Reviewed, UniProtKB/Swiss-Prot Q9GZM8 (NDEL1_HUMAN)

Names and origin

Protein names

Recommended name:
    Nuclear distribution protein nudE-like 1
      Short name=Protein Nudel
Alternative name(s):
    Mitosin-associated protein 1

Gene names

Name:	NDEL1
Synonyms:	EOPA, MITAP1, NUDEL

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	345 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL By similarity. Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1.
Subunit structure	Interacts with YWHAE. Interacts directly with NEFL and indirectly with NEFH. Interacts with microtubules By similarity. Self-associates. Interacts with DISC1, dynein, dynactin, tubulin gamma, KATNA1, KATNB1, PAFAH1B1, PCM1 and PCNT. Interacts (via C-terminus) with CENPF.
Subcellular location	Cytoplasm › cytoskeleton. Cytoplasm › cytoskeleton › centrosome. Kinetochore. Cytoplasm › cytoskeleton › spindle. Note: Localizes to the cell body of the motor neurons and colocalizes with assembled neurofilaments within axonal processes. Localizes to the microtubules of the manchette in elongated spermatids By similarity. Localizes to the interphase centrosome and the mitotic spindle. Localizes to the kinetochore in a CENPF-dependent manner.
Tissue specificity	Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle. Ref.12
Developmental stage	Expression peaks in mitosis. Ref.13
Post-translational modification	Phosphorylated in mitosis. Can be phosphorylated by CDC2, CDK5 and MAPK1. Phosphorylation by CDK5 promotes interaction with KATNA1 and YWHAE. Ref.13 Ref.1 Ref.2 Ref.16
Sequence similarities	Belongs to the nudE family.
Caution	Was originally (Ref.3) thought to function as an oligopeptidase (NUDEL-oligopeptidase or endooligopeptidase A) which could regulate peptide levels relevant to brain function.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Transport
Cellular component	Cytoplasm Cytoskeleton Kinetochore Microtubule
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW chromosome segregation Ref.15 Inferred from mutant phenotype. Source: UniProtKB nervous system development Inferred from electronic annotation. Source: UniProtKB-KW transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	centrosome Inferred from electronic annotation. Source: UniProtKB-SubCell condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule Inferred from electronic annotation. Source: UniProtKB-KW spindle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Ref.6 Ref.15 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC2	P06493	1	EBI-928842,EBI-444308
DISC1	Q9NRI5	9	EBI-928842,EBI-529989
ZNF365	Q70YC5	1	EBI-928842,EBI-941182

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9GZM8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9GZM8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     316-345: AVNGFDPAPPPPGLGSSRPSSAPGMLPLSV → SSSSCAIRAS...APPPTLLLET

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 345

345

Nuclear distribution protein nudE-like 1

PRO_0000240210

Regions

Region

56 – 166

111

Self-association By similarity

Region

64 – 189

126

Interaction with KATNB1 By similarity

Region

114 – 133

20

Required for interaction with PAFAH1B1

Region

175 – 345

171

Interaction with CENPF

Region

189 – 256

68

Interaction with YWHAE By similarity

Region

191 – 345

155

Interaction with NEFL By similarity

Region

195 – 256

62

Interaction with KATNA1 By similarity

Region

241 – 280

40

Interaction with DISC1

Region

256 – 291

36

Required for localization to the centrosome and interaction with dynein, dynactin, tubulin gamma, PCM1 and PCNT1

Coiled coil

28 – 190

163

Potential

Amino acid modifications

Modified residue

215

1

Phosphoserine Ref.16

Modified residue

219

1

Phosphothreonine; by CDC2 and MAPK1 Ref.16

Modified residue

241

1

Phosphothreonine Ref.16

Modified residue

242

1

Phosphoserine; by CDC2

Modified residue

245

1

Phosphothreonine; by CDC2 and MAPK1 Ref.16

Natural variations

Alternative sequence

316 – 345

30

AVNGF…LPLSV → SSSSCAIRASRRRFSSSSAD LAGRGGGDGSIPAQHSTGAS GKAPPPTLLLET in isoform 2.

VSP_019310

Experimental info

Mutagenesis

198

1

S → A: Abrogates mitotic phosphorylation; when associated with V-219; A-231; A-242 and V-245. Abrogates phosphorylation by CDK5; when associated with A-219 and A-231. Ref.1 Ref.2

Mutagenesis

198

1

S → E: Enhances interaction with PAFAH1B1 and impairs centrosomal localization; when associated with E-219; E-231; E-242 and E-245. Ref.1 Ref.2

Mutagenesis

219

1

T → A: Abrogates phosphorylation by CDK5; when associated with A-198 and A-231. Ref.1 Ref.2

Mutagenesis

219

1

T → E: Enhances interaction with PAFAH1B1 and impairs centrosomal localization; when associated with E-198; E-231; E-242 and E-245. Ref.1 Ref.2

Mutagenesis

219

1

T → V: Abrogates mitotic phosphorylation; when associated with A-198; A-231; A-242 and V-245. Ref.1 Ref.2

Mutagenesis

231

1

S → A: Abrogates mitotic phosphorylation; when associated with A-198; V-219; A-242 and V-245. Abrogates phosphorylation by CDK5; when associated with A-198 and A-219. Ref.1 Ref.2

Mutagenesis

231

1

S → E: Enhances interaction with PAFAH1B1 and impairs centrosomal localization; when associated with E-198; E-219; E-242 and E-245. Ref.1 Ref.2

Mutagenesis

242

1

S → A: Abrogates mitotic phosphorylation; when associated with A-198; V-219; A-231 and V-245. Ref.2

Mutagenesis

242

1

S → E: Enhances interaction with PAFAH1B1 and impairs centrosomal localization; when associated with E-198; E-219; E-231 and E-245. Ref.2

Mutagenesis

245

1

T → E: Enhances interaction with PAFAH1B1 and impairs centrosomal localization; when associated with E-198; E-219; E-231 and E-242. Ref.2

Mutagenesis

245

1

T → V: Abrogates mitotic phosphorylation; when associated with A-198; V-219; A-231 and A-242. Ref.2

Mutagenesis

273

1

C → A: Abolishes oligopeptidase activity. Ref.3

Sequence conflict

322

1

P → T in AAH26101. Ref.5

Secondary structure

1

.

.

.

345

Helix Strand Turn

Details...

Helix

59 – 165

107

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: E91EA053FCA315D7	FASTA	345	38,375
	10 20 30 40 50 60 MDGEDIPDFS SLKEETAYWK ELSLKYKQSF QEARDELVEF QEGSRELEAE LEAQLVQAEQ 70 80 90 100 110 120 RNRDLQADNQ RLKYEVEALK EKLEHQYAQS YKQVSVLEDD LSQTRAIKEQ LHKYVRELEQ 130 140 150 160 170 180 ANDDLERAKR ATIVSLEDFE QRLNQAIERN AFLESELDEK ESLLVSVQRL KDEARDLRQE 190 200 210 220 230 240 LAVRERQQEV TRKSAPSSPT LDCEKMDSAV QASLSLPATP VGKGTENTFP SPKAIPNGFG 250 260 270 280 290 300 TSPLTPSARI SALNIVGDLL RKVGALESKL AACRNFAKDQ ASRKSYISGN VNCGVLNGNG 310 320 330 340 TKFSRSGHTS FFDKGAVNGF DPAPPPPGLG SSRPSSAPGM LPLSV
	Isoform 2. Checksum: EC939E90FAB014BC	FASTA	367	40,616
	10 20 30 40 50 60 MDGEDIPDFS SLKEETAYWK ELSLKYKQSF QEARDELVEF QEGSRELEAE LEAQLVQAEQ 70 80 90 100 110 120 RNRDLQADNQ RLKYEVEALK EKLEHQYAQS YKQVSVLEDD LSQTRAIKEQ LHKYVRELEQ 130 140 150 160 170 180 ANDDLERAKR ATIVSLEDFE QRLNQAIERN AFLESELDEK ESLLVSVQRL KDEARDLRQE 190 200 210 220 230 240 LAVRERQQEV TRKSAPSSPT LDCEKMDSAV QASLSLPATP VGKGTENTFP SPKAIPNGFG 250 260 270 280 290 300 TSPLTPSARI SALNIVGDLL RKVGALESKL AACRNFAKDQ ASRKSYISGN VNCGVLNGNG 310 320 330 340 350 360 TKFSRSGHTS FFDKGSSSSC AIRASRRRFS SSSADLAGRG GGDGSIPAQH STGASGKAPP PTLLLET

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NUDEL is a novel cdk5 substrate that associates with LIS1 and cytoplasmic dynein." Niethammer M., Smith D.S., Ayala R., Peng J., Ko J., Lee M.-S., Morabito M., Tsai L.-H. Neuron 28:697-711(2000) [PubMed: 11163260] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH DYNEIN AND PAFAH1B1, SUBCELLULAR LOCATION, PHOSPHORYLATION BY CDK5, MUTAGENESIS OF SER-198; THR-219 AND SER-231. Tissue: Brain.
[2]	"Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle." Yan X., Li F., Liang Y., Shen Y., Zhao X., Huang Q., Zhu X. Mol. Cell. Biol. 23:1239-1250(2003) [PubMed: 12556484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH PAFAH1B1, SUBCELLULAR LOCATION, PHOSPHORYLATION BY CDC2 AND MAPK1, MUTAGENESIS OF SER-198; THR-219; SER-231; SER-242 AND THR-245.
[3]	"Inhibition of NUDEL (nuclear distribution element-like)-oligopeptidase activity by disrupted-in-schizophrenia 1." Hayashi M.A.F., Portaro F.C.V., Bastos M.F., Guerreiro J.R., Oliveira V., Gorrao S.S., Tambourgi D.V., Sant'Anna O.A., Whiting P.J., Camargo L.M., Konno K., Brandon N.J., de Camargo A.C.M. Proc. Natl. Acad. Sci. U.S.A. 102:3828-3833(2005) [PubMed: 15728732] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PUTATIVE FUNCTION AS AN OLIGOPEPTIDASE, INTERACTION WITH DISC1, MUTAGENESIS OF CYS-273. Tissue: Brain.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Spinal cord.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation." Morris J.A., Kandpal G., Ma L., Austin C.P. Hum. Mol. Genet. 12:1591-1608(2003) [PubMed: 12812986] [Abstract] Cited for: INTERACTION WITH DISC1, SUBCELLULAR LOCATION.
[7]	"Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth." Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., Okawa M., Yamada N., Hatten M.E., Snyder S.H., Ross C.A., Sawa A. Proc. Natl. Acad. Sci. U.S.A. 100:289-294(2003) [PubMed: 12506198] [Abstract] Cited for: INTERACTION WITH DISC1.
[8]	Erratum Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., Okawa M., Yamada N., Hatten M.E., Snyder S.H., Ross C.A., Sawa A. Proc. Natl. Acad. Sci. U.S.A. 101:13969-13969(2004)
[9]	"Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein." Liang Y., Yu W., Li Y., Yang Z., Yan X., Huang Q., Zhu X. J. Cell Biol. 164:557-566(2004) [PubMed: 14970193] [Abstract] Cited for: FUNCTION, SELF-ASSOCIATION, INTERACTION WITH DYNACTIN; DYNEIN AND PAFAH1B1, SUBCELLULAR LOCATION.
[10]	"Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders." Brandon N.J., Handford E.J., Schurov I., Rain J.-C., Pelling M., Duran-Jimeniz B., Camargo L.M., Oliver K.R., Beher D., Shearman M.S., Whiting P.J. Mol. Cell. Neurosci. 25:42-55(2004) [PubMed: 14962739] [Abstract] Cited for: INTERACTION WITH DISC1.
[11]	"Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase." Tarricone C., Perrina F., Monzani S., Massimiliano L., Kim M.-H., Derewenda Z.S., Knapp S., Tsai L.-H., Musacchio A. Neuron 44:809-821(2004) [PubMed: 15572112] [Abstract] Cited for: SELF-ASSOCIATION, INTERACTION WITH PAFAH1B1.
[12]	"Cloning and characterization of the human and rabbit NUDEL-oligopeptidase promoters and their negative regulation." Guerreiro J.R., Winnischofer S.M.B., Bastos M.F., Portaro F.C.V., Sogayar M.C., de Camargo A.C.M., Hayashi M.A.F. Biochim. Biophys. Acta 1730:77-84(2005) [PubMed: 16005531] [Abstract] Cited for: TISSUE SPECIFICITY.
[13]	"Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration." Toyo-Oka K., Sasaki S., Yano Y., Mori D., Kobayashi T., Toyoshima Y.Y., Tokuoka S.M., Ishii S., Shimizu T., Muramatsu M., Hiraiwa N., Yoshiki A., Wynshaw-Boris A., Hirotsune S. Hum. Mol. Genet. 14:3113-3128(2005) [PubMed: 16203747] [Abstract] Cited for: INTERACTION WITH KATNA1 AND KATNB1, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PHOSPHORYLATION.
[14]	"Nudel contributes to microtubule anchoring at the mother centriole and is involved in both dynein-dependent and -independent centrosomal protein assembly." Guo J., Yang Z., Song W., Chen Q., Wang F., Zhang Q., Zhu X. Mol. Biol. Cell 17:680-689(2006) [PubMed: 16291865] [Abstract] Cited for: FUNCTION, INTERACTION WITH DYNACTIN; TUBULIN GAMMA; PAFAH1B1; PCM1; PCNT, SUBCELLULAR LOCATION.
[15]	"Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes." Vergnolle M.A.S., Taylor S.S. Curr. Biol. 17:1173-1179(2007) [PubMed: 17600710] [Abstract] Cited for: FUNCTION, INTERACTION WITH CENPF, SUBCELLULAR LOCATION.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; THR-219; THR-241 AND THR-245, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AY004871 mRNA. Translation: AAF97497.1.
AF182078 mRNA. Translation: AAG43425.1.
AF217798 mRNA. Translation: AAF24516.3.
AL832648 mRNA. Translation: CAD89957.3.
BC026101 mRNA. Translation: AAH26101.1.

IPI

IPI00384038.
IPI00940808.

RefSeq

NP_001020750.1.
NP_110435.1.

UniGene

Hs.372123

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V66	X-ray	2.10	B/C/D/E	58-168	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9GZM8. 25 interactions.

STRING

Q9GZM8.

PTM databases

PhosphoSite

Q9GZM8.

Proteomic databases

PRIDE

Q9GZM8.

Genome annotation databases

Ensembl

ENST00000299734; ENSP00000299734; ENSG00000166579; Homo sapiens. [Genome view]
ENST00000334527; ENSP00000333982; ENSG00000166579; Homo sapiens. [Genome view]
ENST00000380025; ENSP00000369364; ENSG00000166579; Homo sapiens. [Genome view]
ENST00000402554; ENSP00000384963; ENSG00000166579; Homo sapiens. [Genome view]
ENST00000415727; ENSP00000413442; ENSG00000166579; Homo sapiens. [Genome view]

GeneID

81565.

KEGG

hsa:81565.

UCSC

uc002glj.1. human.

Organism-specific databases

CTD

81565.

GeneCards

GC17P008279.

H-InvDB

HIX0039120.

HGNC

HGNC:17620. NDEL1.

HPA

HPA017916.

MIM

607538. gene.

PharmGKB

PA134887314.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9GZM8.

OMA

NATKFSH.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_a_pathway. Aurora A signaling.
lis1pathway. Lissencephaly gene (LIS1) in neuronal migration and development.

Reactome

REACT_152. Cell Cycle, Mitotic.

Gene expression databases

ArrayExpress

Q9GZM8.

Bgee

Q9GZM8.

CleanEx

HS_NDEL1.

Genevestigator

Q9GZM8.

GermOnline

ENSG00000166579. Homo sapiens.

Family and domain databases

InterPro

IPR006964. NUDE_C.
[Graphical view]

Pfam

PF04880. NUDE_C. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

71846.

SOURCE

Search...

Entry information

Entry name

NDEL1_HUMAN

Accession

Primary (citable) accession number: Q9GZM8
Secondary accession number(s): Q86T80, Q8TAR7, Q9UH50

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 13, 2006
Last sequence update:	March 1, 2001
Last modified:	November 3, 2009
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.