CKAP5_XENLA
ID CKAP5_XENLA Reviewed; 2065 AA.
AC Q9PT63;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Cytoskeleton-associated protein 5-A;
DE AltName: Full=Microtubule-associated protein 215 kDa;
DE AltName: Full=XMAP215;
GN Name=ckap5-a; Synonyms=xmap215;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355 {ECO:0000312|EMBL:CAB61894.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10620801; DOI=10.1038/71330;
RA Tournebize R., Popov A., Kinoshita K., Ashford A.J., Rybina S.,
RA Pozniakovsky A., Mayer T.U., Walczak C.E., Karsenti E., Hyman A.A.;
RT "Control of microtubule dynamics by the antagonistic activities of XMAP215
RT and XKCM1 in Xenopus egg extracts.";
RL Nat. Cell Biol. 2:13-19(2000).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=11157747; DOI=10.1093/emboj/20.3.397;
RA Popov A.V., Pozniakovsky A., Arnal I., Antony C., Ashford A.J.,
RA Kinoshita K., Tournebize R., Hyman A.A., Karsenti E.;
RT "XMAP215 regulates microtubule dynamics through two distinct domains.";
RL EMBO J. 20:397-410(2001).
RN [3]
RP FUNCTION.
RX PubMed=12176362; DOI=10.1016/s0960-9822(02)01033-3;
RA Popov A.V., Severin F., Karsenti E.;
RT "XMAP215 is required for the microtubule-nucleating activity of
RT centrosomes.";
RL Curr. Biol. 12:1326-1330(2002).
RN [4]
RP FUNCTION.
RX PubMed=18191222; DOI=10.1016/j.cell.2007.11.043;
RA Brouhard G.J., Stear J.H., Noetzel T.L., Al-Bassam J., Kinoshita K.,
RA Harrison S.C., Howard J., Hyman A.A.;
RT "XMAP215 is a processive microtubule polymerase.";
RL Cell 132:79-88(2008).
RN [5]
RP FUNCTION, TOG DOMAIN, AND MUTAGENESIS OF TRP-21; LYS-102; TRP-292; LYS-373;
RP TRP-610; LYS-691; TRP-870; LYS-950; PHE-1250 AND LYS-1335.
RX PubMed=21282620; DOI=10.1073/pnas.1016498108;
RA Widlund P.O., Stear J.H., Pozniakovsky A., Zanic M., Reber S.,
RA Brouhard G.J., Hyman A.A., Howard J.;
RT "XMAP215 polymerase activity is built by combining multiple tubulin-binding
RT TOG domains and a basic lattice-binding region.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2741-2746(2011).
RN [6]
RP FUNCTION.
RX PubMed=23974040; DOI=10.1038/ncb2834;
RA Reber S.B., Baumgart J., Widlund P.O., Pozniakovsky A., Howard J.,
RA Hyman A.A., Juelicher F.;
RT "XMAP215 activity sets spindle length by controlling the total mass of
RT spindle microtubules.";
RL Nat. Cell Biol. 15:1116-1122(2013).
RN [7]
RP SUBCELLULAR LOCATION, INTERACTION WITH TACC3, AND MUTAGENESIS OF LEU-2053;
RP LYS-2054; ILE-2060 AND LYS-2061.
RX PubMed=25262927; DOI=10.1038/ncomms6072;
RA Mortuza G.B., Cavazza T., Garcia-Mayoral M.F., Hermida D., Peset I.,
RA Pedrero J.G., Merino N., Blanco F.J., Lyngsoe J., Bruix M., Pedersen J.S.,
RA Vernos I., Montoya G.;
RT "XTACC3-XMAP215 association reveals an asymmetric interaction promoting
RT microtubule elongation.";
RL Nat. Commun. 5:5072-5072(2014).
CC -!- FUNCTION: Binds to the plus end of microtubules and regulates
CC microtubule dynamics and microtubule organization. Acts as processive
CC microtubule polymerase. Promotes cytoplasmic microtubule nucleation and
CC elongation (PubMed:12176362, PubMed:18191222, PubMed:21282620). Plays a
CC major role in organizing spindle poles (PubMed:23974040). In spindle
CC formation protects kinetochore microtubules from depolymerization by
CC kif2c and has an essential role in centrosomal microtubule assembly
CC independently of kif2c activity. Contributes to centrosome integrity.
CC Acts as component of the TACC3/ch-TOG/clathrin complex proposed to
CC contribute to stabilization of kinetochore fibers of the mitotic
CC spindle by acting as inter-microtubule bridge. Enhances the strength of
CC NDC80 complex-mediated kinetochore-tip microtubule attachments (By
CC similarity). {ECO:0000250|UniProtKB:Q14008,
CC ECO:0000269|PubMed:12176362, ECO:0000269|PubMed:18191222,
CC ECO:0000269|PubMed:21282620, ECO:0000269|PubMed:23974040}.
CC -!- SUBUNIT: Interacts with tacc3; two molecules of ckap5 interact with 1
CC molecule of tacc3 probably mediated by coiled coil domains forming a
CC four-helix bundle. Interacts with tacc3 and clathrin forming the
CC TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules
CC bridges. Interacts with ndc80; indicative for an association with the
CC NDC80 comnplex (By similarity). {ECO:0000250|UniProtKB:Q14008,
CC ECO:0000269|PubMed:25262927}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000269|PubMed:25262927}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:Q14008}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:11157747}. Cytoplasm,
CC cytoskeleton {ECO:0000269|PubMed:11157747}. Chromosome, centromere,
CC kinetochore {ECO:0000250|UniProtKB:Q14008}.
CC -!- DOMAIN: The TOG (tumor overexpressed gene) domains are arranged in a N-
CC terminal pentameric array with each domain composed of six (for the
CC most part non-canonical) HEAT repeats forming a oblong paddle-like
CC structure. Intra-HEAT loops are positioned along a face of the TOG
CC domain and bind to a single alpha/beta-tubulin heterodimer. The TOG
CC domains in the array seem to be structurally and functionally
CC polarized. Differential functions may range from microtubule (MT)
CC lattice binding and/or free tubulin heterodimer binding to potentiating
CC stable incorporation of tubulin into the MT lattice. TOG 1 and TOG 2
CC are critical for microtubule polymerase activity.
CC {ECO:0000250|UniProtKB:Q14008, ECO:0000305|PubMed:21282620}.
CC -!- SIMILARITY: Belongs to the TOG/XMAP215 family. {ECO:0000305}.
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DR EMBL; AJ251130; CAB61894.1; -; mRNA.
DR RefSeq; NP_001090169.1; NM_001096700.1.
DR AlphaFoldDB; Q9PT63; -.
DR IntAct; Q9PT63; 4.
DR GeneID; 779014; -.
DR KEGG; xla:779014; -.
DR CTD; 779014; -.
DR Xenbase; XB-GENE-6253126; ckap5.L.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 779014; Expressed in egg cell and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0000776; C:kinetochore; IEA:UniProtKB-KW.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0061863; F:microtubule plus end polymerase; IEA:InterPro.
DR GO; GO:0051010; F:microtubule plus-end binding; IEA:InterPro.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0030951; P:establishment or maintenance of microtubule cytoskeleton polarity; IEA:InterPro.
DR GO; GO:0046785; P:microtubule polymerization; IEA:InterPro.
DR GO; GO:0051128; P:regulation of cellular component organization; IEA:UniProt.
DR GO; GO:0007051; P:spindle organization; IEA:InterPro.
DR Gene3D; 1.25.10.10; -; 5.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR024395; CLASP_N_dom.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR034085; TOG.
DR InterPro; IPR045110; XMAP215.
DR PANTHER; PTHR12609; PTHR12609; 1.
DR Pfam; PF12348; CLASP_N; 3.
DR SMART; SM01349; TOG; 5.
DR SUPFAM; SSF48371; SSF48371; 2.
DR PROSITE; PS50077; HEAT_REPEAT; 2.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Centromere; Chromosome; Cytoplasm; Cytoskeleton;
KW Kinetochore; Mitosis; Reference proteome; Repeat.
FT CHAIN 1..2065
FT /note="Cytoskeleton-associated protein 5-A"
FT /id="PRO_0000437573"
FT REPEAT 120..157
FT /note="HEAT 1"
FT /evidence="ECO:0000255"
FT REPEAT 160..197
FT /note="HEAT 2"
FT /evidence="ECO:0000255"
FT REPEAT 270..311
FT /note="HEAT 3"
FT /evidence="ECO:0000255"
FT REPEAT 314..352
FT /note="HEAT 4"
FT /evidence="ECO:0000255"
FT REPEAT 356..393
FT /note="HEAT 5"
FT /evidence="ECO:0000255"
FT REPEAT 395..432
FT /note="HEAT 6"
FT /evidence="ECO:0000255"
FT REPEAT 436..477
FT /note="HEAT 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00103"
FT REPEAT 652..689
FT /note="HEAT 8"
FT /evidence="ECO:0000255"
FT REPEAT 748..785
FT /note="HEAT 9"
FT /evidence="ECO:0000255"
FT REPEAT 852..889
FT /note="HEAT 10"
FT /evidence="ECO:0000255"
FT REPEAT 892..929
FT /note="HEAT 11"
FT /evidence="ECO:0000255"
FT REPEAT 933..970
FT /note="HEAT 12"
FT /evidence="ECO:0000255"
FT REPEAT 1015..1052
FT /note="HEAT 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00103"
FT REPEAT 1251..1288
FT /note="HEAT 14"
FT /evidence="ECO:0000255"
FT REPEAT 1295..1318
FT /note="HEAT 15"
FT /evidence="ECO:0000255"
FT REPEAT 1319..1355
FT /note="HEAT 16"
FT /evidence="ECO:0000255"
FT REPEAT 1357..1390
FT /note="HEAT 17"
FT /evidence="ECO:0000255"
FT REPEAT 1395..1432
FT /note="HEAT 18"
FT /evidence="ECO:0000255"
FT REGION 1..240
FT /note="TOG 1"
FT /evidence="ECO:0000305"
FT REGION 264..515
FT /note="TOG 2"
FT /evidence="ECO:0000305"
FT REGION 500..574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 644..808
FT /note="TOG 3"
FT /evidence="ECO:0000305"
FT REGION 809..849
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 846..1090
FT /note="TOG 4"
FT /evidence="ECO:0000305"
FT REGION 1074..1192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1150..1235
FT /note="Interaction with microtubule lattice"
FT /evidence="ECO:0000269|PubMed:21282620"
FT REGION 1191..1460
FT /note="TOG 5"
FT /evidence="ECO:0000305"
FT REGION 1982..2001
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2002..2065
FT /note="Interaction with tacc3"
FT /evidence="ECO:0000269|PubMed:25262927"
FT REGION 2028..2065
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1092..1115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1128..1167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2028..2050
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 21
FT /note="W->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-102; A-292; A-
FT 373; A-610; A-691; A-870; A-950; A-1250 and A-1335. Greatly
FT impairs microtubule polymerase activity; when associated
FT with A-102; A-292 and A-373."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 102
FT /note="K->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-292; A-
FT 373; A-610; A-691; A-870; A-950; A-1250 and A-1335. Greatly
FT impairs microtubule polymerase activity; when associated
FT with A-21; A-292 and A-373."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 292
FT /note="W->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-102; A-
FT 373; A-610; A-691; A-870; A-950; A-1250 and A-1335. Greatly
FT impairs microtubule polymerase activity; when associated
FT with A-21; A-102 and A-373."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 373
FT /note="K->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-102; A-
FT 292; A-610; A-691; A-870; A-950; A-1250 and A-1335. Greatly
FT impairs microtubule polymerase activity; when associated
FT with A-21; A-102 and A-292."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 610
FT /note="W->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-102; A-
FT 292; A-373; A-691; A-870; A-950; A-1250 and A-1335.
FT Slightly impairs microtubule polymerase activity; when
FT associated with A-691; A-870; A-950; A-1250 and A-1335."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 691
FT /note="K->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-102; A-
FT 292; A-373; A-610; A-870; A-950; A-1250 and A-1335.
FT Slightly impairs microtubule polymerase activity; when
FT associated with A-610; A-870; A-950; A-1250 and A-1335."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 870
FT /note="W->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-102; A-
FT 292; A-373; A-610; A-691; A-950; A-1250 and A-1335.
FT Slightly impairs microtubule polymerase activity; when
FT associated with A-610; A-691; A-950; A-1250 and A-1335."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 950
FT /note="K->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-102; A-
FT 292; A-373; A-610; A-691; A-870; A-1250 and A-1335.
FT Slightly impairs microtubule polymerase activity; when
FT associated with A-610; A-691; A-870; A-1250 and A-1335."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 1250
FT /note="F->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-102; A-
FT 292; A-373; A-610; A-691; A-870; A-950 and A-1335. Slightly
FT impairs microtubule polymerase activity; when associated
FT with A-1335."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 1335
FT /note="K->A: Abolishes binding to tubulin and microtubule
FT polymerase activity; when associated with A-21; A-102; A-
FT 292; A-373; A-610; A-691; A-870; A-950 and A-1250. Slightly
FT impairs microtubule polymerase activity; when associated
FT with A-1250."
FT /evidence="ECO:0000269|PubMed:21282620"
FT MUTAGEN 2053
FT /note="L->S: Disrupts interaction with tacc3; when
FT associated with S-2060."
FT /evidence="ECO:0000269|PubMed:25262927"
FT MUTAGEN 2054
FT /note="K->D: Disrupts interaction with tacc3; when
FT associated with D-2061."
FT /evidence="ECO:0000269|PubMed:25262927"
FT MUTAGEN 2060
FT /note="I->S: Disrupts interaction with tacc3; when
FT associated with S-2053."
FT /evidence="ECO:0000269|PubMed:25262927"
FT MUTAGEN 2061
FT /note="K->D: Disrupts interaction with tacc3; when
FT associated with D-2054."
FT /evidence="ECO:0000269|PubMed:25262927"
SQ SEQUENCE 2065 AA; 228390 MW; 4C879F481E86D5CB CRC64;
MGDDSEWMKL PIDQKCEHKV WKARLNGYEE AVKLFQKIVD EKSPEWSKYL GLIKRFVTES
NAVAQLKGLE AALVYVENAH VAGKTTGEVV NGVVNKVFNQ PKARAKELGA DICLMYVEIE
KAEVVQEELL KGLDNKNPKI VVACVETVRK ALSEFGSKIM TLKPIIKVLP KLFESREKAI
RDEAKLLAVE IYRWIRDALR PPLQNINPVQ LKELEEEWVK LPQSAPKQTR FLRSQQDLKA
KFEQQQAAGD DGGDDGEEEI VPQVDAYELL EAVEILSKLP KDFYDKIEAK KWQERKEALE
AVEALVKNPK IEAGDFADLV KALKTVVGKD TNVMLVALAA KCIAGLAAGL RKKFGSYAGH
IVPTILEKFK EKKPQVVQAL QEAIDAVFLT TTLQNISEDV LAVMDNKNPA IKQQTSLFLA
RSFRHCTPST LPKSLLKPFC VALLKQINDS APEVRDAAFE ALGTAQKVVG EKAVNPFLAE
VDKLKLDRIK ECADKAELAN GKKGGAAAGE KKETKAPAAA PGKPVPNQGA AAEKDAGKAA
AAPKKAPAAK PGGPVKKAKA PASSGATAKG KKAVENKEII EQELSPEACE ERAAAVLPAS
CMQQLDSSNW KERLASMEEF QKTVESMERN DIPCQALVKM LAKKPGFKET NFQVMQMKLH
IVALIAQKGN FSKTSACAVL DGLVDKVGDV KCGGNAKEAL SGIAEACTLP WTAEQVVSLA
FAQKNPKNQS ETLNWLSNAI KEFGFTGINV KAFISNVKTA LAATNPAIRT SAITLLGVMY
LYMGAPLRMF FEEEKPALLS QIDAEFEKMK GQTPPVSIRG SKHGSGRDEG EEGEEQDEDA
PADVTDLLPR TDISDKISSD LVSKIEDKNW KIRKEGLDEV TAIINEAKFI QPSIGELPSA
LKGRLNDSNK ILVQQTLTIL QQLSTAMGHN IKQHVKNLGM PIITVLGDSK ANVRAAALGT
LKSWVDQTGM KDWLEGEDLS EELKKENPFL RQELLGWLAE KLPSMRTVPS DLQLCVPYLY
NCLEDRNGDV RKKAQEALPI FMMHIGFEKM SKATSKLKPA SKDQVVALLE KAKASMPAKP
AGPPGKASSK QPPAVAQASA SPPPAASSDS GSSTSDYKPD PKKTKPGTQA SKAKTQSVSS
EGNTSLNPSN TSLTPSKANT SLSKAKPAKQ TLPGKKAPSK PNAKDEEDKS GPIYIIVPNG
KEQRVKDEKA LKVLKWNFTT PRDEYIEQLK TQMSPCIARW LQDELFHADF QRQIKGLAVM
TEHLESEKEG VISCLDLVLK WFTLRFFDTN TSVLMKCLEY LKLLFIMLSQ EEYHLTEMEG
TSFLPYLMLK VGEPKDIVRK DVRAILTKMC QVYPASKMFN FVMEGTKSKN SKQRAECLEE
LGCLVESYGM NVCQPTPAKA LKEIAIHIGD RDTTVRNAAL NTIVTVYNVH GEQVFKLIGN
LSEKDMSMLE ERIKRAGKKQ AAAAPAKQVE EKPQRVQSAN ASILRKAPPE DMSSKLNQAR
NMGGHTEPSH SVPREFQLDL DEIENDNGTV RCEMPALVQH KLDEIFEPVL IPEPKIRAVS
PHFDDMHSNT ASTINFVISQ VASVDINASI QALAQIDEVL RQEDKAEAMS GHIDQFLIAT
FMQLRLAYNT HMADERLDKD DIVRLYSCII GNMISLFQME SLAREASTGV LKDLMHGLIS
LMLDARIEDL EEGQQVVRSV NLLVVKVLEK SDQTNIISAL LMLLQDSLLA TASSPNFSEL
VMKCLWRMIR LLPEAINNLN LDRILLDIHN FMRVLPKEKL KQHKSEMPMR TLKTLLHTLC
KLKGPKIMDH LSMIENKHES ELEAHLLRVM KHSIDRTGSK GDKETEKGAS CIEDKVGKAN
VSDFLAEMFK KIGSKENTKE GLAELYEYKK KYSDADIKPF LKNSSQFFQS YVERGLRLIE
MEREGKARIA PNTGMSTHVT EMTPLPTVTN TAAPVSNTNG EEVGPSVYLE RLKILRQRCG
LDNAKQDERP PLTSLLSKSS APAVVSSTDM LHSKLSQLRE SREQFQHVEL DSNQTYPSTT
TSSSASSTNI DDLKKRLERI KSSRK
