UniProt: Q8TAM2 | HGNC:20087 | Gene: TTC8 (synonym BBS8) | 541 aa | Chr 14
TTC8/BBS8 is a tetratricopeptide-repeat (TPR) superhelical protein and one of the eight
core subunits of the BBSome (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, BBIP10/BBIP1).
The BBSome is a coat-like, octameric adaptor that traffics specific membrane/signaling
proteins (GPCRs and other cargo) into and out of the primary cilium, coupled to intraflagellar
transport (IFT) and the small GTPase ARL6/BBS3. It also cooperates with the Rab8 GEF
Rabin8/RAB3IP to promote ciliary membrane biogenesis. Loss of function causes Bardet–Biedl
syndrome type 8 (BBS8, MIM:615985) and nonsyndromic retinitis pigmentosa 51 (RP51, MIM:613464).
BBSome subunit / coat for ciliary trafficking: The BBSome is a complex of seven highly
conserved BBS proteins (later eight, with BBIP10) that localizes to centriolar satellites in
the cytoplasm and to the ciliary membrane; required for ciliogenesis but dispensable for
centriolar satellite function. PMID:17574030 BBS8/TTC8 is one of the
identified subunits (by MS) in that paper. The BBSome's ciliogenic function involves the Rab8
GEF (Rabin8/RAB3IP) at the basal body. PMID:17574030
BBIP10/BBSome paper confirms TTC8 as subunit, ciliary localization: PMID:19081074.
ComplexPortal curated this annotation (BBSome part_of; ciliary membrane IDA).
BBS8 cloning, ciliary/basal body localization, situs defects: PMID:14520415. This supports cilium, centrosome, basal body localization (all IDA),
PCM1 interaction (IPI), and the left-right asymmetry / establishment of structure orientation
phenotype (IMP, GO:0048560).
LZTFL1 regulates BBSome ciliary trafficking: BBSome (incl. TTC8) cytoplasmic localization
and ciliary trafficking; LZTFL1 controls SMO and BBSome ciliary entry. PMID:22072986 Supports cytoplasm (EXP) and
BBSome/SHH-pathway role.
NPHP5/Cep290 regulate BBSome integrity; BBS8 interacts with NPHP5/IQCB1: Depletion of
Cep290 causes dissociation/loss of ciliary BBS8. PMID:25552655 BBS8–IQCB1(NPHP5) interaction is
the basis of the IPI protein-binding annotation (WITH UniProtKB:Q15051) and an IntAct entry.
AZI1/CEP131 (Q9UPN4) interacts with BBS4, regulates BBSome trafficking: PMID:24550735
BBSome IDA and a TTC8–CEP131 IPI (WITH Q9UPN4).
PKD1 interaction / ciliary trafficking of polycystin-1: BBS1 and BBS3 regulate ciliary
trafficking of PKD1; TTC8 IPI annotations WITH P98161(PKD1), Q8N3I7, Q8NFJ9, Q96RK4. PMID:24939912
CCDC28B interaction: BBS8 interacts with CCDC28B (Q9BUN5) in oligogenic BBS epistasis
study. PMID:16327777 Basis of IPI (WITH Q9BUN5).
Transcriptional regulation (BBS7-centric): BBS7 has a nuclear role and interacts with the
PcG member RNF2; "our data supports a similar role for other BBS proteins." PMID:22302990 The TTC8 IPI annotation to
RNA Pol II transcription factor binding (GO:0061629, WITH RNF2/Q99496, assigned by MGI) derives
from this. The abstract foregrounds BBS7; full text reportedly assays additional BBS proteins.
Treat as peripheral/non-core, not a core MF.
PCM1 recruitment / DISC1-BBS4: PMID:18762586 is primarily about PCM1 recruitment by DISC1
and BBS4; the TTC8 IPI (WITH PCM1/Q9NRI5, assigned SYSCILIA_CCNET) reflects the BBS8–PCM1
interaction (consistent with PMID:14520415).
BBSome assembly chaperonins: BBS6/BBS10/BBS12 + CCT/TRiC mediate BBSome assembly; TTC8 is a
BBSome component (IDA). PMID:20080638
Mitochondrion (HTP): PMID:34800366 is a high-throughput human mitochondrial proteome study.
TTC8 is a cytoplasmic/ciliary BBSome subunit; a single HTP hit in a mito-proteome screen is most
plausibly a contaminant/co-purification, not a genuine mitochondrial localization. Not core.
Five isoforms (Q8TAM2-1..-6). A retina-specific exon is important in photoreceptors; a splice-site
mutation in a retina-specific exon causes nonsyndromic RP51 [UniProt; PMID:20451172]. GOA
annotations are not isoform-tagged, so no isoform field is added per-annotation.
protein binding (GO:0005515) IPI entries: uninformative MF per guidelines; keep but mark as