CXA8_CHICK
ID CXA8_CHICK Reviewed; 400 AA.
AC P36381; Q92144;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Gap junction alpha-8 protein;
DE AltName: Full=Connexin-45.6 {ECO:0000303|PubMed:8049527};
DE Short=Cx45.6;
GN Name=GJA8;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Lens;
RX PubMed=8049527; DOI=10.1091/mbc.5.3.363;
RA Jiang J.X., White T.W., Goodenough D.A., Paul D.L.;
RT "Molecular cloning and functional characterization of chick lens fiber
RT connexin 45.6.";
RL Mol. Biol. Cell 5:363-373(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-236.
RC TISSUE=Lens fibers;
RX PubMed=8840185;
RA Sawada K., Agata K., Eguchi G.;
RT "Characterization of terminally differentiated cell state by categorizing
RT cDNA clones derived from chicken lens fibers.";
RL Int. J. Dev. Biol. 40:531-535(1996).
RN [3]
RP PHOSPHORYLATION AT SER-364, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP MUTAGENESIS OF SER-364.
RX PubMed=10702244; DOI=10.1074/jbc.275.10.6850;
RA Yin X., Jedrzejewski P.T., Jiang J.X.;
RT "Casein kinase II phosphorylates lens connexin 45.6 and is involved in its
RT degradation.";
RL J. Biol. Chem. 275:6850-6856(2000).
RN [4]
RP PHOSPHORYLATION AT SER-364, CLEAVAGE SITE, AND MUTAGENESIS OF ASP-365 AND
RP GLU-368.
RX PubMed=11448971; DOI=10.1074/jbc.m106073200;
RA Yin X., Gu S., Jiang J.X.;
RT "The development-associated cleavage of lens connexin 45.6 by caspase-3-
RT like protease is regulated by casein kinase II-mediated phosphorylation.";
RL J. Biol. Chem. 276:34567-34572(2001).
RN [5]
RP INTERACTION WITH MIP.
RX PubMed=14762116; DOI=10.1242/jcs.00945;
RA Yu X.S., Jiang J.X.;
RT "Interaction of major intrinsic protein (aquaporin-0) with fiber connexins
RT in lens development.";
RL J. Cell Sci. 117:871-880(2004).
CC -!- FUNCTION: Structural component of eye lens gap junctions
CC (PubMed:8049527). Gap junctions are dodecameric channels that connect
CC the cytoplasm of adjoining cells. They are formed by the docking of two
CC hexameric hemichannels, one from each cell membrane (By similarity).
CC Small molecules and ions diffuse from one cell to a neighboring cell
CC via the central pore (PubMed:8049527). {ECO:0000250|UniProtKB:P55917,
CC ECO:0000269|PubMed:8049527}.
CC -!- SUBUNIT: A hemichannel or connexon is composed of a hexamer of
CC connexins. A functional gap junction is formed by the apposition of two
CC hemichannels. Forms heteromeric channels with GJA3 (By similarity).
CC During early stages of lens development, interacts with the C-terminus
CC of MIP (PubMed:14762116). {ECO:0000250|UniProtKB:P55917,
CC ECO:0000269|PubMed:14762116}.
CC -!- INTERACTION:
CC P36381; P28238: MIP; NbExp=11; IntAct=EBI-867402, EBI-867385;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8049527};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P55917}. Cell
CC junction, gap junction {ECO:0000305|PubMed:8049527}.
CC -!- PTM: Proteolytically cleaved by caspase-3 during lens development.
CC {ECO:0000269|PubMed:11448971}.
CC -!- PTM: Phosphorylated on Ser-364; which inhibits cleavage by caspase-3.
CC {ECO:0000269|PubMed:10702244, ECO:0000269|PubMed:11448971}.
CC -!- SIMILARITY: Belongs to the connexin family. Alpha-type (group II)
CC subfamily. {ECO:0000305}.
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DR EMBL; L24799; AAA57134.1; -; Genomic_DNA.
DR EMBL; D26333; BAA05381.1; -; mRNA.
DR PIR; I50219; I50219.
DR RefSeq; NP_990328.1; NM_204997.1.
DR AlphaFoldDB; P36381; -.
DR SMR; P36381; -.
DR IntAct; P36381; 1.
DR STRING; 9031.ENSGALP00000036053; -.
DR iPTMnet; P36381; -.
DR PaxDb; P36381; -.
DR PRIDE; P36381; -.
DR GeneID; 395846; -.
DR KEGG; gga:395846; -.
DR CTD; 2703; -.
DR VEuPathDB; HostDB:geneid_395846; -.
DR eggNOG; ENOG502QV1K; Eukaryota.
DR InParanoid; P36381; -.
DR OrthoDB; 814925at2759; -.
DR PhylomeDB; P36381; -.
DR PRO; PR:P36381; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005922; C:connexin complex; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005243; F:gap junction channel activity; ISS:UniProtKB.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:1990349; P:gap junction-mediated intercellular transport; ISS:UniProtKB.
DR Gene3D; 1.20.1440.80; -; 1.
DR InterPro; IPR000500; Connexin.
DR InterPro; IPR002266; Connexin50.
DR InterPro; IPR019570; Connexin_CCC.
DR InterPro; IPR017990; Connexin_CS.
DR InterPro; IPR013092; Connexin_N.
DR InterPro; IPR038359; Connexin_N_sf.
DR PANTHER; PTHR11984; PTHR11984; 1.
DR PANTHER; PTHR11984:SF19; PTHR11984:SF19; 1.
DR Pfam; PF00029; Connexin; 1.
DR Pfam; PF03509; Connexin50; 1.
DR PRINTS; PR00206; CONNEXIN.
DR PRINTS; PR01137; CONNEXINA8.
DR SMART; SM00037; CNX; 1.
DR SMART; SM01089; Connexin_CCC; 1.
DR PROSITE; PS00407; CONNEXINS_1; 1.
DR PROSITE; PS00408; CONNEXINS_2; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Disulfide bond; Gap junction; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT CHAIN 2..400
FT /note="Gap junction alpha-8 protein"
FT /id="PRO_0000057833"
FT INTRAMEM 2..12
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT TOPO_DOM 13..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT TOPO_DOM 43..71
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT TOPO_DOM 93..156
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT TOPO_DOM 178..205
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT TOPO_DOM 227..400
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 104..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 323..400
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..122
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..348
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 383..400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 368..369
FT /note="Cleavage; by caspase-3"
FT MOD_RES 364
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:10702244,
FT ECO:0000269|PubMed:11448971"
FT DISULFID 54..196
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT DISULFID 61..190
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT DISULFID 65..185
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT MUTAGEN 364
FT /note="S->A: Prevents degradation."
FT /evidence="ECO:0000269|PubMed:10702244"
FT MUTAGEN 365
FT /note="D->A: Prevents cleavage by caspase-3."
FT /evidence="ECO:0000269|PubMed:11448971"
FT MUTAGEN 368
FT /note="E->A: Prevents cleavage by caspase-3."
FT /evidence="ECO:0000269|PubMed:11448971"
FT MUTAGEN 368
FT /note="E->D: Increases cleavage by caspase-3."
FT /evidence="ECO:0000269|PubMed:11448971"
FT CONFLICT 146..147
FT /note="EG -> DL (in Ref. 2; BAA05381)"
FT /evidence="ECO:0000305"
FT CONFLICT 188..189
FT /note="WP -> D (in Ref. 2; BAA05381)"
FT /evidence="ECO:0000305"
FT CONFLICT 234..236
FT /note="IRR -> SEL (in Ref. 2; BAA05381)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 400 AA; 45616 MW; 6B380599F37C0856 CRC64;
MGDWSFLGNI LEQVNEQSTV IGRVWLTVLF IFRILILGTA AELVWGDEQS DFVCNTQQPG
CENVCYDEAF PISHIRLWVL QIIFVSTPSL VYFGHAVHHV RMEEKRKERE EAERRQQAEV
DEEKLPLAPN QNKGNNPDGT KKFRLEGTLL RTYILHIIFK TLFEVGFIVG QYFLYGFRIL
PLYRCGRWPC PNLVDCFVSR PTEKTIFIMF MLVVAAVSLF LNLVEISHLI LKRIRRALRR
PAEEQMGEVP EKPLHAIAVS SIPKAKGYKL LEEEKPVSHY FPLTEVGVEP SPLPSAFNEF
EEKIGMGPLE DLSRAFDERL PSYAQAKEPE EEKVKAEEEE EQEEEQQAPQ EEPGVKKAEE
EVVSDEVEGP SAPAELATDV RSLSRLSKAS SRARSDDLTV
