O14777 (NDC80_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kinetochore protein NDC80 homolog

Alternative name(s):
Highly expressed in cancer protein
Kinetochore protein Hec1
Short name=HsHec1
Kinetochore-associated protein 2
Retinoblastoma-associated protein HEC

Gene names

Name:	NDC80
Synonyms:	HEC, HEC1, KNTC2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	642 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.20 Ref.22
Subunit structure	Component of the NDC80 complex, which consists of NDC80/HEC1, CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24-SPBC25. Each subcomplex is formed by parallel interactions through the coiled-coil domains of individual subunits. Formation of a tetrameric complex is mediated by interactions between the C-terminal regions of both subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 complex has an elongated rod-like structure with globular domains at either end. Interacts with isoform 1 of NEK2 and ZWINT specifically during mitosis. Interacts with CENPH and MIS12. May interact with AURKB, PSMC2, PSMC5 and SMC1A. May interact with RB1 during G2 phase and mitosis. Ref.3 Ref.4 Ref.5 Ref.6 Ref.13 Ref.15 Ref.16 Ref.19 Ref.21 Ref.22
Subcellular location	Nucleus. Chromosome › centromere › kinetochore. Note: Localizes to kinetochores from late prophase to anaphase. Localizes specifically to the outer plate of the kinetochore. Ref.1 Ref.3 Ref.7 Ref.8 Ref.12 Ref.14 Ref.17 Ref.18 Ref.20 Ref.22
Developmental stage	Expression peaks in mitosis. Ref.1 Ref.3 Ref.22
Post-translational modification	Phosphorylation begins in S phase of the cell cycle and peaks in mitosis. Phosphorylated by NEK2. May also be phosphorylated by AURKA and AURKB. Ref.6 Ref.15
Sequence similarities	Belongs to the NDC80/HEC1 family.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Centromere Chromosome Kinetochore Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	attachment of spindle microtubules to kinetochore Inferred from mutant phenotype PubMed 19468067. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW establishment of mitotic spindle orientation Inferred from mutant phenotype PubMed 19468067. Source: UniProtKB mitotic prometaphase Traceable author statement. Source: Reactome mitotic sister chromatid segregation Traceable author statement Ref.1. Source: ProtInc mitotic spindle organization Inferred from mutant phenotype Ref.13. Source: UniProtKB phosphatidylinositol-mediated signaling Non-traceable author statement PubMed 15504738. Source: UniProtKB
Cellular_component	Ndc80 complex Inferred from direct assay Ref.13. Source: UniProtKB condensed nuclear chromosome outer kinetochore Inferred from direct assay PubMed 18195732. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CENPH	Q9H3R5	3	EBI-715849,EBI-1003700
NUF2	Q9BZD4	10	EBI-715849,EBI-724102
SPC25	Q9HBM1	9	EBI-715849,EBI-999909
ZWINT	O95229	11	EBI-715849,EBI-1001132

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 642

642

Kinetochore protein NDC80 homolog

PRO_0000249550

Regions

Region

1 – 445

445

Interaction with the N-terminus of CDCA1

Region

1 – 250

250

Nuclear localization

Region

128 – 251

124

Interaction with RB1

Region

251 – 618

368

Interaction with NEK2 and ZWINT

Region

251 – 431

181

Interaction with SMC1A

Region

361 – 547

187

Interaction with PSMC2 and SMC1A

Region

446 – 642

197

Interaction with the C-terminus of CDCA1 and the SPBC24-SPBC25 subcomplex

Coiled coil

261 – 403

143

Potential

Coiled coil

458 – 642

185

Potential

Amino acid modifications

Modified residue

69

1

Phosphoserine Ref.23

Modified residue

165

1

Phosphoserine; by NEK2 Ref.6

Natural variations

Natural variant

66

1

S → A.
Corresponds to variant rs16943490 [ dbSNP | Ensembl ].

VAR_027436

Natural variant

348

1

E → D.
Corresponds to variant rs12456560 [ dbSNP | Ensembl ].

VAR_027437

Natural variant

605

1

A → P.
Corresponds to variant rs1983346 [ dbSNP | Ensembl ].

VAR_027438

Experimental info

Mutagenesis

234

1

E → K: Abrogates binding to RB1. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

642

Helix Strand Turn

Details...

Helix

89 – 105

17

Turn

114 – 117

4

Helix

122 – 133

12

Turn

134 – 136

3

Helix

147 – 157

11

Helix

166 – 170

5

Turn

171 – 173

3

Turn

175 – 177

3

Helix

178 – 194

17

Helix

222 – 238

17

Helix

244 – 258

15

Helix

264 – 286

23

Sequences

	Sequence		Length	Mass (Da)
	O14777 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 6A82DA4D8B77ECDC	FASTA	642	73,913
	10 20 30 40 50 60 MKRSSVSSGG AGRLSMQELR SQDVNKQGLY TPQTKEKPTF GKLSINKPTS ERKVSLFGKR 70 80 90 100 110 120 TSGHGSRNSQ LGIFSSSEKI KDPRPLNDKA FIQQCIRQLC EFLTENGYAH NVSMKSLQAP 130 140 150 160 170 180 SVKDFLKIFT FLYGFLCPSY ELPDTKFEEE VPRIFKDLGY PFALSKSSMY TVGAPHTWPH 190 200 210 220 230 240 IVAALVWLID CIKIHTAMKE SSPLFDDGQP WGEETEDGIM HNKLFLDYTI KCYESFMSGA 250 260 270 280 290 300 DSFDEMNAEL QSKLKDLFNV DAFKLESLEA KNRALNEQIA RLEQEREKEP NRLESLRKLK 310 320 330 340 350 360 ASLQGDVQKY QAYMSNLESH SAILDQKLNG LNEEIARVEL ECETIKQENT RLQNIIDNQK 370 380 390 400 410 420 YSVADIERIN HERNELQQTI NKLTKDLEAE QQKLWNEELK YARGKEAIET QLAEYHKLAR 430 440 450 460 470 480 KLKLIPKGAE NSKGYDFEIK FNPEAGANCL VKYRAQVYVP LKELLNETEE EINKALNKKM 490 500 510 520 530 540 GLEDTLEQLN AMITESKRSV RTLKEEVQKL DDLYQQKIKE AEEEDEKCAS ELESLEKHKH 550 560 570 580 590 600 LLESTVNQGL SEAMNELDAV QREYQLVVQT TTEERRKVGN NLQRLLEMVA THVGSVEKHL 610 620 630 640 EEQIAKVDRE YEECMSEDLS ENIKEIRDKY EKKATLIKSS EE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"HEC, a novel nuclear protein rich in leucine heptad repeats specifically involved in mitosis." Chen Y., Riley D.J., Chen P.-L., Lee W.-H. Mol. Cell. Biol. 17:6049-6056(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Lymph.
[3]	"HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins." Chen Y., Sharp Z.D., Lee W.-H. J. Biol. Chem. 272:24081-24087(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEK2; PSMC2; PSMC5 AND SMC1A, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[4]	"Hec1p, an evolutionarily conserved coiled-coil protein, modulates chromosome segregation through interaction with SMC proteins." Zheng L., Chen Y., Lee W.-H. Mol. Cell. Biol. 19:5417-5428(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEK2; PSMC2; PSMC5; RB1 AND SMC1A.
[5]	"Retinoblastoma protein enhances the fidelity of chromosome segregation mediated by hsHec1p." Zheng L., Chen Y., Riley D.J., Chen P.-L., Lee W.-H. Mol. Cell. Biol. 20:3529-3537(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RB1 AND SMC1A, MUTAGENESIS OF GLU-234.
[6]	"Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is essential for faithful chromosome segregation." Chen Y., Riley D.J., Zheng L., Chen P.-L., Lee W.-H. J. Biol. Chem. 277:49408-49416(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEK2, PHOSPHORYLATION AT SER-165 BY NEK2.
[7]	"Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2." Martin-Lluesma S., Stucke V.M., Nigg E.A. Science 297:2267-2270(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores." DeLuca J.G., Howell B.J., Canman J.C., Hickey J.M., Fang G., Salmon E.D. Curr. Biol. 13:2103-2109(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]	"Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1." Stucke V.M., Baumann C., Nigg E.A. Chromosoma 113:1-15(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo." Joseph J., Liu S.-T., Jablonski S.A., Yen T.J., Dasso M. Curr. Biol. 14:611-617(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Timing and checkpoints in the regulation of mitotic progression." Meraldi P., Draviam V.M., Sorger P.K. Dev. Cell 7:45-60(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Sgt1 is required for human kinetochore assembly." Steensgaard P., Garre M., Muradore I., Transidico P., Nigg E.A., Kitagawa K., Earnshaw W.C., Faretta M., Musacchio A. EMBO Rep. 5:626-631(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[13]	"Identification of two novel components of the human NDC80 kinetochore complex." Bharadwaj R., Qi W., Yu H. J. Biol. Chem. 279:13076-13085(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE NDC80 COMPLEX.
[14]	"NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling." Lou Y., Yao J., Zereshki A., Dou Z., Ahmed K., Wang H., Hu J., Wang Y., Yao X. J. Biol. Chem. 279:20049-20057(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[15]	"Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model." Tien A.-C., Lin M.-H., Su L.-J., Hong Y.-R., Cheng T.-S., Lee Y.-C.G., Lin W.-J., Still I.H., Huang C.-Y.F. Mol. Cell. Proteomics 3:93-104(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AURKB AND CDCA1, PHOSPHORYLATION BY AURKA AND AURKB.
[16]	"A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1." Obuse C., Iwasaki O., Kiyomitsu T., Goshima G., Toyoda Y., Yanagida M. Nat. Cell Biol. 6:1135-1141(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH MIS12.
[17]	"Polo-like kinase 1 creates the tension-sensing 3F3/2 phosphoepitope and modulates the association of spindle-checkpoint proteins at kinetochores." Ahonen L.J., Kallio M.J., Daum J.R., Bolton M., Manke I.A., Yaffe M.B., Stukenberg P.T., Gorbsky G.J. Curr. Biol. 15:1078-1089(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[18]	"Architecture of the human Ndc80-Hec1 complex, a critical constituent of the outer kinetochore." Ciferri C., De Luca J., Monzani S., Ferrari K.J., Ristic D., Wyman C., Stark H., Kilmartin J., Salmon E.D., Musacchio A. J. Biol. Chem. 280:29088-29095(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE NDC80 COMPLEX, SUBCELLULAR LOCATION.
[19]	"ZW10 links mitotic checkpoint signaling to the structural kinetochore." Kops G.J.P.L., Kim Y., Weaver B.A.A., Mao Y., McLeod I., Yates J.R. III, Tagaya M., Cleveland D.W. J. Cell Biol. 169:49-60(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH ZWINT.
[20]	"Hec1 and Nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites." DeLuca J.G., Dong Y., Hergert P., Strauss J., Hickey J.M., Salmon E.D., McEwen B.F. Mol. Biol. Cell 16:519-531(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[21]	"The functional region of CENP-H interacts with the Nuf2 complex that localizes to centromere during mitosis." Mikami Y., Hori T., Kimura H., Fukagawa T. Mol. Cell. Biol. 25:1958-1970(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CENPH.
[22]	"Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful chromosome segregation and spindle checkpoint control." Lin Y.-T., Chen Y., Wu G., Lee W.-H. Oncogene 25:6901-6914(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZWINT, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[23]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[24]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF017790 mRNA. Translation: AAB80726.1.
BC010171 mRNA. No translation available.

IPI

IPI00005791.

RefSeq

NP_006092.1. NM_006101.2.

UniGene

Hs.414407.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IGP	X-ray	1.80	A	81-196	[»]
2VE7	X-ray	2.88	A/B	80-286	[»]
3IZ0	electron microscopy	-	C/E	80-286	[»]

ProteinModelPortal

O14777.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14777. 23 interactions.

MINT

MINT-1411676.

STRING

9606.ENSP00000261597.

PTM databases

PhosphoSite

O14777.

Proteomic databases

PaxDb

O14777.

PeptideAtlas

O14777.

PRIDE

O14777.

Protocols and materials databases

DNASU

10403.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261597; ENSP00000261597; ENSG00000080986.

GeneID

10403.

KEGG

hsa:10403.

UCSC

uc002kli.3. human.

Organism-specific databases

CTD

10403.

GeneCards

GC18P002571.

HGNC

HGNC:16909. NDC80.

MIM

607272. gene.

neXtProt

NX_O14777.

PharmGKB

PA162397359.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5185.

HOGENOM

HOG000012981.

HOVERGEN

HBG081861.

InParanoid

O14777.

KO

K11547.

OMA

REYEECM.

OrthoDB

EOG4V9TQF.

PhylomeDB

O14777.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_b_pathway. Aurora B signaling.

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

Gene expression databases

ArrayExpress

O14777.

Bgee

O14777.

CleanEx

HS_NDC80.

Genevestigator

O14777.

GermOnline

ENSG00000080986. Homo sapiens.

Family and domain databases

InterPro

IPR005550. Kinetochore_Ndc80.
[Graphical view]

PANTHER

PTHR10643. PTHR10643. 1 hit.

Pfam

PF03801. Ndc80_HEC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5660.

ChiTaRS

NDC80. human.

EvolutionaryTrace

O14777.

GenomeRNAi

10403.

NextBio

39424.

SOURCE

Search...

Entry information

Entry name

NDC80_HUMAN

Accession

Primary (citable) accession number: O14777
Secondary accession number(s): Q6PJX2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2006
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.