ID HV146_HUMAN Reviewed; 117 AA. AC P01743; A0A0B4J1V4; P06326; P80421; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2016, sequence version 2. DT 16-JAN-2019, entry version 127. DE RecName: Full=Immunoglobulin heavy variable 1-46 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.6}; DE AltName: Full=Ig heavy chain V-I region DOT {ECO:0000305|PubMed:7737190}; DE AltName: Full=Ig heavy chain V-I region HG3 {ECO:0000305|PubMed:6298778}; DE AltName: Full=Ig heavy chain V-I region Mot {ECO:0000305|PubMed:3084950}; DE Flags: Precursor; GN Name=IGHV1-46 {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 [GENOMIC DNA] (IMGT ALLELE IGHV1-46*02), AND RP VARIANT ASN-49. RX PubMed=6298778; DOI=10.1073/pnas.80.3.855; RA Rechavi G., Ram D., Glazer L., Zakut R., Givol D.; RT "Evolutionary aspects of immunoglobulin heavy chain variable region RT (VH) gene subgroups."; RL Proc. Natl. Acad. Sci. U.S.A. 80:855-859(1983). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE RP IGHV1-46*01). 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 [3] RP PROTEIN SEQUENCE OF 20-117, AND VARIANT ASN-49. RX PubMed=3084950; DOI=10.1016/0161-5890(86)90039-8; RA Kojima M., Koide T., Odani S., Ono T.; RT "Amino acid sequence of the variable region of heavy chain in RT immunoglobulin (Mot) having unusual papain cleavage sites."; RL Mol. Immunol. 23:169-174(1986). RN [4] RP PROTEIN SEQUENCE OF 20-117. RX PubMed=7737190; DOI=10.1111/j.1432-1033.1995.tb20336.x; RA Stoppini M., Bellotti V., Negri A., Merlini G., Garver F., Ferri G.; RT "Characterization of the two unique human anti-flavin monoclonal RT immunoglobulins."; RL Eur. J. Biochem. 228:886-893(1995). 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 IGHV1-46*01. {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; J00240; AAA52988.1; -; Genomic_DNA. DR EMBL; AC244452; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A02024; HVHUHG. DR PIR; A02025; HVHUMO. DR ProteinModelPortal; P01743; -. DR SMR; P01743; -. DR IMGT_GENE-DB; IGHV1-46; -. DR iPTMnet; P01743; -. DR PhosphoSitePlus; P01743; -. DR BioMuta; IGHV1-46; -. DR DMDM; 123799; -. DR jPOST; P01743; -. DR PeptideAtlas; P01743; -. DR PRIDE; P01743; -. DR ProteomicsDB; 51457; -. DR ProteomicsDB; 51894; -. DR ProteomicsDB; 57685; -. DR Ensembl; ENST00000390622; ENSP00000375031; ENSG00000211962. DR Ensembl; ENST00000632105; ENSP00000488713; ENSG00000282131. DR EuPathDB; HostDB:ENSG00000211962.2; -. DR GeneCards; IGHV1-46; -. DR HGNC; HGNC:5554; IGHV1-46. DR neXtProt; NX_P01743; -. DR OpenTargets; ENSG00000211962; -. DR GeneTree; ENSGT00940000153088; -. DR HOGENOM; HOG000154831; -. DR HOVERGEN; HBG018013; -. DR OMA; EWMGIIN; -. DR PhylomeDB; P01743; -. 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; IGHV1-46; human. DR PRO; PR:P01743; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000211962; Expressed in 73 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; Reference proteome; Secreted; Signal. FT SIGNAL 1 19 {ECO:0000269|PubMed:3084950, FT ECO:0000269|PubMed:7737190}. FT CHAIN 20 117 Immunoglobulin heavy variable 1-46. FT {ECO:0000269|PubMed:3084950, FT ECO:0000269|PubMed:7737190}. FT /FTId=PRO_0000015244. FT DOMAIN 20 >117 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT DISULFID 41 115 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VARIANT 49 49 T -> N (in IMGT allele IGHV1-46*02). FT /FTId=VAR_076712. FT CONFLICT 20 20 Q -> A (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 28 32 AEVKK -> VERKV (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 35 35 A -> S (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 37 39 VKV -> ARL (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 38 39 KV -> RI (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 43 43 A -> V (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 46 47 YT -> DD (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 47 50 TFTS -> AFEN (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 50 50 S -> T (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 52 53 YM -> DI (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 53 53 M -> I (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 62 62 Q -> L (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 62 62 Q -> R (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 68 71 GIIN -> AVVH (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 70 70 I -> F (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 73 81 SGGSTSYAQ -> VAGAVSSE (in Ref. 4; AA FT sequence). {ECO:0000305}. FT CONFLICT 74 76 GGS -> DDR (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 78 78 S -> T (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 80 83 AQKF -> GPRS (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 84 91 QGRVTMTR -> RDRLVMSS (in Ref. 4; AA FT sequence). {ECO:0000305}. FT CONFLICT 85 85 G -> A (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 87 87 V -> F (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 89 89 M -> V (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 93 93 T -> S (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 95 96 TS -> AN (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 96 96 S -> T (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 99 104 YMELSS -> SMQLRN (in Ref. 4; AA FT sequence). {ECO:0000305}. FT CONFLICT 103 104 SS -> TA (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 106 106 R -> I (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 108 108 E -> A (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 108 108 E -> D (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 111 114 AVYY -> GRYF (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 112 112 V -> I (in Ref. 3; AA sequence). FT {ECO:0000305}. FT NON_TER 117 117 SQ SEQUENCE 117 AA; 12933 MW; B3CD92FC7538FFF2 CRC64; MDWTWRVFCL LAVAPGAHSQ VQLVQSGAEV KKPGASVKVS CKASGYTFTS YYMHWVRQAP GQGLEWMGII NPSGGSTSYA QKFQGRVTMT RDTSTSTVYM ELSSLRSEDT AVYYCAR //