O94811 (TPPP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tubulin polymerization-promoting protein
Short name=TPPP

Alternative name(s):
25 kDa brain-specific protein
TPPP/p25
p24
p25-alpha

Gene names

Name:	TPPP
Synonyms:	TPPP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	219 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in the polymerization of tubulin into microtubules, microtubule bundling and the stabilization of existing microtubules, thus maintaining the integrity of the microtubule network. May play a role in mitotic spindle assembly and nuclear envelope breakdown. Ref.6 Ref.8 Ref.9
Subunit structure	Homodimer. Binds tubulin; binding is inhibited by GTP By similarity. Interacts with GSK3 By similarity. 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. Ref.4 Ref.8 Ref.9
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton. Nucleus. Note: Localizes to glial Lewy bodies in the brains of individuals with synucleinopathies. Ref.4 Ref.6 Ref.7
Tissue specificity	Widely expressed. Ref.1
Post-translational modification	Poor substrate for GSK3 By similarity. Phosphorylated by LIMK1 on serine residues. Phosphorylation may alter the tubulin polymerization activity. Ref.5 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Miscellaneous	Unstructured protein. Interacts with aggregated SNCA and may have a pro-aggregatory role in synucleinopathies.
Sequence similarities	Belongs to the TPPP family.
Sequence caution	The sequence AAH40496.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Nucleus
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	microtubule bundle formation Inferred from direct assay Ref.6. Source: UniProtKB microtubule polymerization Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of protein polymerization Inferred from direct assay Ref.4. Source: HGNC
Cellular component	focal adhesion Inferred from direct assay. Source: HPA nucleus Inferred from direct assay Ref.8. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay Ref.4. Source: HGNC soluble fraction Inferred from sequence or structural similarity. Source: HGNC
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro microtubule binding Inferred from sequence or structural similarity. Source: HGNC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 219	219	Tubulin polymerization-promoting protein		PRO_0000221135
Regions
	Region	1 – 116	116	Mediates interaction with LIMK1
Amino acid modifications
	Modified residue	14	1	Phosphothreonine; by CDK5; in vitro Ref.5 Ref.9 Ref.11
	Modified residue	18	1	Phosphoserine; by CDK5 and MAPK1; in vitro Ref.5 Ref.9 Ref.11
	Modified residue	32	1	Phosphoserine; by PKA; in vitro Ref.9 Ref.10 Ref.11
	Modified residue	35	1	Phosphoserine Ref.11
	Modified residue	45	1	Phosphoserine Ref.11
	Modified residue	92	1	Phosphothreonine; by PKA; in vitro Ref.9
	Modified residue	159	1	Phosphoserine; by PKA; in vitro Ref.9
	Modified residue	160	1	Phosphoserine; by CDK5 and MAPK1; in vitro Ref.9 Ref.11 Ref.12
	Glycosylation	152	1	O-linked (GlcNAc) By similarity

Sequences

	Sequence		Length	Mass (Da)
	O94811 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: F8B2C814EA59129A	FASTA	219	23,694
	10 20 30 40 50 60 MADKAKPAKA ANRTPPKSPG DPSKDRAAKR LSLESEGAGE GAAASPELSA LEEAFRRFAV 70 80 90 100 110 120 HGDARATGRE MHGKNWSKLC KDCQVIDGRN VTVTDVDIVF SKIKGKSCRT ITFEQFQEAL 130 140 150 160 170 180 EELAKKRFKD KSSEEAVREV HRLIEGKAPI ISGVTKAISS PTVSRLTDTT KFTGSHKERF 190 200 210 DPSGKGKGKA GRVDLVDESG YVSGYKHAGT YDQKVQGGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel human gene whose product shares significant homology with the bovine brain-specific protein p25 on chromosome 5p15.3." Seki N., Hattori A., Sugano S., Suzuki Y., Nakagawara A., Muramatsu M.-A., Hori T.-A., Saito T. J. Hum. Genet. 44:121-122(1999) [PubMed: 10083737] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Neuroblastoma.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"p25alpha Stimulates alpha-synuclein aggregation and is co-localized with aggregated alpha-synuclein in alpha-synucleinopathies." Lindersson E., Lundvig D., Petersen C., Madsen P., Nyengaard J.R., Hoejrup P., Moos T., Otzen D., Gai W.-P., Blumbergs P.C., Jensen P.H. J. Biol. Chem. 280:5703-5715(2005) [PubMed: 15590652] [Abstract] Cited for: INTERACTION WITH AGGREGATED SNCA, SUBCELLULAR LOCATION.
[5]	"Phosphoproteomic analysis of synaptosomes from human cerebral cortex." DeGiorgis J.A., Jaffe H., Moreira J.E., Carlotti C.G. Jr., Leite J.P., Pant H.C., Dosemeci A. J. Proteome Res. 4:306-315(2005) [PubMed: 15822905] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND SER-18, MASS SPECTROMETRY. Tissue: Brain cortex.
[6]	"Tubulin polymerization promoting proteins (TPPPs): members of a new family with distinct structures and functions." Vincze O., Toekesi N., Olah J., Hlavanda E., Zotter A., Horvath I., Lehotzky A., Tirian L., Medzihradszky K.F., Kovacs J., Orosz F., Ovadi J. Biochemistry 45:13818-13826(2006) [PubMed: 17105200] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"Interaction of TPPP/p25 protein with glyceraldehyde-3-phosphate dehydrogenase and their co-localization in Lewy bodies." Olah J., Toekesi N., Vincze O., Horvath I., Lehotzky A., Erdei A., Szajli E., Medzihradszky K.F., Orosz F., Kovacs G.G., Ovadi J. FEBS Lett. 580:5807-5814(2006) [PubMed: 17027006] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules." Acevedo K., Li R., Soo P., Suryadinata R., Sarcevic B., Valova V.A., Graham M.E., Robinson P.J., Bernard O. Exp. Cell Res. 313:4091-4106(2007) [PubMed: 18028908] [Abstract] Cited for: FUNCTION, INTERACTION WITH LIMK1, PHOSPHORYLATION.
[9]	"Phosphorylation blocks the activity of tubulin polymerization-promoting protein (TPPP): identification of sites targeted by different kinases." Hlavanda E., Klement E., Kokai E., Kovacs J., Vincze O., Toekesi N., Orosz F., Medzihradszky K.F., Dombradi V., Ovadi J. J. Biol. Chem. 282:29531-29539(2007) [PubMed: 17693641] [Abstract] Cited for: FUNCTION, HOMODIMERIZATION, PHOSPHORYLATION AT THR-14; SER-18; SER-32; THR-92; SER-159 AND SER-160.
[10]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; SER-18; SER-32; SER-35; SER-45 AND SER-160, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160, MASS SPECTROMETRY. Tissue: Embryonic kidney.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB017016 mRNA. Translation: BAA36164.1. BT020035 mRNA. Translation: AAV38838.1. BC040496 mRNA. Translation: AAH40496.1. Different initiation.
IPI	IPI00013043.
RefSeq	NP_008961.1. NM_007030.2.
UniGene	Hs.481466.
3D structure databases
ProteinModelPortal	O94811.
SMR	O94811. Positions 43-216.
ModBase	Search...
Protein-protein interaction databases
IntAct	O94811. 1 interaction.
MINT	MINT-2798227.
STRING	O94811.
PTM databases
PhosphoSite	O94811.
2D gel databases
UCD-2DPAGE	O94811.
Proteomic databases
PRIDE	O94811.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360578; ENSP00000353785; ENSG00000171368.
GeneID	11076.
KEGG	hsa:11076.
UCSC	uc003jbg.2. human.
Organism-specific databases
CTD	11076.
GeneCards	GC05M000659.
H-InvDB	HIX0004710.
HGNC	HGNC:24164. TPPP.
HPA	HPA036575.
MIM	608773. gene.
neXtProt	NX_O94811.
PharmGKB	PA162406809.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG520967.
HOVERGEN	HBG036683.
InParanoid	O94811.
OMA	KGKSCRT.
OrthoDB	EOG4HQDKK.
PhylomeDB	O94811.
Gene expression databases
ArrayExpress	O94811.
Bgee	O94811.
CleanEx	HS_TPPP.
Genevestigator	O94811.
Family and domain databases
InterPro	IPR011992. EF-hand-like_dom. IPR008907. P25-alpha. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
PANTHER	PTHR12932. P25-alpha. 1 hit.
Pfam	PF05517. p25-alpha. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	42106.
SOURCE	Search...

Entry information

Entry name

TPPP_HUMAN

Accession

Primary (citable) accession number: O94811

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 12, 2003
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.