TPPP_HUMAN
ID TPPP_HUMAN Reviewed; 219 AA.
AC O94811;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Tubulin polymerization-promoting protein {ECO:0000303|PubMed:17105200};
DE Short=TPPP {ECO:0000303|PubMed:17105200};
DE EC=3.6.5.- {ECO:0000269|PubMed:21316364, ECO:0000269|PubMed:21995432};
DE AltName: Full=25 kDa brain-specific protein {ECO:0000303|PubMed:15590652};
DE AltName: Full=TPPP/p25 {ECO:0000303|PubMed:15590652};
DE AltName: Full=p24;
DE AltName: Full=p25-alpha {ECO:0000303|PubMed:15590652};
GN Name=TPPP {ECO:0000303|PubMed:17105200, ECO:0000312|HGNC:HGNC:24164};
GN Synonyms=TPPP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Neuroblastoma;
RX PubMed=10083737; DOI=10.1007/s100380050122;
RA Seki N., Hattori A., Sugano S., Suzuki Y., Nakagawara A., Muramatsu M.-A.,
RA Hori T.-A., Saito T.;
RT "A novel human gene whose product shares significant homology with the
RT bovine brain-specific protein p25 on chromosome 5p15.3.";
RL J. Hum. Genet. 44:121-122(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [4]
RP INTERACTION WITH AGGREGATED SNCA, AND SUBCELLULAR LOCATION.
RX PubMed=15590652; DOI=10.1074/jbc.m410409200;
RA Lindersson E., Lundvig D., Petersen C., Madsen P., Nyengaard J.R.,
RA Hoejrup P., Moos T., Otzen D., Gai W.-P., Blumbergs P.C., Jensen P.H.;
RT "p25alpha Stimulates alpha-synuclein aggregation and is co-localized with
RT aggregated alpha-synuclein in alpha-synucleinopathies.";
RL J. Biol. Chem. 280:5703-5715(2005).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17105200; DOI=10.1021/bi061305e;
RA Vincze O., Toekesi N., Olah J., Hlavanda E., Zotter A., Horvath I.,
RA Lehotzky A., Tirian L., Medzihradszky K.F., Kovacs J., Orosz F., Ovadi J.;
RT "Tubulin polymerization promoting proteins (TPPPs): members of a new family
RT with distinct structures and functions.";
RL Biochemistry 45:13818-13826(2006).
RN [6]
RP SUBCELLULAR LOCATION.
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LIMK1, AND
RP PHOSPHORYLATION.
RX PubMed=18028908; DOI=10.1016/j.yexcr.2007.08.012;
RA Acevedo K., Li R., Soo P., Suryadinata R., Sarcevic B., Valova V.A.,
RA Graham M.E., Robinson P.J., Bernard O.;
RT "The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to
RT assemble microtubules.";
RL Exp. Cell Res. 313:4091-4106(2007).
RN [8]
RP FUNCTION, HOMODIMERIZATION, AND PHOSPHORYLATION AT THR-14; SER-18; SER-32;
RP THR-92; SER-159 AND SER-160.
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).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; SER-18; SER-32; SER-35
RP AND SER-45, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH HDAC6.
RX PubMed=20308065; DOI=10.1074/jbc.m109.096578;
RA Tokesi N., Lehotzky A., Horvath I., Szabo B., Olah J., Lau P., Ovadi J.;
RT "TPPP/p25 promotes tubulin acetylation by inhibiting histone deacetylase
RT 6.";
RL J. Biol. Chem. 285:17896-17906(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, ZINC-BINDING, AND DOMAIN.
RX PubMed=21995432; DOI=10.1021/bi201447w;
RA Zotter A., Olah J., Hlavanda E., Bodor A., Perczel A., Szigeti K., Fidy J.,
RA Ovadi J.;
RT "Zn2+-induced rearrangement of the disordered TPPP/p25 affects its
RT microtubule assembly and GTPase activity.";
RL Biochemistry 50:9568-9578(2011).
RN [15]
RP INDUCTION.
RX PubMed=21565174; DOI=10.1016/j.bbrc.2011.04.130;
RA Vincze O., Olah J., Zadori D., Klivenyi P., Vecsei L., Ovadi J.;
RT "A new myelin protein, TPPP/p25, reduced in demyelinated lesions is
RT enriched in cerebrospinal fluid of multiple sclerosis.";
RL Biochem. Biophys. Res. Commun. 409:137-141(2011).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND
RP DOMAIN.
RX PubMed=21316364; DOI=10.1016/j.febslet.2011.02.006;
RA Zotter A., Bodor A., Olah J., Hlavanda E., Orosz F., Perczel A., Ovadi J.;
RT "Disordered TPPP/p25 binds GTP and displays Mg2+-dependent GTPase
RT activity.";
RL FEBS Lett. 585:803-808(2011).
RN [17]
RP SUBUNIT.
RX PubMed=22484033; DOI=10.1016/j.bbagen.2012.03.011;
RA Olah J., Zotter A., Hlavanda E., Szunyogh S., Orosz F., Szigeti K.,
RA Fidy J., Ovadi J.;
RT "Microtubule assembly-derived by dimerization of TPPP/p25. Evaluation of
RT thermodynamic parameters for multiple equilibrium system from ITC data.";
RL Biochim. Biophys. Acta 1820:785-794(2012).
RN [18]
RP FUNCTION, INTERACTION WITH HDAC6, PHOSPHORYLATION AT SER-32; SER-107 AND
RP SER-159, AND MUTAGENESIS OF SER-32; SER-107 AND SER-159.
RX PubMed=23093407; DOI=10.1074/jbc.m112.394965;
RA Schofield A.V., Steel R., Bernard O.;
RT "Rho-associated coiled-coil kinase (ROCK) protein controls microtubule
RT dynamics in a novel signaling pathway that regulates cell migration.";
RL J. Biol. Chem. 287:43620-43629(2012).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LIMK1 AND LIMK2, AND
RP PHOSPHORYLATION.
RX PubMed=22328514; DOI=10.1242/jcs.096818;
RA Heng Y.W., Lim H.H., Mina T., Utomo P., Zhong S., Lim C.T., Koh C.G.;
RT "TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule
RT organization and spindle orientation.";
RL J. Cell Sci. 125:1579-1590(2012).
RN [20]
RP PHOSPHORYLATION AT THR-14; SER-18; SER-32; SER-45; SER-107; SER-159 AND
RP SER-160, AND MUTAGENESIS OF THR-14; SER-18; SER-32; SER-45; SER-107;
RP SER-159 AND SER-160.
RX PubMed=23355470; DOI=10.1074/jbc.m112.441048;
RA Schofield A.V., Gamell C., Suryadinata R., Sarcevic B., Bernard O.;
RT "Tubulin polymerization promoting protein 1 (Tppp1) phosphorylation by Rho-
RT associated coiled-coil kinase (rock) and cyclin-dependent kinase 1 (Cdk1)
RT inhibits microtubule dynamics to increase cell proliferation.";
RL J. Biol. Chem. 288:7907-7917(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND SER-159, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP DEGRADATION.
RX PubMed=25445539; DOI=10.1016/j.bbadis.2014.10.015;
RA Lehotzky A., Olah J., Szunyogh S., Szabo A., Berki T., Ovadi J.;
RT "Zinc-induced structural changes of the disordered tppp/p25 inhibits its
RT degradation by the proteasome.";
RL Biochim. Biophys. Acta 1852:83-91(2015).
RN [23]
RP FUNCTION, AND SUBUNIT.
RX PubMed=26289831; DOI=10.1038/srep13242;
RA DeBonis S., Neumann E., Skoufias D.A.;
RT "Self protein-protein interactions are involved in TPPP/p25 mediated
RT microtubule bundling.";
RL Sci. Rep. 5:13242-13242(2015).
RN [24]
RP INTERACTION WITH DYNLL1.
RX PubMed=31505170; DOI=10.1016/j.bbamcr.2019.118556;
RA Olah J., Szunyogh S., Szenasi T., Szaniszlo T., Szabo A., Lehotzky A.,
RA Berki T., Nyitray L., Ovadi J.;
RT "Interactions between two regulatory proteins of microtubule dynamics,
RT HDAC6, TPPP/p25, and the hub protein, DYNLL/LC8.";
RL Biochim. Biophys. Acta 2019:118556-118556(2019).
RN [25]
RP FUNCTION.
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).
RN [26]
RP INTERACTION WITH S100A2; S100A6 AND S100B, AND FUNCTION.
RX PubMed=33831707; DOI=10.1016/j.ceca.2021.102404;
RA Doi S., Fujioka N., Ohtsuka S., Kondo R., Yamamoto M., Denda M., Magari M.,
RA Kanayama N., Hatano N., Morishita R., Hasegawa T., Tokumitsu H.;
RT "Regulation of the tubulin polymerization-promoting protein by Ca2+/S100
RT proteins.";
RL Cell Calcium 96:102404-102404(2021).
CC -!- FUNCTION: Regulator of microtubule dynamics that plays a key role in
CC myelination by promoting elongation of the myelin sheath
CC (PubMed:31522887). 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
CC (PubMed:31522887, PubMed:33831707). Required for both uniform polarized
CC growth of distal microtubules as well as directing the branching of
CC proximal processes (PubMed:31522887). Shows magnesium-dependent GTPase
CC activity; the role of the GTPase activity is unclear (PubMed:21995432,
CC PubMed:21316364). In addition to microtubule nucleation activity, also
CC involved in microtubule bundling and stabilization of existing
CC microtubules, thereby maintaining the integrity of the microtubule
CC network (PubMed:17105200, PubMed:17693641, PubMed:18028908,
CC PubMed:26289831). Regulates microtubule dynamics by promoting tubulin
CC acetylation: acts by inhibiting the tubulin deacetylase activity of
CC HDAC6 (PubMed:20308065, PubMed:23093407). Also regulates cell
CC migration: phosphorylation by ROCK1 inhibits interaction with HDAC6,
CC resulting in decreased acetylation of tubulin and increased cell
CC motility (PubMed:23093407). Plays a role in cell proliferation by
CC regulating the G1/S-phase transition (PubMed:23355470). Involved in
CC astral microtubule organization and mitotic spindle orientation during
CC early stage of mitosis; this process is regulated by phosphorylation by
CC LIMK2 (PubMed:22328514). {ECO:0000269|PubMed:17105200,
CC ECO:0000269|PubMed:17693641, ECO:0000269|PubMed:18028908,
CC ECO:0000269|PubMed:20308065, ECO:0000269|PubMed:21316364,
CC ECO:0000269|PubMed:21995432, ECO:0000269|PubMed:22328514,
CC ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470,
CC ECO:0000269|PubMed:26289831, ECO:0000269|PubMed:31522887}.
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:0000269|PubMed:21316364, ECO:0000269|PubMed:21995432};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000269|PubMed:21316364, ECO:0000269|PubMed:21995432};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:21316364};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=kcat is 0.018 min(-1) for GTP. {ECO:0000269|PubMed:21316364};
CC -!- SUBUNIT: Homodimer (PubMed:17693641, PubMed:22484033, PubMed:26289831,
CC PubMed:33831707). Binds tubulin; binding is inhibited by GTP
CC (PubMed:17105200, PubMed:26289831). Interacts with MAPK1 (By
CC similarity). Interacts with GAPDH; the interaction is direct (By
CC similarity). Interacts with LIMK1 (via the PDZ domain); the interaction
CC is direct (PubMed:18028908, PubMed:22328514). Interacts with LIMK2
CC (PubMed:22328514). Interacts with HDAC6; thereby inhibiting the tubulin
CC deacetylase activity of HDAC6 (PubMed:20308065, PubMed:23093407).
CC Interacts with aggregated SNCA; may have a pro-aggregatory role in
CC synucleinopathies (PubMed:15590652, PubMed:17027006). Interacts with
CC DYNLL1 (PubMed:31505170). Interacts (via C-terminus) with S100A2,
CC S100A6 and S100B; these interactions inhibit TPPP dimerization
CC (PubMed:33831707). {ECO:0000250|UniProtKB:Q27957,
CC ECO:0000269|PubMed:15590652, ECO:0000269|PubMed:17027006,
CC ECO:0000269|PubMed:17105200, ECO:0000269|PubMed:17693641,
CC ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:20308065,
CC ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:22484033,
CC ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:26289831,
CC ECO:0000269|PubMed:31505170, ECO:0000269|PubMed:33831707}.
CC -!- INTERACTION:
CC O94811; Q02539: H1-1; NbExp=2; IntAct=EBI-3927802, EBI-932603;
CC O94811; Q8N7X4: MAGEB6; NbExp=3; IntAct=EBI-3927802, EBI-6447163;
CC O94811; P37840: SNCA; NbExp=8; IntAct=EBI-3927802, EBI-985879;
CC O94811; P45880: VDAC2; NbExp=3; IntAct=EBI-3927802, EBI-354022;
CC O94811; Q8NC26: ZNF114; NbExp=3; IntAct=EBI-3927802, EBI-10265237;
CC -!- SUBCELLULAR LOCATION: Golgi outpost {ECO:0000250|UniProtKB:D3ZQL7}.
CC Cytoplasm, cytoskeleton, microtubule organizing center
CC {ECO:0000250|UniProtKB:D3ZQL7}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:17105200}. Nucleus {ECO:0000269|PubMed:18028908}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:22328514}.
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 (PubMed:18028908).
CC Also found in the nucleus; however, nuclear localization is unclear and
CC requires additional evidences (PubMed:18028908). Localizes to glial
CC Lewy bodies in the brains of individuals with synucleinopathies
CC (PubMed:15590652, PubMed:17027006). During mitosis, colocalizes with
CC LIMK2 at the mitotic spindle (PubMed:22328514).
CC {ECO:0000250|UniProtKB:D3ZQL7, ECO:0000269|PubMed:15590652,
CC ECO:0000269|PubMed:17027006, ECO:0000269|PubMed:18028908,
CC ECO:0000269|PubMed:22328514}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10083737}.
CC -!- INDUCTION: enriched in cerebrospinal fluid of multiple sclerosis
CC patients (at protein level). {ECO:0000269|PubMed:21565174}.
CC -!- DOMAIN: Most of the protein is composed of disordered regions
CC (PubMed:21316364). Zinc-binding induces structural rearrangement by
CC promoting molten globule state formation (PubMed:21995432).
CC {ECO:0000269|PubMed:21316364, ECO:0000269|PubMed:21995432}.
CC -!- PTM: Phosphorylated by LIMK1 on serine residues; phosphorylation may
CC alter the tubulin polymerization activity (PubMed:17693641,
CC PubMed:18028908). Phosphorylation by LIMK2, but not LIMK1, regulates
CC astral microtubule organization at early stage of mitosis
CC (PubMed:22328514). Phosphorylation by ROCK1 at Ser-32, Ser-107 and Ser-
CC 159 inhibits interaction with HDAC6, resulting in decreased acetylation
CC of tubulin, increased cell motility and entry into S-phase
CC (PubMed:23093407, PubMed:23355470). Phosphorylation by CDK1 inhibits
CC the microtubule polymerizing activity (PubMed:23355470).
CC {ECO:0000269|PubMed:17693641, ECO:0000269|PubMed:18028908,
CC ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23093407,
CC ECO:0000269|PubMed:23355470}.
CC -!- PTM: Degraded by the proteasome; zinc-binding inhibits degradation by
CC the proteasome. {ECO:0000269|PubMed:25445539}.
CC -!- SIMILARITY: Belongs to the TPPP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH40496.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB017016; BAA36164.1; -; mRNA.
DR EMBL; BT020035; AAV38838.1; -; mRNA.
DR EMBL; BC040496; AAH40496.1; ALT_INIT; mRNA.
DR CCDS; CCDS3856.1; -.
DR RefSeq; NP_008961.1; NM_007030.2.
DR RefSeq; XP_005248294.2; XM_005248237.3.
DR RefSeq; XP_016864483.1; XM_017008994.1.
DR AlphaFoldDB; O94811; -.
DR SMR; O94811; -.
DR BioGRID; 116259; 36.
DR IntAct; O94811; 15.
DR MINT; O94811; -.
DR STRING; 9606.ENSP00000353785; -.
DR BindingDB; O94811; -.
DR GlyGen; O94811; 4 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; O94811; -.
DR PhosphoSitePlus; O94811; -.
DR BioMuta; TPPP; -.
DR UCD-2DPAGE; O94811; -.
DR EPD; O94811; -.
DR jPOST; O94811; -.
DR MassIVE; O94811; -.
DR PaxDb; O94811; -.
DR PeptideAtlas; O94811; -.
DR PRIDE; O94811; -.
DR ProteomicsDB; 50451; -.
DR Antibodypedia; 22256; 267 antibodies from 36 providers.
DR DNASU; 11076; -.
DR Ensembl; ENST00000360578.7; ENSP00000353785.5; ENSG00000171368.12.
DR GeneID; 11076; -.
DR KEGG; hsa:11076; -.
DR MANE-Select; ENST00000360578.7; ENSP00000353785.5; NM_007030.3; NP_008961.1.
DR CTD; 11076; -.
DR DisGeNET; 11076; -.
DR GeneCards; TPPP; -.
DR HGNC; HGNC:24164; TPPP.
DR HPA; ENSG00000171368; Tissue enriched (brain).
DR MIM; 608773; gene.
DR neXtProt; NX_O94811; -.
DR OpenTargets; ENSG00000171368; -.
DR PharmGKB; PA162406809; -.
DR VEuPathDB; HostDB:ENSG00000171368; -.
DR eggNOG; KOG4070; Eukaryota.
DR GeneTree; ENSGT00940000153875; -.
DR HOGENOM; CLU_091734_0_0_1; -.
DR InParanoid; O94811; -.
DR OMA; TRFTGSH; -.
DR OrthoDB; 1317210at2759; -.
DR PhylomeDB; O94811; -.
DR TreeFam; TF314440; -.
DR PathwayCommons; O94811; -.
DR SignaLink; O94811; -.
DR SIGNOR; O94811; -.
DR BioGRID-ORCS; 11076; 4 hits in 1067 CRISPR screens.
DR GeneWiki; TPPP; -.
DR GenomeRNAi; 11076; -.
DR Pharos; O94811; Tbio.
DR PRO; PR:O94811; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O94811; protein.
DR Bgee; ENSG00000171368; Expressed in Brodmann (1909) area 23 and 188 other tissues.
DR ExpressionAtlas; O94811; baseline and differential.
DR Genevisible; O94811; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005874; C:microtubule; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0150051; C:postsynaptic Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:HGNC-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0030953; P:astral microtubule organization; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0001578; P:microtubule bundle formation; IDA:UniProtKB.
DR GO; GO:0051418; P:microtubule nucleation by microtubule organizing center; IDA:UniProtKB.
DR GO; GO:0046785; P:microtubule polymerization; IDA:UniProtKB.
DR GO; GO:0032288; P:myelin assembly; ISS:UniProtKB.
DR GO; GO:1904428; P:negative regulation of tubulin deacetylation; IDA: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; IDA:HGNC-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISS:HGNC-UCL.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IDA: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..219
FT /note="Tubulin polymerization-promoting protein"
FT /id="PRO_0000221135"
FT REGION 1..116
FT /note="Mediates interaction with LIMK1"
FT /evidence="ECO:0000269|PubMed:18028908"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 171..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 19..33
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 61
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:21995432"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:21995432"
FT BINDING 80
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:21995432"
FT BINDING 83
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:21995432"
FT MOD_RES 14
FT /note="Phosphothreonine; by CDK1 and CDK5"
FT /evidence="ECO:0000269|PubMed:17693641,
FT ECO:0000269|PubMed:23355470, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 18
FT /note="Phosphoserine; by CDK1, CDK5 and MAPK1"
FT /evidence="ECO:0000269|PubMed:17693641,
FT ECO:0000269|PubMed:23355470, ECO:0007744|PubMed:18669648"
FT MOD_RES 32
FT /note="Phosphoserine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:17693641,
FT ECO:0000269|PubMed:23093407, ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 45
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:23355470,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 92
FT /note="Phosphothreonine; by PKA; in vitro"
FT /evidence="ECO:0000269|PubMed:17693641"
FT MOD_RES 107
FT /note="Phosphoserine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:23093407"
FT MOD_RES 159
FT /note="Phosphoserine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:17693641,
FT ECO:0000269|PubMed:23093407, ECO:0007744|PubMed:24275569"
FT MOD_RES 160
FT /note="Phosphoserine; by CDK1, CDK5 and MAPK1"
FT /evidence="ECO:0000269|PubMed:17693641,
FT ECO:0000269|PubMed:23355470"
FT CARBOHYD 152
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q7TQD2"
FT MUTAGEN 14
FT /note="T->A: In 4Ala; abolished phosphorylation by CDK1
FT without affecting G1/S-phase transition; when associated
FT with A-18, A-45 and A-160."
FT /evidence="ECO:0000269|PubMed:23355470"
FT MUTAGEN 14
FT /note="T->E: In 4Glu; phosphomimetic mutant, does not
FT affect G1/S-phase transition; when associated with E-18, E-
FT 45 and E-160."
FT /evidence="ECO:0000269|PubMed:23355470"
FT MUTAGEN 18
FT /note="S->A: In 4Ala; abolished phosphorylation by CDK1
FT without affecting G1/S-phase transition; when associated
FT with A-14, A-45 and A-160."
FT /evidence="ECO:0000269|PubMed:23355470"
FT MUTAGEN 18
FT /note="S->E: In 4Glu; phosphomimetic mutant, does not
FT affect G1/S-phase transition; when associated with E-14, E-
FT 45 and E-160."
FT /evidence="ECO:0000269|PubMed:23355470"
FT MUTAGEN 32
FT /note="S->A: In 3Ala; abolished phosphorylation by ROCK1,
FT leading to delayed entry into S-phase; when associated with
FT A-107 and A-159."
FT /evidence="ECO:0000269|PubMed:23093407,
FT ECO:0000269|PubMed:23355470"
FT MUTAGEN 32
FT /note="S->E: In 3Glu; phosphomimetic mutant, leading to
FT decreased transition of the G1/S-phase; when associated
FT with E-07 and E-159."
FT /evidence="ECO:0000269|PubMed:23093407,
FT ECO:0000269|PubMed:23355470"
FT MUTAGEN 45
FT /note="S->A: In 4Ala; abolished phosphorylation by CDK1
FT without affecting G1/S-phase transition; when associated
FT with A-14, A-18 and A-160."
FT /evidence="ECO:0000269|PubMed:23355470"
FT MUTAGEN 45
FT /note="S->E: In 4Glu; phosphomimetic mutant, does not
FT affect G1/S-phase transition; when associated with E-14, E-
FT 18 and E-160."
FT /evidence="ECO:0000269|PubMed:23355470"
FT MUTAGEN 107
FT /note="S->A: In 3Ala; abolished phosphorylation by ROCK1,
FT leading to delayed entry into S-phase; when associated with
FT A-32 and A-159."
FT /evidence="ECO:0000269|PubMed:23093407,
FT ECO:0000269|PubMed:23355470"
FT MUTAGEN 107
FT /note="S->E: In 3Glu; phosphomimetic mutant, leading to
FT decreased transition of the G1/S-phase; when associated
FT with E-32 and E-159."
FT /evidence="ECO:0000269|PubMed:23093407,
FT ECO:0000269|PubMed:23355470"
FT MUTAGEN 159
FT /note="S->A: In 3Ala; abolished phosphorylation by ROCK1,
FT leading to delayed entry into S-phase; when associated with
FT A-32 and A-107."
FT /evidence="ECO:0000269|PubMed:23093407,
FT ECO:0000269|PubMed:23355470"
FT MUTAGEN 159
FT /note="S->E: In 3Glu; phosphomimetic mutant, leading to
FT decreased transition of the G1/S-phase; when associated
FT with E-32 and E-107."
FT /evidence="ECO:0000269|PubMed:23093407,
FT ECO:0000269|PubMed:23355470"
FT MUTAGEN 160
FT /note="S->A: In 4Ala; abolished phosphorylation by CDK1
FT without affecting G1/S-phase transition; when associated
FT with A-14, A-18 and A-45."
FT /evidence="ECO:0000269|PubMed:23355470"
FT MUTAGEN 160
FT /note="S->E: In 4Glu; phosphomimetic mutant, does not
FT affect G1/S-phase transition; when associated with E-14, E-
FT 18 and E-45."
FT /evidence="ECO:0000269|PubMed:23355470"
SQ SEQUENCE 219 AA; 23694 MW; F8B2C814EA59129A CRC64;
MADKAKPAKA ANRTPPKSPG DPSKDRAAKR LSLESEGAGE GAAASPELSA LEEAFRRFAV
HGDARATGRE MHGKNWSKLC KDCQVIDGRN VTVTDVDIVF SKIKGKSCRT ITFEQFQEAL
EELAKKRFKD KSSEEAVREV HRLIEGKAPI ISGVTKAISS PTVSRLTDTT KFTGSHKERF
DPSGKGKGKA GRVDLVDESG YVSGYKHAGT YDQKVQGGK
