ID HV205_HUMAN Reviewed; 119 AA. AC P01817; A0A0A0MS10; P01818; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 07-SEP-2016, sequence version 2. DT 16-JAN-2019, entry version 108. DE RecName: Full=Immunoglobulin heavy variable 2-5 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.5}; DE AltName: Full=Ig heavy chain V-II region HE {ECO:0000305|PubMed:5264153}; DE AltName: Full=Ig heavy chain V-II region MCE {ECO:0000305|PubMed:6780622}; DE Flags: Precursor; GN Name=IGHV2-5 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.5}; 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 IGHV2-5*02). 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 20-119, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=5264153; DOI=10.1073/pnas.64.3.997; RA Cunningham B.A., Pflumm M.N., Rutishauser U., Edelman G.M.; RT "Subgroups of amino acid sequences in the variable regions of RT immunoglobulin heavy chains."; RL Proc. Natl. Acad. Sci. U.S.A. 64:997-1003(1969). RN [3] RP PROTEIN SEQUENCE OF 20-119, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=6780622; RA Gerber-Jenson B., Kazin A., Kehoe J.M., Scheffel C., Erickson B.W., RA Litman G.W.; RT "Molecular basis for the temperature-dependent insolubility of RT cryoglobulins. X. The amino acid sequence of the heavy chain variable RT region of McE."; RL J. Immunol. 126:1212-1216(1981). RN [4] 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 [5] 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 [6] 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 [7] 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 [8] 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 [9] 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 IGHV2-5*02. {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; AC244226; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A02092; MHHUMC. DR PIR; A02093; G1HUHE. DR ProteinModelPortal; P01817; -. DR SMR; P01817; -. DR IMGT_GENE-DB; IGHV2-5; -. DR BioMuta; IGHV2-5; -. DR DMDM; 123825; -. DR jPOST; P01817; -. DR PeptideAtlas; P01817; -. DR PRIDE; P01817; -. DR ProteomicsDB; 51485; -. DR ProteomicsDB; 51486; -. DR Ensembl; ENST00000390597; ENSP00000375006; ENSG00000211937. DR Ensembl; ENST00000560724; ENSP00000473889; ENSG00000277318. DR UCSC; uc059gfq.1; human. DR EuPathDB; HostDB:ENSG00000211937.3; -. DR GeneCards; IGHV2-5; -. DR HGNC; HGNC:5576; IGHV2-5. DR neXtProt; NX_P01817; -. DR OpenTargets; ENSG00000211937; -. DR GeneTree; ENSGT00940000153071; -. DR HOVERGEN; HBG018013; -. DR OMA; YWDDDKY; -. 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 PRO; PR:P01817; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000211937; Expressed in 79 organ(s), highest expression level in adrenal gland. 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:5264153, FT ECO:0000269|PubMed:6780622}. FT CHAIN 20 119 Immunoglobulin heavy variable 2-5. FT {ECO:0000269|PubMed:5264153, FT ECO:0000269|PubMed:6780622}. FT /FTId=PRO_0000059910. FT DOMAIN 20 >119 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT MOD_RES 20 20 Pyrrolidone carboxylic acid. FT {ECO:0000269|PubMed:5264153, FT ECO:0000269|PubMed:6780622}. FT DISULFID 41 116 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT CONFLICT 21 26 ITLKES -> VTLKEN (in Ref. 2; AA FT sequence). {ECO:0000305}. FT CONFLICT 35 35 Q -> E (in Ref. 3; AA sequence and 2; AA FT sequence). {ECO:0000305}. FT CONFLICT 43 54 FSGFSLSTSGVG -> LSGLSLTTDGVA (in Ref. 2; FT AA sequence). {ECO:0000305}. FT CONFLICT 61 64 PPGK -> GPGR (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 61 61 P -> R (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 71 78 LIYWDDDK -> FINWDDDN (in Ref. 3; AA FT sequence). {ECO:0000305}. FT CONFLICT 71 72 LI -> WLL (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 80 80 Y -> F (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 85 85 K -> R (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 90 92 ITK -> VTR (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 90 90 I -> G (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 96 96 K -> R (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 103 103 M -> I (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 117 117 A -> V (in Ref. 2; AA sequence). FT {ECO:0000305}. FT NON_TER 119 119 SQ SEQUENCE 119 AA; 13231 MW; 7403E23CE450BA92 CRC64; MDTLCSTLLL LTIPSWVLSQ ITLKESGPTL VKPTQTLTLT CTFSGFSLST SGVGVGWIRQ PPGKALEWLA LIYWDDDKRY SPSLKSRLTI TKDTSKNQVV LTMTNMDPVD TATYYCAHR //