CXA8_HUMAN
ID CXA8_HUMAN Reviewed; 433 AA.
AC P48165; A7L5M5; Q5VVN9; Q9NP25;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Gap junction alpha-8 protein;
DE AltName: Full=Connexin-50;
DE Short=Cx50 {ECO:0000303|PubMed:7796604};
DE AltName: Full=Lens fiber protein MP70 {ECO:0000303|PubMed:7796604};
GN Name=GJA8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lens;
RX PubMed=7796604; DOI=10.3109/02713689509033517;
RA Church R.L., Wang J.-H., Steele E.;
RT "The human lens intrinsic membrane protein MP70 (Cx50) gene: clonal
RT analysis and chromosome mapping.";
RL Curr. Eye Res. 14:215-221(1995).
RN [2]
RP ERRATUM OF PUBMED:7796604.
RX PubMed=8549164; DOI=10.3109/02713689508995138;
RA Church R.L., Wang J.-H., Steele E.;
RL Curr. Eye Res. 14:979-981(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Mackay D., Shiels A.;
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CTRCT1 GLY-64.
RA Zheng J.Q., Ma Z.W., Sun H.M., Lin Y., Liu P., Fu S.B., Liu S.W.;
RT "A novel mutation in GJA8 associated with autosomal dominant congenital
RT cataract in a family in the Northeast of China.";
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP VARIANT CTRCT1 SER-88.
RX PubMed=9497259; DOI=10.1086/301762;
RA Shiels A., Mackay D., Ionides A., Berry V., Moore A., Bhattacharya S.;
RT "A missense mutation in the human connexin50 gene (GJA8) underlies
RT autosomal dominant 'zonular pulverulent' cataract, on chromosome 1q.";
RL Am. J. Hum. Genet. 62:526-532(1998).
RN [7]
RP VARIANT CTRCT1 LYS-48.
RX PubMed=10480374; DOI=10.1007/s004399900094;
RA Berry V., Mackay D., Khaliq S., Francis P.J., Hameed A., Anwar K.,
RA Mehdi S.Q., Newbold R.J., Ionides A., Shiels A., Moore T.,
RA Bhattacharya S.S.;
RT "Connexin 50 mutation in a family with congenital 'zonular nuclear'
RT pulverulent cataract of Pakistani origin.";
RL Hum. Genet. 105:168-170(1999).
RN [8]
RP VARIANT MET-247, AND INVOLVEMENT IN CTRCT1.
RX PubMed=11846744; DOI=10.1034/j.1399-0004.2001.600614.x;
RA Polyakov A.V., Shagina I.A., Khlebnikova O.V., Evgrafov O.V.;
RT "Mutation in the connexin 50 gene (GJA8) in a Russian family with zonular
RT pulverulent cataract.";
RL Clin. Genet. 60:476-478(2001).
RN [9]
RP VARIANT CTRCT1 THR-23.
RX PubMed=14627691; DOI=10.1136/jmg.40.11.e124;
RA Willoughby C.E., Arab S., Gandhi R., Zeinali S., Arab S., Luk D.,
RA Billingsley G., Munier F.L., Heon E.;
RT "A novel GJA8 mutation in an Iranian family with progressive autosomal
RT dominant congenital nuclear cataract.";
RL J. Med. Genet. 40:E124-E124(2003).
RN [10]
RP VARIANT CTRCT1 GLY-64.
RX PubMed=16234473; DOI=10.1136/bjo.2005.075184;
RA Ma Z.W., Zheng J.Q., Li J., Li X.R., Tang X., Yuan X.Y., Zhang X.M.,
RA Sun H.M.;
RT "Two novel mutations of connexin genes in Chinese families with autosomal
RT dominant congenital nuclear cataract.";
RL Br. J. Ophthalmol. 89:1535-1537(2005).
RN [11]
RP ERRATUM OF PUBMED:16234473.
RA Ma Z.W., Zheng J.Q., Li J., Li X.R., Tang X., Yuan X.Y., Zhang X.M.,
RA Sun H.M.;
RL Br. J. Ophthalmol. 90:125-125(2006).
RN [12]
RP VARIANTS CTRCT1 GLU-44 AND GLN-198.
RX PubMed=16604058;
RA Devi R.R., Vijayalakshmi P.;
RT "Novel mutations in GJA8 associated with autosomal dominant congenital
RT cataract and microcornea.";
RL Mol. Vis. 12:190-195(2006).
RN [13]
RP VARIANT CTRCT1 ASN-47, CHARACTERIZATION OF VARIANT CTRCT1 ASN-47, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=18006672; DOI=10.1136/jmg.2007.051029;
RA Arora A., Minogue P.J., Liu X., Addison P.K., Russel-Eggitt I.,
RA Webster A.R., Hunt D.M., Ebihara L., Beyer E.C., Berthoud V.M., Moore A.T.;
RT "A novel connexin50 mutation associated with congenital nuclear pulverulent
RT cataracts.";
RL J. Med. Genet. 45:155-160(2008).
RN [14]
RP VARIANT CTRCT1 PHE-73.
RX PubMed=19182255; DOI=10.1167/iovs.08-3149;
RA Hansen L., Mikkelsen A., Nuernberg P., Nuernberg G., Anjum I., Eiberg H.,
RA Rosenberg T.;
RT "Comprehensive mutational screening in a cohort of Danish families with
RT hereditary congenital cataract.";
RL Invest. Ophthalmol. Vis. Sci. 50:3291-3303(2009).
RN [15]
RP VARIANT MET-247, CHARACTERIZATION OF VARIANT MET-247, FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19756179;
RA Graw J., Schmidt W., Minogue P.J., Rodriguez J., Tong J.J., Klopp N.,
RA Illig T., Ebihara L., Berthoud V.M., Beyer E.C.;
RT "The GJA8 allele encoding CX50I247M is a rare polymorphism, not a cataract-
RT causing mutation.";
RL Mol. Vis. 15:1881-1885(2009).
RN [16]
RP VARIANTS CTRCT1 ARG-39 AND ARG-46.
RX PubMed=21686328;
RA Sun W., Xiao X., Li S., Guo X., Zhang Q.;
RT "Mutational screening of six genes in Chinese patients with congenital
RT cataract and microcornea.";
RL Mol. Vis. 17:1508-1513(2011).
RN [17]
RP VARIANT CTRCT1 ASN-47.
RX PubMed=21921990;
RA Wang L., Luo Y., Wen W., Zhang S., Lu Y.;
RT "Another evidence for a D47N mutation in GJA8 associated with autosomal
RT dominant congenital cataract.";
RL Mol. Vis. 17:2380-2385(2011).
RN [18]
RP VARIANT CTRCT1 ASN-47, AND CHARACTERIZATION OF VARIANT CTRCT1 ASN-47.
RX PubMed=21174522; DOI=10.3109/13816810.2010.535886;
RA He W., Li X., Chen J., Xu L., Zhang F., Dai Q., Cui H., Wang D.M., Yu J.,
RA Hu S., Lu S.;
RT "Genetic linkage analyses and Cx50 mutation detection in a large multiplex
RT Chinese family with hereditary nuclear cataract.";
RL Ophthalmic Genet. 32:48-53(2011).
RN [19]
RP VARIANTS CTRCT1 GLY-67 AND CYS-76, AND VARIANT MET-247.
RX PubMed=23508780; DOI=10.1007/s00439-013-1289-0;
RA Reis L.M., Tyler R.C., Muheisen S., Raggio V., Salviati L., Han D.P.,
RA Costakos D., Yonath H., Hall S., Power P., Semina E.V.;
RT "Whole exome sequencing in dominant cataract identifies a new causative
RT factor, CRYBA2, and a variety of novel alleles in known genes.";
RL Hum. Genet. 132:761-770(2013).
RN [20]
RP VARIANT CTRCT1 ASN-47, AND SUBCELLULAR LOCATION.
RX PubMed=26004348; DOI=10.3892/mmr.2015.3819;
RA Liang C., Liang H., Yang Y., Ping L., Jie Q.;
RT "Mutation analysis of two families with inherited congenital cataracts.";
RL Mol. Med. Report. 12:3469-3475(2015).
RN [21]
RP VARIANTS CTRCT1 ARG-25; SER-45 AND LYS-162.
RX PubMed=28839118; DOI=10.1534/g3.117.300109;
RA Javadiyan S., Craig J.E., Souzeau E., Sharma S., Lower K.M., Mackey D.A.,
RA Staffieri S.E., Elder J.E., Taranath D., Straga T., Black J., Pater J.,
RA Casey T., Hewitt A.W., Burdon K.P.;
RT "High-Throughput Genetic Screening of 51 Pediatric Cataract Genes
RT Identifies Causative Mutations in Inherited Pediatric Cataract in South
RT Eastern Australia.";
RL G3 (Bethesda) 7:3257-3268(2017).
RN [22]
RP VARIANT CTRCT1 GLU-118.
RX PubMed=28690483; DOI=10.1159/000471992;
RA Patel R., Zenith R.K., Chandra A., Ali A.;
RT "Novel Mutations in the Crystallin Gene in Age-Related Cataract Patients
RT from a North Indian Population.";
RL Mol. Syndromol. 8:179-186(2017).
CC -!- FUNCTION: Structural component of eye lens gap junctions
CC (PubMed:18006672, PubMed:19756179). Gap junctions are dodecameric
CC channels that connect the cytoplasm of adjoining cells. They are formed
CC by the docking of two hexameric hemichannels, one from each cell
CC membrane (By similarity). Small molecules and ions diffuse from one
CC cell to a neighboring cell via the central pore (PubMed:18006672,
CC PubMed:19756179). {ECO:0000250|UniProtKB:P55917,
CC ECO:0000269|PubMed:18006672, ECO:0000269|PubMed:19756179}.
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.
CC {ECO:0000250|UniProtKB:P55917}.
CC -!- INTERACTION:
CC P48165; P00519-2: ABL1; NbExp=3; IntAct=EBI-17458373, EBI-9254597;
CC P48165; O00590: ACKR2; NbExp=3; IntAct=EBI-17458373, EBI-13379418;
CC P48165; P02652: APOA2; NbExp=3; IntAct=EBI-17458373, EBI-1171525;
CC P48165; P05090: APOD; NbExp=3; IntAct=EBI-17458373, EBI-715495;
CC P48165; O95236-2: APOL3; NbExp=3; IntAct=EBI-17458373, EBI-11976321;
CC P48165; P55087: AQP4; NbExp=3; IntAct=EBI-17458373, EBI-10104898;
CC P48165; Q8N6S5: ARL6IP6; NbExp=3; IntAct=EBI-17458373, EBI-2808844;
CC P48165; Q99437: ATP6V0B; NbExp=3; IntAct=EBI-17458373, EBI-3904417;
CC P48165; O14523: C2CD2L; NbExp=3; IntAct=EBI-17458373, EBI-12822627;
CC P48165; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-17458373, EBI-9083477;
CC P48165; P13236: CCL4; NbExp=3; IntAct=EBI-17458373, EBI-2873970;
CC P48165; P19397: CD53; NbExp=3; IntAct=EBI-17458373, EBI-6657396;
CC P48165; Q9H5X1: CIAO2A; NbExp=3; IntAct=EBI-17458373, EBI-752069;
CC P48165; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-17458373, EBI-12256978;
CC P48165; O14493: CLDN4; NbExp=3; IntAct=EBI-17458373, EBI-9316372;
CC P48165; Q8NC01: CLEC1A; NbExp=3; IntAct=EBI-17458373, EBI-11996768;
CC P48165; Q9NWW5: CLN6; NbExp=3; IntAct=EBI-17458373, EBI-6165897;
CC P48165; Q5RI15: COX20; NbExp=3; IntAct=EBI-17458373, EBI-2834035;
CC P48165; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-17458373, EBI-12019274;
CC P48165; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-17458373, EBI-2680384;
CC P48165; P78329: CYP4F2; NbExp=3; IntAct=EBI-17458373, EBI-1752413;
CC P48165; Q5J5C9: DEFB121; NbExp=3; IntAct=EBI-17458373, EBI-10244198;
CC P48165; Q9UPQ8: DOLK; NbExp=3; IntAct=EBI-17458373, EBI-8645574;
CC P48165; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-17458373, EBI-10976398;
CC P48165; P37268: FDFT1; NbExp=3; IntAct=EBI-17458373, EBI-714550;
CC P48165; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-17458373, EBI-713304;
CC P48165; Q8WWP7: GIMAP1; NbExp=3; IntAct=EBI-17458373, EBI-11991950;
CC P48165; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-17458373, EBI-6166686;
CC P48165; P29033: GJB2; NbExp=3; IntAct=EBI-17458373, EBI-3905204;
CC P48165; Q9NPR9: GPR108; NbExp=3; IntAct=EBI-17458373, EBI-11343451;
CC P48165; Q8TDV0: GPR151; NbExp=3; IntAct=EBI-17458373, EBI-11955647;
CC P48165; Q9BZJ8: GPR61; NbExp=3; IntAct=EBI-17458373, EBI-12808020;
CC P48165; Q02747: GUCA2A; NbExp=3; IntAct=EBI-17458373, EBI-12244272;
CC P48165; P24593: IGFBP5; NbExp=3; IntAct=EBI-17458373, EBI-720480;
CC P48165; Q9Y5U4: INSIG2; NbExp=3; IntAct=EBI-17458373, EBI-8503746;
CC P48165; P11215: ITGAM; NbExp=3; IntAct=EBI-17458373, EBI-2568251;
CC P48165; P43628: KIR2DL3; NbExp=3; IntAct=EBI-17458373, EBI-8632435;
CC P48165; Q86VI4: LAPTM4B; NbExp=3; IntAct=EBI-17458373, EBI-3267258;
CC P48165; O43561-2: LAT; NbExp=3; IntAct=EBI-17458373, EBI-8070286;
CC P48165; O95214: LEPROTL1; NbExp=3; IntAct=EBI-17458373, EBI-750776;
CC P48165; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-17458373, EBI-2820517;
CC P48165; P21145: MAL; NbExp=3; IntAct=EBI-17458373, EBI-3932027;
CC P48165; Q13021: MALL; NbExp=3; IntAct=EBI-17458373, EBI-750078;
CC P48165; Q9P0N8: MARCHF2; NbExp=3; IntAct=EBI-17458373, EBI-10317612;
CC P48165; O43934: MFSD11; NbExp=3; IntAct=EBI-17458373, EBI-17633886;
CC P48165; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-17458373, EBI-2858252;
CC P48165; Q99735: MGST2; NbExp=3; IntAct=EBI-17458373, EBI-11324706;
CC P48165; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-17458373, EBI-12070086;
CC P48165; Q53FV1: ORMDL2; NbExp=3; IntAct=EBI-17458373, EBI-11075081;
CC P48165; Q7RTS6: OTOP2; NbExp=3; IntAct=EBI-17458373, EBI-7642372;
CC P48165; Q9BPV8: P2RY13; NbExp=3; IntAct=EBI-17458373, EBI-17459480;
CC P48165; Q9UHJ9-5: PGAP2; NbExp=3; IntAct=EBI-17458373, EBI-12092917;
CC P48165; P26678: PLN; NbExp=3; IntAct=EBI-17458373, EBI-692836;
CC P48165; Q01453: PMP22; NbExp=3; IntAct=EBI-17458373, EBI-2845982;
CC P48165; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-17458373, EBI-8652812;
CC P48165; O60831: PRAF2; NbExp=3; IntAct=EBI-17458373, EBI-2506064;
CC P48165; Q8NFJ6: PROKR2; NbExp=3; IntAct=EBI-17458373, EBI-12902928;
CC P48165; Q16849-3: PTPRN; NbExp=3; IntAct=EBI-17458373, EBI-10200782;
CC P48165; Q96P65: QRFPR; NbExp=3; IntAct=EBI-17458373, EBI-12820497;
CC P48165; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-17458373, EBI-14065960;
CC P48165; Q8N8N0: RNF152; NbExp=3; IntAct=EBI-17458373, EBI-2129725;
CC P48165; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-17458373, EBI-8636004;
CC P48165; Q8TDU9: RXFP4; NbExp=3; IntAct=EBI-17458373, EBI-9519524;
CC P48165; Q9H228: S1PR5; NbExp=3; IntAct=EBI-17458373, EBI-2564169;
CC P48165; Q14162: SCARF1; NbExp=3; IntAct=EBI-17458373, EBI-12056025;
CC P48165; O75396: SEC22B; NbExp=3; IntAct=EBI-17458373, EBI-1058865;
CC P48165; Q9BRL7: SEC22C; NbExp=3; IntAct=EBI-17458373, EBI-10297029;
CC P48165; Q15436: SEC23A; NbExp=3; IntAct=EBI-17458373, EBI-81088;
CC P48165; P11686: SFTPC; NbExp=3; IntAct=EBI-17458373, EBI-10197617;
CC P48165; Q13183: SLC13A2; NbExp=3; IntAct=EBI-17458373, EBI-17460043;
CC P48165; Q86YT5: SLC13A5; NbExp=3; IntAct=EBI-17458373, EBI-12002412;
CC P48165; Q6ZSM3: SLC16A12; NbExp=3; IntAct=EBI-17458373, EBI-17460560;
CC P48165; Q7RTY0: SLC16A13; NbExp=3; IntAct=EBI-17458373, EBI-12243266;
CC P48165; O15427: SLC16A3; NbExp=3; IntAct=EBI-17458373, EBI-7600166;
CC P48165; Q99726: SLC30A3; NbExp=3; IntAct=EBI-17458373, EBI-10294651;
CC P48165; Q96G79: SLC35A4; NbExp=3; IntAct=EBI-17458373, EBI-12363689;
CC P48165; Q5T1Q4: SLC35F1; NbExp=3; IntAct=EBI-17458373, EBI-13365456;
CC P48165; Q8N357: SLC35F6; NbExp=3; IntAct=EBI-17458373, EBI-713484;
CC P48165; Q969I6: SLC38A4; NbExp=3; IntAct=EBI-17458373, EBI-17459810;
CC P48165; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-17458373, EBI-10314552;
CC P48165; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-17458373, EBI-12898013;
CC P48165; Q92504: SLC39A7; NbExp=3; IntAct=EBI-17458373, EBI-1051105;
CC P48165; Q9NUM3: SLC39A9; NbExp=3; IntAct=EBI-17458373, EBI-2823239;
CC P48165; Q9NWF4: SLC52A1; NbExp=3; IntAct=EBI-17458373, EBI-12904614;
CC P48165; Q6ZP29-3: SLC66A1; NbExp=3; IntAct=EBI-17458373, EBI-12889586;
CC P48165; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-17458373, EBI-3907610;
CC P48165; P57103-7: SLC8A3; NbExp=3; IntAct=EBI-17458373, EBI-17459901;
CC P48165; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-17458373, EBI-8640191;
CC P48165; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-17458373, EBI-12188413;
CC P48165; P61266: STX1B; NbExp=3; IntAct=EBI-17458373, EBI-9071709;
CC P48165; Q9UNK0: STX8; NbExp=3; IntAct=EBI-17458373, EBI-727240;
CC P48165; C9JKN6: THSD7B; NbExp=3; IntAct=EBI-17458373, EBI-17192156;
CC P48165; P55061: TMBIM6; NbExp=3; IntAct=EBI-17458373, EBI-1045825;
CC P48165; Q9NV29: TMEM100; NbExp=3; IntAct=EBI-17458373, EBI-8644968;
CC P48165; Q6UX40: TMEM107; NbExp=3; IntAct=EBI-17458373, EBI-12845616;
CC P48165; Q9BTD3: TMEM121; NbExp=3; IntAct=EBI-17458373, EBI-12155101;
CC P48165; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-17458373, EBI-10694905;
CC P48165; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-17458373, EBI-348587;
CC P48165; Q6ZP80: TMEM182; NbExp=3; IntAct=EBI-17458373, EBI-10255122;
CC P48165; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-17458373, EBI-11528917;
CC P48165; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-17458373, EBI-10315004;
CC P48165; Q9BU79: TMEM243; NbExp=3; IntAct=EBI-17458373, EBI-12887458;
CC P48165; Q69YG0: TMEM42; NbExp=3; IntAct=EBI-17458373, EBI-12038591;
CC P48165; Q9NWC5: TMEM45A; NbExp=3; IntAct=EBI-17458373, EBI-10823938;
CC P48165; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-17458373, EBI-2852148;
CC P48165; Q6PI78: TMEM65; NbExp=3; IntAct=EBI-17458373, EBI-6656213;
CC P48165; A0PK05: TMEM72; NbExp=3; IntAct=EBI-17458373, EBI-12878352;
CC P48165; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-17458373, EBI-2548832;
CC P48165; Q86UF1: TSPAN33; NbExp=3; IntAct=EBI-17458373, EBI-12045841;
CC P48165; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-17458373, EBI-10243654;
CC P48165; Q9GZX9: TWSG1; NbExp=3; IntAct=EBI-17458373, EBI-10304067;
CC P48165; O00124: UBXN8; NbExp=3; IntAct=EBI-17458373, EBI-1993850;
CC P48165; Q86WB7-2: UNC93A; NbExp=3; IntAct=EBI-17458373, EBI-13356252;
CC P48165; O75841: UPK1B; NbExp=3; IntAct=EBI-17458373, EBI-12237619;
CC P48165; O95183: VAMP5; NbExp=3; IntAct=EBI-17458373, EBI-10191195;
CC P48165; O95070: YIF1A; NbExp=3; IntAct=EBI-17458373, EBI-2799703;
CC P48165; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-17458373, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18006672,
CC ECO:0000269|PubMed:19756179, ECO:0000269|PubMed:26004348}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P55917}. Cell junction, gap
CC junction {ECO:0000269|PubMed:18006672, ECO:0000269|PubMed:19756179}.
CC -!- TISSUE SPECIFICITY: Eye lens. {ECO:0000269|PubMed:19756179}.
CC -!- DISEASE: Cataract 1, multiple types (CTRCT1) [MIM:116200]: An
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may be
CC static or progressive. CTRCT1 includes congenital, zonular pulverulent,
CC nuclear progressive, nuclear pulverulent, nuclear total, total, and
CC posterior subcapsular types of cataract. Zonular or lamellar cataracts
CC are opacities, broad or narrow, usually consisting of powdery white
CC dots affecting only certain layers or zones between the cortex and
CC nucleus of an otherwise clear lens. The opacity may be so dense as to
CC render the entire central region of the lens completely opaque, or so
CC translucent that vision is hardly if at all impeded. Zonular cataracts
CC generally do not involve the embryonic nucleus, though sometimes they
CC involve the fetal nucleus. Usually sharply separated from a clear
CC cortex outside them, they may have projections from their outer edges
CC known as riders or spokes. In some cases cataract is associated with
CC microcornea without any other systemic anomaly or dysmorphism.
CC Microcornea is defined by a corneal diameter inferior to 10 mm in both
CC meridians in an otherwise normal eye. {ECO:0000269|PubMed:10480374,
CC ECO:0000269|PubMed:11846744, ECO:0000269|PubMed:14627691,
CC ECO:0000269|PubMed:16234473, ECO:0000269|PubMed:16604058,
CC ECO:0000269|PubMed:18006672, ECO:0000269|PubMed:19182255,
CC ECO:0000269|PubMed:21174522, ECO:0000269|PubMed:21686328,
CC ECO:0000269|PubMed:21921990, ECO:0000269|PubMed:23508780,
CC ECO:0000269|PubMed:26004348, ECO:0000269|PubMed:28690483,
CC ECO:0000269|PubMed:28839118, ECO:0000269|PubMed:9497259,
CC ECO:0000269|Ref.4}. Note=The disease is caused by variants affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the connexin family. Alpha-type (group II)
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Eye disease Gap junction protein, alpha 8 (GJA8);
CC Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/GJA8";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U34802; AAA77062.1; -; Genomic_DNA.
DR EMBL; AF217524; AAF32309.1; -; Genomic_DNA.
DR EMBL; EF672108; ABS11172.1; -; Genomic_DNA.
DR EMBL; AL445591; CAH72387.1; -; Genomic_DNA.
DR CCDS; CCDS30834.1; -.
DR PIR; I39176; I39176.
DR RefSeq; NP_005258.2; NM_005267.4.
DR RefSeq; XP_011507718.1; XM_011509416.1.
DR AlphaFoldDB; P48165; -.
DR SMR; P48165; -.
DR BioGRID; 108970; 174.
DR IntAct; P48165; 119.
DR STRING; 9606.ENSP00000358238; -.
DR TCDB; 1.A.24.1.5; the gap junction-forming connexin (connexin) family.
DR iPTMnet; P48165; -.
DR PhosphoSitePlus; P48165; -.
DR BioMuta; GJA8; -.
DR DMDM; 13124697; -.
DR EPD; P48165; -.
DR MassIVE; P48165; -.
DR PaxDb; P48165; -.
DR PeptideAtlas; P48165; -.
DR PRIDE; P48165; -.
DR ProteomicsDB; 55868; -.
DR Antibodypedia; 33981; 258 antibodies from 27 providers.
DR DNASU; 2703; -.
DR Ensembl; ENST00000369235.2; ENSP00000358238.1; ENSG00000121634.6.
DR GeneID; 2703; -.
DR KEGG; hsa:2703; -.
DR MANE-Select; ENST00000369235.2; ENSP00000358238.1; NM_005267.5; NP_005258.2.
DR CTD; 2703; -.
DR DisGeNET; 2703; -.
DR GeneCards; GJA8; -.
DR GeneReviews; GJA8; -.
DR HGNC; HGNC:4281; GJA8.
DR HPA; ENSG00000121634; Tissue enriched (testis).
DR MalaCards; GJA8; -.
DR MIM; 116200; phenotype.
DR MIM; 600897; gene.
DR neXtProt; NX_P48165; -.
DR OpenTargets; ENSG00000121634; -.
DR Orphanet; 1377; Cataract-microcornea syndrome.
DR Orphanet; 98991; Early-onset nuclear cataract.
DR Orphanet; 98985; Early-onset sutural cataract.
DR Orphanet; 91490; Isolated congenital sclerocornea.
DR Orphanet; 98984; Pulverulent cataract.
DR Orphanet; 98994; Total early-onset cataract.
DR PharmGKB; PA28692; -.
DR VEuPathDB; HostDB:ENSG00000121634; -.
DR eggNOG; ENOG502QV1K; Eukaryota.
DR GeneTree; ENSGT01050000244864; -.
DR HOGENOM; CLU_037388_0_0_1; -.
DR InParanoid; P48165; -.
DR OMA; MYVGHAV; -.
DR OrthoDB; 814925at2759; -.
DR PhylomeDB; P48165; -.
DR TreeFam; TF329606; -.
DR PathwayCommons; P48165; -.
DR Reactome; R-HSA-190861; Gap junction assembly.
DR SignaLink; P48165; -.
DR BioGRID-ORCS; 2703; 10 hits in 1061 CRISPR screens.
DR GeneWiki; GJA8; -.
DR GenomeRNAi; 2703; -.
DR Pharos; P48165; Tbio.
DR PRO; PR:P48165; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P48165; protein.
DR Bgee; ENSG00000121634; Expressed in left testis and 16 other tissues.
DR ExpressionAtlas; P48165; baseline and differential.
DR Genevisible; P48165; HS.
DR GO; GO:0005922; C:connexin complex; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005243; F:gap junction channel activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central.
DR GO; GO:1990349; P:gap junction-mediated intercellular transport; IDA:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl.
DR GO; GO:1902551; P:regulation of catalase activity; IEA:Ensembl.
DR GO; GO:1903282; P:regulation of glutathione peroxidase activity; IEA:Ensembl.
DR GO; GO:0032645; P:regulation of granulocyte macrophage colony-stimulating factor production; IEA:Ensembl.
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 Cataract; Cell junction; Cell membrane; Disease variant; Disulfide bond;
KW Gap junction; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT CHAIN 2..433
FT /note="Gap junction alpha-8 protein"
FT /id="PRO_0000057830"
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..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT TOPO_DOM 176..203
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT TOPO_DOM 225..433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 110..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 329..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 119..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 342..390
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 54..194
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT DISULFID 61..188
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT DISULFID 65..183
FT /evidence="ECO:0000250|UniProtKB:P55917"
FT VARIANT 23
FT /note="R -> T (in CTRCT1; nuclear progressive cataract;
FT dbSNP:rs80358203)"
FT /evidence="ECO:0000269|PubMed:14627691"
FT /id="VAR_038797"
FT VARIANT 25
FT /note="W -> R (in CTRCT1; unknown pathological
FT significance; dbSNP:rs1114167309)"
FT /evidence="ECO:0000269|PubMed:28839118"
FT /id="VAR_084810"
FT VARIANT 39
FT /note="T -> R (in CTRCT1; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:21686328"
FT /id="VAR_084811"
FT VARIANT 44
FT /note="V -> E (in CTRCT1; cataract with microcornea;
FT dbSNP:rs80358204)"
FT /evidence="ECO:0000269|PubMed:16604058"
FT /id="VAR_038798"
FT VARIANT 45
FT /note="W -> S (in CTRCT1; unknown pathological
FT significance; dbSNP:rs864309688)"
FT /evidence="ECO:0000269|PubMed:28839118"
FT /id="VAR_084812"
FT VARIANT 46
FT /note="G -> R (in CTRCT1; unknown pathological
FT significance; dbSNP:rs1553242554)"
FT /evidence="ECO:0000269|PubMed:21686328"
FT /id="VAR_084813"
FT VARIANT 47
FT /note="D -> N (in CTRCT1; unknown pathological
FT significance; abolishes localization to the plasma membrane
FT and function; dbSNP:rs121434643)"
FT /evidence="ECO:0000269|PubMed:18006672,
FT ECO:0000269|PubMed:21174522, ECO:0000269|PubMed:21921990,
FT ECO:0000269|PubMed:26004348"
FT /id="VAR_069579"
FT VARIANT 48
FT /note="E -> K (in CTRCT1; zonular pulverulent;
FT dbSNP:rs80358201)"
FT /evidence="ECO:0000269|PubMed:10480374"
FT /id="VAR_038799"
FT VARIANT 64
FT /note="V -> G (in CTRCT1; zonular pulverulent and nuclear
FT progressive cataract)"
FT /evidence="ECO:0000269|PubMed:16234473, ECO:0000269|Ref.4"
FT /id="VAR_037642"
FT VARIANT 67
FT /note="D -> G (in CTRCT1)"
FT /evidence="ECO:0000269|PubMed:23508780"
FT /id="VAR_070021"
FT VARIANT 73
FT /note="S -> F (in CTRCT1)"
FT /evidence="ECO:0000269|PubMed:19182255"
FT /id="VAR_084814"
FT VARIANT 76
FT /note="R -> C (in CTRCT1)"
FT /evidence="ECO:0000269|PubMed:23508780"
FT /id="VAR_070022"
FT VARIANT 88
FT /note="P -> S (in CTRCT1; zonular pulverulent;
FT dbSNP:rs80358200)"
FT /evidence="ECO:0000269|PubMed:9497259"
FT /id="VAR_002005"
FT VARIANT 118
FT /note="A -> E (in CTRCT1; unknown pathological
FT significance; dbSNP:rs782306193)"
FT /evidence="ECO:0000269|PubMed:28690483"
FT /id="VAR_084815"
FT VARIANT 162
FT /note="E -> K (in CTRCT1; unknown pathological
FT significance; dbSNP:rs1114167310)"
FT /evidence="ECO:0000269|PubMed:28839118"
FT /id="VAR_084816"
FT VARIANT 198
FT /note="R -> Q (in CTRCT1; cataract with microcornea;
FT dbSNP:rs80358205)"
FT /evidence="ECO:0000269|PubMed:16604058"
FT /id="VAR_038800"
FT VARIANT 247
FT /note="I -> M (likely benign variant; does not affect gap
FT junctions formation and gap junctional currents;
FT dbSNP:rs80358202)"
FT /evidence="ECO:0000269|PubMed:11846744,
FT ECO:0000269|PubMed:19756179, ECO:0000269|PubMed:23508780"
FT /id="VAR_038801"
FT CONFLICT 110..111
FT /note="EA -> D (in Ref. 1; AAA77062)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 433 AA; 48229 MW; D2BF6CD1C8768636 CRC64;
MGDWSFLGNI LEEVNEHSTV IGRVWLTVLF IFRILILGTA AEFVWGDEQS DFVCNTQQPG
CENVCYDEAF PISHIRLWVL QIIFVSTPSL MYVGHAVHYV RMEEKRKSRE AEELGQQAGT
NGGPDQGSVK KSSGSKGTKK FRLEGTLLRT YICHIIFKTL FEVGFIVGHY FLYGFRILPL
YRCSRWPCPN VVDCFVSRPT EKTIFILFML SVASVSLFLN VMELGHLGLK GIRSALKRPV
EQPLGEIPEK SLHSIAVSSI QKAKGYQLLE EEKIVSHYFP LTEVGMVETS PLPAKPFNQF
EEKISTGPLG DLSRGYQETL PSYAQVGAQE VEGEGPPAEE GAEPEVGEKK EEAERLTTEE
QEKVAVPEGE KVETPGVDKE GEKEEPQSEK VSKQGLPAEK TPSLCPELTT DDARPLSRLS
KASSRARSDD LTV
