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Protein

Kinesin-like protein KIF2C

Gene

KIF2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

In complex with KIF18B, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells (PubMed:21820309). Regulates the turnover of microtubules at the kinetochore and functions in chromosome segregation during mitosis (PubMed:19060894). Plays a role in chromosome congression and is required for the lateral to end-on conversion of the chromosome-microtubule attachment (PubMed:23891108).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei264ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi348 – 355ATP8

GO - Molecular functioni

  • ATPase activity Source: GO_Central
  • ATP binding Source: UniProtKB-KW
  • centromeric DNA binding Source: ProtInc
  • microtubule motor activity Source: ProtInc
  • microtubule plus-end binding Source: UniProtKB

GO - Biological processi

  • antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
  • attachment of mitotic spindle microtubules to kinetochore Source: UniProtKB
  • cell division Source: UniProtKB-KW
  • cell proliferation Source: ProtInc
  • establishment or maintenance of microtubule cytoskeleton polarity Source: HGNC
  • metaphase plate congression Source: UniProtKB
  • microtubule-based movement Source: GO_Central
  • microtubule depolymerization Source: UniProtKB
  • mitotic metaphase plate congression Source: UniProtKB
  • mitotic nuclear division Source: ProtInc
  • regulation of chromosome segregation Source: UniProtKB
  • retrograde vesicle-mediated transport, Golgi to ER Source: Reactome
  • sister chromatid cohesion Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Chromosome partition, Mitosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000142945-MONOMER.
ReactomeiR-HSA-2132295. MHC class II antigen presentation.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-6811434. COPI-dependent Golgi-to-ER retrograde traffic.
R-HSA-68877. Mitotic Prometaphase.
R-HSA-983189. Kinesins.
SIGNORiQ99661.

Names & Taxonomyi

Protein namesi
Recommended name:
Kinesin-like protein KIF2C
Alternative name(s):
Kinesin-like protein 6
Mitotic centromere-associated kinesin
Short name:
MCAK
Gene namesi
Name:KIF2C
Synonyms:KNSL6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6393. KIF2C.

Subcellular locationi

GO - Cellular componenti

  • chromosome, centromeric region Source: UniProtKB
  • condensed chromosome kinetochore Source: UniProtKB-SubCell
  • cytosol Source: Reactome
  • kinesin complex Source: ProtInc
  • kinetochore Source: UniProtKB
  • membrane Source: UniProtKB
  • microtubule cytoskeleton Source: LIFEdb
  • microtubule plus-end Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Microtubule, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi95S → E: Alters interaction with MAPRE1 and association with microtubule growing ends; when associated with E-109 and E-111. 1 Publication1
Mutagenesisi100 – 101IP → NN: Loss of interaction with MAPRE1 and association with microtubule growing ends. 1 Publication2
Mutagenesisi109S → E: Alters interaction with MAPRE1 and association with microtubule growing ends; when associated with E-95 and E-111. 1 Publication1
Mutagenesisi111S → E: Alters interaction with MAPRE1 and association with microtubule growing ends; when associated with E-95 and E-109. 1 Publication1

Organism-specific databases

DisGeNETi11004.
OpenTargetsiENSG00000142945.
PharmGKBiPA30182.

Chemistry databases

ChEMBLiCHEMBL5967.

Polymorphism and mutation databases

BioMutaiKIF2C.
DMDMi20141607.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001254182 – 725Kinesin-like protein KIF2CAdd BLAST724

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei6PhosphoserineCombined sources1
Modified residuei22PhosphoserineCombined sources1
Modified residuei95Phosphoserine; by AURKB1 Publication1
Modified residuei106PhosphoserineCombined sources1
Modified residuei109PhosphoserineBy similarity1
Modified residuei111PhosphoserineBy similarity1
Modified residuei115PhosphoserineCombined sources1
Modified residuei166PhosphoserineCombined sources1
Modified residuei175PhosphoserineCombined sources1
Modified residuei187PhosphoserineCombined sources1
Modified residuei192PhosphoserineBy similarity1
Modified residuei519PhosphoserineCombined sources1
Modified residuei621PhosphoserineCombined sources1
Modified residuei633PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation by AURKB, regulates association with centromeres and kinetochores and the microtubule depolymerization activity.1 Publication
Ubiquitinated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99661.
MaxQBiQ99661.
PaxDbiQ99661.
PeptideAtlasiQ99661.
PRIDEiQ99661.

PTM databases

iPTMnetiQ99661.
PhosphoSitePlusiQ99661.

Expressioni

Tissue specificityi

Expressed at high levels in thymus and testis, at low levels in small intestine, the mucosal lining of colon, and placenta, and at very low levels in spleen and ovary; expression is not detected in prostate, peripheral blood Leukocytes, heart, brain, lung, liver, skeletal muscle, kidney or pancreas. Isoform 2 is testis-specific.2 Publications

Developmental stagei

Isoform 2 is expressed in fetal testis.1 Publication

Gene expression databases

BgeeiENSG00000142945.
CleanExiHS_KIF2C.
ExpressionAtlasiQ99661. baseline and differential.
GenevisibleiQ99661. HS.

Organism-specific databases

HPAiHPA006432.

Interactioni

Subunit structurei

Interacts with CENPH. Interacts with MTUS2/TIP150; the interaction is direct. Interacts with MAPRE1; the interaction is direct, regulated by phosphorylation and is probably required for targeting to growing microtubule plus ends. Interacts with KIF18B at microtubule tips; this interaction increases the affinity of both partners for microtubule plus ends and is required for robust microtubule depolymerization. Phosphorylation by AURKA or AURKB strongly reduces KIF18B-binding.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAPRE1Q156917EBI-1642317,EBI-1004115
MTUS2Q5JR594EBI-1642317,EBI-742948

GO - Molecular functioni

  • microtubule plus-end binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116195. 75 interactors.
IntActiQ99661. 44 interactors.
MINTiMINT-4725759.
STRINGi9606.ENSP00000361298.

Chemistry databases

BindingDBiQ99661.

Structurei

Secondary structure

1725
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi230 – 242Combined sources13
Beta strandi258 – 265Combined sources8
Helixi270 – 274Combined sources5
Beta strandi285 – 296Combined sources12
Beta strandi302 – 310Combined sources9
Beta strandi312 – 315Combined sources4
Helixi321 – 327Combined sources7
Helixi330 – 337Combined sources8
Beta strandi341 – 348Combined sources8
Helixi354 – 358Combined sources5
Helixi373 – 385Combined sources13
Helixi388 – 391Combined sources4
Turni392 – 394Combined sources3
Beta strandi396 – 405Combined sources10
Beta strandi408 – 411Combined sources4
Turni412 – 416Combined sources5
Beta strandi420 – 423Combined sources4
Beta strandi429 – 432Combined sources4
Beta strandi437 – 441Combined sources5
Helixi442 – 455Combined sources14
Helixi467 – 469Combined sources3
Beta strandi470 – 492Combined sources23
Beta strandi507 – 509Combined sources3
Helixi514 – 531Combined sources18
Helixi539 – 541Combined sources3
Helixi543 – 547Combined sources5
Helixi549 – 552Combined sources4
Beta strandi557 – 565Combined sources9
Helixi569 – 571Combined sources3
Helixi572 – 585Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HEHX-ray2.15A225-593[»]
4UBFX-ray3.00A/B/C/D225-593[»]
P709-720[»]
4Y05X-ray2.59A216-599[»]
ProteinModelPortaliQ99661.
SMRiQ99661.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99661.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini258 – 588Kinesin motorPROSITE-ProRule annotationAdd BLAST331

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 254GlobularSequence analysisAdd BLAST253
Regioni207 – 238Negative regulator of microtubule-bindingBy similarityAdd BLAST32

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili618 – 658Sequence analysisAdd BLAST41

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi98 – 101Microtubule tip localization signal4
Motifi415 – 418Nuclear localization signalSequence analysis4

Domaini

The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.1 Publication

Sequence similaritiesi

Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. MCAK/KIF2 subfamily.PROSITE-ProRule annotation
Contains 1 kinesin motor domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0246. Eukaryota.
COG5059. LUCA.
GeneTreeiENSGT00860000133670.
HOVERGENiHBG003875.
InParanoidiQ99661.
KOiK10393.
OMAiFAFDETA.
OrthoDBiEOG091G06V3.
PhylomeDBiQ99661.
TreeFamiTF105222.

Family and domain databases

Gene3Di3.40.850.10. 1 hit.
InterProiIPR027640. Kinesin-like_fam.
IPR019821. Kinesin_motor_CS.
IPR001752. Kinesin_motor_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR24115. PTHR24115. 3 hits.
PfamiPF00225. Kinesin. 1 hit.
[Graphical view]
PRINTSiPR00380. KINESINHEAVY.
SMARTiSM00129. KISc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS00411. KINESIN_MOTOR_1. 1 hit.
PS50067. KINESIN_MOTOR_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99661-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAMDSSLQAR LFPGLAIKIQ RSNGLIHSAN VRTVNLEKSC VSVEWAEGGA
60 70 80 90 100
TKGKEIDFDD VAAINPELLQ LLPLHPKDNL PLQENVTIQK QKRRSVNSKI
110 120 130 140 150
PAPKESLRSR STRMSTVSEL RITAQENDME VELPAAANSR KQFSVPPAPT
160 170 180 190 200
RPSCPAVAEI PLRMVSEEME EQVHSIRGSS SANPVNSVRR KSCLVKEVEK
210 220 230 240 250
MKNKREEKKA QNSEMRMKRA QEYDSSFPNW EFARMIKEFR ATLECHPLTM
260 270 280 290 300
TDPIEEHRIC VCVRKRPLNK QELAKKEIDV ISIPSKCLLL VHEPKLKVDL
310 320 330 340 350
TKYLENQAFC FDFAFDETAS NEVVYRFTAR PLVQTIFEGG KATCFAYGQT
360 370 380 390 400
GSGKTHTMGG DLSGKAQNAS KGIYAMASRD VFLLKNQPCY RKLGLEVYVT
410 420 430 440 450
FFEIYNGKLF DLLNKKAKLR VLEDGKQQVQ VVGLQEHLVN SADDVIKMID
460 470 480 490 500
MGSACRTSGQ TFANSNSSRS HACFQIILRA KGRMHGKFSL VDLAGNERGA
510 520 530 540 550
DTSSADRQTR MEGAEINKSL LALKECIRAL GQNKAHTPFR ESKLTQVLRD
560 570 580 590 600
SFIGENSRTC MIATISPGIS SCEYTLNTLR YADRVKELSP HSGPSGEQLI
610 620 630 640 650
QMETEEMEAC SNGALIPGNL SKEEEELSSQ MSSFNEAMTQ IRELEEKAME
660 670 680 690 700
ELKEIIQQGP DWLELSEMTE QPDYDLETFV NKAESALAQQ AKHFSALRDV
710 720
IKALRLAMQL EEQASRQISS KKRPQ
Length:725
Mass (Da):81,313
Last modified:January 23, 2002 - v2
Checksum:i5BDECC133AB4B55C
GO
Isoform 2 (identifier: Q99661-2) [UniParc]FASTAAdd to basket
Also known as: tsMCAK

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: MAMDSSLQARLFPGLAIKIQRSNGLIHSANVRTVNLEKSCVSVEWAEGGATKGKE → M

Show »
Length:671
Mass (Da):75,561
Checksum:i6A493B16911472C8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti698R → P in AAH08764 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049683449I → L.3 PublicationsCorresponds to variant rs4342887dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0028661 – 55MAMDS…TKGKE → M in isoform 2. 1 PublicationAdd BLAST55

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63743 mRNA. Translation: AAC27660.1.
AY026505 mRNA. Translation: AAK20168.1.
BT006759 mRNA. Translation: AAP35405.1.
CR450302 mRNA. Translation: CAG29298.1.
AB264115 mRNA. Translation: BAG50306.1.
AL592166 Genomic DNA. Translation: CAI12997.1.
AL592166 Genomic DNA. Translation: CAI12999.1.
CH471059 Genomic DNA. Translation: EAX07025.1.
BC008764 mRNA. Translation: AAH08764.1.
BC014924 mRNA. Translation: AAH14924.1.
CCDSiCCDS512.1. [Q99661-1]
CCDS72774.1. [Q99661-2]
RefSeqiNP_001284584.1. NM_001297655.1.
NP_001284585.1. NM_001297656.1. [Q99661-2]
NP_001284586.1. NM_001297657.1.
NP_006836.2. NM_006845.3. [Q99661-1]
UniGeneiHs.720061.

Genome annotation databases

EnsembliENST00000372217; ENSP00000361291; ENSG00000142945. [Q99661-2]
ENST00000372224; ENSP00000361298; ENSG00000142945. [Q99661-1]
GeneIDi11004.
KEGGihsa:11004.
UCSCiuc001cmg.5. human. [Q99661-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63743 mRNA. Translation: AAC27660.1.
AY026505 mRNA. Translation: AAK20168.1.
BT006759 mRNA. Translation: AAP35405.1.
CR450302 mRNA. Translation: CAG29298.1.
AB264115 mRNA. Translation: BAG50306.1.
AL592166 Genomic DNA. Translation: CAI12997.1.
AL592166 Genomic DNA. Translation: CAI12999.1.
CH471059 Genomic DNA. Translation: EAX07025.1.
BC008764 mRNA. Translation: AAH08764.1.
BC014924 mRNA. Translation: AAH14924.1.
CCDSiCCDS512.1. [Q99661-1]
CCDS72774.1. [Q99661-2]
RefSeqiNP_001284584.1. NM_001297655.1.
NP_001284585.1. NM_001297656.1. [Q99661-2]
NP_001284586.1. NM_001297657.1.
NP_006836.2. NM_006845.3. [Q99661-1]
UniGeneiHs.720061.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HEHX-ray2.15A225-593[»]
4UBFX-ray3.00A/B/C/D225-593[»]
P709-720[»]
4Y05X-ray2.59A216-599[»]
ProteinModelPortaliQ99661.
SMRiQ99661.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116195. 75 interactors.
IntActiQ99661. 44 interactors.
MINTiMINT-4725759.
STRINGi9606.ENSP00000361298.

Chemistry databases

BindingDBiQ99661.
ChEMBLiCHEMBL5967.

PTM databases

iPTMnetiQ99661.
PhosphoSitePlusiQ99661.

Polymorphism and mutation databases

BioMutaiKIF2C.
DMDMi20141607.

Proteomic databases

EPDiQ99661.
MaxQBiQ99661.
PaxDbiQ99661.
PeptideAtlasiQ99661.
PRIDEiQ99661.

Protocols and materials databases

DNASUi11004.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372217; ENSP00000361291; ENSG00000142945. [Q99661-2]
ENST00000372224; ENSP00000361298; ENSG00000142945. [Q99661-1]
GeneIDi11004.
KEGGihsa:11004.
UCSCiuc001cmg.5. human. [Q99661-1]

Organism-specific databases

CTDi11004.
DisGeNETi11004.
GeneCardsiKIF2C.
HGNCiHGNC:6393. KIF2C.
HPAiHPA006432.
MIMi604538. gene.
neXtProtiNX_Q99661.
OpenTargetsiENSG00000142945.
PharmGKBiPA30182.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0246. Eukaryota.
COG5059. LUCA.
GeneTreeiENSGT00860000133670.
HOVERGENiHBG003875.
InParanoidiQ99661.
KOiK10393.
OMAiFAFDETA.
OrthoDBiEOG091G06V3.
PhylomeDBiQ99661.
TreeFamiTF105222.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000142945-MONOMER.
ReactomeiR-HSA-2132295. MHC class II antigen presentation.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-6811434. COPI-dependent Golgi-to-ER retrograde traffic.
R-HSA-68877. Mitotic Prometaphase.
R-HSA-983189. Kinesins.
SIGNORiQ99661.

Miscellaneous databases

ChiTaRSiKIF2C. human.
EvolutionaryTraceiQ99661.
GeneWikiiKIF2C.
GenomeRNAii11004.
PROiQ99661.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142945.
CleanExiHS_KIF2C.
ExpressionAtlasiQ99661. baseline and differential.
GenevisibleiQ99661. HS.

Family and domain databases

Gene3Di3.40.850.10. 1 hit.
InterProiIPR027640. Kinesin-like_fam.
IPR019821. Kinesin_motor_CS.
IPR001752. Kinesin_motor_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR24115. PTHR24115. 3 hits.
PfamiPF00225. Kinesin. 1 hit.
[Graphical view]
PRINTSiPR00380. KINESINHEAVY.
SMARTiSM00129. KISc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS00411. KINESIN_MOTOR_1. 1 hit.
PS50067. KINESIN_MOTOR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKIF2C_HUMAN
AccessioniPrimary (citable) accession number: Q99661
Secondary accession number(s): B3ITR9
, Q5JR88, Q6ICU1, Q96C18, Q96HB8, Q9BWV8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 23, 2002
Last modified: November 30, 2016
This is version 173 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.