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KHDC3_RAT
ID   KHDC3_RAT               Reviewed;         434 AA.
AC   D3ZVV1;
DT   03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT   20-APR-2010, sequence version 1.
DT   03-AUG-2022, entry version 66.
DE   RecName: Full=KH domain-containing protein 3 {ECO:0000250|UniProtKB:Q587J8};
DE   AltName: Full=Protein Filia {ECO:0000250|UniProtKB:Q9CWU5};
GN   Name=Khdc3 {ECO:0000312|RGD:1311617};
GN   Synonyms=Ecat1 {ECO:0000303|PubMed:17913455};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   IDENTIFICATION.
RX   PubMed=17913455; DOI=10.1016/j.ygeno.2007.06.003;
RA   Pierre A., Gautier M., Callebaut I., Bontoux M., Jeanpierre E.,
RA   Pontarotti P., Monget P.;
RT   "Atypical structure and phylogenomic evolution of the new eutherian
RT   oocyte- and embryo-expressed KHDC1/DPPA5/ECAT1/OOEP gene family.";
RL   Genomics 90:583-594(2007).
CC   -!- FUNCTION: As part of the OOEP-KHDC3 scaffold, recruits BLM and TRIM25
CC       to DNA replication forks, thereby promoting the ubiquitination of BLM
CC       by TRIM25, enhancing BLM retainment at replication forks and therefore
CC       promoting stalled replication fork restart (By similarity). Regulates
CC       homologous recombination-mediated DNA repair via recruitment of RAD51
CC       to sites of DNA double-strand breaks, and sustainment of PARP1
CC       activity, which in turn modulates downstream ATM activation (By
CC       similarity). Activation of ATM or ATR in response to DNA double-strand
CC       breaks may be cell-type specific (By similarity). Its role in DNA
CC       double-strand break repair is independent of its role in restarting
CC       stalled replication forks (By similarity). As a member of the
CC       subcortical maternal complex (SCMC), plays an essential role for
CC       zygotes to progress beyond the first embryonic cell divisions via
CC       regulation of actin dynamics (By similarity). Required for maintenance
CC       of euploidy during cleavage-stage embryogenesis (By similarity).
CC       Required for the formation of F-actin cytoplasmic lattices in oocytes
CC       which in turn are responsible for symmetric division of zygotes via the
CC       regulation of mitotic spindle formation and positioning (By
CC       similarity). Ensures proper spindle assembly by regulating the
CC       localization of AURKA via RHOA signaling and of PLK1 via a RHOA-
CC       independent process (By similarity). Required for the localization of
CC       MAD2L1 to kinetochores to enable spindle assembly checkpoint function
CC       (By similarity). Promotes neural stem cell neurogenesis and neuronal
CC       differentiation in the hippocampus (By similarity). May regulate normal
CC       development of learning, memory and anxiety (By similarity). Capable of
CC       binding RNA (By similarity). {ECO:0000250|UniProtKB:Q9CWU5}.
CC   -!- SUBUNIT: Component of the subcortical maternal complex (SCMC), at least
CC       composed of NLRP5, KHDC3, OOEP, and TLE6 (By similarity). Within the
CC       complex, interacts with NLRP5, KHDC3 and TLE6 (By similarity). The SCMC
CC       may facilitate translocation of its components between the nuclear and
CC       cytoplasmic compartments (By similarity). Forms a scaffold complex with
CC       OOEP/FLOPED, and interacts with BLM and TRIM25 at DNA replication forks
CC       (By similarity). Interacts with PARP1; the interaction is increased
CC       following the formation of DNA double-strand breaks (By similarity).
CC       Interacts (via C-terminus) with NUMA1 (By similarity).
CC       {ECO:0000250|UniProtKB:Q587J8, ECO:0000250|UniProtKB:Q9CWU5}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC       {ECO:0000250|UniProtKB:Q9CWU5}. Nucleus {ECO:0000250|UniProtKB:Q9CWU5}.
CC       Mitochondrion {ECO:0000250|UniProtKB:Q9CWU5}. Cytoplasm, cytoskeleton,
CC       microtubule organizing center, centrosome
CC       {ECO:0000250|UniProtKB:Q9CWU5}. Chromosome
CC       {ECO:0000250|UniProtKB:Q587J8}. Note=Localized to centrosomes during
CC       interphase and mitosis (By similarity). Localizes to sites of DNA
CC       double-strand break repair (By similarity).
CC       {ECO:0000250|UniProtKB:Q587J8, ECO:0000250|UniProtKB:Q9CWU5}.
CC   -!- DOMAIN: Contains 1 atypical KH domain. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the KHDC1 family. {ECO:0000305}.
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DR   EMBL; CH474041; EDL84106.1; -; Genomic_DNA.
DR   RefSeq; NP_001100307.1; NM_001106837.1.
DR   AlphaFoldDB; D3ZVV1; -.
DR   SMR; D3ZVV1; -.
DR   STRING; 10116.ENSRNOP00000032705; -.
DR   PaxDb; D3ZVV1; -.
DR   Ensembl; ENSRNOT00000113238; ENSRNOP00000088813; ENSRNOG00000054460.
DR   GeneID; 300826; -.
DR   KEGG; rno:300826; -.
DR   UCSC; RGD:1311617; rat.
DR   CTD; 66991; -.
DR   RGD; 1311617; Khdc3.
DR   eggNOG; ENOG502QQIF; Eukaryota.
DR   GeneTree; ENSGT00940000162601; -.
DR   HOGENOM; CLU_050702_0_0_1; -.
DR   InParanoid; D3ZVV1; -.
DR   OMA; AVWRADY; -.
DR   OrthoDB; 913590at2759; -.
DR   PhylomeDB; D3ZVV1; -.
DR   TreeFam; TF338690; -.
DR   PRO; PR:D3ZVV1; -.
DR   Proteomes; UP000002494; Chromosome 8.
DR   Proteomes; UP000234681; Chromosome 8.
DR   Bgee; ENSRNOG00000054460; Expressed in thymus and 4 other tissues.
DR   GO; GO:0045179; C:apical cortex; ISO:RGD.
DR   GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR   GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR   GO; GO:0106333; C:subcortical maternal complex; ISO:RGD.
DR   GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR   GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR   GO; GO:0051656; P:establishment of organelle localization; ISS:UniProtKB.
DR   GO; GO:0090307; P:mitotic spindle assembly; ISO:RGD.
DR   GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:1900006; P:positive regulation of dendrite development; ISS:UniProtKB.
DR   GO; GO:2000781; P:positive regulation of double-strand break repair; ISS:UniProtKB.
DR   GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR   GO; GO:0040019; P:positive regulation of embryonic development; ISS:UniProtKB.
DR   GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR   GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
DR   GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR   CDD; cd12795; FILIA_N_like; 1.
DR   Gene3D; 3.30.1370.10; -; 1.
DR   InterPro; IPR036612; KH_dom_type_1_sf.
DR   InterPro; IPR031952; MOEP19_KH-like.
DR   Pfam; PF16005; MOEP19; 1.
PE   3: Inferred from homology;
KW   Cell cycle; Chromosome; Cytoplasm; Cytoskeleton; Developmental protein;
KW   Mitochondrion; Nucleus; Phosphoprotein; Reference proteome.
FT   CHAIN           1..434
FT                   /note="KH domain-containing protein 3"
FT                   /id="PRO_0000407379"
FT   DOMAIN          40..118
FT                   /note="KH; atypical"
FT   REGION          1..39
FT                   /note="Involved in RNA binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q9CWU5"
FT   REGION          334..434
FT                   /note="Required for interaction with NUMA1 and regulation
FT                   of apoptosis in response to DNA damage"
FT                   /evidence="ECO:0000250|UniProtKB:Q9CWU5"
FT   MOD_RES         267
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q587J8"
FT   MOD_RES         279
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q587J8"
SQ   SEQUENCE   434 AA;  47179 MW;  8A0F47AF5AF819AB CRC64;
     MATLKTFRTL VQLKHKLGKA YEIVGEPRLP KWFHVEYLED PKKMYVEPTL VEIMFGKDGE
     HIPHVECTLH VLIHVNVWGP EKQAEILIFG PPNFQKDVAQ MLSNVAHFCR MKLMEKEALE
     AGVERRLMAA SKATTQPTPV KVRDAATQVA PVQVRDAAIQ PAPVKVRDAA TQVAPVQVHE
     VATQPVPVQV RDAATQPVPV RVRDAATQPV PVRVRDAATQ PVPVRVRDAA TQPVPVRVRD
     AATEPVPVQV RDAATQPAPV QVRDAATQPA PVQVRDAATQ PAPVQVRDAA TQPAPVQVRD
     AATQPAPVQV RDAATQPAPV QVRDAATQPA PVQVREAATQ QTPVEVADDT QLVQLKAGEA
     FAQHTSGKVH QDVNGQSPIE VCEGATQRHS VDASEALSQK CPEDLEGGDT ETSLDDSYVI
     IRPSRAVWEP FVML
 
 
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