Full text data of TUBB1
TUBB1
[Confidence: low (only semi-automatic identification from reviews)]
Tubulin beta-1 chain
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Tubulin beta-1 chain
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9H4B7
ID TBB1_HUMAN Reviewed; 451 AA.
AC Q9H4B7;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 106.
DE RecName: Full=Tubulin beta-1 chain;
GN Name=TUBB1;
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].
RA Gross C., Kussmann S., Hehr A., Hansmann I., Schlote D.;
RT "Mapping and characterization of the human TUBB1 gene.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 38-46 AND 263-281.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [5]
RP INTERACTION WITH RANBP10.
RX PubMed=18347012; DOI=10.1074/jbc.M709397200;
RA Schulze H., Dose M., Korpal M., Meyer I., Italiano J.E. Jr.,
RA Shivdasani R.A.;
RT "RanBP10 is a cytoplasmic guanine nucleotide exchange factor that
RT modulates noncentrosomal microtubules.";
RL J. Biol. Chem. 283:14109-14119(2008).
RN [6]
RP GLYCYLATION.
RX PubMed=19524510; DOI=10.1016/j.cell.2009.05.020;
RA Rogowski K., Juge F., van Dijk J., Wloga D., Strub J.-M.,
RA Levilliers N., Thomas D., Bre M.-H., Van Dorsselaer A., Gaertig J.,
RA Janke C.;
RT "Evolutionary divergence of enzymatic mechanisms for posttranslational
RT polyglycylation.";
RL Cell 137:1076-1087(2009).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=20191564; DOI=10.1002/cm.20436;
RA Leandro-Garcia L.J., Leskela S., Landa I., Montero-Conde C.,
RA Lopez-Jimenez E., Leton R., Cascon A., Robledo M.,
RA Rodriguez-Antona C.;
RT "Tumoral and tissue-specific expression of the major human beta-
RT tubulin isotypes.";
RL Cytoskeleton 67:214-223(2010).
RN [8]
RP VARIANT PRO-43.
RX PubMed=15956286; DOI=10.1182/blood-2005-02-0723;
RA Freson K., De Vos R., Wittevrongel C., Thys C., Defoor J., Vanhees L.,
RA Vermylen J., Peerlinck K., Van Geet C.;
RT "The TUBB1 Q43P functional polymorphism reduces the risk of
RT cardiovascular disease in men by modulating platelet function and
RT structure.";
RL Blood 106:2356-2362(2005).
RN [9]
RP VARIANTS PRO-43 AND HIS-307, VARIANT MAD-TUBB1 TRP-318, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18849486; DOI=10.1182/blood-2008-06-162610;
RA Kunishima S., Kobayashi R., Itoh T.J., Hamaguchi M., Saito H.;
RT "Mutation of the beta1-tubulin gene associated with congenital
RT macrothrombocytopenia affecting microtubule assembly.";
RL Blood 113:458-461(2009).
CC -!- FUNCTION: Tubulin is the major constituent of microtubules. It
CC binds two moles of GTP, one at an exchangeable site on the beta
CC chain and one at a non-exchangeable site on the alpha chain (By
CC similarity).
CC -!- SUBUNIT: Dimer of alpha and beta chains. A typical microtubule is
CC a hollow water-filled tube with an outer diameter of 25 nm and an
CC inner diameter of 15 nM. Alpha-beta heterodimers associate head-
CC to-tail to form protofilaments running lengthwise along the
CC microtubule wall with the beta-tubulin subunit facing the
CC microtubule plus end conferring a structural polarity.
CC Microtubules usually have 13 protofilaments but different
CC protofilament numbers can be found in some organisms and
CC specialized cells. Interacts with RANBP10.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- TISSUE SPECIFICITY: Hematopoietic cell-specific. Major isotype in
CC leukocytes, where it represents 50% of all beta-tubulins.
CC -!- PTM: Some glutamate residues at the C-terminus are
CC polyglutamylated. This modification occurs exclusively on
CC glutamate residues and results in polyglutamate chains on the
CC gamma-carboxyl group. Also monoglycylated but not polyglycylated
CC due to the absence of functional TTLL10 in human. Monoglycylation
CC is mainly limited to tubulin incorporated into axonemes (cilia and
CC flagella) whereas glutamylation is prevalent in neuronal cells,
CC centrioles, axonemes, and the mitotic spindle. Both modifications
CC can coexist on the same protein on adjacent residues, and lowering
CC glycylation levels increases polyglutamylation, and reciprocally.
CC The precise function of such modifications is still unclear but
CC they regulate the assembly and dynamics of axonemal microtubules
CC (Probable).
CC -!- DISEASE: Macrothrombocytopenia, autosomal dominant, TUBB1-related
CC (MAD-TUBB1) [MIM:613112]: A congenital blood disorder
CC characterized by increased platelet size and decreased number of
CC circulating platelets. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tubulin family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AJ292757; CAC16605.1; -; mRNA.
DR EMBL; AL109840; CAC09371.2; -; Genomic_DNA.
DR EMBL; BC033679; AAH33679.1; -; mRNA.
DR RefSeq; NP_110400.1; NM_030773.3.
DR UniGene; Hs.303023; -.
DR ProteinModelPortal; Q9H4B7; -.
DR SMR; Q9H4B7; 1-430.
DR IntAct; Q9H4B7; 11.
DR MINT; MINT-1891365; -.
DR STRING; 9606.ENSP00000217133; -.
DR BindingDB; Q9H4B7; -.
DR ChEMBL; CHEMBL1915; -.
DR DrugBank; DB01394; Colchicine.
DR DrugBank; DB01248; Docetaxel.
DR DrugBank; DB01229; Paclitaxel.
DR DrugBank; DB00309; Vindesine.
DR PhosphoSite; Q9H4B7; -.
DR DMDM; 62903515; -.
DR OGP; Q9H4B7; -.
DR PaxDb; Q9H4B7; -.
DR PeptideAtlas; Q9H4B7; -.
DR PRIDE; Q9H4B7; -.
DR DNASU; 81027; -.
DR Ensembl; ENST00000217133; ENSP00000217133; ENSG00000101162.
DR GeneID; 81027; -.
DR KEGG; hsa:81027; -.
DR UCSC; uc002yak.3; human.
DR CTD; 81027; -.
DR GeneCards; GC20P057594; -.
DR HGNC; HGNC:16257; TUBB1.
DR HPA; CAB004286; -.
DR HPA; HPA043640; -.
DR HPA; HPA046280; -.
DR MIM; 612901; gene.
DR MIM; 613112; phenotype.
DR neXtProt; NX_Q9H4B7; -.
DR Orphanet; 140957; Autosomal dominant macrothrombocytopenia.
DR PharmGKB; PA38100; -.
DR eggNOG; COG5023; -.
DR HOGENOM; HOG000165710; -.
DR HOVERGEN; HBG000089; -.
DR InParanoid; Q9H4B7; -.
DR KO; K07375; -.
DR OMA; ACIFRGK; -.
DR OrthoDB; EOG7ZKS9Z; -.
DR PhylomeDB; Q9H4B7; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; TUBB1; -.
DR GenomeRNAi; 81027; -.
DR NextBio; 71348; -.
DR PRO; PR:Q9H4B7; -.
DR Bgee; Q9H4B7; -.
DR CleanEx; HS_TUBB1; -.
DR Genevestigator; Q9H4B7; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IEA:Ensembl.
DR GO; GO:0051084; P:'de novo' posttranslational protein folding; TAS:Reactome.
DR GO; GO:0051258; P:protein polymerization; IEA:InterPro.
DR GO; GO:0051225; P:spindle assembly; IEA:Ensembl.
DR Gene3D; 1.10.287.600; -; 1.
DR Gene3D; 3.30.1330.20; -; 1.
DR Gene3D; 3.40.50.1440; -; 1.
DR InterPro; IPR013838; Beta-tubulin_BS.
DR InterPro; IPR002453; Beta_tubulin.
DR InterPro; IPR008280; Tub_FtsZ_C.
DR InterPro; IPR000217; Tubulin.
DR InterPro; IPR018316; Tubulin/FtsZ_2-layer-sand-dom.
DR InterPro; IPR023123; Tubulin_C.
DR InterPro; IPR017975; Tubulin_CS.
DR InterPro; IPR003008; Tubulin_FtsZ_GTPase.
DR PANTHER; PTHR11588; PTHR11588; 1.
DR Pfam; PF00091; Tubulin; 1.
DR Pfam; PF03953; Tubulin_C; 1.
DR PRINTS; PR01163; BETATUBULIN.
DR PRINTS; PR01161; TUBULIN.
DR SMART; SM00864; Tubulin; 1.
DR SMART; SM00865; Tubulin_C; 1.
DR SUPFAM; SSF52490; SSF52490; 1.
DR SUPFAM; SSF55307; SSF55307; 1.
DR PROSITE; PS00227; TUBULIN; 1.
DR PROSITE; PS00228; TUBULIN_B_AUTOREG; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Disease mutation; GTP-binding; Microtubule; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 451 Tubulin beta-1 chain.
FT /FTId=PRO_0000048242.
FT NP_BIND 140 146 GTP (Potential).
FT MOD_RES 172 172 Phosphoserine; by CDK1 (By similarity).
FT VARIANT 43 43 Q -> H (in dbSNP:rs415064).
FT /FTId=VAR_034542.
FT VARIANT 43 43 Q -> P (in dbSNP:rs463312).
FT /FTId=VAR_034543.
FT VARIANT 274 274 T -> M (in dbSNP:rs35565630).
FT /FTId=VAR_052671.
FT VARIANT 307 307 R -> H (in dbSNP:rs6070697).
FT /FTId=VAR_052672.
FT VARIANT 318 318 R -> W (in MAD-TUBB1; dbSNP:rs121918555).
FT /FTId=VAR_063411.
SQ SEQUENCE 451 AA; 50327 MW; 6A3E5208C1C89AE4 CRC64;
MREIVHIQIG QCGNQIGAKF WEMIGEEHGI DLAGSDRGAS ALQLERISVY YNEAYGRKYV
PRAVLVDLEP GTMDSIRSSK LGALFQPDSF VHGNSGAGNN WAKGHYTEGA ELIENVLEVV
RHESESCDCL QGFQIVHSLG GGTGSGMGTL LMNKIREEYP DRIMNSFSVM PSPKVSDTVV
EPYNAVLSIH QLIENADACF CIDNEALYDI CFRTLKLTTP TYGDLNHLVS LTMSGITTSL
RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTAQGSQQ YRALSVAELT QQMFDARNTM
AACDLRRGRY LTVACIFRGK MSTKEVDQQL LSVQTRNSSC FVEWIPNNVK VAVCDIPPRG
LSMAATFIGN NTAIQEIFNR VSEHFSAMFK RKAFVHWYTS EGMDINEFGE AENNIHDLVS
EYQQFQDAKA VLEEDEEVTE EAEMEPEDKG H
//
ID TBB1_HUMAN Reviewed; 451 AA.
AC Q9H4B7;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 106.
DE RecName: Full=Tubulin beta-1 chain;
GN Name=TUBB1;
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].
RA Gross C., Kussmann S., Hehr A., Hansmann I., Schlote D.;
RT "Mapping and characterization of the human TUBB1 gene.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 38-46 AND 263-281.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [5]
RP INTERACTION WITH RANBP10.
RX PubMed=18347012; DOI=10.1074/jbc.M709397200;
RA Schulze H., Dose M., Korpal M., Meyer I., Italiano J.E. Jr.,
RA Shivdasani R.A.;
RT "RanBP10 is a cytoplasmic guanine nucleotide exchange factor that
RT modulates noncentrosomal microtubules.";
RL J. Biol. Chem. 283:14109-14119(2008).
RN [6]
RP GLYCYLATION.
RX PubMed=19524510; DOI=10.1016/j.cell.2009.05.020;
RA Rogowski K., Juge F., van Dijk J., Wloga D., Strub J.-M.,
RA Levilliers N., Thomas D., Bre M.-H., Van Dorsselaer A., Gaertig J.,
RA Janke C.;
RT "Evolutionary divergence of enzymatic mechanisms for posttranslational
RT polyglycylation.";
RL Cell 137:1076-1087(2009).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=20191564; DOI=10.1002/cm.20436;
RA Leandro-Garcia L.J., Leskela S., Landa I., Montero-Conde C.,
RA Lopez-Jimenez E., Leton R., Cascon A., Robledo M.,
RA Rodriguez-Antona C.;
RT "Tumoral and tissue-specific expression of the major human beta-
RT tubulin isotypes.";
RL Cytoskeleton 67:214-223(2010).
RN [8]
RP VARIANT PRO-43.
RX PubMed=15956286; DOI=10.1182/blood-2005-02-0723;
RA Freson K., De Vos R., Wittevrongel C., Thys C., Defoor J., Vanhees L.,
RA Vermylen J., Peerlinck K., Van Geet C.;
RT "The TUBB1 Q43P functional polymorphism reduces the risk of
RT cardiovascular disease in men by modulating platelet function and
RT structure.";
RL Blood 106:2356-2362(2005).
RN [9]
RP VARIANTS PRO-43 AND HIS-307, VARIANT MAD-TUBB1 TRP-318, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18849486; DOI=10.1182/blood-2008-06-162610;
RA Kunishima S., Kobayashi R., Itoh T.J., Hamaguchi M., Saito H.;
RT "Mutation of the beta1-tubulin gene associated with congenital
RT macrothrombocytopenia affecting microtubule assembly.";
RL Blood 113:458-461(2009).
CC -!- FUNCTION: Tubulin is the major constituent of microtubules. It
CC binds two moles of GTP, one at an exchangeable site on the beta
CC chain and one at a non-exchangeable site on the alpha chain (By
CC similarity).
CC -!- SUBUNIT: Dimer of alpha and beta chains. A typical microtubule is
CC a hollow water-filled tube with an outer diameter of 25 nm and an
CC inner diameter of 15 nM. Alpha-beta heterodimers associate head-
CC to-tail to form protofilaments running lengthwise along the
CC microtubule wall with the beta-tubulin subunit facing the
CC microtubule plus end conferring a structural polarity.
CC Microtubules usually have 13 protofilaments but different
CC protofilament numbers can be found in some organisms and
CC specialized cells. Interacts with RANBP10.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- TISSUE SPECIFICITY: Hematopoietic cell-specific. Major isotype in
CC leukocytes, where it represents 50% of all beta-tubulins.
CC -!- PTM: Some glutamate residues at the C-terminus are
CC polyglutamylated. This modification occurs exclusively on
CC glutamate residues and results in polyglutamate chains on the
CC gamma-carboxyl group. Also monoglycylated but not polyglycylated
CC due to the absence of functional TTLL10 in human. Monoglycylation
CC is mainly limited to tubulin incorporated into axonemes (cilia and
CC flagella) whereas glutamylation is prevalent in neuronal cells,
CC centrioles, axonemes, and the mitotic spindle. Both modifications
CC can coexist on the same protein on adjacent residues, and lowering
CC glycylation levels increases polyglutamylation, and reciprocally.
CC The precise function of such modifications is still unclear but
CC they regulate the assembly and dynamics of axonemal microtubules
CC (Probable).
CC -!- DISEASE: Macrothrombocytopenia, autosomal dominant, TUBB1-related
CC (MAD-TUBB1) [MIM:613112]: A congenital blood disorder
CC characterized by increased platelet size and decreased number of
CC circulating platelets. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tubulin family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AJ292757; CAC16605.1; -; mRNA.
DR EMBL; AL109840; CAC09371.2; -; Genomic_DNA.
DR EMBL; BC033679; AAH33679.1; -; mRNA.
DR RefSeq; NP_110400.1; NM_030773.3.
DR UniGene; Hs.303023; -.
DR ProteinModelPortal; Q9H4B7; -.
DR SMR; Q9H4B7; 1-430.
DR IntAct; Q9H4B7; 11.
DR MINT; MINT-1891365; -.
DR STRING; 9606.ENSP00000217133; -.
DR BindingDB; Q9H4B7; -.
DR ChEMBL; CHEMBL1915; -.
DR DrugBank; DB01394; Colchicine.
DR DrugBank; DB01248; Docetaxel.
DR DrugBank; DB01229; Paclitaxel.
DR DrugBank; DB00309; Vindesine.
DR PhosphoSite; Q9H4B7; -.
DR DMDM; 62903515; -.
DR OGP; Q9H4B7; -.
DR PaxDb; Q9H4B7; -.
DR PeptideAtlas; Q9H4B7; -.
DR PRIDE; Q9H4B7; -.
DR DNASU; 81027; -.
DR Ensembl; ENST00000217133; ENSP00000217133; ENSG00000101162.
DR GeneID; 81027; -.
DR KEGG; hsa:81027; -.
DR UCSC; uc002yak.3; human.
DR CTD; 81027; -.
DR GeneCards; GC20P057594; -.
DR HGNC; HGNC:16257; TUBB1.
DR HPA; CAB004286; -.
DR HPA; HPA043640; -.
DR HPA; HPA046280; -.
DR MIM; 612901; gene.
DR MIM; 613112; phenotype.
DR neXtProt; NX_Q9H4B7; -.
DR Orphanet; 140957; Autosomal dominant macrothrombocytopenia.
DR PharmGKB; PA38100; -.
DR eggNOG; COG5023; -.
DR HOGENOM; HOG000165710; -.
DR HOVERGEN; HBG000089; -.
DR InParanoid; Q9H4B7; -.
DR KO; K07375; -.
DR OMA; ACIFRGK; -.
DR OrthoDB; EOG7ZKS9Z; -.
DR PhylomeDB; Q9H4B7; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; TUBB1; -.
DR GenomeRNAi; 81027; -.
DR NextBio; 71348; -.
DR PRO; PR:Q9H4B7; -.
DR Bgee; Q9H4B7; -.
DR CleanEx; HS_TUBB1; -.
DR Genevestigator; Q9H4B7; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IEA:Ensembl.
DR GO; GO:0051084; P:'de novo' posttranslational protein folding; TAS:Reactome.
DR GO; GO:0051258; P:protein polymerization; IEA:InterPro.
DR GO; GO:0051225; P:spindle assembly; IEA:Ensembl.
DR Gene3D; 1.10.287.600; -; 1.
DR Gene3D; 3.30.1330.20; -; 1.
DR Gene3D; 3.40.50.1440; -; 1.
DR InterPro; IPR013838; Beta-tubulin_BS.
DR InterPro; IPR002453; Beta_tubulin.
DR InterPro; IPR008280; Tub_FtsZ_C.
DR InterPro; IPR000217; Tubulin.
DR InterPro; IPR018316; Tubulin/FtsZ_2-layer-sand-dom.
DR InterPro; IPR023123; Tubulin_C.
DR InterPro; IPR017975; Tubulin_CS.
DR InterPro; IPR003008; Tubulin_FtsZ_GTPase.
DR PANTHER; PTHR11588; PTHR11588; 1.
DR Pfam; PF00091; Tubulin; 1.
DR Pfam; PF03953; Tubulin_C; 1.
DR PRINTS; PR01163; BETATUBULIN.
DR PRINTS; PR01161; TUBULIN.
DR SMART; SM00864; Tubulin; 1.
DR SMART; SM00865; Tubulin_C; 1.
DR SUPFAM; SSF52490; SSF52490; 1.
DR SUPFAM; SSF55307; SSF55307; 1.
DR PROSITE; PS00227; TUBULIN; 1.
DR PROSITE; PS00228; TUBULIN_B_AUTOREG; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Disease mutation; GTP-binding; Microtubule; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 451 Tubulin beta-1 chain.
FT /FTId=PRO_0000048242.
FT NP_BIND 140 146 GTP (Potential).
FT MOD_RES 172 172 Phosphoserine; by CDK1 (By similarity).
FT VARIANT 43 43 Q -> H (in dbSNP:rs415064).
FT /FTId=VAR_034542.
FT VARIANT 43 43 Q -> P (in dbSNP:rs463312).
FT /FTId=VAR_034543.
FT VARIANT 274 274 T -> M (in dbSNP:rs35565630).
FT /FTId=VAR_052671.
FT VARIANT 307 307 R -> H (in dbSNP:rs6070697).
FT /FTId=VAR_052672.
FT VARIANT 318 318 R -> W (in MAD-TUBB1; dbSNP:rs121918555).
FT /FTId=VAR_063411.
SQ SEQUENCE 451 AA; 50327 MW; 6A3E5208C1C89AE4 CRC64;
MREIVHIQIG QCGNQIGAKF WEMIGEEHGI DLAGSDRGAS ALQLERISVY YNEAYGRKYV
PRAVLVDLEP GTMDSIRSSK LGALFQPDSF VHGNSGAGNN WAKGHYTEGA ELIENVLEVV
RHESESCDCL QGFQIVHSLG GGTGSGMGTL LMNKIREEYP DRIMNSFSVM PSPKVSDTVV
EPYNAVLSIH QLIENADACF CIDNEALYDI CFRTLKLTTP TYGDLNHLVS LTMSGITTSL
RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTAQGSQQ YRALSVAELT QQMFDARNTM
AACDLRRGRY LTVACIFRGK MSTKEVDQQL LSVQTRNSSC FVEWIPNNVK VAVCDIPPRG
LSMAATFIGN NTAIQEIFNR VSEHFSAMFK RKAFVHWYTS EGMDINEFGE AENNIHDLVS
EYQQFQDAKA VLEEDEEVTE EAEMEPEDKG H
//
MIM
612901
*RECORD*
*FIELD* NO
612901
*FIELD* TI
*612901 TUBULIN, BETA-1; TUBB1
;;TUBULIN, BETA, CLASS VI
*FIELD* TX
DESCRIPTION
Microtubules are involved in a wide variety of cellular processes,
read moreincluding mitosis, morphogenesis, platelet formation, and mobility of
cilia and flagella. Circulating platelets carry a single marginal
microtubule coil that is wound in 8 to 12 turns and is responsible for
platelet shape. TUBB1 is the major beta-tubulin expressed in platelets
and megakaryocytes and is required for optimal platelet assembly (Wang
et al., 1986; Schulze et al., 2004).
CLONING
Wang et al. (1986) cloned mouse Tubb1 from a bone marrow cDNA library.
Northern blot analysis of several adult mouse tissues detected highest
Tubb1 expression in spleen, with much lower expression in lung. Weak
expression was detected in spleen, liver, and lung of young mice.
Using database analysis, Leandro-Garcia et al. (2010) identified 8 major
beta-tubulins, including TUBB1. Quantitative RT-PCR of 21 normal human
tissues detected high TUBB1 expression in hematopoietic tissues,
predominantly blood leukocytes, where it was the predominant
beta-tubulin, with lower expression in fetal liver and bone marrow.
Little to no expression was detected in other tissues.
GENE FUNCTION
Using a yeast 2-hybrid screen, Schulze et al. (2004) found that the C
terminus of mouse Tubb1 interacted with the protease inhibitor Slpi
(107285). Association of Slpi with microtubules and its capacity to
inhibit neutrophil elastase (ELA2; 130130) was lost in Tubb1 -/-
platelets.
MAPPING
Freson et al. (2005) stated that the TUBB1 gene maps to chromosome
20q13.3.
Schulze et al. (2004) stated that the mouse Tubb1 gene maps to
chromosome 2.
MOLECULAR GENETICS
Freson et al. (2005) identified a heterozygous gln43-to-pro (Q43P) SNP
in the TUBB1 gene in 8 (24.2%) of 33 unrelated individuals with
macrothrombocytopenia (613112). However, since inheritance in these 8
families was more consistent with autosomal recessive inheritance and no
other TUBB1 variants were identified, it was unclear how much this SNP
contributed to the phenotype. Freson et al. (2005) found the
heterozygous Q43P change in 10.6% of 272 healthy control individuals.
Control individuals with the Q43P change had normal platelet counts, but
larger and rounder, more spherical platelets compared to those without
the change. The abnormally round platelets showed disturbed tubulin
organization and decreased TUBB1 protein levels. Functional studies
showed slightly decreased aggregation under certain conditions. A
case-control study identified the Q43P change in 5.2% of 573 patients
with cardiovascular disease, about half of the prevalence in controls.
Stratification by sex showed the effect only in men. The authors
suggested that this common SNP may protect against cardiovascular
disease in men.
In a Japanese boy and his mother with autosomal dominant
macrothrombocytopenia (613112), Kunishima et al. (2009) identified a
heterozygous mutation in the TUBB1 gene (R318W; 612901.0001).
ANIMAL MODEL
Schwer et al. (2001) obtained Tubb1 -/- mice at the expected mendelian
frequency. Tubb1 -/- mice appeared normal and showed no sign of
hemorrhage, but their average platelet counts were less than 50% of
wildtype. Tubb1 +/- heterozygotes had intermediate platelet levels.
About half of megakaryocytes cultured from wildtype fetal mouse livers
showed a rich network of proplatelets. A smaller fraction of Tubb1 +/-
cells showed these extensions, whereas Tubb1 -/- cells elaborated very
few proplatelets. Circulating platelets of Tubb1 -/- mice lacked the
characteristic discoid shape and had defective marginal bands with
reduced microtubule coilings. Tubb1 -/- mice had prolonged bleeding
time, and their platelets showed an attenuated response to thrombin (F2;
176930).
Cavalier King Charles Spaniel dogs have a high prevalence of inherited
macrothrombocytopenia. Davis et al. (2008) identified an asp249-to-asn
(D249N) mutation in the canine Tubb1 gene as causative of the disorder.
Electron microscopy and immunofluorescence studies suggested that
platelet microtubules were present, but were most likely unstable and
decreased in number.
*FIELD* AV
.0001
MACROTHROMBOCYTOPENIA, AUTOSOMAL DOMINANT, TUBB1-RELATED
TUBB1, ARG318TRP
In a Japanese boy and his mother with autosomal dominant
macrothrombocytopenia (613112), Kunishima et al. (2009) identified a
heterozygous 952C-T transition in the TUBB1 gene, resulting in an
arg318-to-trp (R318W) substitution. The mutation was not found in 108
healthy controls. The substitution was predicted to be buried inside the
3-dimension molecule near the alpha and beta intradimer interface and
may disrupt side chain interactions. Studies of resting patient
platelets showed normal TUBB1 localization in the marginal microtubule
band and normal electrophoretic mobility, but decreased expression
levels compared to controls. Cultured mature megakaryocytes from the
patient showed large and irregular bleb protrusions, suggesting impaired
megakaryocyte fragmentation and release of large platelets. Platelet
aggregation studies were normal. Further studies indicated that the
thrombocytopenia resulted from peripheral destruction, not platelet
underproduction. Overall, the results suggested that the TUBB1 R318W
mutation resulted in instability of the protein. Kunishima et al. (2009)
suggested that the mutation may dominantly affect microtubule assembly
in some manner. Alternatively, mutant TUBB1 was not transported properly
from megakaryocytes into platelets.
*FIELD* RF
1. Davis, B.; Toivio-Kinnucan, M.; Schuller, S.; Boudreaux, M. K.
: Mutation in beta-1-tubulin correlates with macrothrombocytopenia
in Cavalier King Charles Spaniels. J. Vet. Intern. Med. 22: 540-545,
2008.
2. Freson, K.; De Vos, R.; Wittevrongel, C.; Thys, C.; Defoor, J.;
Vanhees, L.; Vermylen, J.; Peerlinck, K.; Van Geet, C.: The TUBB1
Q43P functional polymorphism reduces the risk of cardiovascular disease
in men by modulating platelet function and structure. Blood 106:
2356-2362, 2005.
3. Kunishima, S.; Kobayashi, R.; Itoh, T. J.; Hamaguchi, M.; Saito,
H.: Mutation of the beta-1-tubulin gene associated with congenital
macrothrombocytopenia affecting microtubule assembly. Blood 113-458-461,
2009.
4. Leandro-Garcia, L. J.; Leskela, S.; Landa, I.; Montero-Conde, C.;
Lopez-Jimenez, E.; Leton, R.; Cascon, A.; Robledo, M.; Rodriguez-Antona,
C.: Tumoral and tissue-specific expression of the major human beta-tubulin
isotypes. Cytoskeleton 67: 214-223, 2010.
5. Schulze, H.; Korpal, M.; Bergmeier, W.; Italiano, J. E., Jr.; Wahl,
S. M.; Shivdasani, R. A.: Interactions between the megakaryocyte/platelet-specific
beta-1 tubulin and the secretory leukocyte protease inhibitor SLPI
suggest a role for regulated proteolysis in platelet functions. Blood 104:
3949-3957, 2004.
6. Schwer, H. D.; Lecine, P.; Tiwari, S.; Italiano, J. E., Jr.; Hartwig,
J. H.; Shivdasani, R. A.: A lineage-restricted and divergent beta-tubulin
isoform is essential for the biogenesis, structure, and function of
blood platelets. Curr. Biol. 11: 579-586, 2001.
7. Wang, D.; Villasante, A.; Lewis, S. A.; Cowan, N. J.: The mammalian
beta-tubulin repertoire: hematopoietic expression of a novel, heterologous
beta-tubulin isotype. J. Cell Biol. 103: 1903-1910, 1986.
*FIELD* CN
Patricia A. Hartz - updated: 02/28/2013
Cassandra L. Kniffin - updated: 11/12/2009
*FIELD* CD
Patricia A. Hartz: 7/9/2009
*FIELD* ED
mgross: 02/28/2013
terry: 12/1/2009
carol: 11/16/2009
ckniffin: 11/12/2009
mgross: 7/9/2009
*RECORD*
*FIELD* NO
612901
*FIELD* TI
*612901 TUBULIN, BETA-1; TUBB1
;;TUBULIN, BETA, CLASS VI
*FIELD* TX
DESCRIPTION
Microtubules are involved in a wide variety of cellular processes,
read moreincluding mitosis, morphogenesis, platelet formation, and mobility of
cilia and flagella. Circulating platelets carry a single marginal
microtubule coil that is wound in 8 to 12 turns and is responsible for
platelet shape. TUBB1 is the major beta-tubulin expressed in platelets
and megakaryocytes and is required for optimal platelet assembly (Wang
et al., 1986; Schulze et al., 2004).
CLONING
Wang et al. (1986) cloned mouse Tubb1 from a bone marrow cDNA library.
Northern blot analysis of several adult mouse tissues detected highest
Tubb1 expression in spleen, with much lower expression in lung. Weak
expression was detected in spleen, liver, and lung of young mice.
Using database analysis, Leandro-Garcia et al. (2010) identified 8 major
beta-tubulins, including TUBB1. Quantitative RT-PCR of 21 normal human
tissues detected high TUBB1 expression in hematopoietic tissues,
predominantly blood leukocytes, where it was the predominant
beta-tubulin, with lower expression in fetal liver and bone marrow.
Little to no expression was detected in other tissues.
GENE FUNCTION
Using a yeast 2-hybrid screen, Schulze et al. (2004) found that the C
terminus of mouse Tubb1 interacted with the protease inhibitor Slpi
(107285). Association of Slpi with microtubules and its capacity to
inhibit neutrophil elastase (ELA2; 130130) was lost in Tubb1 -/-
platelets.
MAPPING
Freson et al. (2005) stated that the TUBB1 gene maps to chromosome
20q13.3.
Schulze et al. (2004) stated that the mouse Tubb1 gene maps to
chromosome 2.
MOLECULAR GENETICS
Freson et al. (2005) identified a heterozygous gln43-to-pro (Q43P) SNP
in the TUBB1 gene in 8 (24.2%) of 33 unrelated individuals with
macrothrombocytopenia (613112). However, since inheritance in these 8
families was more consistent with autosomal recessive inheritance and no
other TUBB1 variants were identified, it was unclear how much this SNP
contributed to the phenotype. Freson et al. (2005) found the
heterozygous Q43P change in 10.6% of 272 healthy control individuals.
Control individuals with the Q43P change had normal platelet counts, but
larger and rounder, more spherical platelets compared to those without
the change. The abnormally round platelets showed disturbed tubulin
organization and decreased TUBB1 protein levels. Functional studies
showed slightly decreased aggregation under certain conditions. A
case-control study identified the Q43P change in 5.2% of 573 patients
with cardiovascular disease, about half of the prevalence in controls.
Stratification by sex showed the effect only in men. The authors
suggested that this common SNP may protect against cardiovascular
disease in men.
In a Japanese boy and his mother with autosomal dominant
macrothrombocytopenia (613112), Kunishima et al. (2009) identified a
heterozygous mutation in the TUBB1 gene (R318W; 612901.0001).
ANIMAL MODEL
Schwer et al. (2001) obtained Tubb1 -/- mice at the expected mendelian
frequency. Tubb1 -/- mice appeared normal and showed no sign of
hemorrhage, but their average platelet counts were less than 50% of
wildtype. Tubb1 +/- heterozygotes had intermediate platelet levels.
About half of megakaryocytes cultured from wildtype fetal mouse livers
showed a rich network of proplatelets. A smaller fraction of Tubb1 +/-
cells showed these extensions, whereas Tubb1 -/- cells elaborated very
few proplatelets. Circulating platelets of Tubb1 -/- mice lacked the
characteristic discoid shape and had defective marginal bands with
reduced microtubule coilings. Tubb1 -/- mice had prolonged bleeding
time, and their platelets showed an attenuated response to thrombin (F2;
176930).
Cavalier King Charles Spaniel dogs have a high prevalence of inherited
macrothrombocytopenia. Davis et al. (2008) identified an asp249-to-asn
(D249N) mutation in the canine Tubb1 gene as causative of the disorder.
Electron microscopy and immunofluorescence studies suggested that
platelet microtubules were present, but were most likely unstable and
decreased in number.
*FIELD* AV
.0001
MACROTHROMBOCYTOPENIA, AUTOSOMAL DOMINANT, TUBB1-RELATED
TUBB1, ARG318TRP
In a Japanese boy and his mother with autosomal dominant
macrothrombocytopenia (613112), Kunishima et al. (2009) identified a
heterozygous 952C-T transition in the TUBB1 gene, resulting in an
arg318-to-trp (R318W) substitution. The mutation was not found in 108
healthy controls. The substitution was predicted to be buried inside the
3-dimension molecule near the alpha and beta intradimer interface and
may disrupt side chain interactions. Studies of resting patient
platelets showed normal TUBB1 localization in the marginal microtubule
band and normal electrophoretic mobility, but decreased expression
levels compared to controls. Cultured mature megakaryocytes from the
patient showed large and irregular bleb protrusions, suggesting impaired
megakaryocyte fragmentation and release of large platelets. Platelet
aggregation studies were normal. Further studies indicated that the
thrombocytopenia resulted from peripheral destruction, not platelet
underproduction. Overall, the results suggested that the TUBB1 R318W
mutation resulted in instability of the protein. Kunishima et al. (2009)
suggested that the mutation may dominantly affect microtubule assembly
in some manner. Alternatively, mutant TUBB1 was not transported properly
from megakaryocytes into platelets.
*FIELD* RF
1. Davis, B.; Toivio-Kinnucan, M.; Schuller, S.; Boudreaux, M. K.
: Mutation in beta-1-tubulin correlates with macrothrombocytopenia
in Cavalier King Charles Spaniels. J. Vet. Intern. Med. 22: 540-545,
2008.
2. Freson, K.; De Vos, R.; Wittevrongel, C.; Thys, C.; Defoor, J.;
Vanhees, L.; Vermylen, J.; Peerlinck, K.; Van Geet, C.: The TUBB1
Q43P functional polymorphism reduces the risk of cardiovascular disease
in men by modulating platelet function and structure. Blood 106:
2356-2362, 2005.
3. Kunishima, S.; Kobayashi, R.; Itoh, T. J.; Hamaguchi, M.; Saito,
H.: Mutation of the beta-1-tubulin gene associated with congenital
macrothrombocytopenia affecting microtubule assembly. Blood 113-458-461,
2009.
4. Leandro-Garcia, L. J.; Leskela, S.; Landa, I.; Montero-Conde, C.;
Lopez-Jimenez, E.; Leton, R.; Cascon, A.; Robledo, M.; Rodriguez-Antona,
C.: Tumoral and tissue-specific expression of the major human beta-tubulin
isotypes. Cytoskeleton 67: 214-223, 2010.
5. Schulze, H.; Korpal, M.; Bergmeier, W.; Italiano, J. E., Jr.; Wahl,
S. M.; Shivdasani, R. A.: Interactions between the megakaryocyte/platelet-specific
beta-1 tubulin and the secretory leukocyte protease inhibitor SLPI
suggest a role for regulated proteolysis in platelet functions. Blood 104:
3949-3957, 2004.
6. Schwer, H. D.; Lecine, P.; Tiwari, S.; Italiano, J. E., Jr.; Hartwig,
J. H.; Shivdasani, R. A.: A lineage-restricted and divergent beta-tubulin
isoform is essential for the biogenesis, structure, and function of
blood platelets. Curr. Biol. 11: 579-586, 2001.
7. Wang, D.; Villasante, A.; Lewis, S. A.; Cowan, N. J.: The mammalian
beta-tubulin repertoire: hematopoietic expression of a novel, heterologous
beta-tubulin isotype. J. Cell Biol. 103: 1903-1910, 1986.
*FIELD* CN
Patricia A. Hartz - updated: 02/28/2013
Cassandra L. Kniffin - updated: 11/12/2009
*FIELD* CD
Patricia A. Hartz: 7/9/2009
*FIELD* ED
mgross: 02/28/2013
terry: 12/1/2009
carol: 11/16/2009
ckniffin: 11/12/2009
mgross: 7/9/2009
MIM
613112
*RECORD*
*FIELD* NO
613112
*FIELD* TI
#613112 MACROTHROMBOCYTOPENIA, AUTOSOMAL DOMINANT, TUBB1-RELATED
*FIELD* TX
A number sign (#) is used with this entry because macrothrombocytopenia
read moreis caused by mutation in the TUBB1 gene (612901) on chromosome 20q13.3.
CLINICAL FEATURES
Kunishima et al. (2009) reported a Japanese boy who was incidentally
found to have thrombocytopenia (40-60 x 10(9) platelets). Peripheral
blood smears showed prominent giant platelets. Platelet aggregation
function was normal, and bone marrow biopsy showed normal megakaryocyte
number and morphology. The mother of the patient also had
macrothrombocytopenia. Cultured mature megakaryocytes from the proband
showed large and irregular bleb protrusions, suggesting impaired
megakaryocyte fragmentation and release of large platelets. Further
studies indicated that the thrombocytopenia resulted from peripheral
destruction, not platelet underproduction.
MOLECULAR GENETICS
Freson et al. (2005) identified a heterozygous gln43-to-pro (Q43P) SNP
in the TUBB1 gene in 8 (24.2%) of 33 unrelated individuals with
macrothrombocytopenia. However, since inheritance in these 8 families
was more consistent with autosomal recessive inheritance and no other
TUBB1 variants were identified, it was unclear how much this SNP
contributed to the phenotype. The change, along with other factors, may
predispose to development of macrothrombocytopenia.
In a Japanese boy and his mother with macrothrombocytopenia, Kunishima
et al. (2009) identified a heterozygous mutation in the TUBB1 gene
(R318W; 612901.0001).
ANIMAL MODEL
Cavalier King Charles Spaniel dogs have a high prevalence of inherited
macrothrombocytopenia. Davis et al. (2008) identified an asp249-to-asn
(D249N) mutation in the canine Tubb1 gene as causative of the disorder.
Electron microscopy and immunofluorescence studies suggested that
platelet microtubules were present, but were most likely unstable and
decreased in number.
*FIELD* RF
1. Davis, B.; Toivio-Kinnucan, M.; Schuller, S.; Boudreaux, M. K.
: Mutation in beta-1-tubulin correlates with macrothrombocytopenia
in Cavalier King Charles Spaniels. J. Vet. Intern. Med. 22: 540-545,
2008.
2. Freson, K.; De Vos, R.; Wittevrongel, C.; Thys, C.; Defoor, J.;
Vanhees, L.; Vermylen, J.; Peerlinck, K.; Van Geet, C.: The TUBB1
Q43P functional polymorphism reduces the risk of cardiovascular disease
in men by modulating platelet function and structure. Blood 106:
2356-2362, 2005.
3. Kunishima, S.; Kobayashi, R.; Itoh, T. J.; Hamaguchi, M.; Saito,
H.: Mutation of the beta-1-tubulin gene associated with congenital
macrothrombocytopenia affecting microtubule assembly. Blood 113:
458-461, 2009.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEMATOLOGY:
Macrothrombocytopenia;
Large, spherical platelets;
Decreased number of platelets;
Decreased beta-tubulin in platelets;
Megakaryocytes show large and irregular bleb protrusions;
Normal platelet aggregation
MISCELLANEOUS:
As of 2009, one family has been reported;
No clinical manifestations were noted (incidental laboratory finding)
MOLECULAR BASIS:
Caused by mutation in the tubulin beta-1 gene (TUBB1, 612901.0001).
*FIELD* CD
Cassandra L. Kniffin: 11/12/2009
*FIELD* ED
joanna: 12/02/2009
ckniffin: 11/12/2009
*FIELD* CD
Cassandra L. Kniffin: 11/4/2009
*FIELD* ED
terry: 12/01/2009
carol: 11/16/2009
ckniffin: 11/12/2009
*RECORD*
*FIELD* NO
613112
*FIELD* TI
#613112 MACROTHROMBOCYTOPENIA, AUTOSOMAL DOMINANT, TUBB1-RELATED
*FIELD* TX
A number sign (#) is used with this entry because macrothrombocytopenia
read moreis caused by mutation in the TUBB1 gene (612901) on chromosome 20q13.3.
CLINICAL FEATURES
Kunishima et al. (2009) reported a Japanese boy who was incidentally
found to have thrombocytopenia (40-60 x 10(9) platelets). Peripheral
blood smears showed prominent giant platelets. Platelet aggregation
function was normal, and bone marrow biopsy showed normal megakaryocyte
number and morphology. The mother of the patient also had
macrothrombocytopenia. Cultured mature megakaryocytes from the proband
showed large and irregular bleb protrusions, suggesting impaired
megakaryocyte fragmentation and release of large platelets. Further
studies indicated that the thrombocytopenia resulted from peripheral
destruction, not platelet underproduction.
MOLECULAR GENETICS
Freson et al. (2005) identified a heterozygous gln43-to-pro (Q43P) SNP
in the TUBB1 gene in 8 (24.2%) of 33 unrelated individuals with
macrothrombocytopenia. However, since inheritance in these 8 families
was more consistent with autosomal recessive inheritance and no other
TUBB1 variants were identified, it was unclear how much this SNP
contributed to the phenotype. The change, along with other factors, may
predispose to development of macrothrombocytopenia.
In a Japanese boy and his mother with macrothrombocytopenia, Kunishima
et al. (2009) identified a heterozygous mutation in the TUBB1 gene
(R318W; 612901.0001).
ANIMAL MODEL
Cavalier King Charles Spaniel dogs have a high prevalence of inherited
macrothrombocytopenia. Davis et al. (2008) identified an asp249-to-asn
(D249N) mutation in the canine Tubb1 gene as causative of the disorder.
Electron microscopy and immunofluorescence studies suggested that
platelet microtubules were present, but were most likely unstable and
decreased in number.
*FIELD* RF
1. Davis, B.; Toivio-Kinnucan, M.; Schuller, S.; Boudreaux, M. K.
: Mutation in beta-1-tubulin correlates with macrothrombocytopenia
in Cavalier King Charles Spaniels. J. Vet. Intern. Med. 22: 540-545,
2008.
2. Freson, K.; De Vos, R.; Wittevrongel, C.; Thys, C.; Defoor, J.;
Vanhees, L.; Vermylen, J.; Peerlinck, K.; Van Geet, C.: The TUBB1
Q43P functional polymorphism reduces the risk of cardiovascular disease
in men by modulating platelet function and structure. Blood 106:
2356-2362, 2005.
3. Kunishima, S.; Kobayashi, R.; Itoh, T. J.; Hamaguchi, M.; Saito,
H.: Mutation of the beta-1-tubulin gene associated with congenital
macrothrombocytopenia affecting microtubule assembly. Blood 113:
458-461, 2009.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEMATOLOGY:
Macrothrombocytopenia;
Large, spherical platelets;
Decreased number of platelets;
Decreased beta-tubulin in platelets;
Megakaryocytes show large and irregular bleb protrusions;
Normal platelet aggregation
MISCELLANEOUS:
As of 2009, one family has been reported;
No clinical manifestations were noted (incidental laboratory finding)
MOLECULAR BASIS:
Caused by mutation in the tubulin beta-1 gene (TUBB1, 612901.0001).
*FIELD* CD
Cassandra L. Kniffin: 11/12/2009
*FIELD* ED
joanna: 12/02/2009
ckniffin: 11/12/2009
*FIELD* CD
Cassandra L. Kniffin: 11/4/2009
*FIELD* ED
terry: 12/01/2009
carol: 11/16/2009
ckniffin: 11/12/2009