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Protein

Tetratricopeptide repeat protein 8

Gene

TTC8

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

Functioni

The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization.2 Publications

GO - Molecular functioni

  • RNA polymerase II repressing transcription factor binding Source: MGI

GO - Biological processi

  • cilium assembly Source: BHF-UCL
  • establishment of anatomical structure orientation Source: BHF-UCL
  • protein transport Source: UniProtKB-KW
  • sensory processing Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Cilium biogenesis/degradation, Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165533-MONOMER.
ReactomeiR-HSA-5620922. BBSome-mediated cargo-targeting to cilium.

Names & Taxonomyi

Protein namesi
Recommended name:
Tetratricopeptide repeat protein 8
Short name:
TPR repeat protein 8
Alternative name(s):
Bardet-Biedl syndrome 8 protein
Gene namesi
Name:TTC8
Synonyms:BBS8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:20087. TTC8.

Subcellular locationi

GO - Cellular componenti

  • BBSome Source: UniProtKB
  • centrosome Source: BHF-UCL
  • ciliary basal body Source: BHF-UCL
  • ciliary membrane Source: UniProtKB-SubCell
  • cilium Source: BHF-UCL
  • cytosol Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Retinitis pigmentosa 51 (RP51)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
See also OMIM:613464
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06370538 – 47Missing in RP51. 10
Bardet-Biedl syndrome 8 (BBS8)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease.
See also OMIM:615985
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017247197 – 198Missing in BBS8. 1 Publication2

Keywords - Diseasei

Bardet-Biedl syndrome, Ciliopathy, Disease mutation, Mental retardation, Obesity, Retinitis pigmentosa

Organism-specific databases

DisGeNETi123016.
MalaCardsiTTC8.
MIMi613464. phenotype.
615985. phenotype.
OpenTargetsiENSG00000165533.
Orphaneti110. Bardet-Biedl syndrome.
791. Retinitis pigmentosa.
PharmGKBiPA134877629.

Polymorphism and mutation databases

BioMutaiTTC8.
DMDMi308153511.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001063881 – 541Tetratricopeptide repeat protein 8Add BLAST541

Proteomic databases

EPDiQ8TAM2.
MaxQBiQ8TAM2.
PaxDbiQ8TAM2.
PeptideAtlasiQ8TAM2.
PRIDEiQ8TAM2.

PTM databases

iPTMnetiQ8TAM2.
PhosphoSitePlusiQ8TAM2.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000165533.
CleanExiHS_TTC8.
ExpressionAtlasiQ8TAM2. baseline and differential.
GenevisibleiQ8TAM2. HS.

Interactioni

Subunit structurei

Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with PCM1. Interacts with CCDC28B. Interacts with PKD1 (PubMed:24939912).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BBS9Q3SYG42EBI-2892638,EBI-2826852
IQCB1Q150515EBI-2892638,EBI-2805823

GO - Molecular functioni

  • RNA polymerase II repressing transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi125811. 6 interactors.
DIPiDIP-60359N.
IntActiQ8TAM2. 11 interactors.
STRINGi9606.ENSP00000370031.

Structurei

3D structure databases

ProteinModelPortaliQ8TAM2.
SMRiQ8TAM2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati14 – 47TPR 1Add BLAST34
Repeati251 – 284TPR 2Add BLAST34
Repeati285 – 317TPR 3Add BLAST33
Repeati318 – 351TPR 4Add BLAST34
Repeati352 – 385TPR 5Add BLAST34
Repeati386 – 419TPR 6Add BLAST34
Repeati423 – 456TPR 7Add BLAST34
Repeati457 – 490TPR 8Add BLAST34

Sequence similaritiesi

Contains 8 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG1129. Eukaryota.
ENOG410Z814. LUCA.
GeneTreeiENSGT00530000063455.
HOVERGENiHBG044570.
InParanoidiQ8TAM2.
KOiK16781.
PhylomeDBiQ8TAM2.
TreeFamiTF314892.

Family and domain databases

Gene3Di1.25.40.10. 3 hits.
InterProiIPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PfamiPF13176. TPR_7. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 8 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 3 hits.
PROSITEiPS50005. TPR. 6 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8TAM2-1) [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
MSSEMEPLLL AWSYFRRRKF QLCADLCTQM LEKSPYDQEP DPELPVHQAA
60 70 80 90 100
WILKARALTE MVYIDEIDVD QEGIAEMMLD ENAIAQVPRP GTSLKLPGTN
110 120 130 140 150
QTGGPSQAVR PITQAGRPIT GFLRPSTQSG RPGTMEQAIR TPRTAYTARP
160 170 180 190 200
ITSSSGRFVR LGTASMLTSP DGPFINLSRL NLTKYSQKPK LAKALFEYIF
210 220 230 240 250
HHENDVKTIH LEDVVLHLGI YPFLLRNKNH IEKNALDLAA LSTEHSQYKD
260 270 280 290 300
WWWKVQIGKC YYRLGMYREA EKQFKSALKQ QEMVDTFLYL AKVYVSLDQP
310 320 330 340 350
VTALNLFKQG LDKFPGEVTL LCGIARIYEE MNNMSSAAEY YKEVLKQDNT
360 370 380 390 400
HVEAIACIGS NHFYSDQPEI ALRFYRRLLQ MGIYNGQLFN NLGLCCFYAQ
410 420 430 440 450
QYDMTLTSFE RALSLAENEE EAADVWYNLG HVAVGIGDTN LAHQCFRLAL
460 470 480 490 500
VNNNNHAEAY NNLAVLEMRK GHVEQARALL QTASSLAPHM YEPHFNFATI
510 520 530 540
SDKIGDLQRS YVAAQKSEAA FPDHVDTQHL IKQLRQHFAM L
Note: No experimental confirmation available.
Length:541
Mass (Da):61,534
Last modified:October 5, 2010 - v2
Checksum:i013CFB0FDEBF385B
GO
Isoform 2 (identifier: Q8TAM2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     39-329: Missing.

Note: No experimental confirmation available.
Show »
Length:250
Mass (Da):28,704
Checksum:iCBA3587C05459CF2
GO
Isoform 3 (identifier: Q8TAM2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     164-193: Missing.
     209-234: Missing.

Show »
Length:485
Mass (Da):55,125
Checksum:i7328CE9A99FC630B
GO
Isoform 4 (identifier: Q8TAM2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     209-234: Missing.

Show »
Length:515
Mass (Da):58,427
Checksum:i26ADB39CA21EA677
GO
Isoform 5 (identifier: Q8TAM2-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     194-196: ALF → VCT
     197-541: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Show »
Length:196
Mass (Da):21,712
Checksum:iCCD7B057CE734AE8
GO

Sequence cautioni

The sequence CAD61928 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
The sequence CAD62360 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti177L → I in BAG54067 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06370538 – 47Missing in RP51. 10
Natural variantiVAR_017247197 – 198Missing in BBS8. 1 Publication2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00782139 – 329Missing in isoform 2. 1 PublicationAdd BLAST291
Alternative sequenceiVSP_007822164 – 193Missing in isoform 3. 3 PublicationsAdd BLAST30
Alternative sequenceiVSP_041151194 – 196ALF → VCT in isoform 5. 1 Publication3
Alternative sequenceiVSP_041152197 – 541Missing in isoform 5. 1 PublicationAdd BLAST345
Alternative sequenceiVSP_007823209 – 234Missing in isoform 3 and isoform 4. 6 PublicationsAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY366523 mRNA. Translation: AAR02192.1.
AY366524 mRNA. Translation: AAR02193.1.
BX161472 mRNA. Translation: CAD61928.1. Sequence problems.
BX248071 mRNA. Translation: CAD62360.1. Different initiation.
BX248248 mRNA. Translation: CAD62576.1.
AY373972 mRNA. Translation: AAR19043.1.
AK124675 mRNA. Translation: BAG54067.1.
AL833901 mRNA. Translation: CAD38757.2.
AL121768 Genomic DNA. No translation available.
AL133238 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81400.1.
CH471061 Genomic DNA. Translation: EAW81402.1.
BC001563 mRNA. Translation: AAH01563.1.
BC026351 mRNA. Translation: AAH26351.1.
BC095433 mRNA. Translation: AAH95433.1.
CCDSiCCDS32137.1. [Q8TAM2-4]
RefSeqiNP_001275710.1. NM_001288781.1.
NP_001275711.1. NM_001288782.1.
NP_001275712.1. NM_001288783.1.
NP_653197.2. NM_144596.3. [Q8TAM2-4]
NP_938051.1. NM_198309.3.
NP_938052.1. NM_198310.3.
XP_006720098.1. XM_006720035.1.
XP_006720100.1. XM_006720037.2.
XP_011534734.1. XM_011536432.1.
UniGeneiHs.303055.

Genome annotation databases

EnsembliENST00000345383; ENSP00000339486; ENSG00000165533. [Q8TAM2-4]
ENST00000354441; ENSP00000346427; ENSG00000165533. [Q8TAM2-2]
ENST00000380656; ENSP00000370031; ENSG00000165533. [Q8TAM2-4]
GeneIDi123016.
KEGGihsa:123016.
UCSCiuc001xxi.5. human. [Q8TAM2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY366523 mRNA. Translation: AAR02192.1.
AY366524 mRNA. Translation: AAR02193.1.
BX161472 mRNA. Translation: CAD61928.1. Sequence problems.
BX248071 mRNA. Translation: CAD62360.1. Different initiation.
BX248248 mRNA. Translation: CAD62576.1.
AY373972 mRNA. Translation: AAR19043.1.
AK124675 mRNA. Translation: BAG54067.1.
AL833901 mRNA. Translation: CAD38757.2.
AL121768 Genomic DNA. No translation available.
AL133238 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81400.1.
CH471061 Genomic DNA. Translation: EAW81402.1.
BC001563 mRNA. Translation: AAH01563.1.
BC026351 mRNA. Translation: AAH26351.1.
BC095433 mRNA. Translation: AAH95433.1.
CCDSiCCDS32137.1. [Q8TAM2-4]
RefSeqiNP_001275710.1. NM_001288781.1.
NP_001275711.1. NM_001288782.1.
NP_001275712.1. NM_001288783.1.
NP_653197.2. NM_144596.3. [Q8TAM2-4]
NP_938051.1. NM_198309.3.
NP_938052.1. NM_198310.3.
XP_006720098.1. XM_006720035.1.
XP_006720100.1. XM_006720037.2.
XP_011534734.1. XM_011536432.1.
UniGeneiHs.303055.

3D structure databases

ProteinModelPortaliQ8TAM2.
SMRiQ8TAM2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125811. 6 interactors.
DIPiDIP-60359N.
IntActiQ8TAM2. 11 interactors.
STRINGi9606.ENSP00000370031.

PTM databases

iPTMnetiQ8TAM2.
PhosphoSitePlusiQ8TAM2.

Polymorphism and mutation databases

BioMutaiTTC8.
DMDMi308153511.

Proteomic databases

EPDiQ8TAM2.
MaxQBiQ8TAM2.
PaxDbiQ8TAM2.
PeptideAtlasiQ8TAM2.
PRIDEiQ8TAM2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345383; ENSP00000339486; ENSG00000165533. [Q8TAM2-4]
ENST00000354441; ENSP00000346427; ENSG00000165533. [Q8TAM2-2]
ENST00000380656; ENSP00000370031; ENSG00000165533. [Q8TAM2-4]
GeneIDi123016.
KEGGihsa:123016.
UCSCiuc001xxi.5. human. [Q8TAM2-1]

Organism-specific databases

CTDi123016.
DisGeNETi123016.
GeneCardsiTTC8.
GeneReviewsiTTC8.
H-InvDBHIX0011874.
HGNCiHGNC:20087. TTC8.
MalaCardsiTTC8.
MIMi608132. gene.
613464. phenotype.
615985. phenotype.
neXtProtiNX_Q8TAM2.
OpenTargetsiENSG00000165533.
Orphaneti110. Bardet-Biedl syndrome.
791. Retinitis pigmentosa.
PharmGKBiPA134877629.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1129. Eukaryota.
ENOG410Z814. LUCA.
GeneTreeiENSGT00530000063455.
HOVERGENiHBG044570.
InParanoidiQ8TAM2.
KOiK16781.
PhylomeDBiQ8TAM2.
TreeFamiTF314892.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165533-MONOMER.
ReactomeiR-HSA-5620922. BBSome-mediated cargo-targeting to cilium.

Miscellaneous databases

GeneWikiiTTC8.
GenomeRNAii123016.
PROiQ8TAM2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165533.
CleanExiHS_TTC8.
ExpressionAtlasiQ8TAM2. baseline and differential.
GenevisibleiQ8TAM2. HS.

Family and domain databases

Gene3Di1.25.40.10. 3 hits.
InterProiIPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PfamiPF13176. TPR_7. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 8 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 3 hits.
PROSITEiPS50005. TPR. 6 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTTC8_HUMAN
AccessioniPrimary (citable) accession number: Q8TAM2
Secondary accession number(s): A6NFG2
, B3KWA5, Q67B97, Q86SY0, Q86TV9, Q86U26, Q8NDH9, Q96DG8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2003
Last sequence update: October 5, 2010
Last modified: November 30, 2016
This is version 149 of the entry and version 2 of the sequence. [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 14
    Human chromosome 14: 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.