Full text data of TUBG1
TUBG1
(TUBG)
[Confidence: low (only semi-automatic identification from reviews)]
Tubulin gamma-1 chain (Gamma-1-tubulin; Gamma-tubulin complex component 1; GCP-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Tubulin gamma-1 chain (Gamma-1-tubulin; Gamma-tubulin complex component 1; GCP-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P23258
ID TBG1_HUMAN Reviewed; 451 AA.
AC P23258; Q53X79; Q9BW59;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Tubulin gamma-1 chain;
DE AltName: Full=Gamma-1-tubulin;
DE AltName: Full=Gamma-tubulin complex component 1;
DE Short=GCP-1;
GN Name=TUBG1; Synonyms=TUBG;
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].
RX PubMed=1904010; DOI=10.1016/0092-8674(91)90389-G;
RA Zheng Y., Jung M.K., Oakley B.R.;
RT "Gamma-tubulin is present in Drosophila melanogaster and Homo sapiens
RT and is associated with the centrosome.";
RL Cell 65:817-823(1991).
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
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [6]
RP MASS SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=11840567;
RX DOI=10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H;
RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A.,
RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J.,
RA Zvelebil M.J.;
RT "Cluster analysis of an extensive human breast cancer cell line
RT protein expression map database.";
RL Proteomics 2:212-223(2002).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=9566969; DOI=10.1083/jcb.141.3.689;
RA Tassin A.-M., Celati C., Moudjou M., Bornens M.;
RT "Characterization of the human homologue of the yeast spc98p and its
RT association with gamma-tubulin.";
RL J. Cell Biol. 141:689-701(1998).
RN [8]
RP INTERACTION WITH CDK5RAP2.
RX PubMed=17959831; DOI=10.1091/mbc.E07-04-0371;
RA Fong K.W., Choi Y.K., Rattner J.B., Qi R.Z.;
RT "CDK5RAP2 is a pericentriolar protein that functions in centrosomal
RT attachment of the gamma-tubulin ring complex.";
RL Mol. Biol. Cell 19:115-125(2008).
RN [9]
RP INTERACTION WITH PIFO.
RX PubMed=20643351; DOI=10.1016/j.devcel.2010.06.005;
RA Kinzel D., Boldt K., Davis E.E., Burtscher I., Trumbach D., Diplas B.,
RA Attie-Bitach T., Wurst W., Katsanis N., Ueffing M., Lickert H.;
RT "Pitchfork regulates primary cilia disassembly and left-right
RT asymmetry.";
RL Dev. Cell 19:66-77(2010).
RN [10]
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).
CC -!- FUNCTION: Tubulin is the major constituent of microtubules. The
CC gamma chain is found at microtubule organizing centers (MTOC) such
CC as the spindle poles or the centrosome. Pericentriolar matrix
CC component that regulates alpha/beta chain minus-end nucleation,
CC centrosome duplication and spindle formation.
CC -!- SUBUNIT: Interacts with TUBGCP2 and TUBGCP3. Interacts with B9D2
CC (By similarity). Interacts with CDK5RAP2; the interaction is
CC leading to centrosomal localization of TUBG1 and CDK5RAP2.
CC Interacts with PIFO.
CC -!- INTERACTION:
CC O15169:AXIN1; NbExp=4; IntAct=EBI-302589, EBI-710484;
CC Q96L34:MARK4; NbExp=4; IntAct=EBI-302589, EBI-302319;
CC Q08AG7:MZT1; NbExp=2; IntAct=EBI-302589, EBI-2637198;
CC Q6NZ67:MZT2B; NbExp=2; IntAct=EBI-302589, EBI-1052566;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome.
CC -!- PTM: Phosphorylation at Ser-131 by BRSK1 regulates centrosome
CC duplication, possibly by mediating relocation of gamma-tubulin and
CC its associated proteins from the cytoplasm to the centrosome (By
CC similarity).
CC -!- MASS SPECTROMETRY: Mass=51197.98; Method=MALDI; Range=1-451;
CC Source=PubMed:11840567;
CC -!- SIMILARITY: Belongs to the tubulin family.
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DR EMBL; M61764; AAA52620.1; -; mRNA.
DR EMBL; BT019931; AAV38734.1; -; mRNA.
DR EMBL; CR407642; CAG28570.1; -; mRNA.
DR EMBL; AK313339; BAG36143.1; -; mRNA.
DR EMBL; BC000619; AAH00619.1; -; mRNA.
DR PIR; A39527; UBHUG.
DR RefSeq; NP_001061.2; NM_001070.4.
DR UniGene; Hs.279669; -.
DR PDB; 1Z5V; X-ray; 2.71 A; A=1-449.
DR PDB; 1Z5W; X-ray; 3.00 A; A=1-449.
DR PDB; 3CB2; X-ray; 2.30 A; A/B=1-451.
DR PDBsum; 1Z5V; -.
DR PDBsum; 1Z5W; -.
DR PDBsum; 3CB2; -.
DR ProteinModelPortal; P23258; -.
DR SMR; P23258; 2-446.
DR DIP; DIP-29890N; -.
DR IntAct; P23258; 30.
DR MINT; MINT-4051249; -.
DR STRING; 9606.ENSP00000251413; -.
DR PhosphoSite; P23258; -.
DR DMDM; 20455518; -.
DR REPRODUCTION-2DPAGE; IPI00295081; -.
DR PaxDb; P23258; -.
DR PRIDE; P23258; -.
DR DNASU; 7283; -.
DR Ensembl; ENST00000251413; ENSP00000251413; ENSG00000131462.
DR GeneID; 7283; -.
DR KEGG; hsa:7283; -.
DR UCSC; uc002ian.3; human.
DR CTD; 7283; -.
DR GeneCards; GC17P040761; -.
DR HGNC; HGNC:12417; TUBG1.
DR HPA; CAB004608; -.
DR MIM; 191135; gene.
DR neXtProt; NX_P23258; -.
DR PharmGKB; PA37079; -.
DR eggNOG; COG5023; -.
DR HOGENOM; HOG000165714; -.
DR HOVERGEN; HBG098558; -.
DR InParanoid; P23258; -.
DR KO; K10389; -.
DR OMA; EGFMLMH; -.
DR OrthoDB; EOG70S755; -.
DR PhylomeDB; P23258; -.
DR Reactome; REACT_115566; Cell Cycle.
DR EvolutionaryTrace; P23258; -.
DR GeneWiki; TUBG1; -.
DR GenomeRNAi; 7283; -.
DR NextBio; 28475; -.
DR PMAP-CutDB; P23258; -.
DR PRO; PR:P23258; -.
DR ArrayExpress; P23258; -.
DR Bgee; P23258; -.
DR CleanEx; HS_TUBG1; -.
DR Genevestigator; P23258; -.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0005814; C:centriole; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IEA:Ensembl.
DR GO; GO:0000794; C:condensed nuclear chromosome; ISS:UniProtKB.
DR GO; GO:0005881; C:cytoplasmic microtubule; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000930; C:gamma-tubulin complex; TAS:UniProtKB.
DR GO; GO:0000242; C:pericentriolar material; IEA:Ensembl.
DR GO; GO:0005827; C:polar microtubule; IDA:UniProtKB.
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; TAS:ProtInc.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IEA:InterPro.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0000212; P:meiotic spindle organization; ISS:UniProtKB.
DR GO; GO:0007020; P:microtubule nucleation; IEA:InterPro.
DR GO; GO:0051258; P:protein polymerization; IEA:InterPro.
DR Gene3D; 1.10.287.600; -; 1.
DR Gene3D; 3.30.1330.20; -; 1.
DR Gene3D; 3.40.50.1440; -; 1.
DR InterPro; IPR002454; Gamma_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 PANTHER; PTHR11588:SF7; PTHR11588:SF7; 1.
DR Pfam; PF00091; Tubulin; 1.
DR Pfam; PF03953; Tubulin_C; 1.
DR PRINTS; PR01164; GAMMATUBULIN.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Cytoskeleton; GTP-binding;
KW Microtubule; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 451 Tubulin gamma-1 chain.
FT /FTId=PRO_0000048465.
FT NP_BIND 142 148 GTP (Potential).
FT MOD_RES 131 131 Phosphoserine; by BRSK1 (By similarity).
FT VARIANT 413 413 M -> V (in dbSNP:rs13663).
FT /FTId=VAR_052674.
FT CONFLICT 35 35 G -> A (in Ref. 1; AAA52620).
FT CONFLICT 202 202 V -> L (in Ref. 1; AAA52620).
FT STRAND 5 10
FT HELIX 11 28
FT STRAND 33 35
FT HELIX 48 50
FT STRAND 52 54
FT STRAND 60 62
FT STRAND 64 71
FT HELIX 72 79
FT TURN 81 85
FT HELIX 88 90
FT STRAND 91 93
FT HELIX 104 127
FT STRAND 134 144
FT HELIX 145 160
FT STRAND 164 172
FT HELIX 184 197
FT STRAND 200 206
FT HELIX 207 216
FT HELIX 225 239
FT TURN 240 243
FT STRAND 244 247
FT STRAND 248 250
FT HELIX 253 260
FT STRAND 262 265
FT STRAND 268 274
FT HELIX 290 296
FT HELIX 300 302
FT STRAND 303 305
FT STRAND 317 327
FT HELIX 330 342
FT STRAND 350 352
FT STRAND 356 361
FT STRAND 374 381
FT HELIX 382 384
FT HELIX 385 400
FT HELIX 406 409
FT HELIX 412 414
FT HELIX 419 437
FT HELIX 441 443
SQ SEQUENCE 451 AA; 51170 MW; E2A4C0179ED0CFE8 CRC64;
MPREIITLQL GQCGNQIGFE FWKQLCAEHG ISPEGIVEEF ATEGTDRKDV FFYQADDEHY
IPRAVLLDLE PRVIHSILNS PYAKLYNPEN IYLSEHGGGA GNNWASGFSQ GEKIHEDIFD
IIDREADGSD SLEGFVLCHS IAGGTGSGLG SYLLERLNDR YPKKLVQTYS VFPNQDEMSD
VVVQPYNSLL TLKRLTQNAD CVVVLDNTAL NRIATDRLHI QNPSFSQINQ LVSTIMSAST
TTLRYPGYMN NDLIGLIASL IPTPRLHFLM TGYTPLTTDQ SVASVRKTTV LDVMRRLLQP
KNVMVSTGRD RQTNHCYIAI LNIIQGEVDP TQVHKSLQRI RERKLANFIP WGPASIQVAL
SRKSPYLPSA HRVSGLMMAN HTSISSLFER TCRQYDKLRK REAFLEQFRK EDMFKDNFDE
MDTSREIVQQ LIDEYHAATR PDYISWGTQE Q
//
ID TBG1_HUMAN Reviewed; 451 AA.
AC P23258; Q53X79; Q9BW59;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Tubulin gamma-1 chain;
DE AltName: Full=Gamma-1-tubulin;
DE AltName: Full=Gamma-tubulin complex component 1;
DE Short=GCP-1;
GN Name=TUBG1; Synonyms=TUBG;
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].
RX PubMed=1904010; DOI=10.1016/0092-8674(91)90389-G;
RA Zheng Y., Jung M.K., Oakley B.R.;
RT "Gamma-tubulin is present in Drosophila melanogaster and Homo sapiens
RT and is associated with the centrosome.";
RL Cell 65:817-823(1991).
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
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [6]
RP MASS SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=11840567;
RX DOI=10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H;
RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A.,
RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J.,
RA Zvelebil M.J.;
RT "Cluster analysis of an extensive human breast cancer cell line
RT protein expression map database.";
RL Proteomics 2:212-223(2002).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=9566969; DOI=10.1083/jcb.141.3.689;
RA Tassin A.-M., Celati C., Moudjou M., Bornens M.;
RT "Characterization of the human homologue of the yeast spc98p and its
RT association with gamma-tubulin.";
RL J. Cell Biol. 141:689-701(1998).
RN [8]
RP INTERACTION WITH CDK5RAP2.
RX PubMed=17959831; DOI=10.1091/mbc.E07-04-0371;
RA Fong K.W., Choi Y.K., Rattner J.B., Qi R.Z.;
RT "CDK5RAP2 is a pericentriolar protein that functions in centrosomal
RT attachment of the gamma-tubulin ring complex.";
RL Mol. Biol. Cell 19:115-125(2008).
RN [9]
RP INTERACTION WITH PIFO.
RX PubMed=20643351; DOI=10.1016/j.devcel.2010.06.005;
RA Kinzel D., Boldt K., Davis E.E., Burtscher I., Trumbach D., Diplas B.,
RA Attie-Bitach T., Wurst W., Katsanis N., Ueffing M., Lickert H.;
RT "Pitchfork regulates primary cilia disassembly and left-right
RT asymmetry.";
RL Dev. Cell 19:66-77(2010).
RN [10]
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).
CC -!- FUNCTION: Tubulin is the major constituent of microtubules. The
CC gamma chain is found at microtubule organizing centers (MTOC) such
CC as the spindle poles or the centrosome. Pericentriolar matrix
CC component that regulates alpha/beta chain minus-end nucleation,
CC centrosome duplication and spindle formation.
CC -!- SUBUNIT: Interacts with TUBGCP2 and TUBGCP3. Interacts with B9D2
CC (By similarity). Interacts with CDK5RAP2; the interaction is
CC leading to centrosomal localization of TUBG1 and CDK5RAP2.
CC Interacts with PIFO.
CC -!- INTERACTION:
CC O15169:AXIN1; NbExp=4; IntAct=EBI-302589, EBI-710484;
CC Q96L34:MARK4; NbExp=4; IntAct=EBI-302589, EBI-302319;
CC Q08AG7:MZT1; NbExp=2; IntAct=EBI-302589, EBI-2637198;
CC Q6NZ67:MZT2B; NbExp=2; IntAct=EBI-302589, EBI-1052566;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome.
CC -!- PTM: Phosphorylation at Ser-131 by BRSK1 regulates centrosome
CC duplication, possibly by mediating relocation of gamma-tubulin and
CC its associated proteins from the cytoplasm to the centrosome (By
CC similarity).
CC -!- MASS SPECTROMETRY: Mass=51197.98; Method=MALDI; Range=1-451;
CC Source=PubMed:11840567;
CC -!- SIMILARITY: Belongs to the tubulin family.
CC -----------------------------------------------------------------------
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DR EMBL; M61764; AAA52620.1; -; mRNA.
DR EMBL; BT019931; AAV38734.1; -; mRNA.
DR EMBL; CR407642; CAG28570.1; -; mRNA.
DR EMBL; AK313339; BAG36143.1; -; mRNA.
DR EMBL; BC000619; AAH00619.1; -; mRNA.
DR PIR; A39527; UBHUG.
DR RefSeq; NP_001061.2; NM_001070.4.
DR UniGene; Hs.279669; -.
DR PDB; 1Z5V; X-ray; 2.71 A; A=1-449.
DR PDB; 1Z5W; X-ray; 3.00 A; A=1-449.
DR PDB; 3CB2; X-ray; 2.30 A; A/B=1-451.
DR PDBsum; 1Z5V; -.
DR PDBsum; 1Z5W; -.
DR PDBsum; 3CB2; -.
DR ProteinModelPortal; P23258; -.
DR SMR; P23258; 2-446.
DR DIP; DIP-29890N; -.
DR IntAct; P23258; 30.
DR MINT; MINT-4051249; -.
DR STRING; 9606.ENSP00000251413; -.
DR PhosphoSite; P23258; -.
DR DMDM; 20455518; -.
DR REPRODUCTION-2DPAGE; IPI00295081; -.
DR PaxDb; P23258; -.
DR PRIDE; P23258; -.
DR DNASU; 7283; -.
DR Ensembl; ENST00000251413; ENSP00000251413; ENSG00000131462.
DR GeneID; 7283; -.
DR KEGG; hsa:7283; -.
DR UCSC; uc002ian.3; human.
DR CTD; 7283; -.
DR GeneCards; GC17P040761; -.
DR HGNC; HGNC:12417; TUBG1.
DR HPA; CAB004608; -.
DR MIM; 191135; gene.
DR neXtProt; NX_P23258; -.
DR PharmGKB; PA37079; -.
DR eggNOG; COG5023; -.
DR HOGENOM; HOG000165714; -.
DR HOVERGEN; HBG098558; -.
DR InParanoid; P23258; -.
DR KO; K10389; -.
DR OMA; EGFMLMH; -.
DR OrthoDB; EOG70S755; -.
DR PhylomeDB; P23258; -.
DR Reactome; REACT_115566; Cell Cycle.
DR EvolutionaryTrace; P23258; -.
DR GeneWiki; TUBG1; -.
DR GenomeRNAi; 7283; -.
DR NextBio; 28475; -.
DR PMAP-CutDB; P23258; -.
DR PRO; PR:P23258; -.
DR ArrayExpress; P23258; -.
DR Bgee; P23258; -.
DR CleanEx; HS_TUBG1; -.
DR Genevestigator; P23258; -.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0005814; C:centriole; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IEA:Ensembl.
DR GO; GO:0000794; C:condensed nuclear chromosome; ISS:UniProtKB.
DR GO; GO:0005881; C:cytoplasmic microtubule; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000930; C:gamma-tubulin complex; TAS:UniProtKB.
DR GO; GO:0000242; C:pericentriolar material; IEA:Ensembl.
DR GO; GO:0005827; C:polar microtubule; IDA:UniProtKB.
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; TAS:ProtInc.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IEA:InterPro.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0000212; P:meiotic spindle organization; ISS:UniProtKB.
DR GO; GO:0007020; P:microtubule nucleation; IEA:InterPro.
DR GO; GO:0051258; P:protein polymerization; IEA:InterPro.
DR Gene3D; 1.10.287.600; -; 1.
DR Gene3D; 3.30.1330.20; -; 1.
DR Gene3D; 3.40.50.1440; -; 1.
DR InterPro; IPR002454; Gamma_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 PANTHER; PTHR11588:SF7; PTHR11588:SF7; 1.
DR Pfam; PF00091; Tubulin; 1.
DR Pfam; PF03953; Tubulin_C; 1.
DR PRINTS; PR01164; GAMMATUBULIN.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Cytoskeleton; GTP-binding;
KW Microtubule; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 451 Tubulin gamma-1 chain.
FT /FTId=PRO_0000048465.
FT NP_BIND 142 148 GTP (Potential).
FT MOD_RES 131 131 Phosphoserine; by BRSK1 (By similarity).
FT VARIANT 413 413 M -> V (in dbSNP:rs13663).
FT /FTId=VAR_052674.
FT CONFLICT 35 35 G -> A (in Ref. 1; AAA52620).
FT CONFLICT 202 202 V -> L (in Ref. 1; AAA52620).
FT STRAND 5 10
FT HELIX 11 28
FT STRAND 33 35
FT HELIX 48 50
FT STRAND 52 54
FT STRAND 60 62
FT STRAND 64 71
FT HELIX 72 79
FT TURN 81 85
FT HELIX 88 90
FT STRAND 91 93
FT HELIX 104 127
FT STRAND 134 144
FT HELIX 145 160
FT STRAND 164 172
FT HELIX 184 197
FT STRAND 200 206
FT HELIX 207 216
FT HELIX 225 239
FT TURN 240 243
FT STRAND 244 247
FT STRAND 248 250
FT HELIX 253 260
FT STRAND 262 265
FT STRAND 268 274
FT HELIX 290 296
FT HELIX 300 302
FT STRAND 303 305
FT STRAND 317 327
FT HELIX 330 342
FT STRAND 350 352
FT STRAND 356 361
FT STRAND 374 381
FT HELIX 382 384
FT HELIX 385 400
FT HELIX 406 409
FT HELIX 412 414
FT HELIX 419 437
FT HELIX 441 443
SQ SEQUENCE 451 AA; 51170 MW; E2A4C0179ED0CFE8 CRC64;
MPREIITLQL GQCGNQIGFE FWKQLCAEHG ISPEGIVEEF ATEGTDRKDV FFYQADDEHY
IPRAVLLDLE PRVIHSILNS PYAKLYNPEN IYLSEHGGGA GNNWASGFSQ GEKIHEDIFD
IIDREADGSD SLEGFVLCHS IAGGTGSGLG SYLLERLNDR YPKKLVQTYS VFPNQDEMSD
VVVQPYNSLL TLKRLTQNAD CVVVLDNTAL NRIATDRLHI QNPSFSQINQ LVSTIMSAST
TTLRYPGYMN NDLIGLIASL IPTPRLHFLM TGYTPLTTDQ SVASVRKTTV LDVMRRLLQP
KNVMVSTGRD RQTNHCYIAI LNIIQGEVDP TQVHKSLQRI RERKLANFIP WGPASIQVAL
SRKSPYLPSA HRVSGLMMAN HTSISSLFER TCRQYDKLRK REAFLEQFRK EDMFKDNFDE
MDTSREIVQQ LIDEYHAATR PDYISWGTQE Q
//
MIM
191135
*RECORD*
*FIELD* NO
191135
*FIELD* TI
*191135 TUBULIN, GAMMA-1; TUBG1
;;TUBG;;
TUBULIN-GAMMA COMPLEX-ASSOCIATED PROTEIN 1; TUBGCP1
read more*FIELD* TX
DESCRIPTION
The TUBG1 gene encodes gamma-tubulin, a structural component of the
centrosome that associates with at least 6 other proteins to form the
gamma-tubulin ring complex, which functions in microtubule nucleation
(summary by Poirier et al., 2013).
CLONING
Oakley and Oakley (1989) identified gamma-tubulin, which is essential
for nuclear division and microtubule assembly in Aspergillus nidulans.
By low stringency hybridizations, Zheng et al. (1991) cloned Drosophila
and human cDNAs, the predicted products of which share more than 66%
amino acid identity with A. nidulans gamma-tubulin.
Gamma-tubulin-specific antibodies stained centrosomes of Drosophila,
human, and mouse cell lines. Staining was most intense in prophase
through metaphase when microtubule assembly from centrosomes was
maximal. The findings suggested that gamma-tubulin is a universal
component of microtubule organizing centers.
Stearns et al. (1991) cloned and characterized gamma-tubulin genes from
5 other species, indicating further the ubiquitous and highly conserved
nature of this protein. Gamma-tubulin is present at less than 1% the
level of alpha- (see 602529) and beta-tubulins (see 602660) and is
limited to the centrosome. In particular, it is associated with the
pericentriolar material, the microtubule-nucleating material of the
centrosome.
MAPPING
Rommens et al. (1995) mapped the TUBG1 gene within a 700-kb region of a
YAC of chromosome 17. By radiation hybrid analysis, Wise et al. (2000)
mapped TUBG1 within 20 kb of TUBG2 (605785) at 17q21.
GENE FUNCTION
Simerly et al. (1995) demonstrated by microscopy of inseminated human
oocytes that the sperm introduces the centrosome. The centrosome then
nucleates the new microtubule assembly to form the sperm aster, a step
essential for successful fertilization. They showed further that oocytes
from some infertile patients fail to complete fertilization because of
defects in uniting the sperm and egg nuclei, indicating that failure to
effect properly the cytoplasmic motions uniting the nuclei results in
human infertility.
BIOCHEMICAL FEATURES
- Crystal Structure
Aldaz et al. (2005) reported the 2.7-angstrom crystal structure of human
gamma-tubulin bound to GTP-gamma-S (a nonhydrolysable GTP analog). The
authors observed a curved conformation for gamma-tubulin-GTP-gamma-S,
similar to that seen for GDP-bound, unpolymerized alpha-beta-tubulin.
Tubulins are thought to represent a distinct class of GTP-binding
proteins, and conformational switching in gamma-tubulin might differ
from the nucleotide-dependent switching of signaling GTPases. A crystal
packing interaction replicates the lateral contacts between alpha- and
beta-tubulins in the microtubule, and this association probably forms
the basis for gamma-tubulin oligomerization within the gamma-tubulin
ring complex. Laterally associated gamma-tubulins in the gamma-tubulin
ring complex might promote microtubule nucleation by providing a
template that enhances the intrinsically weak lateral interaction
between alpha-beta-tubulin heterodimers. Because they are dimeric,
alpha-beta-tubulins cannot form microtubule-like lateral associations in
the curved conformation. The lateral array of gamma-tubulins they
observed in the crystal revealed a unique functional property of a
monomeric tubulin.
MOLECULAR GENETICS
In 3 unrelated patients with complex cortical malformations-4 (CDCBM4;
615412), Poirier et al. (2013) identified heterozygous mutations in the
TUBG1 gene (191135.0001-191135.0003). Two of the mutations were
confirmed to be de novo, whereas DNA from the third patient's father was
unavailable. The first 2 mutations were found by whole-exome sequencing
and were not present in several genomic databases, including dbSNP, 1000
Genomes, the Exome Variant Server, and a local Paris Descartes
Bioinformatics platform database. The third mutation was found by
screening 162 individuals with various malformations of cortical
development for variants in the same gene. In vitro functional
expression studies of some of the mutations suggested that they caused
defects in mitotic microtubule organization. Knockdown of Tubg1 in mouse
embryos altered cortical radial neuronal migration, with an arrest of
migrating cells in the subventricular and intermediate zone and impaired
migration to the cortical plate. Poirier et al. (2013) postulated a
dominant-negative effect. The findings indicated that TUBG1 has a role
in neuronal migration during corticogenesis, and extended the
association between microtubule-based cellular processes and proper
cortical development.
*FIELD* AV
.0001
CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 4
TUBG1, LEU387PRO
In a 21-year-old patient with complex cortical dysplasia with other
brain malformations-4 (CDCBM4; 615412), Poirier et al. (2013) identified
a de novo heterozygous c.1160T-C transition in the TUBG1 gene, resulting
in a leu387-to-pro (L387P) substitution at a highly conserved residue.
The mutation was found by whole-exome sequencing and was not present in
several genomic databases, including dbSNP, 1000 Genomes, the Exome
Variant Server, and a local Paris Descartes Bioinformatics platform
database. The patient had microcephaly (-5.5 SD) and early-onset
epilepsy, and he was bedridden with spastic tetraplegia. Brain MRI
showed posterior agyria, frontal pachygyria, and a thick cortex. In
vitro functional expression studies suggested that the
chaperonin-dependent folding, and hence the yield, of monomeric
gamma-tubulin is compromised. In yeast, some cells expressing the mutant
protein also had abnormal mitotic features, consistent with incorrect
nuclear positioning and a defect in mitotic microtubule organization.
.0002
CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 4
TUBG1, TYR92CYS
In a 1.5-year-old patient with CDCBM4 (615412), Poirier et al. (2013)
identified a de novo heterozygous c.275A-G transition in the TUBG1 gene,
resulting in a tyr92-to-cys (Y92C) substitution at a highly conserved
residue in the vicinity of the GTPase domain. The mutation was found by
whole-exome sequencing and was not present in several genomic databases,
including dbSNP, 1000 Genomes, the Exome Variant Server, and a local
Paris Descartes Bioinformatics platform database. The patient had
microcephaly (-4 SD) and infantile spasms, and he was bedridden with
spastic tetraplegia. Brain MRI showed posterior agyria, frontal
pachygyria, a thick cortex, and thick, dysmorphic corpus callosum.
Studies in yeast showed that the mutation caused an enhancement in the
number and average maximal length of astral microtubules, as well as a
decrease in the frequency of nucleation of new microtubules from the
spindle pole body. A number of cells expressing the mutant protein also
had abnormal mitotic features, consistent with incorrect nuclear
positioning and a defect in mitotic microtubule organization.
.0003
CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 4
TUBG1, THR331PRO
In a 31-year-old patient with CDCBM4 (615412), Poirier et al. (2013)
identified a heterozygous c.991A-C transversion in the TUBG1 gene,
resulting in a thr331-to-pro (T331P) substitution at a highly conserved
residue in the gamma-gamma interaction domain. The mutation was not
present in the mother, but DNA from the father was not available. The
mutation was found by screening 162 individuals with various
malformations of cortical development for variants in the TUBG1 gene.
The patient had normocephaly, moderate intellectual disability, and
early-onset epilepsy. Brain MRI showed posterior pachygyria, posterior
subcortical band heterotopia, and thick, dysmorphic corpus callosum.
*FIELD* RF
1. Aldaz, H.; Rice, L. M.; Stearns, T.; Agard, D. A.: Insights into
microtubule nucleation from the crystal structure of human gamma-tubulin.
(Letter) Nature 435: 523-527, 2005.
2. Oakley, C. E.; Oakley, B. R.: Identification of gamma-tubulin,
a new member of the tubulin superfamily encoded by mipA gene of Aspergillus
nidulans. Nature 338: 662-664, 1989.
3. Poirier, K.; Lebrun, N.; Broix, L.; Tian, G.; Saillour, Y.; Boscheron,
C.; Parrini, E.; Valence, S.; Saint Pierre, B.; Oger, M.; Lacombe,
D.; Genevieve, D.; and 23 others: Mutations in TUBG1, DYNC1H1,
KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nature
Genet. 45: 639-647, 2013. Note: Erratum: Nature Genet. 45: 962 only,
2013.
4. Rommens, J. M.; Durocher, F.; McArthur, J.; Tonin, P.; LeBlanc,
J.-F.; Allen, T.; Samson, C.; Ferri, L.; Narod, S.; Morgan, K.; Simard,
J.: Generation of a transcription map at the HSD17B locus centromeric
to BRCA1 at 17q21. Genomics 28: 530-542, 1995.
5. Simerly, C.; Wu, G.-J.; Zoran, S.; Ord, T.; Rawlins, R.; Jones,
J.; Navara, C.; Gerrity, M.; Rinehart, J.; Binor, Z.; Asch, R.; Schatten,
G.: The paternal inheritance of the centrosome, the cell's microtubule-organizing
center, in humans, and the implications for infertility. Nature Med. 1:
47-52, 1995. Note: Erratum: Nature Med. 1: 599, 1995.
6. Stearns, T.; Evans, L.; Kirschner, M.: Gamma-tubulin is a highly
conserved component of the centrosome. Cell 65: 825-836, 1991.
7. Wise, D. O.; Krahe, R.; Oakley, B. R.: The gamma-tubulin gene
family in humans. Genomics 67: 164-170, 2000.
8. Zheng, Y.; Jung, M. K.; Oakley, B. R.: Gamma-tubulin is present
in Drosophila melanogaster and Homo sapiens and is associated with
the centrosome. Cell 65: 817-823, 1991.
*FIELD* CN
Cassandra L. Kniffin - updated: 9/16/2013
Ada Hamosh - updated: 6/15/2005
*FIELD* CD
Victor A. McKusick: 6/21/1991
*FIELD* ED
carol: 09/17/2013
ckniffin: 9/16/2013
terry: 3/14/2013
alopez: 1/6/2009
alopez: 6/17/2005
terry: 6/15/2005
mcapotos: 3/30/2001
carol: 3/27/2001
mgross: 1/20/2000
carol: 1/17/1995
carol: 4/16/1993
supermim: 3/16/1992
carol: 6/21/1991
*RECORD*
*FIELD* NO
191135
*FIELD* TI
*191135 TUBULIN, GAMMA-1; TUBG1
;;TUBG;;
TUBULIN-GAMMA COMPLEX-ASSOCIATED PROTEIN 1; TUBGCP1
read more*FIELD* TX
DESCRIPTION
The TUBG1 gene encodes gamma-tubulin, a structural component of the
centrosome that associates with at least 6 other proteins to form the
gamma-tubulin ring complex, which functions in microtubule nucleation
(summary by Poirier et al., 2013).
CLONING
Oakley and Oakley (1989) identified gamma-tubulin, which is essential
for nuclear division and microtubule assembly in Aspergillus nidulans.
By low stringency hybridizations, Zheng et al. (1991) cloned Drosophila
and human cDNAs, the predicted products of which share more than 66%
amino acid identity with A. nidulans gamma-tubulin.
Gamma-tubulin-specific antibodies stained centrosomes of Drosophila,
human, and mouse cell lines. Staining was most intense in prophase
through metaphase when microtubule assembly from centrosomes was
maximal. The findings suggested that gamma-tubulin is a universal
component of microtubule organizing centers.
Stearns et al. (1991) cloned and characterized gamma-tubulin genes from
5 other species, indicating further the ubiquitous and highly conserved
nature of this protein. Gamma-tubulin is present at less than 1% the
level of alpha- (see 602529) and beta-tubulins (see 602660) and is
limited to the centrosome. In particular, it is associated with the
pericentriolar material, the microtubule-nucleating material of the
centrosome.
MAPPING
Rommens et al. (1995) mapped the TUBG1 gene within a 700-kb region of a
YAC of chromosome 17. By radiation hybrid analysis, Wise et al. (2000)
mapped TUBG1 within 20 kb of TUBG2 (605785) at 17q21.
GENE FUNCTION
Simerly et al. (1995) demonstrated by microscopy of inseminated human
oocytes that the sperm introduces the centrosome. The centrosome then
nucleates the new microtubule assembly to form the sperm aster, a step
essential for successful fertilization. They showed further that oocytes
from some infertile patients fail to complete fertilization because of
defects in uniting the sperm and egg nuclei, indicating that failure to
effect properly the cytoplasmic motions uniting the nuclei results in
human infertility.
BIOCHEMICAL FEATURES
- Crystal Structure
Aldaz et al. (2005) reported the 2.7-angstrom crystal structure of human
gamma-tubulin bound to GTP-gamma-S (a nonhydrolysable GTP analog). The
authors observed a curved conformation for gamma-tubulin-GTP-gamma-S,
similar to that seen for GDP-bound, unpolymerized alpha-beta-tubulin.
Tubulins are thought to represent a distinct class of GTP-binding
proteins, and conformational switching in gamma-tubulin might differ
from the nucleotide-dependent switching of signaling GTPases. A crystal
packing interaction replicates the lateral contacts between alpha- and
beta-tubulins in the microtubule, and this association probably forms
the basis for gamma-tubulin oligomerization within the gamma-tubulin
ring complex. Laterally associated gamma-tubulins in the gamma-tubulin
ring complex might promote microtubule nucleation by providing a
template that enhances the intrinsically weak lateral interaction
between alpha-beta-tubulin heterodimers. Because they are dimeric,
alpha-beta-tubulins cannot form microtubule-like lateral associations in
the curved conformation. The lateral array of gamma-tubulins they
observed in the crystal revealed a unique functional property of a
monomeric tubulin.
MOLECULAR GENETICS
In 3 unrelated patients with complex cortical malformations-4 (CDCBM4;
615412), Poirier et al. (2013) identified heterozygous mutations in the
TUBG1 gene (191135.0001-191135.0003). Two of the mutations were
confirmed to be de novo, whereas DNA from the third patient's father was
unavailable. The first 2 mutations were found by whole-exome sequencing
and were not present in several genomic databases, including dbSNP, 1000
Genomes, the Exome Variant Server, and a local Paris Descartes
Bioinformatics platform database. The third mutation was found by
screening 162 individuals with various malformations of cortical
development for variants in the same gene. In vitro functional
expression studies of some of the mutations suggested that they caused
defects in mitotic microtubule organization. Knockdown of Tubg1 in mouse
embryos altered cortical radial neuronal migration, with an arrest of
migrating cells in the subventricular and intermediate zone and impaired
migration to the cortical plate. Poirier et al. (2013) postulated a
dominant-negative effect. The findings indicated that TUBG1 has a role
in neuronal migration during corticogenesis, and extended the
association between microtubule-based cellular processes and proper
cortical development.
*FIELD* AV
.0001
CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 4
TUBG1, LEU387PRO
In a 21-year-old patient with complex cortical dysplasia with other
brain malformations-4 (CDCBM4; 615412), Poirier et al. (2013) identified
a de novo heterozygous c.1160T-C transition in the TUBG1 gene, resulting
in a leu387-to-pro (L387P) substitution at a highly conserved residue.
The mutation was found by whole-exome sequencing and was not present in
several genomic databases, including dbSNP, 1000 Genomes, the Exome
Variant Server, and a local Paris Descartes Bioinformatics platform
database. The patient had microcephaly (-5.5 SD) and early-onset
epilepsy, and he was bedridden with spastic tetraplegia. Brain MRI
showed posterior agyria, frontal pachygyria, and a thick cortex. In
vitro functional expression studies suggested that the
chaperonin-dependent folding, and hence the yield, of monomeric
gamma-tubulin is compromised. In yeast, some cells expressing the mutant
protein also had abnormal mitotic features, consistent with incorrect
nuclear positioning and a defect in mitotic microtubule organization.
.0002
CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 4
TUBG1, TYR92CYS
In a 1.5-year-old patient with CDCBM4 (615412), Poirier et al. (2013)
identified a de novo heterozygous c.275A-G transition in the TUBG1 gene,
resulting in a tyr92-to-cys (Y92C) substitution at a highly conserved
residue in the vicinity of the GTPase domain. The mutation was found by
whole-exome sequencing and was not present in several genomic databases,
including dbSNP, 1000 Genomes, the Exome Variant Server, and a local
Paris Descartes Bioinformatics platform database. The patient had
microcephaly (-4 SD) and infantile spasms, and he was bedridden with
spastic tetraplegia. Brain MRI showed posterior agyria, frontal
pachygyria, a thick cortex, and thick, dysmorphic corpus callosum.
Studies in yeast showed that the mutation caused an enhancement in the
number and average maximal length of astral microtubules, as well as a
decrease in the frequency of nucleation of new microtubules from the
spindle pole body. A number of cells expressing the mutant protein also
had abnormal mitotic features, consistent with incorrect nuclear
positioning and a defect in mitotic microtubule organization.
.0003
CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 4
TUBG1, THR331PRO
In a 31-year-old patient with CDCBM4 (615412), Poirier et al. (2013)
identified a heterozygous c.991A-C transversion in the TUBG1 gene,
resulting in a thr331-to-pro (T331P) substitution at a highly conserved
residue in the gamma-gamma interaction domain. The mutation was not
present in the mother, but DNA from the father was not available. The
mutation was found by screening 162 individuals with various
malformations of cortical development for variants in the TUBG1 gene.
The patient had normocephaly, moderate intellectual disability, and
early-onset epilepsy. Brain MRI showed posterior pachygyria, posterior
subcortical band heterotopia, and thick, dysmorphic corpus callosum.
*FIELD* RF
1. Aldaz, H.; Rice, L. M.; Stearns, T.; Agard, D. A.: Insights into
microtubule nucleation from the crystal structure of human gamma-tubulin.
(Letter) Nature 435: 523-527, 2005.
2. Oakley, C. E.; Oakley, B. R.: Identification of gamma-tubulin,
a new member of the tubulin superfamily encoded by mipA gene of Aspergillus
nidulans. Nature 338: 662-664, 1989.
3. Poirier, K.; Lebrun, N.; Broix, L.; Tian, G.; Saillour, Y.; Boscheron,
C.; Parrini, E.; Valence, S.; Saint Pierre, B.; Oger, M.; Lacombe,
D.; Genevieve, D.; and 23 others: Mutations in TUBG1, DYNC1H1,
KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nature
Genet. 45: 639-647, 2013. Note: Erratum: Nature Genet. 45: 962 only,
2013.
4. Rommens, J. M.; Durocher, F.; McArthur, J.; Tonin, P.; LeBlanc,
J.-F.; Allen, T.; Samson, C.; Ferri, L.; Narod, S.; Morgan, K.; Simard,
J.: Generation of a transcription map at the HSD17B locus centromeric
to BRCA1 at 17q21. Genomics 28: 530-542, 1995.
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*FIELD* CN
Cassandra L. Kniffin - updated: 9/16/2013
Ada Hamosh - updated: 6/15/2005
*FIELD* CD
Victor A. McKusick: 6/21/1991
*FIELD* ED
carol: 09/17/2013
ckniffin: 9/16/2013
terry: 3/14/2013
alopez: 1/6/2009
alopez: 6/17/2005
terry: 6/15/2005
mcapotos: 3/30/2001
carol: 3/27/2001
mgross: 1/20/2000
carol: 1/17/1995
carol: 4/16/1993
supermim: 3/16/1992
carol: 6/21/1991