TPPP_RAT
ID TPPP_RAT Reviewed; 218 AA.
AC D3ZQL7; A0A0G2K2D6;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Tubulin polymerization-promoting protein {ECO:0000303|PubMed:31522887};
DE Short=TPPP {ECO:0000303|PubMed:31522887};
DE EC=3.6.5.- {ECO:0000250|UniProtKB:O94811};
DE AltName: Full=25 kDa brain-specific protein {ECO:0000303|PubMed:8417144};
DE AltName: Full=TPPP/p25 {ECO:0000303|PubMed:8417144};
DE AltName: Full=p25-alpha {ECO:0000303|PubMed:8417144};
GN Name=Tppp {ECO:0000303|PubMed:31522887, ECO:0000312|RGD:1310121};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=8417144; DOI=10.1111/j.1471-4159.1993.tb05842.x;
RA Takahashi M., Tomizawa K., Fujita S.C., Sato K., Uchida T., Imahori K.;
RT "A brain-specific protein p25 is localized and associated with
RT oligodendrocytes, neuropil, and fiber-like structures of the CA3
RT hippocampal region in the rat brain.";
RL J. Neurochem. 60:228-235(1993).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=19606501; DOI=10.1002/glia.20909;
RA Lehotzky A., Lau P., Tokesi N., Muja N., Hudson L.D., Ovadi J.;
RT "Tubulin polymerization-promoting protein (TPPP/p25) is critical for
RT oligodendrocyte differentiation.";
RL Glia 58:157-168(2010).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=31522887; DOI=10.1016/j.cell.2019.08.025;
RA Fu M.M., McAlear T.S., Nguyen H., Oses-Prieto J.A., Valenzuela A.,
RA Shi R.D., Perrino J.J., Huang T.T., Burlingame A.L., Bechstedt S.,
RA Barres B.A.;
RT "The Golgi outpost protein TPPP nucleates microtubules and is critical for
RT myelination.";
RL Cell 0:0-0(2019).
CC -!- FUNCTION: Regulator of microtubule dynamics that plays a key role in
CC myelination by promoting elongation of the myelin sheath
CC (PubMed:19606501). Acts as a microtubule nucleation factor in
CC oligodendrocytes: specifically localizes to the postsynaptic Golgi
CC apparatus region, also named Golgi outpost, and promotes microtubule
CC nucleation, an important step for elongation of the myelin sheath (By
CC similarity). Required for both uniform polarized growth of distal
CC microtubules as well as directing the branching of proximal processes
CC (By similarity). Shows magnesium-dependent GTPase activity; the role of
CC the GTPase activity is unclear (By similarity). In addition to
CC microtubule nucleation activity, also involved in microtubule bundling
CC and stabilization of existing microtubules, thereby maintaining the
CC integrity of the microtubule network (By similarity). Regulates
CC microtubule dynamics by promoting tubulin acetylation: acts by
CC inhibiting the tubulin deacetylase activity of HDAC6 (By similarity).
CC Also regulates cell migration: phosphorylation by ROCK1 inhibits
CC interaction with HDAC6, resulting in decreased acetylation of tubulin
CC and increased cell motility (By similarity). Plays a role in cell
CC proliferation by regulating the G1/S-phase transition (By similarity).
CC Involved in astral microtubule organization and mitotic spindle
CC orientation during early stage of mitosis; this process is regulated by
CC phosphorylation by LIMK2 (By similarity).
CC {ECO:0000250|UniProtKB:O94811, ECO:0000269|PubMed:19606501}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:O94811};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:O94811};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O94811};
CC -!- SUBUNIT: Homodimer. Binds tubulin; binding is inhibited by GTP (By
CC similarity). Interacts with MAPK1. Interacts with GAPDH; the
CC interaction is direct (By similarity). Interacts with LIMK1 (via the
CC PDZ domain); the interaction is direct. Interacts with LIMK2. Interacts
CC with HDAC6; thereby inhibiting the tubulin deacetylase activity of
CC HDAC6. Interacts with aggregated SNCA; may have a pro-aggregatory role
CC in synucleinopathies. Interacts with DYNLL1 (By similarity). Interacts
CC (via C-terminus) with S100A2, S100A6 and S100B; these interactions
CC inhibit TPPP dimerization (By similarity).
CC {ECO:0000250|UniProtKB:O94811, ECO:0000250|UniProtKB:Q27957}.
CC -!- SUBCELLULAR LOCATION: Golgi outpost {ECO:0000269|PubMed:31522887}.
CC Cytoplasm, cytoskeleton, microtubule organizing center
CC {ECO:0000269|PubMed:31522887}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:O94811}. Nucleus {ECO:0000250|UniProtKB:O94811}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:O94811}.
CC Note=Specifically localizes to the postsynaptic Golgi apparatus region,
CC also named Golgi outpost, which shapes dendrite morphology by
CC functioning as sites of acentrosomal microtubule nucleation
CC (PubMed:31522887). Mainly localizes to the cytoskeleton. Also found in
CC the nucleus; however, nuclear localization is unclear and requires
CC additional evidences. Localizes to glial Lewy bodies in the brains of
CC individuals with synucleinopathies. During mitosis, colocalizes with
CC LIMK2 at the mitotic spindle (By similarity).
CC {ECO:0000250|UniProtKB:O94811, ECO:0000269|PubMed:31522887}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in mature oligodendrocytes.
CC {ECO:0000269|PubMed:8417144}.
CC -!- INDUCTION: Strongly up-regulated during the differentiation of primary
CC oligodendrocyte cells. {ECO:0000269|PubMed:19606501}.
CC -!- DOMAIN: Most of the protein is composed of disordered regions. Zinc-
CC binding induces structural rearrangement by promoting molten globule
CC state formation. {ECO:0000250|UniProtKB:O94811}.
CC -!- PTM: Phosphorylated by LIMK1 on serine residues; phosphorylation may
CC alter the tubulin polymerization activity. Phosphorylation by LIMK2,
CC but not LIMK1, regulates astral microtubule organization at early stage
CC of mitosis. Phosphorylation by ROCK1 at Ser-31, Ser-106 and Ser-158
CC inhibits interaction with HDAC6, resulting in decreased acetylation of
CC tubulin, increased cell motility and entry into S-phase.
CC Phosphorylation by CDK1 inhibits the microtubule polymerizing activity.
CC {ECO:0000250|UniProtKB:O94811}.
CC -!- PTM: Degraded by the proteasome; zinc-binding inhibits degradation by
CC the proteasome. {ECO:0000250|UniProtKB:O94811}.
CC -!- SIMILARITY: Belongs to the TPPP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AABR07071856; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AABR07071856; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474002; EDL87672.1; -; Genomic_DNA.
DR RefSeq; NP_001101931.1; NM_001108461.1.
DR RefSeq; XP_006227855.1; XM_006227793.2.
DR RefSeq; XP_006227856.1; XM_006227794.2.
DR AlphaFoldDB; D3ZQL7; -.
DR SMR; D3ZQL7; -.
DR STRING; 10116.ENSRNOP00000034617; -.
DR GlyGen; D3ZQL7; 1 site.
DR jPOST; D3ZQL7; -.
DR PaxDb; D3ZQL7; -.
DR PeptideAtlas; D3ZQL7; -.
DR PRIDE; D3ZQL7; -.
DR Ensembl; ENSRNOT00000039166; ENSRNOP00000034617; ENSRNOG00000028261.
DR GeneID; 361466; -.
DR KEGG; rno:361466; -.
DR UCSC; RGD:1310121; rat.
DR CTD; 11076; -.
DR RGD; 1310121; Tppp.
DR eggNOG; KOG4070; Eukaryota.
DR GeneTree; ENSGT00940000153875; -.
DR HOGENOM; CLU_091734_0_0_1; -.
DR InParanoid; D3ZQL7; -.
DR OrthoDB; 1317210at2759; -.
DR PhylomeDB; D3ZQL7; -.
DR TreeFam; TF314440; -.
DR PRO; PR:D3ZQL7; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000028261; Expressed in frontal cortex and 18 other tissues.
DR ExpressionAtlas; D3ZQL7; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR GO; GO:0150051; C:postsynaptic Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; ISS:BHF-UCL.
DR GO; GO:0030953; P:astral microtubule organization; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0001578; P:microtubule bundle formation; ISS:UniProtKB.
DR GO; GO:0051418; P:microtubule nucleation by microtubule organizing center; ISS:UniProtKB.
DR GO; GO:0046785; P:microtubule polymerization; ISS:BHF-UCL.
DR GO; GO:0032288; P:myelin assembly; IMP:UniProtKB.
DR GO; GO:1904428; P:negative regulation of tubulin deacetylation; ISS:UniProtKB.
DR GO; GO:0014003; P:oligodendrocyte development; ISS:UniProtKB.
DR GO; GO:0048709; P:oligodendrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0031643; P:positive regulation of myelination; IMP:UniProtKB.
DR GO; GO:0032273; P:positive regulation of protein polymerization; ISS:BHF-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISS:BHF-UCL.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:UniProtKB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR008907; P25-alpha.
DR InterPro; IPR030792; TPPP1.
DR PANTHER; PTHR12932; PTHR12932; 1.
DR PANTHER; PTHR12932:SF18; PTHR12932:SF18; 1.
DR Pfam; PF05517; p25-alpha; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cytoplasm; Cytoskeleton; Glycoprotein;
KW Golgi apparatus; Hydrolase; Magnesium; Metal-binding; Mitosis; Nucleus;
KW Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..218
FT /note="Tubulin polymerization-promoting protein"
FT /id="PRO_0000448593"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..115
FT /note="Mediates interaction with LIMK1"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT REGION 165..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 170..192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT BINDING 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT MOD_RES 15
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT MOD_RES 91
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT CARBOHYD 151
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q7TQD2"
SQ SEQUENCE 218 AA; 23547 MW; 1E4980424E85706D CRC64;
MADSKAKPTK AANKTPPKSP GDPAKAAKRL SLESEGANEG AAAAPELSAL EEAFRRFAVH
GDTRATGKEM HGKNWSKLCK DCHVIDGKNV TVTDVDIVFS KIKGKSCRTI TFEQFQEALE
ELAKKRFKDK SSEEAVREVH RLIEGRAPVI SGVTKAVSSP TVSRLTDTSK FTGSHKERFD
QSGKGKGKAG RVDLVDESGY VPGYKHAGTY DQKVQGGK
