Khdc3
entrez
66991
canonical
uniprot
Q9CWU5
canonical
ensembl
ENSMUSG00000092622
resolver
ensp
ENSMUSP00000034737
resolver
ensp
ENSMUSP00000133915
resolver
genesymbol
Khdc3
resolver
uniprot
A7YIL2
resolver
uniprot
Q9CRD6
resolver
uniprot_entry
KHDC3_MOUSE
resolver
uniprot_sec
A7YIL2
resolver
uniprot_sec
Q9CRD6
resolver
amino_acid_sequence
MASLKRFQTLVPLDHKQGTLFEIIGEPKLPKWFHVECLEDPKRLYVEPRLLEIMFGKDGEHIPHLESMLHTLIHVNVWGPERRAEIWIFGPPPFRRDVDRMLTDLAHYCRMKLMEIEALEAGVERRRMAAHKAATQPAPVKVREAAPRPASVKVPETATQPAPVKVREAAPQPAPVQEVREAAPQQASVQEEVREAATEQAPVQEVREAATEQAPVQEVSEAATEQAPVQEVNEAATEQASVQAVREAATRPAPGKVRKAATQPAPVQVCQEATQLAPVKVREAATQPASGKVREAATQLAPVKVRKAATQLAPVKVHEAATQPAPGKVSDAATQSASVQVREAATQLSPVEATDTSQLAQVKADEAFAQHTSGEAHQVANGQSPIEVCETATGQHSLDVSRALSQKCPEVFEWETQSCLDGSYVIVQPPRDAWESFIIL
uniprot
proteins
function
FUNCTION: Component of the subcortical maternal complex (SCMC), a multiprotein complex that plays a key role in early embryonic development (PubMed:18804437, PubMed:19376971, PubMed:25208553, PubMed:28992324, PubMed:29125140, PubMed:31575650, PubMed:37922900). The SCMC complex is a structural constituent of cytoplasmic lattices, which consist in fibrous structures found in the cytoplasm of oocytes and preimplantation embryos (PubMed:31575650, PubMed:37922900, PubMed:41845018, PubMed:41917274, PubMed:41986725). They are required to store maternal proteins critical for embryonic development, such as ribosomal proteins, cytoskeletal tubulins and proteins controlling epigenetic reprogramming of the preimplantation embryo, in a poised but restrained state, regulating their availability for early embryonic development (PubMed:37922900, PubMed:41845018, PubMed:41917274, PubMed:41986725). Cytoplasmic lattices also tightly control ubiquitination during the oocyte-to-embryo transition by trapping E3 ubiquitin-protein ligase UHRF1 in a compact autoinhibited conformation and maintaining SCF ubiquitin ligase complexes inactive (PubMed:41845018, PubMed:41917274, PubMed:41986725). KHDC3 ensures proper spindle assembly by regulating the localization of AURKA via RHOA signaling and of PLK1 via a RHOA-independent process (PubMed:19376971). Required for the localization of MAD2L1 to kinetochores to enable spindle assembly checkpoint function (PubMed:19376971). As part of the OOEP-KHDC3 scaffold, recruits BLM and TRIM25 to DNA replication forks, thereby promoting the ubiquitination of BLM by TRIM25, enhancing BLM retainment at replication forks and therefore promoting stalled replication fork restart (PubMed:29125140, PubMed:33115731). Regulates homologous recombination-mediated DNA repair via recruitment of RAD51 to sites of DNA double-strand breaks, and sustainment of PARP1 activity, which in turn modulates downstream ATM or ATR activation (PubMed:25936915, PubMed:33115731). Activation of ATM or ATR in response to DNA double-strand breaks may be cell-type specific (PubMed:25936915, PubMed:33115731). Its role in DNA double-strand break repair is independent of its role in restarting stalled replication forks (PubMed:29125140). Promotes neural stem cell neurogenesis and neuronal differentiation in the hippocampus (PubMed:33115731). May regulate normal development of learning, memory and anxiety (PubMed:33115731). Capable of binding RNA (PubMed:22276159). {ECO:0000269|PubMed:18804437, ECO:0000269|PubMed:19376971, ECO:0000269|PubMed:22276159, ECO:0000269|PubMed:25208553, ECO:0000269|PubMed:25936915, ECO:0000269|PubMed:28992324, ECO:0000269|PubMed:29125140, ECO:0000269|PubMed:31575650, ECO:0000269|PubMed:33115731, ECO:0000269|PubMed:37922900, ECO:0000269|PubMed:41845018, ECO:0000269|PubMed:41917274, ECO:0000269|PubMed:41986725}.
uniprot
proteins
mass_dalton
47995
uniprot
proteins
mutagenesis
MUTAGEN 151; /note="S->A: Reduces restart of stalled replication forks and cells show an increase in DNA double strand breaks. Decreases phosphorylation of ATR at 'S-428'. Reduces TRIM25 ubiquitination of BLM and subsequent localization to DNA replication forks. Reduces phosphorylation and activation of ATR. No effect on Filia distribution at replication forks or nascent DNA degradation following DNA damage. Not effect on interaction with OOEP."; /evidence="ECO:0000269|PubMed:29125140"; MUTAGEN 151; /note="S->D: No effect on localization at replication forks, nascent DNA degradation following DNA damage, restart of stalled replication forks or levels of DNA damage."; /evidence="ECO:0000269|PubMed:29125140"; MUTAGEN 349; /note="S->A: Abolishes localization to the nucleus and enhances localization to the mitochondrion. Reduces stalled replication fork restart. Abolishes ATR-mediated phosphorylation of S-151. No effect on phosphorylation and activation of ATR. No effect on localization to centrosomes or centrosome integrity."; /evidence="ECO:0000269|PubMed:25936915, ECO:0000269|PubMed:29125140"; MUTAGEN 349; /note="S->D: Abolishes DNA double-strand break repair and subsequent regulation of apoptosis. Abolishes localization to the mitochondrion. No effect on localization to centrosomes or centrosome integrity."; /evidence="ECO:0000269|PubMed:25936915
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-151 is required to promote stalled fork restart. {ECO:0000269|PubMed:29125140}.
uniprot
proteins
protein_family
KHDC1 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17913455
uniprot
proteins
pubmed
18057100
uniprot
proteins
pubmed
18804437
uniprot
proteins
pubmed
19376971
uniprot
proteins
pubmed
20823540
uniprot
proteins
pubmed
22276159
uniprot
proteins
pubmed
25208553
uniprot
proteins
pubmed
25936915
uniprot
proteins
pubmed
28992324
uniprot
proteins
pubmed
29125140
uniprot
proteins
pubmed
31575650
uniprot
proteins
pubmed
33115731
uniprot
proteins
pubmed
37922900
uniprot
proteins
pubmed
38177687
uniprot
proteins
pubmed
41845018
uniprot
proteins
pubmed
41917274
uniprot
proteins
pubmed
41986725
uniprot
proteins
sequence_length
440
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:37922900}. Cytoplasm, cell cortex {ECO:0000269|PubMed:18057100, ECO:0000269|PubMed:18804437, ECO:0000269|PubMed:25936915}. Nucleus {ECO:0000269|PubMed:25936915, ECO:0000269|PubMed:29125140, ECO:0000269|PubMed:33115731}. Mitochondrion {ECO:0000269|PubMed:25936915}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:25936915}. Chromosome {ECO:0000250|UniProtKB:Q587J8}. Note=Core component of cytoplasmic lattices in oocytes (PubMed:37922900). Expressed in the subcortex of oocytes (PubMed:25208553). Located throughout the cell cortex of ovulated eggs in a complex with NLRP5 (PubMed:18057100). After fertilization, restricted to the apical cortex and excluded from regions of cell-cell contact (PubMed:18057100). Localized to centrosomes during interphase and mitosis (PubMed:25936915). Localizes to sites of DNA double-strand break repair (By similarity). Localization to the mitochondrion during apoptosis following phosphorylation of Ser-349 (PubMed:25936915). {ECO:0000250|UniProtKB:Q587J8, ECO:0000269|PubMed:18057100, ECO:0000269|PubMed:25208553, ECO:0000269|PubMed:25936915, ECO:0000269|PubMed:37922900}.
uniprot
proteins