Reviewed, UniProtKB/Swiss-Prot O14777 (NDC80_HUMAN)

Names and origin

Protein names

Recommended name:
    Kinetochore protein NDC80 homolog
Alternative name(s):
    Kinetochore protein Hec1
      Short name=HsHec1
    Kinetochore-associated protein 2
    Highly expressed in cancer protein
    Retinoblastoma-associated protein HEC

Gene names

Name:	NDC80
Synonyms:	HEC, HEC1, KNTC2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	642 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 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.22 Ref.3 Ref.4 Ref.5 Ref.6 Ref.15 Ref.21
Subcellular location	Nucleus. Kinetochore. Note: Localizes to kinetochores from late prophase to anaphase. Localizes specifically to the outer plate of the kinetochore. Ref.1 Ref.7 Ref.8 Ref.20 Ref.22 Ref.3 Ref.12 Ref.14 Ref.17 Ref.18
Developmental stage	Expression peaks in mitosis. Ref.1 Ref.22 Ref.3
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 Ref.23
Sequence similarities	Belongs to the NDC80/HEC1 family.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Kinetochore Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW mitotic sister chromatid segregation Ref.1 Traceable author statement. Source: ProtInc phosphoinositide-mediated signaling Non-traceable author statement. Source: UniProtKB spindle organization Non-traceable author statement. Source: UniProtKB
Cellular component	condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.13 Ref.18 Ref.21 Ref.22 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CENPH	Q9H3R5	2	EBI-715849,EBI-1003700
NUF2	Q9BZD4	1	EBI-715849,EBI-999865
SPC25	Q9HBM1	3	EBI-715849,EBI-999909
ZWINT	O95229	2	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

55

1

Phosphoserine Ref.23

Modified residue

62

1

Phosphoserine Ref.23

Modified residue

76

1

Phosphoserine Ref.23

Modified residue

77

1

Phosphoserine Ref.23

Modified residue

165

1

Phosphoserine; by NEK2 Ref.6

Natural variations

Natural variant

66

1

S → A: dbSNP rs16943490.

VAR_027436

Natural variant

348

1

E → D: dbSNP rs12456560.

VAR_027437

Natural variant

605

1

A → P: dbSNP rs1983346.

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

196 – 200

5

Helix

222 – 238

17

Helix

244 – 258

15

Helix

264 – 290

27

Turn

291 – 295

5

Helix

296 – 306

11

Sequences

	Sequence		Length	Mass (Da)
	O14777-1 [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: 9315664] [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: 15489334] [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: 9295362] [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: 10409732] [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: 10779342] [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: 12386167] [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: 12351790] [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: 14654001] [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: 15235793] [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: 15062103] [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: 15239953] [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: 15133482] [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: 14699129] [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: 14978040] [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: 14602875] [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: 15502821] [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: 15964272] [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: 15961401] [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: 15824131] [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: 15548592] [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: 15713649] [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: 16732327] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZWINT, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[23]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55; SER-62; SER-76 AND SER-77, MASS SPECTROMETRY. Tissue: Epithelium.
[24]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

IPI

IPI00005791.

RefSeq

NP_006092.1.

UniGene

Hs.414407

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

IntAct

O14777. 16 interactions.

PTM databases

PhosphoSite

O14777.

Proteomic databases

PeptideAtlas

O14777.

PRIDE

O14777.

Genome annotation databases

Ensembl

ENSG00000080986. Homo sapiens. [Contig view]

GeneID

10403.

KEGG

hsa:10403.

Organism-specific databases

GeneCards

GC18P002562.

H-InvDB

HIX0027354.

HGNC

HGNC:16909. NDC80.

MIM

607272. gene.

PharmGKB

PA134883275.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O14777.

OMA

O14777. LEMVATH.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_b_pathway. Aurora B signaling.

Reactome

REACT_152. Cell Cycle, Mitotic.

Gene expression databases

ArrayExpress

O14777.

Bgee

O14777.

CleanEx

HS_NDC80.

GermOnline

ENSG00000080986. Homo sapiens.

Family and domain databases

InterPro

IPR005550. Kinetochore_Ndc80.
[Graphical view]

PANTHER

PTHR10643. Ndc80_HEC. 1 hit.

Pfam

PF03801. Ndc80_HEC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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:	June 16, 2009
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)