TBCB_HUMAN
ID TBCB_HUMAN Reviewed; 244 AA.
AC Q99426; O00111; O00674; O14728; Q6FGY5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Tubulin-folding cofactor B;
DE AltName: Full=Cytoskeleton-associated protein 1;
DE AltName: Full=Cytoskeleton-associated protein CKAPI;
DE AltName: Full=Tubulin-specific chaperone B;
GN Name=TBCB; Synonyms=CG22, CKAP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBUNIT.
RX PubMed=9265649; DOI=10.1083/jcb.138.4.821;
RA Tian G., Lewis S.A., Feierbach B., Stearns T., Rommelaere H., Ampe C.,
RA Cowan N.J.;
RT "Tubulin subunits exist in an activated conformational state generated and
RT maintained by protein cofactors.";
RL J. Cell Biol. 138:821-832(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, and Uterus;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 52-244 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=8978778; DOI=10.1159/000134191;
RA Watanabe T.K., Shimizu F., Nagata M., Kawai A., Fujiwara T., Nakamura Y.,
RA Takahashi E., Hirai Y.;
RT "Cloning, expression, and mapping of CKAPI, which encodes a putative
RT cytoskeleton-associated protein containing a CAP-Gly domain.";
RL Cytogenet. Cell Genet. 72:208-211(1996).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-98, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [8]
RP INTERACTION WITH GAN, UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
RX PubMed=16303566; DOI=10.1016/j.cub.2005.10.052;
RA Wang W., Ding J., Allen E., Zhu P., Zhang L., Vogel H., Yang Y.;
RT "Gigaxonin interacts with tubulin folding cofactor B and controls its
RT degradation through the ubiquitin-proteasome pathway.";
RL Curr. Biol. 15:2050-2055(2005).
RN [9]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-65 AND SER-128, AND
RP MUTAGENESIS OF SER-65 AND SER-128.
RX PubMed=15831477; DOI=10.1128/mcb.25.9.3726-3736.2005;
RA Vadlamudi R.K., Barnes C.J., Rayala S., Li F., Balasenthil S., Marcus S.,
RA Goodson H.V., Sahin A.A., Kumar R.;
RT "p21-activated kinase 1 regulates microtubule dynamics by phosphorylating
RT tubulin cofactor B.";
RL Mol. Cell. Biol. 25:3726-3736(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-98, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-219, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [13]
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., Buerckstuemmer T.,
RA 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 [14]
RP INTERACTION WITH DCTN1, AND SUBCELLULAR LOCATION.
RX PubMed=22777741; DOI=10.1007/s00441-012-1463-z;
RA Kuh G.F., Stockmann M., Meyer-Ohlendorf M., Linta L., Proepper C.,
RA Ludolph A.C., Bockmann J., Boeckers T.M., Liebau S.;
RT "Tubulin-binding cofactor B is a direct interaction partner of the dynactin
RT subunit p150(Glued).";
RL Cell Tissue Res. 350:13-26(2012).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, 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., Meinnel T.,
RA 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP GLYCOSYLATION (MICROBIAL INFECTION).
RX PubMed=32366039; DOI=10.3390/ijms21093193;
RA Araujo-Garrido J.L., Baison-Olmo F., Bernal-Bayard J., Romero F.,
RA Ramos-Morales F.;
RT "Tubulin folding cofactor TBCB is a target of the salmonella effector
RT protein SseK1.";
RL Int. J. Mol. Sci. 21:0-0(2020).
CC -!- FUNCTION: Binds to alpha-tubulin folding intermediates after their
CC interaction with cytosolic chaperonin in the pathway leading from newly
CC synthesized tubulin to properly folded heterodimer (PubMed:9265649).
CC Involved in regulation of tubulin heterodimer dissociation. May
CC function as a negative regulator of axonal growth (By similarity).
CC {ECO:0000250|UniProtKB:Q9D1E6, ECO:0000269|PubMed:9265649}.
CC -!- SUBUNIT: Supercomplex made of cofactors A to E. Cofactors A and D
CC function by capturing and stabilizing tubulin in a quasi-native
CC conformation. Cofactor E binds to the cofactor D-tubulin complex;
CC interaction with cofactor C then causes the release of tubulin
CC polypeptides that are committed to the native state (PubMed:9265649).
CC Cofactors B and E can form a heterodimer which binds to alpha-tubulin
CC and enhances their ability to dissociate tubulin heterodimers (By
CC similarity). Interacts with GAN (PubMed:16303566). Interacts with DCTN1
CC (PubMed:22777741). {ECO:0000250|UniProtKB:Q9D1E6,
CC ECO:0000269|PubMed:16303566, ECO:0000269|PubMed:22777741,
CC ECO:0000269|PubMed:9265649}.
CC -!- INTERACTION:
CC Q99426; Q9H2C0: GAN; NbExp=3; IntAct=EBI-764356, EBI-764342;
CC Q99426; Q93009: USP7; NbExp=2; IntAct=EBI-764356, EBI-302474;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15831477,
CC ECO:0000269|PubMed:22777741}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:15831477}. Note=Colocalizes with microtubules. In
CC differentiated neurons, located in the cytoplasm. In differentiating
CC neurons, accumulates at the growth cone. {ECO:0000269|PubMed:15831477}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99426-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99426-2; Sequence=VSP_055521;
CC -!- TISSUE SPECIFICITY: Found in most tissues.
CC -!- PTM: Phosphorylation by PAK1 is required for normal function.
CC {ECO:0000269|PubMed:15831477}.
CC -!- PTM: Ubiquitinated in the presence of GAN which targets it for
CC degradation by the proteasome. {ECO:0000269|PubMed:16303566}.
CC -!- PTM: (Microbial infection) Glycosylated residues by S.typhimurium
CC protein Ssek1: arginine GlcNAcylation promotes microtubule stability.
CC {ECO:0000269|PubMed:32366039}.
CC -!- SIMILARITY: Belongs to the TBCB family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB51182.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF013488; AAB67716.1; -; mRNA.
DR EMBL; BT007424; AAP36092.1; -; mRNA.
DR EMBL; CR541971; CAG46769.1; -; mRNA.
DR EMBL; AD001527; AAB51182.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC005969; AAH05969.1; -; mRNA.
DR EMBL; BC052812; AAH52812.1; -; mRNA.
DR EMBL; D49738; BAA08572.1; -; mRNA.
DR CCDS; CCDS12488.1; -. [Q99426-1]
DR CCDS; CCDS74344.1; -. [Q99426-2]
DR RefSeq; NP_001272.2; NM_001281.2. [Q99426-1]
DR RefSeq; NP_001287900.1; NM_001300971.1. [Q99426-2]
DR AlphaFoldDB; Q99426; -.
DR SMR; Q99426; -.
DR BioGRID; 107575; 91.
DR CORUM; Q99426; -.
DR DIP; DIP-34409N; -.
DR IntAct; Q99426; 21.
DR MINT; Q99426; -.
DR STRING; 9606.ENSP00000221855; -.
DR GlyGen; Q99426; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q99426; -.
DR PhosphoSitePlus; Q99426; -.
DR SwissPalm; Q99426; -.
DR BioMuta; TBCB; -.
DR DMDM; 3023518; -.
DR OGP; Q99426; -.
DR CPTAC; CPTAC-444; -.
DR CPTAC; CPTAC-445; -.
DR EPD; Q99426; -.
DR jPOST; Q99426; -.
DR MassIVE; Q99426; -.
DR MaxQB; Q99426; -.
DR PaxDb; Q99426; -.
DR PeptideAtlas; Q99426; -.
DR PRIDE; Q99426; -.
DR ProteomicsDB; 78261; -. [Q99426-1]
DR Antibodypedia; 29702; 297 antibodies from 29 providers.
DR DNASU; 1155; -.
DR Ensembl; ENST00000221855.8; ENSP00000221855.3; ENSG00000105254.12. [Q99426-1]
DR Ensembl; ENST00000585746.1; ENSP00000467487.1; ENSG00000105254.12. [Q99426-2]
DR GeneID; 1155; -.
DR KEGG; hsa:1155; -.
DR MANE-Select; ENST00000221855.8; ENSP00000221855.3; NM_001281.3; NP_001272.2.
DR UCSC; uc002odg.2; human. [Q99426-1]
DR CTD; 1155; -.
DR DisGeNET; 1155; -.
DR GeneCards; TBCB; -.
DR HGNC; HGNC:1989; TBCB.
DR HPA; ENSG00000105254; Tissue enhanced (brain).
DR MIM; 601303; gene.
DR neXtProt; NX_Q99426; -.
DR OpenTargets; ENSG00000105254; -.
DR PharmGKB; PA162405357; -.
DR VEuPathDB; HostDB:ENSG00000105254; -.
DR eggNOG; KOG3206; Eukaryota.
DR GeneTree; ENSGT00940000156119; -.
DR HOGENOM; CLU_067577_0_0_1; -.
DR InParanoid; Q99426; -.
DR OMA; IGVKYDE; -.
DR OrthoDB; 1550378at2759; -.
DR PhylomeDB; Q99426; -.
DR TreeFam; TF313444; -.
DR PathwayCommons; Q99426; -.
DR Reactome; R-HSA-389977; Post-chaperonin tubulin folding pathway.
DR SignaLink; Q99426; -.
DR SIGNOR; Q99426; -.
DR BioGRID-ORCS; 1155; 639 hits in 1077 CRISPR screens.
DR ChiTaRS; TBCB; human.
DR GeneWiki; TBCB; -.
DR GenomeRNAi; 1155; -.
DR Pharos; Q99426; Tbio.
DR PRO; PR:Q99426; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q99426; protein.
DR Bgee; ENSG00000105254; Expressed in C1 segment of cervical spinal cord and 208 other tissues.
DR ExpressionAtlas; Q99426; baseline and differential.
DR Genevisible; Q99426; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; TAS:ProtInc.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR CDD; cd01789; Ubl_TBCB; 1.
DR Gene3D; 2.30.30.190; -; 1.
DR InterPro; IPR036859; CAP-Gly_dom_sf.
DR InterPro; IPR000938; CAP-Gly_domain.
DR InterPro; IPR045172; TBCB_N_Ubl.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF01302; CAP_GLY; 1.
DR Pfam; PF14560; Ubiquitin_2; 1.
DR SMART; SM01052; CAP_GLY; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF74924; SSF74924; 1.
DR PROSITE; PS00845; CAP_GLY_1; 1.
DR PROSITE; PS50245; CAP_GLY_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Chaperone; Cytoplasm; Cytoskeleton;
KW Developmental protein; Differentiation; Glycoprotein; Microtubule;
KW Neurogenesis; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..244
FT /note="Tubulin-folding cofactor B"
FT /id="PRO_0000083534"
FT DOMAIN 183..225
FT /note="CAP-Gly"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00045"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 65
FT /note="Phosphoserine; by PAK1"
FT /evidence="ECO:0000269|PubMed:15831477"
FT MOD_RES 98
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:15592455"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 128
FT /note="Phosphoserine; by PAK1"
FT /evidence="ECO:0000269|PubMed:15831477"
FT MOD_RES 219
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..51
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_055521"
FT MUTAGEN 65
FT /note="S->A: Reduced phosphorylation by PAK1. Reduced
FT microtubule polymerization and loss of phosphorylation by
FT PAK1; when associated with A-128."
FT /evidence="ECO:0000269|PubMed:15831477"
FT MUTAGEN 128
FT /note="S->A: Reduced phosphorylation by PAK1. Reduced
FT microtubule polymerization and loss of phosphorylation by
FT PAK1; when associated with A-65."
FT /evidence="ECO:0000269|PubMed:15831477"
FT CONFLICT 128
FT /note="S -> R (in Ref. 1; AAB67716)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 244 AA; 27326 MW; E984C7C74A105384 CRC64;
MEVTGVSAPT VTVFISSSLN TFRSEKRYSR SLTIAEFKCK LELLVGSPAS CMELELYGVD
DKFYSKLDQE DALLGSYPVD DGCRIHVIDH SGARLGEYED VSRVEKYTIS QEAYDQRQDT
VRSFLKRSKL GRYNEEERAQ QEAEAAQRLA EEKAQASSIP VGSRCEVRAA GQSPRRGTVM
YVGLTDFKPG YWIGVRYDEP LGKNDGSVNG KRYFECQAKY GAFVKPAVVT VGDFPEEDYG
LDEI
