Gene Ontology annotation through association of InterPro records with GO terms

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:21922595

Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia.

Human BICC1 blocks canonical Wnt signaling similar to mouse counterpart. Mutations in KH domain cause complete loss of Wnt inhibitory activity, while SAM domain mutations reduce activity by 22%.

"In mice, Bicc1 blocks canonical Wnt signaling, mostly via its SAM domain. We show that the human BICC1, similar to its mouse counterpart, blocks canonical Wnt signaling. The nonsense mutation identified results in a complete loss of Wnt inhibitory activity. The point mutation in the SAM domain has a similar effect to a complete SAM domain deletion, resulting in a 22% loss of activity."

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

BICC1 identified as RNA-binding protein through interactome capture in HeLa cells using UV crosslinking methodology.

"We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria, adding more than 300 RBPs to those previously known and shedding light on RBPs in disease, RNA-binding enzymes of intermediary metabolism, RNA-binding kinases, and RNA-binding architectures."

file:human/BICC1/BICC1-deep-research-openai.md

Deep research on BICC1 gene function (OpenAI o3-deep-research, January 2026)

BICC1 is an RNA-binding protein that acts as a translational repressor, binding specific mRNA 3'UTRs via KH domains and recruiting silencing machinery including the CCR4-NOT deadenylase complex.

"BICC1 primarily acts as a post-transcriptional regulator of gene expression. It recognizes specific RNA sequences/structures in the 3' untranslated regions (3'UTRs) of target mRNAs and typically represses their translation or reduces their stability."
BICC1 localizes to cytoplasmic P-bodies where it forms oligomeric silencing platforms through SAM domain-mediated self-polymerization.

"Endogenous BICC1 protein concentrates in discrete cytoplasmic foci that co-localize with P-body markers (e.g. GW182 and HEDLS). P-bodies are sites of mRNA storage, decay, and microRNA-mediated silencing."
BICC1 negatively regulates canonical Wnt signaling by inhibiting Dishevelled-2 (DVL2). Loss of BICC1 causes ectopic Wnt/beta-catenin activity during embryonic development.

"A study by Rothe et al. (2015) showed that BICC1 normally inhibits Dishevelled-2 (DVL2), a central Wnt signal transducer: BICC1 binds the Dvl2 mRNA or interacts with DVL2 protein complexes, and when BICC1 polymerization is disrupted, DVL2 levels and Wnt activity rise abnormally."
BICC1 is essential for kidney development and homeostasis. Loss of BICC1 causes polycystic kidney disease in mice and humans through dysregulation of PKD2 and cAMP signaling.

"BICC1 safeguards kidney tubule morphology by regulating specific mRNAs tied to epithelial differentiation and signaling. A key target is PKD2 (Polycystin-2), a Ca2+-permeable channel essential for renal tubule integrity. Wessely and colleagues (2010) discovered that BICC1 binds to and stabilizes Pkd2 mRNA, enhancing Polycystin-2 expression."
Mouse Bicc1 knockout mutants exhibit left-right patterning defects due to misregulation of Dand5 mRNA at the embryonic node.

"Mouse Bicc1 knockout or spontaneous mutants (such as jcpk and bpk alleles) exhibit left-right patterning defects - the visceral organs show random laterality due to disrupted embryonic node signaling."