ID KIF2C_MOUSE Reviewed; 721 AA. AC Q922S8; A2AE71; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 176. DE RecName: Full=Kinesin-like protein KIF2C; DE AltName: Full=Mitotic centromere-associated kinesin; DE Short=MCAK; GN Name=Kif2c; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 183-585 IN COMPLEX WITH ADP AND RP ATP ANALOG, FUNCTION, AND MUTAGENESIS OF LYS-293; VAL-294 AND ASP-295. RX PubMed=14980225; DOI=10.1016/s0092-8674(04)00129-1; RA Ogawa T., Nitta R., Okada Y., Hirokawa N.; RT "A common mechanism for microtubule destabilizers-M type kinesins stabilize RT curling of the protofilament using the class-specific neck and loops."; RL Cell 116:591-602(2004). CC -!- FUNCTION: In complex with KIF18B, constitutes the major microtubule CC plus-end depolymerizing activity in mitotic cells (PubMed:14980225). CC Regulates the turnover of microtubules at the kinetochore and functions CC in chromosome segregation during mitosis. Plays a role in chromosome CC congression and is required for the lateral to end-on conversion of the CC chromosome-microtubule attachment (By similarity). CC {ECO:0000250|UniProtKB:Q99661, ECO:0000269|PubMed:14980225}. CC -!- SUBUNIT: Interacts with CENPH. Interacts with MTUS2/TIP150; the CC interaction is direct. Interacts with MAPRE1; the interaction is CC direct, regulated by phosphorylation and is probably required for CC targeting to growing microtubule plus ends. Interacts with KIF18B at CC microtubule tips; this interaction increases the affinity of both CC partners for microtubule plus ends and is required for robust CC microtubule depolymerization. Phosphorylation by AURKA or AURKB CC strongly reduces KIF18B-binding. {ECO:0000250|UniProtKB:Q99661}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:Q99661}. Nucleus {ECO:0000250|UniProtKB:P70096}. CC Chromosome, centromere {ECO:0000250|UniProtKB:Q99661}. Chromosome, CC centromere, kinetochore {ECO:0000250|UniProtKB:Q99661}. Note=Associates CC with the microtubule network at the growing distal tip (the plus-end) CC of microtubules, probably through interaction with MTUS2/TIP150 and CC MAPRE1. Association with microtubule plus ends is also mediated by CC interaction with KIF18B. Centromeric localization requires the presence CC of BUB1 and SGO2. {ECO:0000250|UniProtKB:P70096, CC ECO:0000250|UniProtKB:Q99661}. CC -!- DOMAIN: The microtubule tip localization signal (MtLS) motif; mediates CC interaction with MAPRE1 and targeting to the growing microtubule plus CC ends. {ECO:0000250|UniProtKB:Q99661}. CC -!- PTM: Phosphorylation by AURKB, regulates association with centromeres CC and kinetochores and the microtubule depolymerization activity. CC {ECO:0000250|UniProtKB:Q99661}. CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q99661}. CC -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase CC superfamily. Kinesin family. MCAK/KIF2 subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00283}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL671866; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC006841; AAH06841.1; -; mRNA. DR CCDS; CCDS18531.1; -. DR RefSeq; NP_608301.3; NM_134471.4. DR PDB; 1V8J; X-ray; 3.24 A; A=183-585. DR PDB; 1V8K; X-ray; 2.25 A; A=183-585. DR PDB; 3EDL; EM; 28.00 A; D=255-585. DR PDB; 5XJA; X-ray; 3.43 A; A/B=183-585. DR PDB; 5XJB; X-ray; 3.10 A; A/B=184-585. DR PDBsum; 1V8J; -. DR PDBsum; 1V8K; -. DR PDBsum; 3EDL; -. DR PDBsum; 5XJA; -. DR PDBsum; 5XJB; -. DR AlphaFoldDB; Q922S8; -. DR SMR; Q922S8; -. DR BioGRID; 216265; 23. DR IntAct; Q922S8; 13. DR STRING; 10090.ENSMUSP00000064261; -. DR iPTMnet; Q922S8; -. DR PhosphoSitePlus; Q922S8; -. DR EPD; Q922S8; -. DR jPOST; Q922S8; -. DR MaxQB; Q922S8; -. DR PaxDb; 10090-ENSMUSP00000064261; -. DR ProteomicsDB; 263604; -. DR Pumba; Q922S8; -. DR Antibodypedia; 1212; 499 antibodies from 34 providers. DR DNASU; 73804; -. DR Ensembl; ENSMUST00000065896.9; ENSMUSP00000064261.3; ENSMUSG00000028678.14. DR GeneID; 73804; -. DR KEGG; mmu:73804; -. DR UCSC; uc008uie.3; mouse. DR AGR; MGI:1921054; -. DR CTD; 11004; -. DR MGI; MGI:1921054; Kif2c. DR VEuPathDB; HostDB:ENSMUSG00000028678; -. DR eggNOG; KOG0246; Eukaryota. DR GeneTree; ENSGT00940000154046; -. DR InParanoid; Q922S8; -. DR OMA; RTTLECH; -. DR OrthoDB; 239968at2759; -. DR PhylomeDB; Q922S8; -. DR TreeFam; TF105222; -. DR Reactome; R-MMU-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal. DR Reactome; R-MMU-2132295; MHC class II antigen presentation. DR Reactome; R-MMU-2467813; Separation of Sister Chromatids. DR Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion. DR Reactome; R-MMU-5663220; RHO GTPases Activate Formins. DR Reactome; R-MMU-6811434; COPI-dependent Golgi-to-ER retrograde traffic. DR Reactome; R-MMU-68877; Mitotic Prometaphase. DR Reactome; R-MMU-9648025; EML4 and NUDC in mitotic spindle formation. DR Reactome; R-MMU-983189; Kinesins. DR BioGRID-ORCS; 73804; 9 hits in 80 CRISPR screens. DR ChiTaRS; Kif2c; mouse. DR EvolutionaryTrace; Q922S8; -. DR PRO; PR:Q922S8; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; Q922S8; Protein. DR Bgee; ENSMUSG00000028678; Expressed in otic placode and 202 other cell types or tissues. DR ExpressionAtlas; Q922S8; baseline and differential. DR GO; GO:0005813; C:centrosome; IBA:GO_Central. DR GO; GO:0000775; C:chromosome, centromeric region; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW. DR GO; GO:0005871; C:kinesin complex; IBA:GO_Central. DR GO; GO:0000776; C:kinetochore; ISS:UniProtKB. DR GO; GO:0005874; C:microtubule; IBA:GO_Central. DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI. DR GO; GO:0035371; C:microtubule plus-end; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005819; C:spindle; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central. DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central. DR GO; GO:0003777; F:microtubule motor activity; IBA:GO_Central. DR GO; GO:0051010; F:microtubule plus-end binding; ISS:UniProtKB. DR GO; GO:0051315; P:attachment of mitotic spindle microtubules to kinetochore; ISS:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0030951; P:establishment or maintenance of microtubule cytoskeleton polarity; ISO:MGI. DR GO; GO:0051310; P:metaphase chromosome alignment; ISS:UniProtKB. DR GO; GO:0007019; P:microtubule depolymerization; ISO:MGI. DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central. DR GO; GO:0007080; P:mitotic metaphase chromosome alignment; ISS:UniProtKB. DR GO; GO:0051983; P:regulation of chromosome segregation; ISO:MGI. DR CDD; cd01367; KISc_KIF2_like; 1. DR Gene3D; 3.40.850.10; Kinesin motor domain; 1. DR InterPro; IPR027640; Kinesin-like_fam. DR InterPro; IPR019821; Kinesin_motor_CS. DR InterPro; IPR001752; Kinesin_motor_dom. DR InterPro; IPR036961; Kinesin_motor_dom_sf. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR47971:SF19; KINESIN-LIKE PROTEIN; 1. DR PANTHER; PTHR47971; KINESIN-RELATED PROTEIN 6; 1. DR Pfam; PF00225; Kinesin; 1. DR PRINTS; PR00380; KINESINHEAVY. DR SMART; SM00129; KISc; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00411; KINESIN_MOTOR_1; 1. DR PROSITE; PS50067; KINESIN_MOTOR_2; 1. DR Genevisible; Q922S8; MM. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell cycle; Cell division; Centromere; KW Chromosome; Chromosome partition; Coiled coil; Cytoplasm; Cytoskeleton; KW Kinetochore; Microtubule; Mitosis; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..721 FT /note="Kinesin-like protein KIF2C" FT /id="PRO_0000125420" FT DOMAIN 254..584 FT /note="Kinesin motor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283" FT REGION 1..250 FT /note="Globular" FT /evidence="ECO:0000255" FT REGION 164..188 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 203..234 FT /note="Negative regulator of microtubule-binding" FT COILED 614..652 FT /evidence="ECO:0000255" FT MOTIF 95..98 FT /note="Microtubule tip localization signal" FT BINDING 260 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 344..351 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT MOD_RES 3 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99661" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99661" FT MOD_RES 92 FT /note="Phosphoserine; by AURKB" FT /evidence="ECO:0000250|UniProtKB:Q99661" FT MOD_RES 106 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70096" FT MOD_RES 108 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70096" FT MOD_RES 112 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70096" FT MOD_RES 162 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99661" FT MOD_RES 171 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99661" FT MOD_RES 183 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99661" FT MOD_RES 188 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70096" FT MOD_RES 515 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99661" FT MOD_RES 626 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99661" FT MUTAGEN 293 FT /note="K->A: Loss of microtubule depolymerization FT activity." FT /evidence="ECO:0000269|PubMed:14980225" FT MUTAGEN 294 FT /note="V->A: Loss of microtubule depolymerization FT activity." FT /evidence="ECO:0000269|PubMed:14980225" FT MUTAGEN 295 FT /note="D->A: Loss of microtubule depolymerization FT activity." FT /evidence="ECO:0000269|PubMed:14980225" FT HELIX 226..239 FT /evidence="ECO:0007829|PDB:1V8K" FT TURN 243..247 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:5XJB" FT STRAND 255..261 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 266..270 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 281..292 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 298..306 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 308..311 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 317..323 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 326..328 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 329..333 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 337..345 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 350..355 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 365..367 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 369..381 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 384..387 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 392..401 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 404..407 FT /evidence="ECO:0007829|PDB:1V8K" FT TURN 408..412 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 414..419 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 421..423 FT /evidence="ECO:0007829|PDB:1V8J" FT STRAND 425..428 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 433..437 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 438..450 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 465..488 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 506..508 FT /evidence="ECO:0007829|PDB:1V8J" FT HELIX 509..526 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 539..543 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 546..549 FT /evidence="ECO:0007829|PDB:1V8K" FT STRAND 550..561 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 565..567 FT /evidence="ECO:0007829|PDB:1V8K" FT HELIX 568..582 FT /evidence="ECO:0007829|PDB:1V8K" SQ SEQUENCE 721 AA; 81085 MW; 92FFBFFDA05B7E35 CRC64; MESLHARLFP GLSINIQRSN GLIHPANIST VNVEKSCVSV EWIEGGTTKG KEIDIDDVAA INPELLQLLP LRPKDSLPLQ ENVTVPKQKR KSVNSKIPAL KEGLRSRSTR MSTVSEVRIP AQENEMEVEL PVPTNSRKQF AIPSHPRASC STVTELPLLM VSEEAEEQAH STRSTSSANP GNSVRRKSCI VKEMEKMKNK REEKRAQNSE LRIKRAQEYD SSFPNWEFAR MIKEFRVTME CSPLTVTDPI EEHRICVCVR KRPLNKQELA KKEIDVISVP SKCLLLVHEP KLKVDLTKYL ENQAFCFDFA FDETASNEVV YRFTARPLVQ TIFEGGKATC FAYGQTGSGK THTMGGDLSG KSQNASKGIY AMASRDVFLL KNQPRYRNLN LEVYVTFFEI YNGKVFDLLN KKAKLRVLED SRQQVQVVGL QEYLVTCADD VIKMINMGSA CRTSGQTFAN SNSSRSHACF QILLRTKGRL HGKFSLVDLA GNERGADTSS ADRQTRMEGA EINKSLLALK ECIRALGQNK AHTPFRESKL TQVLRDSFIG ENSRTCMIAM ISPGISSCEY TLNTLRYADR VKELSPHSGP SGEQPVQMET EVMEASSNGT SLTGNEEEEL SSQMSSFNEA MTQIRELEER ALEELREIIQ QGPNWLELSE MTDQPDYDLE TFVNKAESAL TQQAKQAKHF SALREVIKAL RLAMQLEEQA SKQINSKKRH Q //