mouse central nervous system (CNS). Pawlisz et al. (2008) analyzed a
series of Nde1 and Lis1 double mutations in mice and showed that the
Nde1-Lis1 complex was specifically required by the radial
glial/neuroepithelial progenitor cells during CNS development. Besides
mitotic spindle regulation, Lis1 and Nde1 maintained the morphology and
lateral cell-cell contacts of progenitors in the cortical ventricular
zone. This cell shape and organization control appeared necessary for
symmetrical cell division and the self-renewal of neural progenitors
during the early phase of corticogenesis. Loss of Lis1-Nde1 function led
to dramatically increased neuronal differentiation at the onset of
cortical neurogenesis, resulting in overproduction of the earliest-born
preplate and Cajal-Retzius neurons, with consequent loss of the laminar
pattern and over 80% mass and surface area of the cerebral cortex.
Alkuraya et al. (2011) found that mouse embryonic fibroblasts with Nde1
mutations showed defects in mitotic progression, as evidenced by an
increased mitotic index; abnormal spindle structures such as multipolar
spindles; and chromosome misalignment.
*FIELD* AV
.0001
LISSENCEPHALY 4
NDE1, 2-BP DEL, 684AC
In affected members of 2 unrelated consanguineous Pakistani families
with lissencephaly-4 (614019) with extreme microcephaly, Bakircioglu et
al. (2011) identified a homozygous 2-bp deletion (684delAC) in exon 6 of
the NDE1 gene, resulting in a frameshift, loss of amino acids 229 to
335, addition of 84 novel amino acids, and ultimately termination at
position 314. The mutant protein was predicted to lack the highly
conserved C-terminal domain, which is critical for localization to the
centrosome. In vitro functional expression studies showed that the
mutant protein failed to localize properly to the centrosome. Haplotype
analysis indicated a founder effect.
Alkuraya et al. (2011) identified a homozygous 684delAC mutation in 2
sisters, born of consanguineous Saudi Arabian parents, with LIS4.
Immunoblot analysis of patient lymphocytes showed no detectable NDE1
expression, suggesting that the mutant protein was unstable and subject
to degradation. In vitro functional expression studies showed that the
mutant protein could not bind dynein (see 600112), although LIS1
(601545) binding was normal.
.0002
LISSENCEPHALY 4
NDE1, IVS2DS, G-T, +1
In affected members of a consanguineous Turkish family with
lissencephaly-4 (LIS4; 614019), Bakircioglu et al. (2011) identified a
homozygous G-to-T transversion (83+1G-T) in the second exon donor site
of the NDE1 gene. The mutation was shown to result in a frameshift
beginning in exon 3, addition of 113 novel amino acids, and a premature
stop codon at position 114. The resultant protein would lack the highly
conserved C-terminal domain as well as the homodimerization domain.
Immunoblot analysis showed significantly reduced NDE1 protein in patient
cells compared to controls. In vitro functional expression studies
showed that the mutant protein failed to colocalize properly with
gamma-tubulin (TUBG1; 191135) and failed to localize to the centromere.
.0003
LISSENCEPHALY 4
NDE1, 1-BP DUP, 733C
In affected members of a consanguineous Saudi Arabian family with
lissencephaly-4 (LIS4; 614019), Alkuraya et al. (2011) identified a
homozygous 1-bp duplication (733dupC) in exon 7 of the NDE1 gene,
predicted to result in a truncated protein after the addition of 69
novel amino acids. The mutant protein lacked the conserved C-terminal
domain critical for centromere localization. In vitro functional
expression studies showed that the mutant protein could not bind dynein
(see 600112), although LIS1 (601545) binding was normal. In addition,
the mutant protein did not localize properly to the centrosome.
*FIELD* RF
1. Alkuraya, F. S.; Cai, X.; Emery, C.; Mochida, G. H.; Al-Dosari,
M. S.; Felie, J. M.; Hill, R. S.; Barry, B. J.; Partlow, J. N.; Gascon,
G. G.; Kentab, A.; Jan, M.; Shaheen, R.; Feng, Y.; Walsh, C. A.:
Human mutations in NDE1 cause extreme microcephaly with lissencephaly. Am.
J. Hum. Genet. 88: 536-547, 2011. Note: Erratum: Am. J. Hum. Genet.
88: 677 only, 2011.
2. Bakircioglu, M.; Carvalho, O. P.; Khurshid, M.; Cox, J. J.; Tuysuz,
B.; Barak, T.; Yilmaz, S.; Caglayan, O.; Dincer, A.; Nicholas, A.
K.; Quarrell, O.; Springell, K.; and 11 others The essential
role of centrosomal NDE1 in human cerebral cortex neurogenesis. Am.
J. Hum. Genet. 88: 523-535, 2011.
3. Burdick, K. E.; Kamiya, A.; Hodgkinson, C. A.; Lencz, T.; DeRosse,
P.; Ishizuka, K.; Elashvili, S.; Arai, H.; Goldman, D.; Sawa, A.;
Malhotra, A. K.: Elucidating the relationship between DISC1, NDEL1
and NDE1 and the risk for schizophrenia: evidence of epistasis and
competitive binding. Hum. Molec. Genet. 17: 2462-2473, 2008.
4. Feng, Y.; Walsh, C. A.: Mitotic spindle regulation by Nde1 controls
cerebral cortical size. Neuron 44: 279-293, 2004.
5. Kitagawa, M.; Umezu, M.; Aoki, J.; Koizumi, H.; Arai, H.; Inoue,
K.: Direct association of LIS1, the lissencephaly gene product, with
a mammalian homologue of a fungal nuclear distribution protein, rNUDE. FEBS
Lett. 479: 57-62, 2000.
6. Pawlisz, A. S.; Mutch, C.; Wynshaw-Boris, A.; Chenn, A.; Walsh,
C. A.; Feng, Y.: Lis1-Nde1-dependent neuronal fate control determines
cerebral cortical size and lamination. Hum. Molec. Genet. 17: 2441-2445,
2008.
7. Tureci, O.; Sahin, U.; Koslowski, M.; Buss, B.; Bell, C.; Ballweber,
P.; Zwick, C.; Eberle, T.; Zuber, M.; Villena-Heinsen, C.; Seitz,
G.; Pfreundschuh, M.: A novel tumour associated leucine zipper protein
targeting to sites of gene transcription and splicing. Oncogene 21:
3879-3888, 2002.
8. Yan, X.; Li, F.; Liang, Y.; Shen, Y.; Zhao, X.; Huang, Q.; Zhu,
X.: Human Nudel and NudE as regulators of cytoplasmic dynein in poleward
protein transport along the mitotic spindle. Molec. Cell. Biol. 23:
1239-1250, 2003.
*FIELD* CN
Cassandra L. Kniffin - updated: 6/1/2011
Patricia A. Hartz - updated: 11/3/2009
Cassandra L. Kniffin - updated: 8/28/2009
Patricia A. Hartz - updated: 10/12/2006
*FIELD* CD
Patricia A. Hartz: 6/28/2005
*FIELD* ED
wwang: 06/08/2011
wwang: 6/8/2011
ckniffin: 6/1/2011
mgross: 11/3/2009
wwang: 10/30/2009
ckniffin: 8/28/2009
wwang: 10/13/2006
terry: 10/12/2006
mgross: 6/28/2005
*RECORD*
*FIELD* NO
609449
*FIELD* TI
*609449 NUDE, A. NIDULANS, HOMOLOG OF, 1; NDE1
;;NUDE;;
HOM-TES-87
*FIELD* TX
CLONING
read more
Using Lis1 (PAFAH1B1; 601545) as bait in a yeast 2-hybrid screen of a
rat liver cDNA library, Kitagawa et al. (2000) cloned rat Nude. The
deduced 344-amino acid protein contains an asp- and glu-rich N-terminal
half and a ser- and thr-rich C-terminal half. Rat Nude shares
significant homology with a fungal nuclear distribution protein, NudE,
and a Xenopus mitotic phosphoprotein, Mpp43. Northern blot analysis
detected a 2.4-kb Nude transcript in all rat tissues examined.
By subtractive hybridization to isolate testis-specific transcripts,
followed by serologic expression screening with antibodies from a
seminoma patient, Tureci et al. (2002) isolated NDE1, which they
designated HOM-TES-87. Northern blot analysis detected high expression
in testis, and RT-PCR detected NDE1 in other tissues.
By PCR of a placenta cDNA library, Yan et al. (2003) cloned human NUDE.
Western blot analysis detected NUDE at an apparent molecular mass of
about 40 kD in several human cell lines. Western blot analysis of mouse
tissues detected highest expression in brain, with much lower expression
in heart, skeletal muscle, and lung, and little to no expression in
other tissues examined.
Bakircioglu et al. (2011) found NDE1 expression in the apical
neuroepithelium throughout the developing human and mouse brain. NDE1
was strongly expressed in apical precursors in the ventricular zone and
in the newborn neuronal population of the human embryonic brain, but had
reduced expression in the subventricular zone. In the mouse brain, Nde1
localized to the centrosomes of all cells. In apical neuroepithelial
cells, expression of centrosomal Nde1 was greatest during interphase and
early mitosis and reduced during metaphase. In cultured cells, Nde1
colocalized with gamma-tubulin (TUBG1; 191135) at the centrosome and was
present in the cytoplasm, at the centrosome, and on the mitotic spindle.
GENE STRUCTURE
The NDE1 gene contains 9 exons, the last of which is entirely contained
in the neighboring MYH11 gene (160745) (Bakircioglu et al., 2011).
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NDE1
gene to chromosome 16 (TMAP SHGC-60785). Bakircioglu et al. (2011) noted
that the NDE1 gene maps to chromosome 16p13.
GENE FUNCTION
Kitagawa et al. (2000) found that rat Nude and the catalytic subunits of
Pafah (see PAFAH1B2; 602508) interacted with Pafah1b1 in a competitive
manner. They suggested that PAFAH1B1 functions in nuclear migration by
interacting with multiple intracellular proteins, including NUDE.
Yan et al. (2003) found that NUDE was phosphorylated in M phase of the
cell cycle in human cells. A fraction of NUDE bound strongly to
centrosomes in interphase and localized to mitotic spindles in early M
phase. ATP inhibitor assays indicated that NUDE bound cytoplasmic dynein
(see 600112) and migrated with it to spindle poles along microtubules.
Burdick et al. (2008) noted that NDE1 is a homolog of NDEL1 (607538) and
also binds to DISC1 (605210). NDE1 was expressed at constant levels in
the rat cerebral cortex from embryonic day (E) 14 to adulthood, whereas
NDEL1 expression showed a time-course increase peaking at postnatal day
7. Further studies with a ser704-to-cys (S704C) polymorphism in the
DISC1 gene showed that NDE1 bound stronger to ser704, while NDEL1 bound
stronger to cys704. The findings suggested an interaction of these 3
proteins, with possible competitive binding between NDEL1 and NDE1 for
DISC1.
Alkuraya et al. (2011) demonstrated the NDE1 is phosphorylated by CDK1
(116940) and that phosphorylation of NDE1 at thr246 in the C-terminal
domain is required for cells to progress through the G2/M phase of
mitosis.
MOLECULAR GENETICS
By linkage analysis followed by candidate gene sequencing, Bakircioglu
et al. (2011) identified 2 different homozygous truncating mutations in
the NDE1 gene (609449.0001 and 609449.0002, respectively) in affected
members of 3 consanguineous families with lissencephaly-4 (LIS4; 614019)
with extreme microcephaly. The disorder showed dual pathogenesis of
profound early prenatal failure of neuron production and later prenatal
deficiency of cortical lamination.
Alkuraya et al. (2011) independently identified 2 homozygous truncating
mutations in the NDE1 gene (609449.0001 and 609449.0003, respectively)
in affected members from 2 consanguineous Saudi Arabian families with
LIS4. Patient-derived lymphoblast cells showed spindle-structure
defects, including tripolar spindles, misaligned mitotic chromosomes,
nuclear fragmentation, and abnormal microtubule organizations,
supporting an essential role for NDE1 in normal mitotic spindle
function, neuronal proliferation, and human cerebral cortical
neurogenesis.
ANIMAL MODEL
Feng and Walsh (2004) found that Nde1-null mice were viable, but they
showed a small-brain phenotype. At 6 to 8 weeks of age, the brains of
Nde1-null mice were one-third smaller than their wildtype or
heterozygous counterparts. The size reduction predominantly affected the
cerebral cortex, while other brain structures, including the
hippocampus, midbrain, and cerebellum, appeared normal or were only
slightly reduced in size. Cortical lamination was mostly preserved, but
the mutant cortex had fewer neurons and thin superficial cortical layers
II to IV. Bromodeoxyuridine birthdating revealed retarded and modestly
disorganized neuronal migration. More dramatic defects were found in
mitotic progression, mitotic orientation, and chromosome localization in
cortical progenitors. The small cerebral cortex of Nde1-null mice
appeared to reflect both reduced progenitor cell division and altered
neuronal cell fates. In vitro analysis demonstrated that Nde1 was
essential for centrosome duplication and mitotic spindle assembly. Feng
and Walsh (2004) concluded that mitotic spindle function and orientation
are essential for normal cortical development.
Interaction between Nde1 and Lis1 is critical in the development of the
mouse central nervous system (CNS). Pawlisz et al. (2008) analyzed a
series of Nde1 and Lis1 double mutations in mice and showed that the
Nde1-Lis1 complex was specifically required by the radial
glial/neuroepithelial progenitor cells during CNS development. Besides
mitotic spindle regulation, Lis1 and Nde1 maintained the morphology and
lateral cell-cell contacts of progenitors in the cortical ventricular
zone. This cell shape and organization control appeared necessary for
symmetrical cell division and the self-renewal of neural progenitors
during the early phase of corticogenesis. Loss of Lis1-Nde1 function led
to dramatically increased neuronal differentiation at the onset of
cortical neurogenesis, resulting in overproduction of the earliest-born
preplate and Cajal-Retzius neurons, with consequent loss of the laminar
pattern and over 80% mass and surface area of the cerebral cortex.
Alkuraya et al. (2011) found that mouse embryonic fibroblasts with Nde1
mutations showed defects in mitotic progression, as evidenced by an
increased mitotic index; abnormal spindle structures such as multipolar
spindles; and chromosome misalignment.
*FIELD* AV
.0001
LISSENCEPHALY 4
NDE1, 2-BP DEL, 684AC
In affected members of 2 unrelated consanguineous Pakistani families
with lissencephaly-4 (614019) with extreme microcephaly, Bakircioglu et
al. (2011) identified a homozygous 2-bp deletion (684delAC) in exon 6 of
the NDE1 gene, resulting in a frameshift, loss of amino acids 229 to
335, addition of 84 novel amino acids, and ultimately termination at
position 314. The mutant protein was predicted to lack the highly
conserved C-terminal domain, which is critical for localization to the
centrosome. In vitro functional expression studies showed that the
mutant protein failed to localize properly to the centrosome. Haplotype
analysis indicated a founder effect.
Alkuraya et al. (2011) identified a homozygous 684delAC mutation in 2
sisters, born of consanguineous Saudi Arabian parents, with LIS4.
Immunoblot analysis of patient lymphocytes showed no detectable NDE1
expression, suggesting that the mutant protein was unstable and subject
to degradation. In vitro functional expression studies showed that the
mutant protein could not bind dynein (see 600112), although LIS1
(601545) binding was normal.
.0002
LISSENCEPHALY 4
NDE1, IVS2DS, G-T, +1
In affected members of a consanguineous Turkish family with
lissencephaly-4 (LIS4; 614019), Bakircioglu et al. (2011) identified a
homozygous G-to-T transversion (83+1G-T) in the second exon donor site
of the NDE1 gene. The mutation was shown to result in a frameshift
beginning in exon 3, addition of 113 novel amino acids, and a premature
stop codon at position 114. The resultant protein would lack the highly
conserved C-terminal domain as well as the homodimerization domain.
Immunoblot analysis showed significantly reduced NDE1 protein in patient
cells compared to controls. In vitro functional expression studies
showed that the mutant protein failed to colocalize properly with
gamma-tubulin (TUBG1; 191135) and failed to localize to the centromere.
.0003
LISSENCEPHALY 4
NDE1, 1-BP DUP, 733C
In affected members of a consanguineous Saudi Arabian family with
lissencephaly-4 (LIS4; 614019), Alkuraya et al. (2011) identified a
homozygous 1-bp duplication (733dupC) in exon 7 of the NDE1 gene,
predicted to result in a truncated protein after the addition of 69
novel amino acids. The mutant protein lacked the conserved C-terminal
domain critical for centromere localization. In vitro functional
expression studies showed that the mutant protein could not bind dynein
(see 600112), although LIS1 (601545) binding was normal. In addition,
the mutant protein did not localize properly to the centrosome.
*FIELD* RF
1. Alkuraya, F. S.; Cai, X.; Emery, C.; Mochida, G. H.; Al-Dosari,
M. S.; Felie, J. M.; Hill, R. S.; Barry, B. J.; Partlow, J. N.; Gascon,
G. G.; Kentab, A.; Jan, M.; Shaheen, R.; Feng, Y.; Walsh, C. A.:
Human mutations in NDE1 cause extreme microcephaly with lissencephaly. Am.
J. Hum. Genet. 88: 536-547, 2011. Note: Erratum: Am. J. Hum. Genet.
88: 677 only, 2011.
2. Bakircioglu, M.; Carvalho, O. P.; Khurshid, M.; Cox, J. J.; Tuysuz,
B.; Barak, T.; Yilmaz, S.; Caglayan, O.; Dincer, A.; Nicholas, A.
K.; Quarrell, O.; Springell, K.; and 11 others The essential
role of centrosomal NDE1 in human cerebral cortex neurogenesis. Am.
J. Hum. Genet. 88: 523-535, 2011.
3. Burdick, K. E.; Kamiya, A.; Hodgkinson, C. A.; Lencz, T.; DeRosse,
P.; Ishizuka, K.; Elashvili, S.; Arai, H.; Goldman, D.; Sawa, A.;
Malhotra, A. K.: Elucidating the relationship between DISC1, NDEL1
and NDE1 and the risk for schizophrenia: evidence of epistasis and
competitive binding. Hum. Molec. Genet. 17: 2462-2473, 2008.
4. Feng, Y.; Walsh, C. A.: Mitotic spindle regulation by Nde1 controls
cerebral cortical size. Neuron 44: 279-293, 2004.
5. Kitagawa, M.; Umezu, M.; Aoki, J.; Koizumi, H.; Arai, H.; Inoue,
K.: Direct association of LIS1, the lissencephaly gene product, with
a mammalian homologue of a fungal nuclear distribution protein, rNUDE. FEBS
Lett. 479: 57-62, 2000.
6. Pawlisz, A. S.; Mutch, C.; Wynshaw-Boris, A.; Chenn, A.; Walsh,
C. A.; Feng, Y.: Lis1-Nde1-dependent neuronal fate control determines
cerebral cortical size and lamination. Hum. Molec. Genet. 17: 2441-2445,
2008.
7. Tureci, O.; Sahin, U.; Koslowski, M.; Buss, B.; Bell, C.; Ballweber,
P.; Zwick, C.; Eberle, T.; Zuber, M.; Villena-Heinsen, C.; Seitz,
G.; Pfreundschuh, M.: A novel tumour associated leucine zipper protein
targeting to sites of gene transcription and splicing. Oncogene 21:
3879-3888, 2002.
8. Yan, X.; Li, F.; Liang, Y.; Shen, Y.; Zhao, X.; Huang, Q.; Zhu,
X.: Human Nudel and NudE as regulators of cytoplasmic dynein in poleward
protein transport along the mitotic spindle. Molec. Cell. Biol. 23:
1239-1250, 2003.
*FIELD* CN
Cassandra L. Kniffin - updated: 6/1/2011
Patricia A. Hartz - updated: 11/3/2009
Cassandra L. Kniffin - updated: 8/28/2009
Patricia A. Hartz - updated: 10/12/2006
*FIELD* CD
Patricia A. Hartz: 6/28/2005
*FIELD* ED
wwang: 06/08/2011
wwang: 6/8/2011
ckniffin: 6/1/2011
mgross: 11/3/2009
wwang: 10/30/2009
ckniffin: 8/28/2009
wwang: 10/13/2006
terry: 10/12/2006
mgross: 6/28/2005
MIM
614019
*RECORD*
*FIELD* NO
614019
*FIELD* TI
#614019 LISSENCEPHALY 4; LIS4
;;LISSENCEPHALY 4, WITH MICROCEPHALY
*FIELD* TX
A number sign (#) is used with this entry because lissencephaly-4 (LIS4)
read moreis caused by homozygous mutation in the NDE1 gene (609449) on chromosome
16p13.
DESCRIPTION
Lissencephaly-4 is an autosomal recessive neurodevelopmental disorder
characterized by lissencephaly, severe brain atrophy, extreme
microcephaly (head circumference of more than 10 standard deviations
(SD) below the mean), and profound mental retardation. It has also been
referred to as 'microlissencephaly' (summary by Bakircioglu et al., 2011
and Alkuraya et al., 2011).
For a general phenotypic description and a discussion of genetic
heterogeneity of lissencephaly, see LIS1 (607432).
CLINICAL FEATURES
Bakircioglu et al. (2011) reported 6 offspring from 3 consanguineous
families with lissencephaly, extreme congenital microcephaly, and
profound mental retardation. Two families were of Pakistani origin, and
the third was of Turkish origin. The head circumferences of all patients
were at least 10 SD below the mean, with onset at 18 weeks' gestation.
Mental retardation was evident within the first few months of life; none
of the children recognized their parents, and they showed little
response to the outside world, even to painful stimuli. Seizures began
by 3 months and evolved from occasional rhythmic jerks into complex
partial and tonic-clonic seizures. The children gradually adopted a
fetal position over the first 3 years of life, with a paucity of
movements, but were not hypotonic or spastic. All but 1 died in the
first 5 years of life of chest infections and aspiration. Brain imaging,
available from 1 individual from each family, showed severe
microcephaly, simplified gyral pattern of the cerebral cortex, small
cerebellum, normal gross brain architecture, and normal cortical ribbon.
Postmortem examination of 1 patient showed severe hypoplasia of the
frontal lobes with abnormal gyral pattern. The temporal and occipital
lobes were almost smooth, and the only major sulcus visible was the
Sylvian fissure, consistent with lissencephaly. Cortical layering was
abnormal, with several layers jumbled together and disorganized and a
large loss of neurons. The disorder was described as a
'microlissencephaly.'
Alkuraya et al. (2011) reported 2 unrelated consanguineous families from
Saudi Arabia with lissencephaly and severe microcephaly (more than 11 SD
below the mean). In the first family, 2 affected sisters showed marked
hypertonia and lack of development but no seizures. Brain MRI of 1 girl
showed severe microcephaly with a proportionate reduction in the size of
most other brain structures, including the cerebellum and brain stem,
associated with agenesis of the corpus callosum. The gyral folding of
the cerebral cortex was extremely simplified; there were almost no
detectable sulci other than the Sylvian fissure. Brain MRI of the second
girl showed showed microcephaly, severe simplification of the gyral
pattern, agenesis of the corpus callosum, and colpocephaly. In the
second family, a brother and sister were similarly affected with extreme
microcephaly. Clinical details on the girl were not available. At birth,
CT scan of the boy showed small brain size. Seizures developed at age 2
months. Brain MRI at 11 months showed marked decrease in the size of
both cerebral hemispheres, a large midline fluid-filled structure,
dilatation of the right lateral ventricle, small cerebellum, and
agenesis of the corpus callosum. All 4 patients reported by Alkuraya et
al. (2011) showed overall poor growth.
INHERITANCE
Lissencephaly-4 is inherited in an autosomal recessive pattern
(Bakircioglu et al., 2011).
MOLECULAR GENETICS
By linkage analysis followed by candidate gene sequencing, Bakircioglu
et al. (2011) identified 2 different truncating mutations in the NDE1
gene (609449.0001 and 609449.0002, respectively) in affected members of
3 consanguineous families with lissencephaly-4. The disorder showed dual
pathogenesis of profound early prenatal failure of neuron production and
later prenatal deficiency of cortical lamination. The findings suggested
that loss of NDE1 at the centrosomes of apical neuroepithelial cells
plays a critical role in these processes, highlighting the importance of
the centrosome in neurogenesis.
Alkuraya et al. (2011) independently identified 2 truncating mutations
in the NDE1 gene in affected members from 2 Saudi Arabian families with
LIS4. Patient-derived lymphoblast cells showed spindle-structure
defects, including tripolar spindles, misaligned mitotic chromosomes,
nuclear fragmentation, and abnormal microtubule organizations,
supporting an essential role for NDE1 in normal mitotic spindle
function, neuronal proliferation, and human cerebral cortical
neurogenesis.
ANIMAL MODEL
Feng and Walsh (2004) found that Nde1-null mice were viable, but they
showed a small-brain phenotype. At 6 to 8 weeks of age, the brains of
Nde1-null mice were one-third smaller than their wildtype or
heterozygous counterparts. The size reduction predominantly affected the
cerebral cortex, while other brain structures, including the
hippocampus, midbrain, and cerebellum, appeared normal or were only
slightly reduced in size. Cortical lamination was mostly preserved, but
the mutant cortex had fewer neurons and thin superficial cortical layers
II to IV. Bromodeoxyuridine birthdating revealed retarded and modestly
disorganized neuronal migration. More dramatic defects were found in
mitotic progression, mitotic orientation, and chromosome localization in
cortical progenitors. The small cerebral cortex of Nde1-null mice
appeared to reflect both reduced progenitor cell division and altered
neuronal cell fates. In vitro analysis demonstrated that Nde1 was
essential for centrosome duplication and mitotic spindle assembly. Feng
and Walsh (2004) concluded that mitotic spindle function and orientation
are essential for normal cortical development.
*FIELD* RF
1. Alkuraya, F. S.; Cai, X.; Emery, C.; Mochida, G. H.; Al-Dosari,
M. S.; Felie, J. M.; Hill, R. S.; Barry, B. J.; Partlow, J. N.; Gascon,
G. G.; Kentab, A.; Jan, M.; Shaheen, R.; Feng, Y.; Walsh, C. A.:
Human mutations in NDE1 cause extreme microcephaly with lissencephaly. Am.
J. Hum. Genet. 88: 536-547, 2011. Note: Erratum: Am. J. Hum. Genet.
88: 677 only, 2011.
2. Bakircioglu, M.; Carvalho, O. P.; Khurshid, M.; Cox, J. J.; Tuysuz,
B.; Barak, T.; Yilmaz, S.; Caglayan, O.; Dincer, A.; Nicholas, A.
K.; Quarrell, O.; Springell, K.; and 11 others: The essential role
of centrosomal NDE1 in human cerebral cortex neurogenesis. Am. J.
Hum. Genet. 88: 523-535, 2011.
3. Feng, Y.; Walsh, C. A.: Mitotic spindle regulation by Nde1 controls
cerebral cortical size. Neuron 44: 279-293, 2004.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature (in some patients);
[Other];
Poor growth
HEAD AND NECK:
[Head];
Microcephaly, profound (at least 10 SD below mean)
NEUROLOGIC:
[Central nervous system];
Mental retardation, profound;
Lack of psychomotor development;
Seizures (in some patients));
Hypertonia (in some patients));
Lissencephaly;
Small shrunken brain;
Simplified gyral pattern;
Thin cerebral cortex;
Abnormal cortical layering;
Reduced numbers of neurons;
Agenesis of the corpus callosum;
Small cerebellum
MISCELLANEOUS:
Onset in utero;
Lack of psychomotor development;
Four families have been reported (last curated June 2011)
MOLECULAR BASIS:
Caused by mutation in the homolog of the A. nidulans Nude 1 gene (NDE1,
609449.0001)
*FIELD* CD
Cassandra L. Kniffin: 6/1/2011
*FIELD* ED
joanna: 11/30/2012
joanna: 12/29/2011
ckniffin: 6/1/2011
*FIELD* CD
Cassandra L. Kniffin: 6/1/2011
*FIELD* ED
terry: 07/31/2012
wwang: 6/8/2011
ckniffin: 6/1/2011
*RECORD*
*FIELD* NO
614019
*FIELD* TI
#614019 LISSENCEPHALY 4; LIS4
;;LISSENCEPHALY 4, WITH MICROCEPHALY
*FIELD* TX
A number sign (#) is used with this entry because lissencephaly-4 (LIS4)
read moreis caused by homozygous mutation in the NDE1 gene (609449) on chromosome
16p13.
DESCRIPTION
Lissencephaly-4 is an autosomal recessive neurodevelopmental disorder
characterized by lissencephaly, severe brain atrophy, extreme
microcephaly (head circumference of more than 10 standard deviations
(SD) below the mean), and profound mental retardation. It has also been
referred to as 'microlissencephaly' (summary by Bakircioglu et al., 2011
and Alkuraya et al., 2011).
For a general phenotypic description and a discussion of genetic
heterogeneity of lissencephaly, see LIS1 (607432).
CLINICAL FEATURES
Bakircioglu et al. (2011) reported 6 offspring from 3 consanguineous
families with lissencephaly, extreme congenital microcephaly, and
profound mental retardation. Two families were of Pakistani origin, and
the third was of Turkish origin. The head circumferences of all patients
were at least 10 SD below the mean, with onset at 18 weeks' gestation.
Mental retardation was evident within the first few months of life; none
of the children recognized their parents, and they showed little
response to the outside world, even to painful stimuli. Seizures began
by 3 months and evolved from occasional rhythmic jerks into complex
partial and tonic-clonic seizures. The children gradually adopted a
fetal position over the first 3 years of life, with a paucity of
movements, but were not hypotonic or spastic. All but 1 died in the
first 5 years of life of chest infections and aspiration. Brain imaging,
available from 1 individual from each family, showed severe
microcephaly, simplified gyral pattern of the cerebral cortex, small
cerebellum, normal gross brain architecture, and normal cortical ribbon.
Postmortem examination of 1 patient showed severe hypoplasia of the
frontal lobes with abnormal gyral pattern. The temporal and occipital
lobes were almost smooth, and the only major sulcus visible was the
Sylvian fissure, consistent with lissencephaly. Cortical layering was
abnormal, with several layers jumbled together and disorganized and a
large loss of neurons. The disorder was described as a
'microlissencephaly.'
Alkuraya et al. (2011) reported 2 unrelated consanguineous families from
Saudi Arabia with lissencephaly and severe microcephaly (more than 11 SD
below the mean). In the first family, 2 affected sisters showed marked
hypertonia and lack of development but no seizures. Brain MRI of 1 girl
showed severe microcephaly with a proportionate reduction in the size of
most other brain structures, including the cerebellum and brain stem,
associated with agenesis of the corpus callosum. The gyral folding of
the cerebral cortex was extremely simplified; there were almost no
detectable sulci other than the Sylvian fissure. Brain MRI of the second
girl showed showed microcephaly, severe simplification of the gyral
pattern, agenesis of the corpus callosum, and colpocephaly. In the
second family, a brother and sister were similarly affected with extreme
microcephaly. Clinical details on the girl were not available. At birth,
CT scan of the boy showed small brain size. Seizures developed at age 2
months. Brain MRI at 11 months showed marked decrease in the size of
both cerebral hemispheres, a large midline fluid-filled structure,
dilatation of the right lateral ventricle, small cerebellum, and
agenesis of the corpus callosum. All 4 patients reported by Alkuraya et
al. (2011) showed overall poor growth.
INHERITANCE
Lissencephaly-4 is inherited in an autosomal recessive pattern
(Bakircioglu et al., 2011).
MOLECULAR GENETICS
By linkage analysis followed by candidate gene sequencing, Bakircioglu
et al. (2011) identified 2 different truncating mutations in the NDE1
gene (609449.0001 and 609449.0002, respectively) in affected members of
3 consanguineous families with lissencephaly-4. The disorder showed dual
pathogenesis of profound early prenatal failure of neuron production and
later prenatal deficiency of cortical lamination. The findings suggested
that loss of NDE1 at the centrosomes of apical neuroepithelial cells
plays a critical role in these processes, highlighting the importance of
the centrosome in neurogenesis.
Alkuraya et al. (2011) independently identified 2 truncating mutations
in the NDE1 gene in affected members from 2 Saudi Arabian families with
LIS4. Patient-derived lymphoblast cells showed spindle-structure
defects, including tripolar spindles, misaligned mitotic chromosomes,
nuclear fragmentation, and abnormal microtubule organizations,
supporting an essential role for NDE1 in normal mitotic spindle
function, neuronal proliferation, and human cerebral cortical
neurogenesis.
ANIMAL MODEL
Feng and Walsh (2004) found that Nde1-null mice were viable, but they
showed a small-brain phenotype. At 6 to 8 weeks of age, the brains of
Nde1-null mice were one-third smaller than their wildtype or
heterozygous counterparts. The size reduction predominantly affected the
cerebral cortex, while other brain structures, including the
hippocampus, midbrain, and cerebellum, appeared normal or were only
slightly reduced in size. Cortical lamination was mostly preserved, but
the mutant cortex had fewer neurons and thin superficial cortical layers
II to IV. Bromodeoxyuridine birthdating revealed retarded and modestly
disorganized neuronal migration. More dramatic defects were found in
mitotic progression, mitotic orientation, and chromosome localization in
cortical progenitors. The small cerebral cortex of Nde1-null mice
appeared to reflect both reduced progenitor cell division and altered
neuronal cell fates. In vitro analysis demonstrated that Nde1 was
essential for centrosome duplication and mitotic spindle assembly. Feng
and Walsh (2004) concluded that mitotic spindle function and orientation
are essential for normal cortical development.
*FIELD* RF
1. Alkuraya, F. S.; Cai, X.; Emery, C.; Mochida, G. H.; Al-Dosari,
M. S.; Felie, J. M.; Hill, R. S.; Barry, B. J.; Partlow, J. N.; Gascon,
G. G.; Kentab, A.; Jan, M.; Shaheen, R.; Feng, Y.; Walsh, C. A.:
Human mutations in NDE1 cause extreme microcephaly with lissencephaly. Am.
J. Hum. Genet. 88: 536-547, 2011. Note: Erratum: Am. J. Hum. Genet.
88: 677 only, 2011.
2. Bakircioglu, M.; Carvalho, O. P.; Khurshid, M.; Cox, J. J.; Tuysuz,
B.; Barak, T.; Yilmaz, S.; Caglayan, O.; Dincer, A.; Nicholas, A.
K.; Quarrell, O.; Springell, K.; and 11 others: The essential role
of centrosomal NDE1 in human cerebral cortex neurogenesis. Am. J.
Hum. Genet. 88: 523-535, 2011.
3. Feng, Y.; Walsh, C. A.: Mitotic spindle regulation by Nde1 controls
cerebral cortical size. Neuron 44: 279-293, 2004.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature (in some patients);
[Other];
Poor growth
HEAD AND NECK:
[Head];
Microcephaly, profound (at least 10 SD below mean)
NEUROLOGIC:
[Central nervous system];
Mental retardation, profound;
Lack of psychomotor development;
Seizures (in some patients));
Hypertonia (in some patients));
Lissencephaly;
Small shrunken brain;
Simplified gyral pattern;
Thin cerebral cortex;
Abnormal cortical layering;
Reduced numbers of neurons;
Agenesis of the corpus callosum;
Small cerebellum
MISCELLANEOUS:
Onset in utero;
Lack of psychomotor development;
Four families have been reported (last curated June 2011)
MOLECULAR BASIS:
Caused by mutation in the homolog of the A. nidulans Nude 1 gene (NDE1,
609449.0001)
*FIELD* CD
Cassandra L. Kniffin: 6/1/2011
*FIELD* ED
joanna: 11/30/2012
joanna: 12/29/2011
ckniffin: 6/1/2011
*FIELD* CD
Cassandra L. Kniffin: 6/1/2011
*FIELD* ED
terry: 07/31/2012
wwang: 6/8/2011
ckniffin: 6/1/2011