TPPP_BOVIN
ID TPPP_BOVIN Reviewed; 218 AA.
AC Q27957; A2VDP9; Q9TRW3; Q9TRW4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Tubulin polymerization-promoting protein {ECO:0000303|PubMed:14623963};
DE Short=TPPP {ECO:0000303|PubMed:14623963};
DE EC=3.6.5.- {ECO:0000250|UniProtKB:O94811};
DE AltName: Full=25 kDa brain-specific protein {ECO:0000303|PubMed:7647094};
DE AltName: Full=p25-alpha {ECO:0000303|PubMed:7647094};
GN Name=TPPP {ECO:0000303|PubMed:14623963};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7647094; DOI=10.1016/0167-4838(95)00089-d;
RA Shiratsuchi A., Sato S., Oomori A., Ishiguro K., Uchida T., Imahori K.;
RT "cDNA cloning of a novel brain-specific protein p25.";
RL Biochim. Biophys. Acta 1251:66-68(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 1-27, AND PHOSPHORYLATION.
RC TISSUE=Brain;
RX PubMed=1909972; DOI=10.1016/0014-5793(91)80903-g;
RA Takahashi M., Tomizawa K., Ishiguro K., Sato K., Omori A., Sato S.,
RA Shiratsuchi A., Uchida T., Imahori K.;
RT "A novel brain-specific 25 kDa protein (p25) is phosphorylated by a
RT Ser/Thr-Pro kinase (TPK II) from tau protein kinase fractions.";
RL FEBS Lett. 289:37-43(1991).
RN [4]
RP INTERACTION WITH TUBULIN, AND FUNCTION.
RX PubMed=14623963; DOI=10.1073/pnas.2436331100;
RA Tirian L., Hlavanda E., Olah J., Horvath I., Orosz F., Szabo B., Kovacs J.,
RA Szabad J., Ovadi J.;
RT "TPPP/p25 promotes tubulin assemblies and blocks mitotic spindle
RT formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13976-13981(2003).
RN [5]
RP INTERACTION WITH GAPDH.
RX PubMed=17027006; DOI=10.1016/j.febslet.2006.09.037;
RA Olah J., Toekesi N., Vincze O., Horvath I., Lehotzky A., Erdei A.,
RA Szajli E., Medzihradszky K.F., Orosz F., Kovacs G.G., Ovadi J.;
RT "Interaction of TPPP/p25 protein with glyceraldehyde-3-phosphate
RT dehydrogenase and their co-localization in Lewy bodies.";
RL FEBS Lett. 580:5807-5814(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT THR-12; SER-16 AND
RP SER-30, AND INTERACTION WITH MAPK1.
RX PubMed=17693641; DOI=10.1074/jbc.m703466200;
RA Hlavanda E., Klement E., Kokai E., Kovacs J., Vincze O., Toekesi N.,
RA Orosz F., Medzihradszky K.F., Dombradi V., Ovadi J.;
RT "Phosphorylation blocks the activity of tubulin polymerization-promoting
RT protein (TPPP): identification of sites targeted by different kinases.";
RL J. Biol. Chem. 282:29531-29539(2007).
CC -!- FUNCTION: Regulator of microtubule dynamics that plays a key role in
CC myelination by promoting elongation of the myelin sheath (By
CC similarity). 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 (PubMed:14623963). 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:14623963}.
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 (By similarity). Binds tubulin; binding is inhibited
CC by GTP (PubMed:14623963). Interacts with MAPK1 (PubMed:17693641).
CC Interacts with GAPDH; the interaction is direct (PubMed:17027006).
CC Interacts with LIMK1 (via the PDZ domain); the interaction is direct.
CC Interacts with LIMK2. Interacts with HDAC6; thereby inhibiting the
CC tubulin deacetylase activity of HDAC6. Interacts with aggregated SNCA;
CC may have a pro-aggregatory role in synucleinopathies. Interacts with
CC DYNLL1 (By similarity). Interacts (via C-terminus) with S100A2, S100A6
CC and S100B; these interactions inhibit TPPP dimerization (By
CC similarity). {ECO:0000250|UniProtKB:O94811,
CC ECO:0000269|PubMed:14623963, ECO:0000269|PubMed:17027006,
CC ECO:0000269|PubMed:17693641}.
CC -!- INTERACTION:
CC Q27957; P10096: GAPDH; NbExp=2; IntAct=EBI-7025612, EBI-7025562;
CC -!- SUBCELLULAR LOCATION: Golgi outpost {ECO:0000250|UniProtKB:D3ZQL7}.
CC Cytoplasm, cytoskeleton, microtubule organizing center
CC {ECO:0000250|UniProtKB:D3ZQL7}. 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 (By
CC similarity). Mainly localizes to the cytoskeleton. Also found in the
CC 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:D3ZQL7, ECO:0000250|UniProtKB:O94811}.
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: Phosphorylation may alter the tubulin polymerization activity.
CC {ECO:0000269|PubMed:17693641, ECO:0000269|PubMed:1909972}.
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-30, 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}.
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DR EMBL; X85738; CAA59741.1; -; mRNA.
DR EMBL; BC133343; AAI33344.1; -; mRNA.
DR PIR; S58769; S58769.
DR RefSeq; NP_776401.1; NM_173976.2.
DR AlphaFoldDB; Q27957; -.
DR SMR; Q27957; -.
DR BioGRID; 158347; 3.
DR IntAct; Q27957; 4.
DR MINT; Q27957; -.
DR STRING; 9913.ENSBTAP00000054983; -.
DR BindingDB; Q27957; -.
DR ChEMBL; CHEMBL2366491; -.
DR DrugCentral; Q27957; -.
DR iPTMnet; Q27957; -.
DR PaxDb; Q27957; -.
DR PRIDE; Q27957; -.
DR Ensembl; ENSBTAT00000078768; ENSBTAP00000070614; ENSBTAG00000052247.
DR GeneID; 280968; -.
DR KEGG; bta:280968; -.
DR CTD; 11076; -.
DR VEuPathDB; HostDB:ENSBTAG00000052247; -.
DR VGNC; VGNC:36258; TPPP.
DR eggNOG; KOG4070; Eukaryota.
DR GeneTree; ENSGT00940000153875; -.
DR HOGENOM; CLU_091734_0_0_1; -.
DR InParanoid; Q27957; -.
DR OrthoDB; 1317210at2759; -.
DR TreeFam; TF314440; -.
DR PRO; PR:Q27957; -.
DR Proteomes; UP000009136; Chromosome 20.
DR Bgee; ENSBTAG00000052247; Expressed in temporal cortex and 100 other tissues.
DR ExpressionAtlas; Q27957; baseline.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:HGNC-UCL.
DR GO; GO:0150051; C:postsynaptic Golgi apparatus; ISS: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; IDA:HGNC-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IDA:HGNC-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; IDA:HGNC-UCL.
DR GO; GO:0051418; P:microtubule nucleation by microtubule organizing center; ISS:UniProtKB.
DR GO; GO:0046785; P:microtubule polymerization; IDA:HGNC-UCL.
DR GO; GO:0032288; P:myelin assembly; ISS: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; ISS:UniProtKB.
DR GO; GO:0032273; P:positive regulation of protein polymerization; ISS:HGNC-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:HGNC-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;
KW Direct protein sequencing; Glycoprotein; Golgi apparatus; Hydrolase;
KW Magnesium; Metal-binding; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Zinc.
FT CHAIN 1..218
FT /note="Tubulin polymerization-promoting protein"
FT /id="PRO_0000221134"
FT REGION 1..115
FT /note="Mediates interaction with LIMK1"
FT /evidence="ECO:0000250|UniProtKB:O94811"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..31
FT /note="Basic and acidic residues"
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 12
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17693641"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17693641"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17693641"
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; 23473 MW; 55F5DAB42DC3A638 CRC64;
MADSRPKPAN KTPPKSPGEP AKDKAAKRLS LEAEGAGEGA AAAGAELSAL EEAFRKFAVH
GDARASGREM HGKNWSKLCR DCQVIDGRSV TVTDVDIVFS KIKGKSCRTI TFEQFKEALE
ELAKKRFKDK SAEEAVREVH KLIEGKAPII SGVTKAISSP TVSRLTDTSK FTGSHKERFD
PSGRGKGRAG RVDLVDESGY VPGYKHAGTY DQKVQGGK
