CXD4_HUMAN
ID CXD4_HUMAN Reviewed; 370 AA.
AC Q96KN9; Q8N2R7;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Gap junction delta-4 protein;
DE AltName: Full=Connexin-40.1;
DE Short=Cx40.1;
GN Name=GJD4; Synonyms=CX40.1;
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 [MRNA].
RX PubMed=12108537; DOI=10.1515/bc.2002.076;
RA Willecke K., Eiberger J., Degen J., Eckardt D., Romualdi A., Guldenagel M.,
RA Deutsch U., Soehl G.;
RT "Structural and functional diversity of connexin genes in the mouse and
RT human genome.";
RL Biol. Chem. 383:725-737(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12881038; DOI=10.1080/15419060302063;
RA Soehl G., Nielsen P.A., Eiberger J., Willecke K.;
RT "Expression profiles of the novel human connexin genes hCx30.2, hCx40.1,
RT and hCx62 differ from their putative mouse orthologues.";
RL Cell Commun. Adhes. 10:27-36(2003).
RN [6]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-269 AND ARG-271.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: One gap junction consists of a cluster of closely packed
CC pairs of transmembrane channels, the connexons, through which materials
CC of low MW diffuse from one cell to a neighboring cell. {ECO:0000250}.
CC -!- SUBUNIT: A connexon is composed of a hexamer of connexins.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Cell junction, gap junction {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in pancreas, kidney, skeletal muscle,
CC liver, placenta, and heart. {ECO:0000269|PubMed:12881038}.
CC -!- SIMILARITY: Belongs to the connexin family. Delta-type subfamily.
CC {ECO:0000305}.
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DR EMBL; AJ414564; CAC93846.1; -; mRNA.
DR EMBL; AK074504; BAC11028.1; -; mRNA.
DR EMBL; AL121749; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW85910.1; -; Genomic_DNA.
DR CCDS; CCDS7191.1; -.
DR RefSeq; NP_699199.2; NM_153368.2.
DR AlphaFoldDB; Q96KN9; -.
DR SMR; Q96KN9; -.
DR BioGRID; 128574; 19.
DR STRING; 9606.ENSP00000315070; -.
DR TCDB; 1.A.24.1.8; the gap junction-forming connexin (connexin) family.
DR iPTMnet; Q96KN9; -.
DR PhosphoSitePlus; Q96KN9; -.
DR BioMuta; GJD4; -.
DR DMDM; 74751985; -.
DR jPOST; Q96KN9; -.
DR MassIVE; Q96KN9; -.
DR PaxDb; Q96KN9; -.
DR PeptideAtlas; Q96KN9; -.
DR PRIDE; Q96KN9; -.
DR Antibodypedia; 26696; 48 antibodies from 13 providers.
DR DNASU; 219770; -.
DR Ensembl; ENST00000321660.2; ENSP00000315070.1; ENSG00000177291.4.
DR GeneID; 219770; -.
DR KEGG; hsa:219770; -.
DR MANE-Select; ENST00000321660.2; ENSP00000315070.1; NM_153368.3; NP_699199.2.
DR UCSC; uc001iyy.1; human.
DR CTD; 219770; -.
DR DisGeNET; 219770; -.
DR GeneCards; GJD4; -.
DR HGNC; HGNC:23296; GJD4.
DR HPA; ENSG00000177291; Not detected.
DR MIM; 611922; gene.
DR neXtProt; NX_Q96KN9; -.
DR OpenTargets; ENSG00000177291; -.
DR PharmGKB; PA162389714; -.
DR VEuPathDB; HostDB:ENSG00000177291; -.
DR eggNOG; ENOG502QWIV; Eukaryota.
DR GeneTree; ENSGT01050000244962; -.
DR HOGENOM; CLU_037388_3_0_1; -.
DR InParanoid; Q96KN9; -.
DR OMA; KIWLIFM; -.
DR OrthoDB; 721800at2759; -.
DR PhylomeDB; Q96KN9; -.
DR TreeFam; TF329606; -.
DR PathwayCommons; Q96KN9; -.
DR Reactome; R-HSA-190861; Gap junction assembly.
DR BioGRID-ORCS; 219770; 15 hits in 1061 CRISPR screens.
DR ChiTaRS; GJD4; human.
DR GeneWiki; GJD4; -.
DR GenomeRNAi; 219770; -.
DR Pharos; Q96KN9; Tdark.
DR PRO; PR:Q96KN9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96KN9; protein.
DR Bgee; ENSG00000177291; Expressed in apex of heart and 29 other tissues.
DR Genevisible; Q96KN9; HS.
DR GO; GO:0005922; C:connexin complex; IEA:InterPro.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005243; F:gap junction channel activity; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central.
DR GO; GO:0014717; P:regulation of satellite cell activation involved in skeletal muscle regeneration; IEA:Ensembl.
DR Gene3D; 1.20.1440.80; -; 1.
DR InterPro; IPR000500; Connexin.
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; 2.
DR Pfam; PF00029; Connexin; 1.
DR PRINTS; PR00206; CONNEXIN.
DR SMART; SM00037; CNX; 1.
DR SMART; SM01089; Connexin_CCC; 1.
DR PROSITE; PS00407; CONNEXINS_1; 1.
DR PROSITE; PS00408; CONNEXINS_2; 1.
PE 2: Evidence at transcript level;
KW Cell junction; Cell membrane; Gap junction; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..370
FT /note="Gap junction delta-4 protein"
FT /id="PRO_0000312991"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 20..40
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 41..76
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 168..196
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 197..217
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 218..370
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 224..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..260
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 285..301
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..323
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 90
FT /note="A -> V (in dbSNP:rs35398622)"
FT /id="VAR_047626"
FT VARIANT 269
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_037640"
FT VARIANT 271
FT /note="G -> R (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs773395724)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_037641"
FT CONFLICT 205
FT /note="S -> G (in Ref. 2; BAC11028)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 370 AA; 40140 MW; CD49F31743A7F7C2 CRC64;
MEGVDLLGFL IITLNCNVTM VGKLWFVLTM LLRMLVIVLA GRPVYQDEQE RFVCNTLQPG
CANVCYDVFS PVSHLRFWLI QGVCVLLPSA VFSVYVLHRG ATLAALGPRR CPDPREPASG
QRRCPRPFGE RGGLQVPDFS AGYIIHLLLR TLLEAAFGAL HYFLFGFLAP KKFPCTRPPC
TGVVDCYVSR PTEKSLLMLF LWAVSALSFL LGLADLVCSL RRRMRRRPGP PTSPSIRKQS
GASGHAEGRR TDEEGGREEE GAPAPPGARA GGEGAGSPRR TSRVSGHTKI PDEDESEVTS
SASEKLGRQP RGRPHREAAQ DPRGSGSEEQ PSAAPSRLAA PPSCSSLQPP DPPASSSGAP
HLRARKSEWV
