ID HV270_HUMAN Reviewed; 119 AA. AC P01814; A0A0B4J2H3; P01815; P01816; P04438; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2016, sequence version 2. DT 16-JAN-2019, entry version 102. DE RecName: Full=Immunoglobulin heavy variable 2-70 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.6}; DE AltName: Full=Ig heavy chain V-II region COR {ECO:0000305|PubMed:5449120}; DE AltName: Full=Ig heavy chain V-II region DAW {ECO:0000305|PubMed:5449120}; DE AltName: Full=Ig heavy chain V-II region OU {ECO:0000305|PubMed:4742735}; DE AltName: Full=Ig heavy chain V-II region SESS {ECO:0000305|PubMed:6089186}; DE Flags: Precursor; GN Name=IGHV2-70 {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 [MRNA]. RX PubMed=6089186; DOI=10.1073/pnas.81.16.5194; RA Takahashi N., Noma T., Honjo T.; RT "Rearranged immunoglobulin heavy chain variable region (VH) pseudogene RT that deletes the second complementarity-determining region."; RL Proc. Natl. Acad. Sci. U.S.A. 81:5194-5198(1984). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE RP IGHV2-70*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 20-119, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=5449120; DOI=10.1042/bj1170641; RA Press E.M., Hogg N.M.; RT "The amino acid sequences of the Fd fragments of two human gamma-1 RT heavy chains."; RL Biochem. J. 117:641-660(1970). RN [4] RP PROTEIN SEQUENCE OF 20-119, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=4742735; DOI=10.1126/science.182.4109.287; RA Putnam F.W., Florent G., Paul C., Shinoda T., Shimizu A.; RT "Complete amino acid sequence of the Mu heavy chain of a human IgM RT immunoglobulin."; RL Science 182:287-291(1973). 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). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 20-117, AND DISULFIDE BOND. RX PubMed=17947238; DOI=10.1074/jbc.M706190200; RA Makabe K., Nakanishi T., Tsumoto K., Tanaka Y., Kondo H., Umetsu M., RA Sone Y., Asano R., Kumagai I.; RT "Thermodynamic consequences of mutations in vernier zone residues of a RT humanized anti-human epidermal growth factor receptor murine antibody, RT 528."; RL J. Biol. Chem. 283:1156-1166(2008). 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 IGHV2-70*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; AC245369; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A02088; MHHUOU. DR PIR; A02089; G1HUCO. DR PIR; A02090; G2HUCS. DR PIR; A02091; G1HUDW. DR ProteinModelPortal; P01814; -. DR SMR; P01814; -. DR IMGT_GENE-DB; IGHV2-70; -. DR BioMuta; IGHV2-70; -. DR PeptideAtlas; P01814; -. DR PRIDE; P01814; -. DR ProteomicsDB; 51482; -. DR ProteomicsDB; 51483; -. DR ProteomicsDB; 51484; -. DR ProteomicsDB; 51713; -. DR Ensembl; ENST00000617374; ENSP00000485200; ENSG00000274576. DR EuPathDB; HostDB:ENSG00000274576.2; -. DR GeneCards; IGHV2-70; -. DR HGNC; HGNC:5577; IGHV2-70. DR neXtProt; NX_P01814; -. DR OpenTargets; ENSG00000274576; -. DR GeneTree; ENSGT00940000153071; -. DR HOVERGEN; HBG018013; -. DR OMA; WLANIDW; -. DR PhylomeDB; P01814; -. 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:P01814; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000274576; 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; Pyrrolidone carboxylic acid; Reference proteome; KW Secreted; Signal. FT SIGNAL 1 19 {ECO:0000269|PubMed:4742735, FT ECO:0000269|PubMed:5449120}. FT CHAIN 20 119 Immunoglobulin heavy variable 2-70. FT {ECO:0000269|PubMed:4742735, FT ECO:0000269|PubMed:5449120}. FT /FTId=PRO_0000059907. FT DOMAIN 20 >119 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT MOD_RES 20 20 Pyrrolidone carboxylic acid. FT {ECO:0000269|PubMed:4742735, FT ECO:0000269|PubMed:5449120}. FT DISULFID 41 116 {ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17947238}. FT CONFLICT 16 16 W -> G (in Ref. 1). {ECO:0000305}. FT CONFLICT 22 22 T -> N (in Ref. 1). {ECO:0000305}. FT CONFLICT 24 24 R -> T (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 32 32 K -> R (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 33 35 PTQ -> ATH (in Ref. 1). {ECO:0000305}. FT CONFLICT 34 36 TQT -> KQP (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 46 51 FSLSTS -> LSVNTR (in Ref. 1). FT {ECO:0000305}. FT CONFLICT 50 52 TSG -> GET (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 50 51 TS -> ST (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 52 54 GMC -> RMR (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 54 54 C -> S (in Ref. 1). {ECO:0000305}. FT CONFLICT 56 56 S -> A (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 56 56 S -> G (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 60 60 Q -> R (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 64 64 K -> E (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 65 65 A -> G (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 71 75 LIDWD -> WDILN (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 71 71 L -> R (in Ref. 3; AA sequence, 1 and 4; FT AA sequence). {ECO:0000305}. FT CONFLICT 74 74 W -> B (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 77 80 DKYY -> KFYW (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 81 82 ST -> GA (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 81 81 S -> G (in Ref. 1). {ECO:0000305}. FT CONFLICT 81 81 S -> N (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 85 85 K -> E (in Ref. 3; AA sequence and 1). FT {ECO:0000305}. FT CONFLICT 85 85 K -> R (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 89 90 TI -> AV (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 89 89 T -> S (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 93 94 DT -> ND (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 96 96 K -> R (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 102 109 TMTNMDPV -> SMNTVGPG (in Ref. 3; AA FT sequence). {ECO:0000305}. FT CONFLICT 102 107 TMTNMD -> IMINVN (in Ref. 4; AA FT sequence). {ECO:0000305}. FT CONFLICT 102 103 TM -> KV (in Ref. 1). {ECO:0000305}. FT CONFLICT 103 105 Missing (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 109 109 V -> A (in Ref. 1). {ECO:0000305}. FT CONFLICT 119 119 I -> M (in Ref. 1). {ECO:0000305}. FT CONFLICT 119 119 I -> S (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 119 119 I -> V (in Ref. 4; AA sequence). FT {ECO:0000305}. FT NON_TER 119 119 SQ SEQUENCE 119 AA; 13260 MW; 2930DA0C57F34F85 CRC64; MDILCSTLLL LTVPSWVLSQ VTLRESGPAL VKPTQTLTLT CTFSGFSLST SGMCVSWIRQ PPGKALEWLA LIDWDDDKYY STSLKTRLTI SKDTSKNQVV LTMTNMDPVD TATYYCARI //