ID TYB4_HUMAN Reviewed; 44 AA. AC P62328; P01253; P01254; Q546P5; Q63576; Q9UE55; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 11-NOV-2015, entry version 119. DE RecName: Full=Thymosin beta-4; DE Short=T beta-4; DE AltName: Full=Fx; DE Contains: DE RecName: Full=Hematopoietic system regulatory peptide; DE AltName: Full=Seraspenide; GN Name=TMSB4X; Synonyms=TB4X, THYB4, TMSB4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, AND TISSUE SPECIFICITY. RC TISSUE=Peripheral blood leukocyte; RX PubMed=3500230; RA Gondo H., Kudo J., White J.W., Barr C., Selvanayagam P., RA Saunders G.F.; RT "Differential expression of the human thymosin-beta 4 gene in RT lymphocytes, macrophages, and granulocytes."; RL J. Immunol. 139:3840-3848(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=16010977; DOI=10.1007/s11010-005-7642-4; RA Yang S.P., Lee H.J., Su Y.; RT "Molecular cloning and structural characterization of the functional RT human thymosin beta4 gene."; RL Mol. Cell. Biochem. 272:97-105(2005). RN [3] 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 RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP PROTEIN SEQUENCE OF 2-44, INTERACTION WITH ACTIN, CLEAVAGE OF RP INITIATOR METHIONINE, AND ACETYLATION AT SER-2. RX PubMed=1999398; RA Safer D., Elzinga M., Nachmias V.T.; RT "Thymosin beta 4 and Fx, an actin-sequestering peptide, are RT indistinguishable."; RL J. Biol. Chem. 266:4029-4032(1991). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-44, AND INDUCTION. RX PubMed=6548414; DOI=10.1016/0092-8674(84)90270-8; RA Friedman R.L., Manly S.P., McMahon M., Kerr I.M., Stark G.R.; RT "Transcriptional and posttranscriptional regulation of interferon- RT induced gene expression in human cells."; RL Cell 38:745-755(1984). RN [6] RP 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 [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-4; LYS-12; LYS-26; LYS-32 RP AND LYS-39, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE RP SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE RP SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [12] RP STRUCTURE BY NMR OF WILD-TYPE AND OF MUTANTS LYS-12; SER-16 AND LEU-18 RP IN COMPLEX WITH ACTIN. RX PubMed=10848969; DOI=10.1046/j.1432-1327.2000.01380.x; RA Simenel C., Van Troys M., Vandekerckhove J., Ampe C., Delepierre M.; RT "Structural requirements for thymosin beta4 in its contact with actin. RT An NMR-analysis of thymosin beta4 mutants in solution and correlation RT with their biological activity."; RL Eur. J. Biochem. 267:3530-3538(2000). RN [13] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 21-44 IN COMPLEX WITH ACTA1; RP GSN AND COBL, AND SUBUNIT. RX PubMed=23009842; DOI=10.1016/j.bpj.2012.07.030; RA Durer Z.A., Kudryashov D.S., Sawaya M.R., Altenbach C., Hubbell W., RA Reisler E.; RT "Structural states and dynamics of the D-loop in actin."; RL Biophys. J. 103:930-939(2012). CC -!- FUNCTION: Plays an important role in the organization of the CC cytoskeleton (By similarity). Binds to and sequesters actin CC monomers (G actin) and therefore inhibits actin polymerization. CC {ECO:0000250}. CC -!- FUNCTION: Seraspenide inhibits the entry of hematopoietic CC pluripotent stem cells into the S-phase. {ECO:0000250}. CC -!- SUBUNIT: Interacts with SERPINB1 (By similarity). Identified in a CC complex composed of ACTA1, COBL, GSN AND TMSB4X. {ECO:0000250, CC ECO:0000269|PubMed:10848969, ECO:0000269|PubMed:1999398, CC ECO:0000269|PubMed:23009842}. CC -!- INTERACTION: CC P40692:MLH1; NbExp=16; IntAct=EBI-712598, EBI-744248; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. CC -!- TISSUE SPECIFICITY: Expressed in several hemopoietic cell lines CC and lymphoid malignant cells. Decreased levels in myeloma cells. CC {ECO:0000269|PubMed:3500230}. CC -!- INDUCTION: By alpha interferons. Decreased levels in THP-1 cells CC after treatment with recombinant interferon-lambda. CC {ECO:0000269|PubMed:3500230, ECO:0000269|PubMed:6548414}. CC -!- SIMILARITY: Belongs to the thymosin beta family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M17733; AAA36745.1; -; mRNA. DR EMBL; AJ295158; CAC43317.1; -; Genomic_DNA. DR EMBL; BT007090; AAP35753.1; -; mRNA. DR EMBL; X02493; CAA26323.1; -; mRNA. DR CCDS; CCDS35202.1; -. DR PIR; I56000; A38682. DR RefSeq; NP_066932.1; NM_021109.3. DR UniGene; Hs.437277; -. DR UniGene; Hs.703237; -. DR PDB; 1UY5; Model; -; T=2-44. DR PDB; 3TU5; X-ray; 3.00 A; B=21-44. DR PDB; 4PL7; X-ray; 2.30 A; A/B=2-44. DR PDB; 4PL8; X-ray; 2.00 A; H=2-44. DR PDBsum; 1UY5; -. DR PDBsum; 3TU5; -. DR PDBsum; 4PL7; -. DR PDBsum; 4PL8; -. DR DisProt; DP00357; -. DR ProteinModelPortal; P62328; -. DR SMR; P62328; 6-41. DR BioGrid; 112969; 22. DR IntAct; P62328; 22. DR MINT; MINT-6542280; -. DR STRING; 9606.ENSP00000370007; -. DR PhosphoSite; P62328; -. DR BioMuta; TMSB4X; -. DR DMDM; 78103211; -. DR DOSAC-COBS-2DPAGE; P62328; -. DR MaxQB; P62328; -. DR PaxDb; P62328; -. DR PRIDE; P62328; -. DR DNASU; 7114; -. DR Ensembl; ENST00000380633; ENSP00000370007; ENSG00000205542. DR Ensembl; ENST00000380635; ENSP00000370009; ENSG00000205542. DR Ensembl; ENST00000380636; ENSP00000370010; ENSG00000205542. DR Ensembl; ENST00000451311; ENSP00000414376; ENSG00000205542. DR GeneID; 7114; -. DR KEGG; hsa:7114; -. DR UCSC; uc004cvf.3; human. DR CTD; 7114; -. DR GeneCards; TMSB4X; -. DR HGNC; HGNC:11881; TMSB4X. DR HPA; CAB033806; -. DR MIM; 300159; gene. DR neXtProt; NX_P62328; -. DR PharmGKB; PA36581; -. DR eggNOG; KOG4794; Eukaryota. DR eggNOG; ENOG410Y3I4; LUCA. DR GeneTree; ENSGT00390000007040; -. DR HOVERGEN; HBG012534; -. DR InParanoid; P62328; -. DR KO; K05764; -. DR OrthoDB; EOG7TJ3MT; -. DR PhylomeDB; P62328; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR ChiTaRS; TMSB4X; human. DR GeneWiki; Thymosin_beta-4; -. DR GenomeRNAi; 7114; -. DR NextBio; 27851; -. DR PRO; PR:P62328; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; P62328; -. DR CleanEx; HS_TMSB4X; -. DR ExpressionAtlas; P62328; baseline and differential. DR Genevisible; P62328; HS. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0007015; P:actin filament organization; IEA:InterPro. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR GO; GO:0042989; P:sequestering of actin monomers; IEA:InterPro. DR Gene3D; 1.20.5.520; -; 1. DR InterPro; IPR001152; Beta-thymosin. DR PANTHER; PTHR12021; PTHR12021; 1. DR Pfam; PF01290; Thymosin; 1. DR PIRSF; PIRSF001828; Thymosin_beta; 1. DR ProDom; PD005116; Thymosin_b4; 1. DR SMART; SM00152; THY; 1. DR PROSITE; PS00500; THYMOSIN_B4; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Actin-binding; Complete proteome; KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Phosphoprotein; KW Reference proteome. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:22223895, FT ECO:0000269|PubMed:1999398}. FT CHAIN 2 44 Thymosin beta-4. FT /FTId=PRO_0000045920. FT PEPTIDE 2 5 Hematopoietic system regulatory peptide. FT {ECO:0000250}. FT /FTId=PRO_0000034295. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:22223895, FT ECO:0000269|PubMed:1999398}. FT MOD_RES 2 2 Phosphoserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 4 4 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 12 12 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 23 23 Phosphothreonine. FT {ECO:0000250|UniProtKB:P20065}. FT MOD_RES 26 26 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 32 32 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 34 34 Phosphothreonine. FT {ECO:0000250|UniProtKB:P62329}. FT MOD_RES 39 39 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MUTAGEN 12 12 K->P: Very weak actin binding; no FT inhibition of actin polymerization. FT MUTAGEN 16 16 S->A: Binds actin 2.5-fold less than FT wild-type; little change in inhibition of FT actin polymerization. FT MUTAGEN 16 16 S->AS: Very weak actin binding; no FT inhibition of actin polymerization. FT MUTAGEN 18 18 L->A,P: Very weak actin binding; no FT inhibition of actin polymerization. FT HELIX 6 11 {ECO:0000244|PDB:4PL8}. FT HELIX 15 17 {ECO:0000244|PDB:4PL8}. FT HELIX 32 39 {ECO:0000244|PDB:4PL7}. SQ SEQUENCE 44 AA; 5053 MW; 440C6158482DAAD0 CRC64; MSDKPDMAEI EKFDKSKLKK TETQEKNPLP SKETIEQEKQ AGES //