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Protein

Tubulin-specific chaperone D

Gene

TBCD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tubulin-folding protein implicated in the first step of the tubulin folding pathway and required for tubulin complex assembly. Involved in the regulation of microtubule polymerization or depolymerization, it modulates microtubule dynamics by capturing GTP-bound beta-tubulin (TUBB). Its ability to interact with beta tubulin is regulated via its interaction with ARL2. Acts as a GTPase-activating protein (GAP) for ARL2. Induces microtubule disruption in absence of ARL2. Increases degradation of beta tubulin, when overexpressed in polarized cells. Promotes epithelial cell detachment, a process antagonized by ARL2. Induces tight adherens and tight junctions disassembly at the lateral cell membrane (PubMed:10722852, PubMed:10831612, PubMed:11847227, PubMed:20740604, PubMed:27666370, PubMed:28158450). Required for correct assembly and maintenance of the mitotic spindle, and proper progression of mitosis (PubMed:27666370). Involved in neuron morphogenesis (PubMed:27666374).7 Publications

GO - Molecular functioni

  • beta-tubulin binding Source: UniProtKB
  • chaperone binding Source: ProtInc
  • GTPase activator activity Source: UniProtKB

GO - Biological processi

  • adherens junction assembly Source: UniProtKB
  • bicellular tight junction assembly Source: UniProtKB
  • cell morphogenesis involved in neuron differentiation Source: UniProtKB
  • mitotic cell cycle Source: UniProtKB
  • negative regulation of cell-substrate adhesion Source: UniProtKB
  • negative regulation of microtubule polymerization Source: UniProtKB
  • post-chaperonin tubulin folding pathway Source: UniProtKB
  • protein folding Source: UniProtKB
  • tubulin complex assembly Source: UniProtKB

Keywordsi

Molecular functionChaperone, GTPase activation

Enzyme and pathway databases

ReactomeiR-HSA-389977. Post-chaperonin tubulin folding pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Tubulin-specific chaperone D
Alternative name(s):
Beta-tubulin cofactor D
Short name:
tfcD
SSD-1
Tubulin-folding cofactor D
Gene namesi
Name:TBCD
Synonyms:KIAA0988, SSD1, TFCD
ORF Names:PP1096
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000141556.20.
HGNCiHGNC:11581. TBCD.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Tight junction

Pathology & Biotechi

Involvement in diseasei

Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum (PEBAT)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disease with neurodevelopmental and neurodegenerative features. PEBAT is characterized by early-onset cortical atrophy, hypomyelination, microcephaly, thin corpus callosum, delayed psychomotor development, developmental regression, intellectual disability, seizures, optic atrophy, muscle weakness and atrophy, spastic quadriplegia, and respiratory insufficiency due to hypotonia.
See also OMIM:617193
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077968229L → R in PEBAT. 1 PublicationCorresponds to variant dbSNP:rs778417127Ensembl.1
Natural variantiVAR_077969374T → M in PEBAT; severely decreased interaction with beta tubulin; does not affect localization to centrosome. 1 Publication1
Natural variantiVAR_077970377R → Q in PEBAT; decreased protein abundance; severely decreased interaction with beta tubulin; does not affect localization to centrosome. 1 PublicationCorresponds to variant dbSNP:rs764085684Ensembl.1
Natural variantiVAR_077971387M → R in PEBAT; decreased function in neuron morphogenesis; severely decreased interaction with ARL2; decreased interaction with TBCE; decreased interaction with beta tubulin. 1 Publication1
Natural variantiVAR_077972475A → T in PEBAT; decreased function in tubulin complex assembly; increased protein degradation. 2 PublicationsCorresponds to variant dbSNP:rs775014444Ensembl.1
Natural variantiVAR_077973586A → V in PEBAT; decreased function in tubulin complex assembly. 2 Publications1
Natural variantiVAR_077974626A → T in PEBAT; decreased protein abundance; does not affect localization to centrosome. 1 PublicationCorresponds to variant dbSNP:rs749225304Ensembl.1
Natural variantiVAR_077975772R → C in PEBAT; decreased function in neuron morphogenesis; decreased interaction with ARL2; decreased interaction with TBCE; decreased interaction with beta tubulin. 1 PublicationCorresponds to variant dbSNP:rs181969865Ensembl.1
Natural variantiVAR_077976921A → T in PEBAT; decreased interaction with ARL2; decreased interaction with TBCE; decreased interaction with beta tubulin. 1 Publication1
Natural variantiVAR_077977937P → R in PEBAT; decreased interaction with TBCE; decreased interaction with beta tubulin; does not affect interaction with ARL2. 2 Publications1
Natural variantiVAR_077978994T → M in PEBAT; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs867484272Ensembl.1
Natural variantiVAR_0779791105V → M in PEBAT; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs764003906Ensembl.1
Natural variantiVAR_0779801122P → L in PEBAT; severely decreased protein abundance; does not affect localization to centrosome; decreased interaction with ARL2; decreased interaction with TBCE; decreased interaction with beta tubulin. 2 PublicationsCorresponds to variant dbSNP:rs755177846Ensembl.1

Keywords - Diseasei

Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNETi6904.
MIMi617193. phenotype.
OpenTargetsiENSG00000141556.
PharmGKBiPA36345.

Polymorphism and mutation databases

BioMutaiTBCD.
DMDMi296452924.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000800491 – 1192Tubulin-specific chaperone DAdd BLAST1192

Proteomic databases

EPDiQ9BTW9.
MaxQBiQ9BTW9.
PaxDbiQ9BTW9.
PeptideAtlasiQ9BTW9.
PRIDEiQ9BTW9.

PTM databases

iPTMnetiQ9BTW9.
PhosphoSitePlusiQ9BTW9.
SwissPalmiQ9BTW9.

Expressioni

Tissue specificityi

Ubiquitously expressed.2 Publications

Inductioni

Down-regulated by shear stress.1 Publication

Gene expression databases

BgeeiENSG00000141556.
ExpressionAtlasiQ9BTW9. baseline and differential.
GenevisibleiQ9BTW9. HS.

Organism-specific databases

HPAiHPA045200.

Interactioni

Subunit structurei

Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with PPP2CB (By similarity). Part of a supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state (PubMed:10831612). Interacts with ARL2; interaction is enhanced with the GDP-bound form of ARL2 (PubMed:10831612, PubMed:27666374). Does not interact with ARL3, ARL4A and ARL4D (PubMed:10831612). Interacts with beta tubulin (PubMed:10831612, PubMed:27666370, PubMed:27666374). Interacts with TBCE (PubMed:27666374).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ACDQ96AP02EBI-356005,EBI-717666

GO - Molecular functioni

  • beta-tubulin binding Source: UniProtKB
  • chaperone binding Source: ProtInc

Protein-protein interaction databases

BioGridi112767. 54 interactors.
CORUMiQ9BTW9.
IntActiQ9BTW9. 18 interactors.
MINTiMINT-1138609.
STRINGi9606.ENSP00000347719.

Structurei

3D structure databases

ProteinModelPortaliQ9BTW9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati361 – 399HEAT 1Add BLAST39
Repeati557 – 594HEAT 2Add BLAST38
Repeati596 – 632HEAT 3Add BLAST37

Sequence similaritiesi

Belongs to the TBCD family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1943. Eukaryota.
COG5234. LUCA.
GeneTreeiENSGT00390000017103.
HOVERGENiHBG053297.
InParanoidiQ9BTW9.
KOiK21767.
PhylomeDBiQ9BTW9.
TreeFamiTF105754.

Family and domain databases

Gene3Di1.25.10.10. 3 hits.
InterProiView protein in InterPro
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR033162. TBCD.
IPR022577. Tubulin_specific_chaperoneD_C.
PANTHERiPTHR12658:SF3. PTHR12658:SF3. 1 hit.
PfamiView protein in Pfam
PF12612. TFCD_C. 1 hit.
SUPFAMiSSF48371. SSF48371. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BTW9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALSDEPAAG GPEEEAEDET LAFGAALEAF GESAETRALL GRLREVHGGG
60 70 80 90 100
AEREVALERF RVIMDKYQEQ PHLLDPHLEW MMNLLLDIVQ DQTSPASLVH
110 120 130 140 150
LAFKFLYIIT KVRGYKTFLR LFPHEVADVE PVLDLVTIQN PKDHEAWETR
160 170 180 190 200
YMLLLWLSVT CLIPFDFSRL DGNLLTQPGQ ARMSIMDRIL QIAESYLIVS
210 220 230 240 250
DKARDAAAVL VSRFITRPDV KQSKMAEFLD WSLCNLARSS FQTMQGVITM
260 270 280 290 300
DGTLQALAQI FKHGKREDCL PYAATVLRCL DGCRLPESNQ TLLRKLGVKL
310 320 330 340 350
VQRLGLTFLK PKVAAWRYQR GCRSLAANLQ LLTQGQSEQK PLILTEDDDE
360 370 380 390 400
DDDVPEGVER VIEQLLVGLK DKDTVVRWSA AKGIGRMAGR LPRALADDVV
410 420 430 440 450
GSVLDCFSFQ ETDKAWHGGC LALAELGRRG LLLPSRLVDV VAVILKALTY
460 470 480 490 500
DEKRGACSVG TNVRDAACYV CWAFARAYEP QELKPFVTAI SSALVIAAVF
510 520 530 540 550
DRDINCRRAA SAAFQENVGR QGTFPHGIDI LTTADYFAVG NRSNCFLVIS
560 570 580 590 600
VFIAGFPEYT QPMIDHLVTM KISHWDGVIR ELAARALHNL AQQAPEFSAT
610 620 630 640 650
QVFPRLLSMT LSPDLHMRHG SILACAEVAY ALYKLAAQEN RPVTDHLDEQ
660 670 680 690 700
AVQGLKQIHQ QLYDRQLYRG LGGQLMRQAV CVLIEKLSLS KMPFRGDTVI
710 720 730 740 750
DGWQWLINDT LRHLHLISSH SRQQMKDAAV SALAALCSEY YMKEPGEADP
760 770 780 790 800
AIQEELITQY LAELRNPEEM TRCGFSLALG ALPGFLLKGR LQQVLTGLRA
810 820 830 840 850
VTHTSPEDVS FAESRRDGLK AIARICQTVG VKAGAPDEAV CGENVSQIYC
860 870 880 890 900
ALLGCMDDYT TDSRGDVGTW VRKAAMTSLM DLTLLLARSQ PELIEAHTCE
910 920 930 940 950
RIMCCVAQQA SEKIDRFRAH AASVFLTLLH FDSPPIPHVP HRGELEKLFP
960 970 980 990 1000
RSDVASVNWS APSQAFPRIT QLLGLPTYRY HVLLGLVVSL GGLTESTIRH
1010 1020 1030 1040 1050
STQSLFEYMK GIQSDPQALG SFSGTLLQIF EDNLLNERVS VPLLKTLDHV
1060 1070 1080 1090 1100
LTHGCFDIFT TEEDHPFAVK LLALCKKEIK NSKDIQKLLS GIAVFCEMVQ
1110 1120 1130 1140 1150
FPGDVRRQAL LQLCLLLCHR FPLIRKTTAS QVYETLLTYS DVVGADVLDE
1160 1170 1180 1190
VVTVLSDTAW DAELAVVREQ RNRLCDLLGV PRPQLVPQPG AC
Length:1,192
Mass (Da):132,600
Last modified:May 18, 2010 - v2
Checksum:iC46BE2048A5FEBC2
GO
Isoform 2 (identifier: Q9BTW9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1008: Missing.

Note: No experimental confirmation available.
Show »
Length:184
Mass (Da):20,490
Checksum:i93591120628A7A54
GO
Isoform 3 (identifier: Q9BTW9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-546: Missing.
     547-549: LVI → MFN
     662-697: LYDRQLYRGLGGQLMRQAVCVLIEKLSLSKMPFRGD → PCICSWGLMSPESKAEFCVCVCRISLGRQCVHLSGL
     698-1192: Missing.

Show »
Length:151
Mass (Da):16,862
Checksum:i327EBC8C058A1F63
GO
Isoform 4 (identifier: Q9BTW9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1094-1094: V → VDFPSATLVCVGTVQMYAHTHLRLGAPGPHCAHGSAMPR
     1182-1192: RPQLVPQPGAC → SPTWCPAWCLLKPVLEPIPHPCLVRMSCS

Note: No experimental confirmation available.
Show »
Length:1,248
Mass (Da):138,669
Checksum:iC4677BCAFB301E0A
GO
Isoform 5 (identifier: Q9BTW9-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     62-78: Missing.
     739-1156: Missing.

Note: No experimental confirmation available.
Show »
Length:757
Mass (Da):84,263
Checksum:i1EBCE9E996D5C8C8
GO

Sequence cautioni

The sequence AAH39654 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA76832 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31G → S in CAA07022 (PubMed:11110777).Curated1
Sequence conflicti472W → C in BAA76832 (PubMed:10231032).Curated1
Sequence conflicti799 – 801RAV → GAL in CAA07022 (PubMed:11110777).Curated3
Sequence conflicti985G → R in CAA07022 (PubMed:11110777).Curated1
Sequence conflicti1068A → S in AAH12824 (PubMed:15489334).Curated1
Sequence conflicti1075C → V in CAA07022 (PubMed:11110777).Curated1
Sequence conflicti1097E → G in CAA07022 (PubMed:11110777).Curated1
Sequence conflicti1097E → G in BAA76832 (PubMed:10231032).Curated1
Sequence conflicti1097E → G in AAH03094 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077968229L → R in PEBAT. 1 PublicationCorresponds to variant dbSNP:rs778417127Ensembl.1
Natural variantiVAR_077969374T → M in PEBAT; severely decreased interaction with beta tubulin; does not affect localization to centrosome. 1 Publication1
Natural variantiVAR_077970377R → Q in PEBAT; decreased protein abundance; severely decreased interaction with beta tubulin; does not affect localization to centrosome. 1 PublicationCorresponds to variant dbSNP:rs764085684Ensembl.1
Natural variantiVAR_077971387M → R in PEBAT; decreased function in neuron morphogenesis; severely decreased interaction with ARL2; decreased interaction with TBCE; decreased interaction with beta tubulin. 1 Publication1
Natural variantiVAR_077972475A → T in PEBAT; decreased function in tubulin complex assembly; increased protein degradation. 2 PublicationsCorresponds to variant dbSNP:rs775014444Ensembl.1
Natural variantiVAR_077973586A → V in PEBAT; decreased function in tubulin complex assembly. 2 Publications1
Natural variantiVAR_057264617M → T1 PublicationCorresponds to variant dbSNP:rs2292971Ensembl.1
Natural variantiVAR_077974626A → T in PEBAT; decreased protein abundance; does not affect localization to centrosome. 1 PublicationCorresponds to variant dbSNP:rs749225304Ensembl.1
Natural variantiVAR_077975772R → C in PEBAT; decreased function in neuron morphogenesis; decreased interaction with ARL2; decreased interaction with TBCE; decreased interaction with beta tubulin. 1 PublicationCorresponds to variant dbSNP:rs181969865Ensembl.1
Natural variantiVAR_077976921A → T in PEBAT; decreased interaction with ARL2; decreased interaction with TBCE; decreased interaction with beta tubulin. 1 Publication1
Natural variantiVAR_057265923S → N. Corresponds to variant dbSNP:rs3214033Ensembl.1
Natural variantiVAR_077977937P → R in PEBAT; decreased interaction with TBCE; decreased interaction with beta tubulin; does not affect interaction with ARL2. 2 Publications1
Natural variantiVAR_057266943G → V. Corresponds to variant dbSNP:rs8072406Ensembl.1
Natural variantiVAR_077978994T → M in PEBAT; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs867484272Ensembl.1
Natural variantiVAR_0779791105V → M in PEBAT; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs764003906Ensembl.1
Natural variantiVAR_0779801122P → L in PEBAT; severely decreased protein abundance; does not affect localization to centrosome; decreased interaction with ARL2; decreased interaction with TBCE; decreased interaction with beta tubulin. 2 PublicationsCorresponds to variant dbSNP:rs755177846Ensembl.1
Natural variantiVAR_0572671185L → P. Corresponds to variant dbSNP:rs2292969Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0172101 – 1008Missing in isoform 2. 1 PublicationAdd BLAST1008
Alternative sequenceiVSP_0172111 – 546Missing in isoform 3. 1 PublicationAdd BLAST546
Alternative sequenceiVSP_01721262 – 78Missing in isoform 5. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_017215547 – 549LVI → MFN in isoform 3. 1 Publication3
Alternative sequenceiVSP_017213662 – 697LYDRQ…PFRGD → PCICSWGLMSPESKAEFCVC VCRISLGRQCVHLSGL in isoform 3. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_017214698 – 1192Missing in isoform 3. 1 PublicationAdd BLAST495
Alternative sequenceiVSP_017216739 – 1156Missing in isoform 5. 1 PublicationAdd BLAST418
Alternative sequenceiVSP_0172171094V → VDFPSATLVCVGTVQMYAHT HLRLGAPGPHCAHGSAMPR in isoform 4. 1 Publication1
Alternative sequenceiVSP_0172181182 – 1192RPQLVPQPGAC → SPTWCPAWCLLKPVLEPIPH PCLVRMSCS in isoform 4. 1 PublicationAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ006417 mRNA. Translation: CAA07022.1.
AF193042 mRNA. Translation: AAG22470.1.
AB023205 mRNA. Translation: BAA76832.2. Different initiation.
AK091959 mRNA. Translation: BAC03777.1.
AL133562 mRNA. Translation: CAB63716.1.
AL096745 mRNA. Translation: CAB62532.2.
AC024361 Genomic DNA. No translation available.
AC068014 Genomic DNA. No translation available.
AC068584 Genomic DNA. No translation available.
AC087222 Genomic DNA. No translation available.
AC130371 Genomic DNA. No translation available.
BC003094 mRNA. Translation: AAH03094.1.
BC012824 mRNA. Translation: AAH12824.2.
BC039654 mRNA. Translation: AAH39654.1. Different initiation.
CCDSiCCDS45818.1. [Q9BTW9-1]
PIRiT12548.
T43482.
RefSeqiNP_005984.3. NM_005993.4. [Q9BTW9-1]
UniGeneiHs.464391.

Genome annotation databases

EnsembliENST00000355528; ENSP00000347719; ENSG00000141556. [Q9BTW9-1]
GeneIDi6904.
KEGGihsa:6904.
UCSCiuc002kfz.4. human. [Q9BTW9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTBCD_HUMAN
AccessioniPrimary (citable) accession number: Q9BTW9
Secondary accession number(s): O95458
, Q7L8K1, Q8IXP6, Q8NAX0, Q8WYH4, Q96E74, Q9UF82, Q9UG46, Q9Y2J3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: May 18, 2010
Last modified: September 27, 2017
This is version 143 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families