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 24-JAN-2024, entry version 156. 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}. 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; 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 PDB; 8GN7; EM; 3.00 A; A/B/G/J/M/P/S/V/Y/b=1-233. DR PDB; 8GN8; EM; 3.50 A; A/B/C/D/E=1-233. DR PDB; 8GNB; EM; 3.90 A; A/B/C/D/E/F/G/H/I/J=1-233. DR PDBsum; 8GN7; -. DR PDBsum; 8GN8; -. DR PDBsum; 8GNB; -. DR AlphaFoldDB; Q96KN9; -. DR EMDB; EMD-34156; -. DR EMDB; EMD-34157; -. DR EMDB; EMD-34159; -. 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; 9606-ENSP00000315070; -. DR PeptideAtlas; Q96KN9; -. DR Antibodypedia; 26696; 49 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 AGR; HGNC:23296; -. 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; ENSGT01090000260098; -. DR HOGENOM; CLU_037388_3_0_1; -. DR InParanoid; Q96KN9; -. DR OMA; CTRPPCT; -. DR OrthoDB; 5258334at2759; -. DR PhylomeDB; Q96KN9; -. DR TreeFam; TF329606; -. DR PathwayCommons; Q96KN9; -. DR Reactome; R-HSA-190861; Gap junction assembly. DR BioGRID-ORCS; 219770; 17 hits in 1139 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 primordial germ cell in gonad and 30 other cell types or tissues. DR GO; GO:0005922; C:connexin complex; IBA:GO_Central. 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; Gap junction channel protein cysteine-rich domain; 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; CONNEXIN; 1. DR PANTHER; PTHR11984:SF3; GAP JUNCTION DELTA-4 PROTEIN; 1. 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. DR Genevisible; Q96KN9; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell junction; Cell membrane; Gap junction; Membrane; KW Reference proteome; 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 //