ID HV459_HUMAN Reviewed; 116 AA. AC P01825; A0A0C4DH40; A0A0G2JPU1; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2016, sequence version 2. DT 16-JAN-2019, entry version 124. DE RecName: Full=Immunoglobulin heavy variable 4-59 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.4}; DE AltName: Full=Ig heavy chain V-II region NEWM {ECO:0000305|PubMed:407927}; DE Flags: Precursor; GN Name=IGHV4-59 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.4}; 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 IGHV4-59*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 [2] RP PROTEIN SEQUENCE OF 20-116, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=407927; DOI=10.1021/bi00634a019; RA Poljak R.J., Nakashima Y., Chen B.L., Konigsberg W.; RT "Amino acid sequence of the VH region of a human myeloma RT immunoglobulin (IgG New)."; RL Biochemistry 16:3412-3420(1977). RN [3] 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 [4] 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 [5] 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 [6] 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 [7] 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 [8] 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). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF FAB FRAGMENT. RX PubMed=618887; RA Saul F.A., Amzel L.M., Poljak R.J.; RT "Preliminary refinement and structural analysis of the Fab fragment RT from human immunoglobulin new at 2.0-A resolution."; RL J. Biol. Chem. 253:585-597(1978). 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 IGHV4-59*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; AC244452; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A90404; G1HUNM. DR PDB; 7FAB; X-ray; 2.00 A; H=21-116. DR PDBsum; 7FAB; -. DR ProteinModelPortal; P01825; -. DR SMR; P01825; -. DR IMGT_GENE-DB; IGHV4-59; -. DR BioMuta; IGHV4-59; -. DR DMDM; 123828; -. DR jPOST; P01825; -. DR PeptideAtlas; P01825; -. DR PRIDE; P01825; -. DR ProteomicsDB; 51488; -. DR Ensembl; ENST00000390629; ENSP00000375038; ENSG00000224373. DR Ensembl; ENST00000619078; ENSP00000484250; ENSG00000282691. DR EuPathDB; HostDB:ENSG00000224373.3; -. DR GeneCards; IGHV4-59; -. DR HGNC; HGNC:5654; IGHV4-59. DR neXtProt; NX_P01825; -. DR OpenTargets; ENSG00000224373; -. DR GeneTree; ENSGT00940000153119; -. DR HOVERGEN; HBG018013; -. DR OMA; ARYTVWS; -. DR PhylomeDB; P01825; -. 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 EvolutionaryTrace; P01825; -. DR PRO; PR:P01825; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000224373; Expressed in 81 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 3D-structure; 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:407927}. FT CHAIN 20 116 Immunoglobulin heavy variable 4-59. FT {ECO:0000269|PubMed:407927}. FT /FTId=PRO_0000059913. FT DOMAIN 20 >116 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT MOD_RES 20 20 Pyrrolidone carboxylic acid. FT {ECO:0000269|PubMed:407927}. FT DISULFID 41 114 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT CONFLICT 24 25 QE -> EQ (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 32 32 K -> R (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 35 35 E -> Q (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 46 56 GSISSYYWSWI -> STFSNDYYTWV (in Ref. 2; AA FT sequence). {ECO:0000305}. FT CONFLICT 62 62 K -> R (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 70 83 IYYSGSTNYNPSLK -> VFYHGTSDDTTPLR (in Ref. FT 2; AA sequence). {ECO:0000305}. FT CONFLICT 88 89 IS -> ML (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 100 100 K -> R (in Ref. 2; AA sequence). FT {ECO:0000305}. FT NON_TER 116 116 FT STRAND 22 26 {ECO:0000244|PDB:7FAB}. FT STRAND 29 31 {ECO:0000244|PDB:7FAB}. FT STRAND 37 46 {ECO:0000244|PDB:7FAB}. FT STRAND 51 58 {ECO:0000244|PDB:7FAB}. FT STRAND 65 70 {ECO:0000244|PDB:7FAB}. FT STRAND 76 78 {ECO:0000244|PDB:7FAB}. FT HELIX 80 82 {ECO:0000244|PDB:7FAB}. FT TURN 83 85 {ECO:0000244|PDB:7FAB}. FT STRAND 86 91 {ECO:0000244|PDB:7FAB}. FT TURN 92 95 {ECO:0000244|PDB:7FAB}. FT STRAND 96 101 {ECO:0000244|PDB:7FAB}. FT HELIX 106 108 {ECO:0000244|PDB:7FAB}. FT STRAND 110 116 {ECO:0000244|PDB:7FAB}. SQ SEQUENCE 116 AA; 12936 MW; 09C37EE35E4918D5 CRC64; MKHLWFFLLL VAAPRWVLSQ VQLQESGPGL VKPSETLSLT CTVSGGSISS YYWSWIRQPP GKGLEWIGYI YYSGSTNYNP SLKSRVTISV DTSKNQFSLK LSSVTAADTA VYYCAR //