TPX2_MOUSE
ID TPX2_MOUSE Reviewed; 745 AA.
AC A2APB8; Q3U500; Q6P9S6;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Targeting protein for Xklp2;
GN Name=Tpx2;
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 MRNA].
RC STRAIN=NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-72 AND SER-486, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP FUNCTION, INTERACTION WITH AURKA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 8-TYR--ASP-11.
RX PubMed=18663142; DOI=10.1083/jcb.200802005;
RA Bird A.W., Hyman A.A.;
RT "Building a spindle of the correct length in human cells requires the
RT interaction between TPX2 and Aurora A.";
RL J. Cell Biol. 182:289-300(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-737, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486 AND SER-737, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128 AND LYS-375, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [10]
RP INTERACTION WITH BCL2L10, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=27753540; DOI=10.1080/15384101.2016.1243630;
RA Lee S.Y., Kim E.Y., Kim K.H., Lee K.A.;
RT "Bcl2l10, a new Tpx2 binding partner, is a master regulator of Aurora
RT kinase A in mouse oocytes.";
RL Cell Cycle 15:3296-3305(2016).
CC -!- FUNCTION: Spindle assembly factor required for normal assembly of
CC mitotic spindles. Required for normal assembly of microtubules during
CC apoptosis. Required for chromatin and/or kinetochore dependent
CC microtubule nucleation. Mediates AURKA localization to spindle
CC microtubules. Activates AURKA by promoting its autophosphorylation at
CC 'Thr-288' and protects this residue against dephosphorylation. TPX2 is
CC inactivated upon binding to importin-alpha. At the onset of mitosis,
CC GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-
CC alpha, allowing TPX2 to activates AURKA kinase and stimulates local
CC microtubule nucleation. {ECO:0000250|UniProtKB:Q9ULW0,
CC ECO:0000269|PubMed:18663142}.
CC -!- SUBUNIT: Interacts with AURKA (PubMed:18663142). Interacts with
CC importin-alpha; leading to inactivate TPX2 (By similarity). Interacts
CC with HNRNPU; this interaction recruits HNRNPU to spindle microtubules
CC (MTs) (By similarity). Interacts with BCL2L10 (PubMed:27753540).
CC {ECO:0000250|UniProtKB:Q9ULW0, ECO:0000269|PubMed:18663142,
CC ECO:0000269|PubMed:27753540}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9ULW0}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:27753540}.
CC Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q9ULW0}.
CC Note=During mitosis it is strictly associated with the spindle pole and
CC with the mitotic spindle, whereas during S and G2, it is diffusely
CC distributed throughout the nucleus. Is released from the nucleus in
CC apoptotic cells and is detected on apoptotic microtubules.
CC {ECO:0000250|UniProtKB:Q9ULW0}.
CC -!- DEVELOPMENTAL STAGE: Expressed during all phases of oocyte maturation;
CC localized at the meiotic spindle and microtubule organizing center
CC during meiosis. {ECO:0000269|PubMed:27753540}.
CC -!- SIMILARITY: Belongs to the TPX2 family. {ECO:0000305}.
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DR EMBL; AK153957; BAE32280.1; -; mRNA.
DR EMBL; AL833801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL05994.1; -; Genomic_DNA.
DR EMBL; BC060619; AAH60619.1; -; mRNA.
DR CCDS; CCDS16900.1; -.
DR RefSeq; NP_001135447.1; NM_001141975.1.
DR RefSeq; NP_001135448.1; NM_001141976.1.
DR RefSeq; NP_001135449.1; NM_001141977.1.
DR RefSeq; NP_001135450.1; NM_001141978.1.
DR RefSeq; NP_082385.3; NM_028109.4.
DR RefSeq; XP_006500276.1; XM_006500213.2.
DR RefSeq; XP_006500277.1; XM_006500214.2.
DR RefSeq; XP_006500278.1; XM_006500215.2.
DR AlphaFoldDB; A2APB8; -.
DR SMR; A2APB8; -.
DR BioGRID; 215163; 55.
DR IntAct; A2APB8; 51.
DR MINT; A2APB8; -.
DR STRING; 10090.ENSMUSP00000128888; -.
DR iPTMnet; A2APB8; -.
DR PhosphoSitePlus; A2APB8; -.
DR EPD; A2APB8; -.
DR jPOST; A2APB8; -.
DR MaxQB; A2APB8; -.
DR PaxDb; A2APB8; -.
DR PeptideAtlas; A2APB8; -.
DR PRIDE; A2APB8; -.
DR ProteomicsDB; 259077; -.
DR Antibodypedia; 1228; 649 antibodies from 38 providers.
DR DNASU; 72119; -.
DR Ensembl; ENSMUST00000028969; ENSMUSP00000028969; ENSMUSG00000027469.
DR Ensembl; ENSMUST00000109816; ENSMUSP00000105441; ENSMUSG00000027469.
DR Ensembl; ENSMUST00000164120; ENSMUSP00000128888; ENSMUSG00000027469.
DR Ensembl; ENSMUST00000178997; ENSMUSP00000136457; ENSMUSG00000027469.
DR GeneID; 72119; -.
DR KEGG; mmu:72119; -.
DR UCSC; uc008ngo.2; mouse.
DR CTD; 22974; -.
DR MGI; MGI:1919369; Tpx2.
DR VEuPathDB; HostDB:ENSMUSG00000027469; -.
DR eggNOG; ENOG502QVQS; Eukaryota.
DR GeneTree; ENSGT00390000009842; -.
DR HOGENOM; CLU_022592_0_0_1; -.
DR InParanoid; A2APB8; -.
DR OMA; GRHTVSC; -.
DR OrthoDB; 1390734at2759; -.
DR PhylomeDB; A2APB8; -.
DR TreeFam; TF328997; -.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-8854518; AURKA Activation by TPX2.
DR BioGRID-ORCS; 72119; 10 hits in 74 CRISPR screens.
DR ChiTaRS; Tpx2; mouse.
DR PRO; PR:A2APB8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2APB8; protein.
DR Bgee; ENSMUSG00000027469; Expressed in embryonic post-anal tail and 176 other tissues.
DR Genevisible; A2APB8; MM.
DR GO; GO:0005818; C:aster; ISO:MGI.
DR GO; GO:0043203; C:axon hillock; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0005880; C:nuclear microtubule; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; ISO:MGI.
DR GO; GO:0061676; F:importin-alpha family protein binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0030295; F:protein kinase activator activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007020; P:microtubule nucleation; ISO:MGI.
DR GO; GO:0090307; P:mitotic spindle assembly; IMP:UniProtKB.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; ISO:MGI.
DR GO; GO:0060236; P:regulation of mitotic spindle organization; IMP:UniProtKB.
DR GO; GO:0051225; P:spindle assembly; ISO:MGI.
DR InterPro; IPR015128; Aurora-A-bd.
DR InterPro; IPR027329; TPX2_C.
DR InterPro; IPR027330; TPX2_central_dom.
DR InterPro; IPR009675; TPX2_fam.
DR PANTHER; PTHR14326; PTHR14326; 1.
DR Pfam; PF09041; Aurora-A_bind; 1.
DR Pfam; PF06886; TPX2; 1.
DR Pfam; PF12214; TPX2_importin; 1.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; Cell cycle; Cell division; Cytoplasm; Cytoskeleton;
KW Isopeptide bond; Microtubule; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..745
FT /note="Targeting protein for Xklp2"
FT /id="PRO_0000393112"
FT REGION 84..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 91..123
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 124..142
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 164..194
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 72
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MOD_RES 307
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MOD_RES 340
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MOD_RES 369
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MOD_RES 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 737
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT CROSSLNK 477
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT CROSSLNK 500
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT CROSSLNK 640
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT CROSSLNK 739
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9ULW0"
FT MUTAGEN 8..11
FT /note="YSFD->ASAA: Abolishes interaction with AURKA."
FT /evidence="ECO:0000269|PubMed:18663142"
FT CONFLICT 165
FT /note="H -> D (in Ref. 4; AAH60619)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="E -> K (in Ref. 1; BAE32280)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="V -> L (in Ref. 1; BAE32280)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 745 AA; 85894 MW; 4E60692BC52DAE34 CRC64;
MSQVPTTYSF DAPTDFINFS SLDAEEDTEN IDSWFDEKAN LENKFLRQRG IGEPFQGKNS
LRKAKLQQGF VTPLKAVDNT YHKETEKENL QKQSIPSNDC SSLDAKRAVS GNTPVQPQRR
SIRLSAQKDL EQKEKNHVAS VEMKAKRCVA PATDCPPQKR MKVSHKKKLE EEEEGSAPAT
SRKNERETLE KAKGKHTVPG VPPAREKVLK STEEQEIEKR LRMQQEVVEL RRKNEEFKKL
ALAGPGQPVK KSTSQVTKTV DFHFLTDERI KQHPKNQEEY KEVNFMSELR KHSSTPARGT
RGCTIIKPFN LSKGKKRTFD EAASTYVPIA QQVEAFHKRT PNRYHLRNKK DESLLPSKSV
NKIARDPQTP ILQTKYRTRA VTCKSTAEQE AEELEKLQQY KFKARELDPR IFESGPILPK
RAPVKPPTQP VGFDLEIEKR IHERESKKKT EDEQFEFHSR PCPTKILEDV VGVPEKKVIP
ATVPKSPVFA LKNRIRVPIK DEEEEKPVVI KAQPVPHYGV PYKPHIAEAR NVEVCPFSFD
TRDKERQLQK EKKIKEMQKG EVPKFKALPV PHFDTINLPE KKVKNVTQAE PFSLETDKRG
AYKAEMWKHQ LEEEQKQQKD AACFKARPNT VIFQEPFVPK KEKKSLAENP SGSLVQEPFQ
LATERRAKER QELEKKMAEV EAWKLQQLEE VRQQEEEQQK EELARLRKEL VHKANPIRKY
AAVEVKSSEL PLTVPVSPKF STRFQ
