Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O14777 (NDC80_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length642 AA.
Sequence statusComplete.
Protein existenceEvidence 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 1of 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. Chromosomecentromerekinetochore. 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 processCell cycle
Cell division
Mitosis
   Cellular componentCentromere
Chromosome
Kinetochore
Nucleus
   Coding sequence diversityPolymorphism
   DomainCoiled coil
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processattachment of spindle microtubules to kinetochore

Inferred from mutant phenotype PubMed 19468067. Source: UniProtKB

cell cycle

Non-traceable author statement PubMed 15504738. Source: UniProtKB

chromosome segregation

Inferred from mutant phenotype Ref.13. Source: UniProtKB

establishment of mitotic spindle orientation

Inferred from mutant phenotype PubMed 19468067. Source: UniProtKB

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic nuclear division

Traceable author statement Ref.1. Source: ProtInc

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

spindle organization

Non-traceable author statement PubMed 15504738. Source: UniProtKB

   Cellular_componentNdc80 complex

Inferred from direct assay Ref.13. Source: UniProtKB

chromosome, centromeric region

Traceable author statement Ref.1. Source: ProtInc

condensed chromosome kinetochore

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

kinetochore

Inferred from direct assay PubMed 17363900PubMed 19468067. Source: UniProtKB

nucleus

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionprotein binding

Inferred from physical interaction Ref.13. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 642642Kinetochore protein NDC80 homolog
PRO_0000249550

Regions

Region1 – 445445Interaction with the N-terminus of CDCA1
Region1 – 250250Nuclear localization
Region128 – 251124Interaction with RB1
Region251 – 618368Interaction with NEK2 and ZWINT
Region251 – 431181Interaction with SMC1A
Region361 – 547187Interaction with PSMC2 and SMC1A
Region446 – 642197Interaction with the C-terminus of CDCA1 and the SPBC24-SPBC25 subcomplex
Coiled coil261 – 403143 Potential
Coiled coil458 – 642185 Potential

Amino acid modifications

Modified residue691Phosphoserine Ref.23
Modified residue1651Phosphoserine; by NEK2 Ref.6

Natural variations

Natural variant661S → A.
Corresponds to variant rs16943490 [ dbSNP | Ensembl ].
VAR_027436
Natural variant3481E → D.
Corresponds to variant rs12456560 [ dbSNP | Ensembl ].
VAR_027437
Natural variant6051A → P.
Corresponds to variant rs1983346 [ dbSNP | Ensembl ].
VAR_027438

Experimental info

Mutagenesis2341E → K: Abrogates binding to RB1. Ref.5

Secondary structure

...................... 642
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O14777 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 6A82DA4D8B77ECDC

FASTA64273,913
        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 

« Hide

References

« Hide '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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.
CCDSCCDS11827.1.
RefSeqNP_006092.1. NM_006101.2.
UniGeneHs.414407.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IGPX-ray1.80A81-196[»]
2VE7X-ray2.88A/B80-286[»]
3IZ0electron microscopy-C/E80-286[»]
ProteinModelPortalO14777.
SMRO14777. Positions 80-302.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115675. 34 interactions.
IntActO14777. 33 interactions.
MINTMINT-1411676.
STRING9606.ENSP00000261597.

Chemistry

ChEMBLCHEMBL5660.

PTM databases

PhosphoSiteO14777.

Proteomic databases

MaxQBO14777.
PaxDbO14777.
PeptideAtlasO14777.
PRIDEO14777.

Protocols and materials databases

DNASU10403.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261597; ENSP00000261597; ENSG00000080986.
GeneID10403.
KEGGhsa:10403.
UCSCuc002kli.3. human.

Organism-specific databases

CTD10403.
GeneCardsGC18P002571.
HGNCHGNC:16909. NDC80.
MIM607272. gene.
neXtProtNX_O14777.
PharmGKBPA162397359.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5185.
HOGENOMHOG000012981.
HOVERGENHBG081861.
InParanoidO14777.
KOK11547.
OMAREYEECM.
OrthoDBEOG7NSB3P.
PhylomeDBO14777.
TreeFamTF101177.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
SignaLinkO14777.

Gene expression databases

ArrayExpressO14777.
BgeeO14777.
CleanExHS_NDC80.
GenevestigatorO14777.

Family and domain databases

InterProIPR005550. Kinetochore_Ndc80.
[Graphical view]
PANTHERPTHR10643. PTHR10643. 1 hit.
PfamPF03801. Ndc80_HEC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNDC80. human.
EvolutionaryTraceO14777.
GeneWikiNDC80.
GenomeRNAi10403.
NextBio39424.
PROO14777.
SOURCESearch...

Entry information

Entry nameNDC80_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM