ID HV169_HUMAN Reviewed; 117 AA. AC P01742; A0A0B4J1V5; P01760; P01761; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2016, sequence version 2. DT 16-JAN-2019, entry version 110. DE RecName: Full=Immunoglobulin heavy variable 1-69 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.6}; DE AltName: Full=Ig heavy chain V-I region EU {ECO:0000305|PubMed:5489771}; DE AltName: Full=Ig heavy chain V-I region SIE {ECO:0000305|PubMed:7028111}; DE AltName: Full=Ig heavy chain V-I region WOL {ECO:0000305|PubMed:7028111}; DE Flags: Precursor; GN Name=IGHV1-69 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.6}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE RP IGHV1-69*06). RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., RA Quetier F., Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [2] RP PROTEIN SEQUENCE OF 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=5489771; DOI=10.1021/bi00818a008; RA Cunningham B.A., Rutishauser U., Gall W.E., Gottlieb P.D., RA Waxdal M.J., Edelman G.M.; RT "The covalent structure of a human gamma G-immunoglobulin. VII. Amino RT acid sequence of heavy-chain cyanogen bromide fragments H1-H4."; RL Biochemistry 9:3161-3170(1970). RN [3] RP PROTEIN SEQUENCE OF 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=7028111; DOI=10.1021/bi00523a027; RA Andrews D.W., Capra J.D.; RT "Amino acid sequence of the variable regions of heavy chains from two RT idiotypically cross-reactive human IgM anti-gamma-globulins of the Wa RT group."; RL Biochemistry 20:5822-5830(1981). RN [4] RP DISULFIDE BOND. RX PubMed=4923144; DOI=10.1021/bi00818a011; RA Gall W.E., Edelman G.M.; RT "The covalent structure of a human gamma G-immunoglobulin. X. RT Intrachain disulfide bonds."; RL Biochemistry 9:3188-3196(1970). RN [5] RP NOMENCLATURE. RX PubMed=11340299; RA Lefranc M.P.; RT "Nomenclature of the human immunoglobulin heavy (IGH) genes."; RL Exp. Clin. Immunogenet. 18:100-116(2001). RN [6] RP NOMENCLATURE. RA Lefranc M.P., Lefranc G.; RT "The Immunoglobulin FactsBook."; RL (In) Lefranc M.P., Lefranc G. (eds.); RL The Immunoglobulin FactsBook., pp.1-458, Academic Press, London. RL (2001). RN [7] RP REVIEW ON SOMATIC HYPERMUTATION. RX PubMed=17576170; DOI=10.1146/annurev.genet.41.110306.130340; RA Teng G., Papavasiliou F.N.; RT "Immunoglobulin somatic hypermutation."; RL Annu. Rev. Genet. 41:107-120(2007). RN [8] RP REVIEW ON IMMUNOGLOBULINS. RX PubMed=20176268; DOI=10.1016/j.jaci.2009.09.046; RA Schroeder H.W. Jr., Cavacini L.; RT "Structure and function of immunoglobulins."; RL J. Allergy Clin. Immunol. 125:S41-S52(2010). RN [9] RP REVIEW ON FUNCTION. RX PubMed=22158414; DOI=10.1038/nri3128; RA McHeyzer-Williams M., Okitsu S., Wang N., McHeyzer-Williams L.; RT "Molecular programming of B cell memory."; RL Nat. Rev. Immunol. 12:24-34(2012). RN [10] RP NOMENCLATURE. RX PubMed=24600447; DOI=10.3389/fimmu.2014.00022; RA Lefranc M.P.; RT "Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and RT Rise of Immunoinformatics."; RL Front. Immunol. 5:22-22(2014). CC -!- FUNCTION: V region of the variable domain of immunoglobulin heavy CC chains that participates in the antigen recognition CC (PubMed:24600447). Immunoglobulins, also known as antibodies, are CC membrane-bound or secreted glycoproteins produced by B CC lymphocytes. In the recognition phase of humoral immunity, the CC membrane-bound immunoglobulins serve as receptors which, upon CC binding of a specific antigen, trigger the clonal expansion and CC differentiation of B lymphocytes into immunoglobulins-secreting CC plasma cells. Secreted immunoglobulins mediate the effector phase CC of humoral immunity, which results in the elimination of bound CC antigens (PubMed:22158414, PubMed:20176268). The antigen binding CC site is formed by the variable domain of one heavy chain, together CC with that of its associated light chain. Thus, each immunoglobulin CC has two antigen binding sites with remarkable affinity for a CC particular antigen. The variable domains are assembled by a CC process called V-(D)-J rearrangement and can then be subjected to CC somatic hypermutations which, after exposure to antigen and CC selection, allow affinity maturation for a particular antigen CC (PubMed:20176268, PubMed:17576170). {ECO:0000303|PubMed:17576170, CC ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414, CC ECO:0000303|PubMed:24600447}. CC -!- SUBUNIT: Immunoglobulins are composed of two identical heavy CC chains and two identical light chains; disulfide-linked. CC {ECO:0000303|PubMed:20176268}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000303|PubMed:20176268, CC ECO:0000303|PubMed:22158414}. Cell membrane CC {ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}. CC -!- POLYMORPHISM: There are several alleles. The sequence shown is CC that of IMGT allele IGHV1-69*06. {ECO:0000305}. CC -!- CAUTION: For examples of full-length immunoglobulin heavy chains CC (of different isotypes) see AC P0DOX2, AC P0DOX3, AC P0DOX4, AC CC P0DOX5 and AC P0DOX6. {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; AC245369; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A02043; M1HUWL. DR PIR; A02044; M1HUSI. DR PIR; A90563; G1HUEU. DR UniGene; Hs.704366; -. DR ProteinModelPortal; P01742; -. DR SMR; P01742; -. DR IMGT_GENE-DB; IGHV1-69; -. DR iPTMnet; P01742; -. DR PhosphoSitePlus; P01742; -. DR BioMuta; IGHV1-69; -. DR jPOST; P01742; -. DR PeptideAtlas; P01742; -. DR PRIDE; P01742; -. DR ProteomicsDB; 51456; -. DR ProteomicsDB; 51459; -. DR ProteomicsDB; 51460; -. DR Ensembl; ENST00000390633; ENSP00000375042; ENSG00000211973. DR Ensembl; ENST00000632882; ENSP00000488090; ENSG00000282350. DR DisGeNET; 28461; -. DR EuPathDB; HostDB:ENSG00000211973.2; -. DR GeneCards; IGHV1-69; -. DR HGNC; HGNC:5558; IGHV1-69. DR neXtProt; NX_P01742; -. DR OpenTargets; ENSG00000211973; -. DR GeneTree; ENSGT00940000153088; -. DR HOVERGEN; HBG018013; -. DR OMA; YCARNTE; -. DR PhylomeDB; P01742; -. DR Reactome; R-HSA-166663; Initial triggering of complement. DR Reactome; R-HSA-173623; Classical antibody-mediated complement activation. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall. DR Reactome; R-HSA-2029481; FCGR activation. DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-HSA-2168880; Scavenging of heme from plasma. DR Reactome; R-HSA-2454202; Fc epsilon receptor (FCERI) signaling. DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-5690714; CD22 mediated BCR regulation. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR ChiTaRS; IGHV1-69; human. DR PRO; PR:P01742; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000211973; Expressed in 75 organ(s), highest expression level in lymph node. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0042571; C:immunoglobulin complex, circulating; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0003823; F:antigen binding; IBA:GO_Central. DR GO; GO:0034987; F:immunoglobulin receptor binding; IBA:GO_Central. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome. DR GO; GO:0050853; P:B cell receptor signaling pathway; IBA:GO_Central. DR GO; GO:0006956; P:complement activation; TAS:Reactome. DR GO; GO:0006958; P:complement activation, classical pathway; IBA:GO_Central. DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0006955; P:immune response; NAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0006911; P:phagocytosis, engulfment; IBA:GO_Central. DR GO; GO:0006910; P:phagocytosis, recognition; IBA:GO_Central. DR GO; GO:0050871; P:positive regulation of B cell activation; IBA:GO_Central. DR GO; GO:0006898; P:receptor-mediated endocytosis; TAS:Reactome. DR GO; GO:0030449; P:regulation of complement activation; TAS:Reactome. DR GO; GO:0050776; P:regulation of immune response; TAS:Reactome. DR Gene3D; 2.60.40.10; -; 1. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013106; Ig_V-set. DR Pfam; PF07686; V-set; 1. DR SMART; SM00406; IGv; 1. DR SUPFAM; SSF48726; SSF48726; 1. DR PROSITE; PS50835; IG_LIKE; 1. PE 1: Evidence at protein level; KW Adaptive immunity; Cell membrane; Complete proteome; KW Direct protein sequencing; Disulfide bond; Immunity; KW Immunoglobulin domain; Immunoglobulin V region; Membrane; KW Polymorphism; Pyrrolidone carboxylic acid; Reference proteome; KW Secreted; Signal. FT SIGNAL 1 19 {ECO:0000269|PubMed:5489771, FT ECO:0000269|PubMed:7028111}. FT CHAIN 20 117 Immunoglobulin heavy variable 1-69. FT {ECO:0000269|PubMed:5489771, FT ECO:0000269|PubMed:7028111}. FT /FTId=PRO_0000059902. FT DOMAIN 20 >117 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT MOD_RES 20 20 Pyrrolidone carboxylic acid. FT {ECO:0000269|PubMed:5489771, FT ECO:0000269|PubMed:7028111}. FT DISULFID 41 115 {ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:4923144}. FT CONFLICT 24 24 V -> M (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 38 38 K -> R (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 40 40 S -> T (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 43 43 A -> T (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 49 50 SS -> VD (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 50 51 SY -> RS (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 50 50 S -> G (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 52 54 AIS -> KGL (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 52 52 A -> T (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 54 54 S -> I (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 62 62 Q -> K (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 62 62 Q -> R (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 67 67 M -> V (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 69 76 GIIPIFGT -> SP (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 69 69 G -> Q (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 71 77 IPIFGTA -> VPMFGPP (in Ref. 2; AA FT sequence). {ECO:0000305}. FT CONFLICT 71 73 IPI -> PLR (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 75 85 GTANYAQKFQG -> NGEVKNPGSVV (in Ref. 3; AA FT sequence). {ECO:0000305}. FT CONFLICT 78 82 NYAQK -> KWTDP (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 85 85 G -> GVYIKWE (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 88 88 T -> S (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 89 93 ITADK -> VSLKP (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 93 96 KSTS -> ESTN (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 95 97 TST -> FNQ (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 99 99 Y -> H (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 103 104 SS -> VN (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 106 106 R -> F (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 107 107 S -> N (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 110 110 T -> G (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 112 117 VYYCAR -> FYFCAG (in Ref. 2; AA FT sequence). {ECO:0000305}. FT NON_TER 117 117 SQ SEQUENCE 117 AA; 12659 MW; 89671FD4910590DD CRC64; MDWTWRFLFV VAAATGVQSQ VQLVQSGAEV KKPGSSVKVS CKASGGTFSS YAISWVRQAP GQGLEWMGGI IPIFGTANYA QKFQGRVTIT ADKSTSTAYM ELSSLRSEDT AVYYCAR //