PAR6A_MOUSE
ID PAR6A_MOUSE Reviewed; 346 AA.
AC Q9Z101; Q5RL03; Q6P8R2;
DT 16-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Partitioning defective 6 homolog alpha;
DE Short=PAR-6;
DE Short=PAR-6 alpha;
DE Short=PAR-6A;
GN Name=Pard6a; Synonyms=Par6a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9834192; DOI=10.1242/dev.126.1.127;
RA Hung T.-J., Kemphues K.J.;
RT "PAR-6 is a conserved PDZ domain-containing protein that colocalizes with
RT PAR-3 in Caenorhabditis elegans embryos.";
RL Development 126:127-135(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH PARD3; PRKCZ; RAC1 AND CDC42, AND SUBUNIT OF A COMPLEX
RP CONTAINING CDC42 AND PARD3.
RX PubMed=10934475; DOI=10.1038/35019582;
RA Lin D., Edwards A.S., Fawcett J.P., Mbamalu G., Scott J.D., Pawson T.;
RT "A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC
RT signalling and cell polarity.";
RL Nat. Cell Biol. 2:540-547(2000).
RN [4]
RP INTERACTION WITH MAP2K5, AND DOMAIN.
RX PubMed=12813044; DOI=10.1074/jbc.m303221200;
RA Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A.,
RA Michaelsen E., Bjoerkoey G., Johansen T.;
RT "Interaction codes within the family of mammalian Phox and Bem1p domain-
RT containing proteins.";
RL J. Biol. Chem. 278:34568-34581(2003).
RN [5]
RP INTERACTION WITH LLGL1 AND PRKCI.
RX PubMed=12629547; DOI=10.1038/ncb948;
RA Plant P.J., Fawcett J.P., Lin D.C., Holdorf A.D., Binns K., Kulkarni S.,
RA Pawson T.;
RT "A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and
RT regulates mammalian Lgl.";
RL Nat. Cell Biol. 5:301-308(2003).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [7]
RP FUNCTION IN EPITHELIAL TO MESENCHYMAL TRANSITION, INTERACTION WITH TGFBR1,
RP AND PHOSPHORYLATION.
RX PubMed=15761148; DOI=10.1126/science.1105718;
RA Ozdamar B., Bose R., Barrios-Rodiles M., Wang H.R., Zhang Y., Wrana J.L.;
RT "Regulation of the polarity protein Par6 by TGFbeta receptors controls
RT epithelial cell plasticity.";
RL Science 307:1603-1609(2005).
CC -!- FUNCTION: Adapter protein involved in asymmetrical cell division and
CC cell polarization processes. Probably involved in the formation of
CC epithelial tight junctions. Association with PARD3 may prevent the
CC interaction of PARD3 with F11R/JAM1, thereby preventing tight junction
CC assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to
CC atypical protein kinase C proteins (PubMed:15761148). Regulates
CC centrosome organization and function. Essential for the centrosomal
CC recruitment of key proteins that control centrosomal microtubule
CC organization (By similarity). {ECO:0000250|UniProtKB:Q9NPB6,
CC ECO:0000269|PubMed:15761148}.
CC -!- SUBUNIT: Interacts with ECT2 ('Thr-359' phosphorylated form) and PRKCI.
CC Interacts with PALS1 and CRB3 (By similarity). Interacts with PARD3.
CC Interacts with GTP-bound forms of CDC42, RHOQ/TC10 and RAC1. Interacts
CC with the N-terminal part of PRKCI and PRKCZ. Part of a complex with
CC PARD3, CDC42 or RAC1 and PRKCI or PRKCZ. Part of a complex with LLGL1
CC and PRKCI. Interacts with MAP2K5. Interacts with TGFBR1; involved in
CC TGF-beta induced epithelial to mesenchymal transition. Interacts with
CC DCTN1 and PCM1 (By similarity). {ECO:0000250|UniProtKB:Q9NPB6,
CC ECO:0000269|PubMed:10934475, ECO:0000269|PubMed:12629547,
CC ECO:0000269|PubMed:12813044, ECO:0000269|PubMed:15761148}.
CC -!- INTERACTION:
CC Q9Z101; O14641: DVL2; Xeno; NbExp=6; IntAct=EBI-81732, EBI-740850;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Cell junction, tight junction {ECO:0000250}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome, centriolar
CC satellite {ECO:0000250|UniProtKB:Q9NPB6}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q9NPB6}. Note=Colocalizes with GTP-bound CDC42
CC or RAC1 at membrane ruffles and with PARD3 at epithelial tight
CC junctions. Recruited to the centrosome by a microtubule and dynein-
CC dynactin-dependent mechanism. {ECO:0000250|UniProtKB:Q9NPB6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Z101-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Z101-2; Sequence=VSP_015462;
CC Name=3;
CC IsoId=Q9Z101-3; Sequence=VSP_015463;
CC -!- DOMAIN: The PB1 domain mediates interactions with MAP2K5.
CC {ECO:0000269|PubMed:12813044}.
CC -!- DOMAIN: The pseudo-CRIB domain together with the PDZ domain is required
CC for the interaction with Rho small GTPases. {ECO:0000250}.
CC -!- DOMAIN: The PDZ domain mediates the interaction with CRB3.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by the TGF-beta receptor.
CC {ECO:0000269|PubMed:15761148}.
CC -!- SIMILARITY: Belongs to the PAR6 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD15928.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF070970; AAD15928.1; ALT_FRAME; mRNA.
DR EMBL; BC049593; AAH49593.1; -; mRNA.
DR EMBL; BC061114; AAH61114.1; -; mRNA.
DR CCDS; CCDS22609.1; -. [Q9Z101-1]
DR CCDS; CCDS85600.1; -. [Q9Z101-3]
DR CCDS; CCDS85601.1; -. [Q9Z101-2]
DR RefSeq; NP_001040900.1; NM_001047435.2. [Q9Z101-2]
DR RefSeq; NP_062669.2; NM_019695.3. [Q9Z101-1]
DR AlphaFoldDB; Q9Z101; -.
DR SMR; Q9Z101; -.
DR BioGRID; 208027; 12.
DR CORUM; Q9Z101; -.
DR DIP; DIP-32553N; -.
DR IntAct; Q9Z101; 8.
DR MINT; Q9Z101; -.
DR STRING; 10090.ENSMUSP00000090886; -.
DR iPTMnet; Q9Z101; -.
DR PhosphoSitePlus; Q9Z101; -.
DR MaxQB; Q9Z101; -.
DR PaxDb; Q9Z101; -.
DR PRIDE; Q9Z101; -.
DR ProteomicsDB; 294247; -. [Q9Z101-1]
DR ProteomicsDB; 294248; -. [Q9Z101-2]
DR ProteomicsDB; 294249; -. [Q9Z101-3]
DR Antibodypedia; 4052; 294 antibodies from 33 providers.
DR DNASU; 56513; -.
DR Ensembl; ENSMUST00000093195; ENSMUSP00000090886; ENSMUSG00000005699. [Q9Z101-1]
DR Ensembl; ENSMUST00000211888; ENSMUSP00000148821; ENSMUSG00000005699. [Q9Z101-3]
DR Ensembl; ENSMUST00000212430; ENSMUSP00000148603; ENSMUSG00000005699. [Q9Z101-2]
DR GeneID; 56513; -.
DR KEGG; mmu:56513; -.
DR UCSC; uc009ndv.2; mouse. [Q9Z101-1]
DR UCSC; uc009ndx.2; mouse. [Q9Z101-3]
DR CTD; 50855; -.
DR MGI; MGI:1927223; Pard6a.
DR VEuPathDB; HostDB:ENSMUSG00000005699; -.
DR eggNOG; KOG3606; Eukaryota.
DR GeneTree; ENSGT00950000183211; -.
DR HOGENOM; CLU_040653_0_0_1; -.
DR InParanoid; Q9Z101; -.
DR OMA; SQGSPCW; -.
DR PhylomeDB; Q9Z101; -.
DR TreeFam; TF312899; -.
DR Reactome; R-MMU-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
DR Reactome; R-MMU-420029; Tight junction interactions.
DR Reactome; R-MMU-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR BioGRID-ORCS; 56513; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q9Z101; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9Z101; protein.
DR Bgee; ENSMUSG00000005699; Expressed in cerebellum lobe and 250 other tissues.
DR ExpressionAtlas; Q9Z101; baseline and differential.
DR Genevisible; Q9Z101; MM.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0044295; C:axonal growth cone; ISO:MGI.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0005938; C:cell cortex; IDA:MGI.
DR GO; GO:0030054; C:cell junction; TAS:Reactome.
DR GO; GO:0034451; C:centriolar satellite; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0120157; C:PAR polarity complex; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030742; F:GTP-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0045217; P:cell-cell junction maintenance; IDA:UniProtKB.
DR GO; GO:0007098; P:centrosome cycle; ISS:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; TAS:UniProtKB.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:1904781; P:positive regulation of protein localization to centrosome; ISS:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0060341; P:regulation of cellular localization; ISO:MGI.
DR CDD; cd06403; PB1_Par6; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR034872; PAR-6_a.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR034868; PB1_Par6.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR14102:SF9; PTHR14102:SF9; 1.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF00595; PDZ; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cell junction;
KW Cell membrane; Cytoplasm; Cytoskeleton; Membrane; Phosphoprotein;
KW Reference proteome; Tight junction.
FT CHAIN 1..346
FT /note="Partitioning defective 6 homolog alpha"
FT /id="PRO_0000112514"
FT DOMAIN 15..95
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 133..150
FT /note="Pseudo-CRIB"
FT DOMAIN 157..250
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 1..116
FT /note="Interaction with PRKCI and PRKCZ"
FT /evidence="ECO:0000250"
FT REGION 126..253
FT /note="Interaction with PARD3 and CDC42"
FT /evidence="ECO:0000250"
FT REGION 257..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NPB6"
FT VAR_SEQ 66..95
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015463"
FT VAR_SEQ 96
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015462"
FT CONFLICT 183
FT /note="P -> L (in Ref. 2; AAH61114)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 37333 MW; 8F150B83B7E1F36A CRC64;
MARPQRTPAR SPDSIVEVKS KFDAEFRRFA LPRTSVRGFQ EFSRLLCVVH QIPGLDVLLG
YTDAHGDLLP LTNDDSLHRA LASGPPPLRL LVQKRAEGDS SGLAFASNSL QRRKKGLLLR
PVAPLRTRPP LLISLPQDFR QVSSVIDVDL LPETHRRVRL HKHGSDRPLG FYIRDGMSVR
VAPQGLERVP GIFISRLVRG GLAESTGLLA VSDEILEVNG IEVAGKTLDQ VTDMMVANSH
NLIVTVKPAN QRNNVVRGAS GRLTGPSSVG PGPTDPDSDD DSSDLVIENR HPPCSNGLSQ
GPLCWDLQPG CLLPGAGSSL PSLDSREQAN SGWGNGMRGD VSGFSL
