O94811 · TPPP_HUMAN
- ProteinTubulin polymerization-promoting protein
- GeneTPPP
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids219 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath (PubMed:31522887).
Acts as a microtubule nucleation factor in oligodendrocytes: specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, and promotes microtubule nucleation, an important step for elongation of the myelin sheath (PubMed:31522887, PubMed:33831707).
Required for both uniform polarized growth of distal microtubules as well as directing the branching of proximal processes (PubMed:31522887).
Shows magnesium-dependent GTPase activity; the role of the GTPase activity is unclear (PubMed:21316364, PubMed:21995432).
In addition to microtubule nucleation activity, also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network (PubMed:17105200, PubMed:17693641, PubMed:18028908, PubMed:26289831).
Regulates microtubule dynamics by promoting tubulin acetylation: acts by inhibiting the tubulin deacetylase activity of HDAC6 (PubMed:20308065, PubMed:23093407).
Also regulates cell migration: phosphorylation by ROCK1 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin and increased cell motility (PubMed:23093407).
Plays a role in cell proliferation by regulating the G1/S-phase transition (PubMed:23355470).
Involved in astral microtubule organization and mitotic spindle orientation during early stage of mitosis; this process is regulated by phosphorylation by LIMK2 (PubMed:22328514).
Acts as a microtubule nucleation factor in oligodendrocytes: specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, and promotes microtubule nucleation, an important step for elongation of the myelin sheath (PubMed:31522887, PubMed:33831707).
Required for both uniform polarized growth of distal microtubules as well as directing the branching of proximal processes (PubMed:31522887).
Shows magnesium-dependent GTPase activity; the role of the GTPase activity is unclear (PubMed:21316364, PubMed:21995432).
In addition to microtubule nucleation activity, also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network (PubMed:17105200, PubMed:17693641, PubMed:18028908, PubMed:26289831).
Regulates microtubule dynamics by promoting tubulin acetylation: acts by inhibiting the tubulin deacetylase activity of HDAC6 (PubMed:20308065, PubMed:23093407).
Also regulates cell migration: phosphorylation by ROCK1 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin and increased cell motility (PubMed:23093407).
Plays a role in cell proliferation by regulating the G1/S-phase transition (PubMed:23355470).
Involved in astral microtubule organization and mitotic spindle orientation during early stage of mitosis; this process is regulated by phosphorylation by LIMK2 (PubMed:22328514).
Catalytic activity
- GTP + H2O = GDP + H+ + phosphateThis reaction proceeds in the forward direction.
Cofactor
Kinetics
kcat is 0.018 min-1 for GTP.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTubulin polymerization-promoting protein
- EC number
- Short namesTPPP
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO94811
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, which shapes dendrite morphology by functioning as sites of acentrosomal microtubule nucleation (By similarity).
Mainly localizes to the cytoskeleton (PubMed:18028908).
Also found in the nucleus; however, nuclear localization is unclear and requires additional evidences (PubMed:18028908).
Localizes to glial Lewy bodies in the brains of individuals with synucleinopathies (PubMed:15590652, PubMed:17027006).
During mitosis, colocalizes with LIMK2 at the mitotic spindle (PubMed:22328514).
Mainly localizes to the cytoskeleton (PubMed:18028908).
Also found in the nucleus; however, nuclear localization is unclear and requires additional evidences (PubMed:18028908).
Localizes to glial Lewy bodies in the brains of individuals with synucleinopathies (PubMed:15590652, PubMed:17027006).
During mitosis, colocalizes with LIMK2 at the mitotic spindle (PubMed:22328514).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 14 | In 4Ala; abolished phosphorylation by CDK1 without affecting G1/S-phase transition; when associated with A-18, A-45 and A-160. | ||||
Sequence: T → A | ||||||
Mutagenesis | 14 | In 4Glu; phosphomimetic mutant, does not affect G1/S-phase transition; when associated with E-18, E-45 and E-160. | ||||
Sequence: T → E | ||||||
Mutagenesis | 18 | In 4Ala; abolished phosphorylation by CDK1 without affecting G1/S-phase transition; when associated with A-14, A-45 and A-160. | ||||
Sequence: S → A | ||||||
Mutagenesis | 18 | In 4Glu; phosphomimetic mutant, does not affect G1/S-phase transition; when associated with E-14, E-45 and E-160. | ||||
Sequence: S → E | ||||||
Mutagenesis | 32 | In 3Ala; abolished phosphorylation by ROCK1, leading to delayed entry into S-phase; when associated with A-107 and A-159. | ||||
Sequence: S → A | ||||||
Mutagenesis | 32 | In 3Glu; phosphomimetic mutant, leading to decreased transition of the G1/S-phase; when associated with E-07 and E-159. | ||||
Sequence: S → E | ||||||
Mutagenesis | 45 | In 4Ala; abolished phosphorylation by CDK1 without affecting G1/S-phase transition; when associated with A-14, A-18 and A-160. | ||||
Sequence: S → A | ||||||
Mutagenesis | 45 | In 4Glu; phosphomimetic mutant, does not affect G1/S-phase transition; when associated with E-14, E-18 and E-160. | ||||
Sequence: S → E | ||||||
Mutagenesis | 107 | In 3Ala; abolished phosphorylation by ROCK1, leading to delayed entry into S-phase; when associated with A-32 and A-159. | ||||
Sequence: S → A | ||||||
Mutagenesis | 107 | In 3Glu; phosphomimetic mutant, leading to decreased transition of the G1/S-phase; when associated with E-32 and E-159. | ||||
Sequence: S → E | ||||||
Mutagenesis | 159 | In 3Ala; abolished phosphorylation by ROCK1, leading to delayed entry into S-phase; when associated with A-32 and A-107. | ||||
Sequence: S → A | ||||||
Mutagenesis | 159 | In 3Glu; phosphomimetic mutant, leading to decreased transition of the G1/S-phase; when associated with E-32 and E-107. | ||||
Sequence: S → E | ||||||
Mutagenesis | 160 | In 4Ala; abolished phosphorylation by CDK1 without affecting G1/S-phase transition; when associated with A-14, A-18 and A-45. | ||||
Sequence: S → A | ||||||
Mutagenesis | 160 | In 4Glu; phosphomimetic mutant, does not affect G1/S-phase transition; when associated with E-14, E-18 and E-45. | ||||
Sequence: S → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 244 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data), glycosylation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000221135 | 1-219 | UniProt | Tubulin polymerization-promoting protein | |||
Sequence: MADKAKPAKAANRTPPKSPGDPSKDRAAKRLSLESEGAGEGAAASPELSALEEAFRRFAVHGDARATGREMHGKNWSKLCKDCQVIDGRNVTVTDVDIVFSKIKGKSCRTITFEQFQEALEELAKKRFKDKSSEEAVREVHRLIEGKAPIISGVTKAISSPTVSRLTDTTKFTGSHKERFDPSGKGKGKAGRVDLVDESGYVSGYKHAGTYDQKVQGGK | |||||||
Modified residue | 14 | UniProt | Phosphothreonine; by CDK1 and CDK5 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 14 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 18 | UniProt | Phosphoserine; by CDK1, CDK5 and MAPK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 18 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 23 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 32 | UniProt | Phosphoserine; by ROCK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 32 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 35 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 35 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 45 | UniProt | Phosphoserine; by CDK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 45 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 92 | UniProt | Phosphothreonine; by PKA; in vitro | ||||
Sequence: T | |||||||
Modified residue | 107 | UniProt | Phosphoserine; by ROCK1 | ||||
Sequence: S | |||||||
Glycosylation | 152 | UniProt | O-linked (GlcNAc) serine | ||||
Sequence: S | |||||||
Modified residue | 159 | UniProt | Phosphoserine; by ROCK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 159 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 160 | UniProt | Phosphoserine; by CDK1, CDK5 and MAPK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 160 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 203 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated by LIMK1 on serine residues; phosphorylation may alter the tubulin polymerization activity (PubMed:17693641, PubMed:18028908).
Phosphorylation by LIMK2, but not LIMK1, regulates astral microtubule organization at early stage of mitosis (PubMed:22328514).
Phosphorylation by ROCK1 at Ser-32, Ser-107 and Ser-159 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin, increased cell motility and entry into S-phase (PubMed:23093407, PubMed:23355470).
Phosphorylation by CDK1 inhibits the microtubule polymerizing activity (PubMed:23355470).
Phosphorylation by LIMK2, but not LIMK1, regulates astral microtubule organization at early stage of mitosis (PubMed:22328514).
Phosphorylation by ROCK1 at Ser-32, Ser-107 and Ser-159 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin, increased cell motility and entry into S-phase (PubMed:23093407, PubMed:23355470).
Phosphorylation by CDK1 inhibits the microtubule polymerizing activity (PubMed:23355470).
Degraded by the proteasome; zinc-binding inhibits degradation by the proteasome.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed.
Induction
enriched in cerebrospinal fluid of multiple sclerosis patients (at protein level).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (PubMed:17693641, PubMed:22484033, PubMed:26289831, PubMed:33831707).
Binds tubulin; binding is inhibited by GTP (PubMed:17105200, PubMed:26289831).
Interacts with MAPK1 (By similarity).
Interacts with GAPDH; the interaction is direct (By similarity).
Interacts with LIMK1 (via the PDZ domain); the interaction is direct (PubMed:18028908, PubMed:22328514).
Interacts with LIMK2 (PubMed:22328514).
Interacts with HDAC6; thereby inhibiting the tubulin deacetylase activity of HDAC6 (PubMed:20308065, PubMed:23093407).
Interacts with aggregated SNCA; may have a pro-aggregatory role in synucleinopathies (PubMed:15590652, PubMed:17027006).
Interacts with DYNLL1 (PubMed:31505170).
Interacts (via C-terminus) with S100A2, S100A6 and S100B; these interactions inhibit TPPP dimerization (PubMed:33831707).
Binds tubulin; binding is inhibited by GTP (PubMed:17105200, PubMed:26289831).
Interacts with MAPK1 (By similarity).
Interacts with GAPDH; the interaction is direct (By similarity).
Interacts with LIMK1 (via the PDZ domain); the interaction is direct (PubMed:18028908, PubMed:22328514).
Interacts with LIMK2 (PubMed:22328514).
Interacts with HDAC6; thereby inhibiting the tubulin deacetylase activity of HDAC6 (PubMed:20308065, PubMed:23093407).
Interacts with aggregated SNCA; may have a pro-aggregatory role in synucleinopathies (PubMed:15590652, PubMed:17027006).
Interacts with DYNLL1 (PubMed:31505170).
Interacts (via C-terminus) with S100A2, S100A6 and S100B; these interactions inhibit TPPP dimerization (PubMed:33831707).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O94811 | H1-1 Q02539 | 2 | EBI-3927802, EBI-932603 | |
BINARY | O94811 | MAGEB6 Q8N7X4 | 3 | EBI-3927802, EBI-6447163 | |
BINARY | O94811 | SNCA P37840 | 8 | EBI-3927802, EBI-985879 | |
BINARY | O94811 | VDAC2 P45880 | 3 | EBI-3927802, EBI-354022 | |
BINARY | O94811 | ZNF114 Q8NC26 | 3 | EBI-3927802, EBI-10265237 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-46 | Disordered | ||||
Sequence: MADKAKPAKAANRTPPKSPGDPSKDRAAKRLSLESEGAGEGAAASP | ||||||
Region | 1-116 | Mediates interaction with LIMK1 | ||||
Sequence: MADKAKPAKAANRTPPKSPGDPSKDRAAKRLSLESEGAGEGAAASPELSALEEAFRRFAVHGDARATGREMHGKNWSKLCKDCQVIDGRNVTVTDVDIVFSKIKGKSCRTITFEQF | ||||||
Compositional bias | 19-33 | Basic and acidic residues | ||||
Sequence: PGDPSKDRAAKRLSL | ||||||
Region | 171-192 | Disordered | ||||
Sequence: KFTGSHKERFDPSGKGKGKAGR |
Domain
Most of the protein is composed of disordered regions (PubMed:21316364).
Zinc-binding induces structural rearrangement by promoting molten globule state formation (PubMed:21995432).
Zinc-binding induces structural rearrangement by promoting molten globule state formation (PubMed:21995432).
Sequence similarities
Belongs to the TPPP family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length219
- Mass (Da)23,694
- Last updated1999-05-01 v1
- ChecksumF8B2C814EA59129A
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 19-33 | Basic and acidic residues | ||||
Sequence: PGDPSKDRAAKRLSL |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB017016 EMBL· GenBank· DDBJ | BAA36164.1 EMBL· GenBank· DDBJ | mRNA | ||
BT020035 EMBL· GenBank· DDBJ | AAV38838.1 EMBL· GenBank· DDBJ | mRNA | ||
BC040496 EMBL· GenBank· DDBJ | AAH40496.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |