ID HV330_HUMAN Reviewed; 117 AA. AC P01768; A0A0B4J2B7; P01769; P01770; P01773; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2016, sequence version 2. DT 16-JAN-2019, entry version 104. DE RecName: Full=Immunoglobulin heavy variable 3-30 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.8}; DE AltName: Full=Ig heavy chain V-III region BUR {ECO:0000305|PubMed:107164}; DE AltName: Full=Ig heavy chain V-III region CAM {ECO:0000305|PubMed:6774332}; DE AltName: Full=Ig heavy chain V-III region GA {ECO:0000305|PubMed:4208843}; DE AltName: Full=Ig heavy chain V-III region NIE {ECO:0000305|PubMed:826475}; DE Flags: Precursor; GN Name=IGHV3-30 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.8}; 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 IGHV3-30*18). 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=4208843; DOI=10.1021/bi00709a004; RA Florent G., Lehman D., Putnam F.W.; RT "The switch point in mu heavy chains of human IgM immunoglobulins."; RL Biochemistry 13:2482-2498(1974). RN [3] RP PROTEIN SEQUENCE OF 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=826475; RA Ponstingl H., Hilschmann N.; RT "The rule of antibody structure. The primary structure of a monoclonal RT IgG1 immunoglobulin (myeloma protein Nie). III. The chymotryptic RT peptides of the H-chain, alignment of the tryptic peptides and RT discussion of the complete structure."; RL Hoppe-Seyler's Z. Physiol. Chem. 357:1571-1604(1976). RN [4] RP PROTEIN SEQUENCE OF 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=107164; RA Putnam F.W., Liu Y.-S.V., Low T.L.K.; RT "Primary structure of a human IgA1 immunoglobulin. IV. Streptococcal RT IgA1 protease, digestion, Fab and Fc fragments, and the complete amino RT acid sequence of the alpha 1 heavy chain."; RL J. Biol. Chem. 254:2865-2874(1979). RN [5] RP PROTEIN SEQUENCE OF 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=6774332; DOI=10.1073/pnas.77.6.3239; RA Lehman D.W., Putnam F.W.; RT "Amino acid sequence of the variable region of a human mu chain: RT location of a possible JH segment."; RL Proc. Natl. Acad. Sci. U.S.A. 77:3239-3243(1980). RN [6] RP DISULFIDE BOND. RX PubMed=1002129; RA Dreker L., Schwarz J., Reichel W., Hilschmann N.; RT "Rule of antibody structure. The primary structure of a monoclonal RT IgG1 immunoglobulin (myeloma protein Nie), I: purification and RT characterization of the protein, the L- and H-chains, the cyanogen RT bromide cleavage products, and the disulfide bridges."; RL Hoppe-Seyler's Z. Physiol. Chem. 357:1515-1540(1976). RN [7] 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 [8] 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 [9] 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 [10] 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 [11] 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 [12] 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 IGHV3-30*18. {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; AC245166; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A02051; M3HUAM. DR PIR; A02052; M3HUGA. DR PIR; A02056; A1HUBR. DR PIR; A91668; G1HUNI. DR UniGene; Hs.720416; -. DR ProteinModelPortal; P01768; -. DR SMR; P01768; -. DR DrugBank; DB08635; N-(TRANS-4'-NITRO-4-STILBENYL)-N-METHYL-5-AMINO-PENTANOIC ACID. DR IMGT_GENE-DB; IGHV3-30; -. DR BioMuta; IGHV3-30; -. DR DMDM; 123848; -. DR jPOST; P01768; -. DR PeptideAtlas; P01768; -. DR PRIDE; P01768; -. DR ProteomicsDB; 51467; -. DR ProteomicsDB; 51468; -. DR ProteomicsDB; 51469; -. DR ProteomicsDB; 51472; -. DR Ensembl; ENST00000603660; ENSP00000474524; ENSG00000270550. DR Ensembl; ENST00000633400; ENSP00000488205; ENSG00000282777. DR DisGeNET; 28439; -. DR EuPathDB; HostDB:ENSG00000270550.1; -. DR GeneCards; IGHV3-30; -. DR HGNC; HGNC:5591; IGHV3-30. DR neXtProt; NX_P01768; -. DR OpenTargets; ENSG00000270550; -. DR HOVERGEN; HBG018013; -. DR OMA; GIFRCFH; -. DR PhylomeDB; P01768; -. 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; IGHV3-30; human. DR PRO; PR:P01768; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000270550; Expressed in 83 organ(s), highest expression level in lymph node. DR ExpressionAtlas; P01768; baseline and differential. 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:0005615; C:extracellular space; HDA:UniProtKB. 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:107164, FT ECO:0000269|PubMed:4208843, FT ECO:0000269|PubMed:6774332, FT ECO:0000269|PubMed:826475}. FT CHAIN 20 117 Immunoglobulin heavy variable 3-30. FT {ECO:0000269|PubMed:107164, FT ECO:0000269|PubMed:4208843, FT ECO:0000269|PubMed:6774332, FT ECO:0000269|PubMed:826475}. FT /FTId=PRO_0000059919. FT DOMAIN 20 >117 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT MOD_RES 20 20 Pyrrolidone carboxylic acid. FT {ECO:0000269|PubMed:107164, FT ECO:0000269|PubMed:4208843, FT ECO:0000269|PubMed:6774332, FT ECO:0000269|PubMed:826475}. FT DISULFID 41 115 {ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:1002129}. FT CONFLICT 22 22 Q -> E (in Ref. 5; AA sequence). FT {ECO:0000305}. FT CONFLICT 25 25 E -> Q (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 30 30 V -> A (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 33 35 PGR -> AGT (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 42 42 A -> T (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 45 50 GFTFSS -> AFNLSD (in Ref. 4; AA FT sequence). {ECO:0000305}. FT CONFLICT 47 47 T -> S (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 50 53 SYGM -> RYTI (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 50 50 S -> N (in Ref. 5; AA sequence). FT {ECO:0000305}. FT CONFLICT 50 50 S -> T (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 52 52 G -> A (in Ref. 2; AA sequence, 5; AA FT sequence and 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 59 59 A -> P (in Ref. 5; AA sequence). FT {ECO:0000305}. FT CONFLICT 67 68 VA -> LS (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 69 69 V -> L (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 70 70 I -> M (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 73 73 D -> G (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 75 75 S -> B (in Ref. 2; AA sequence, 5; AA FT sequence and 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 77 77 K -> T (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 77 77 K -> Z (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 78 78 Y -> H (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 81 81 D -> A (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 84 84 K -> N (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 84 84 K -> R (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 92 93 DN -> ND (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 93 93 N -> I (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 98 98 L -> M (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 101 101 Q -> E (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 101 101 Q -> N (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 103 104 NS -> KT (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 107 107 A -> P (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 107 107 A -> T (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 109 109 D -> N (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 117 117 K -> R (in Ref. 5; AA sequence, 2; AA FT sequence and 3; AA sequence). FT {ECO:0000305}. FT NON_TER 117 117 SQ SEQUENCE 117 AA; 12947 MW; CA8AF76424DC4208 CRC64; MEFGLSWVFL VALLRGVQCQ VQLVESGGGV VQPGRSLRLS CAASGFTFSS YGMHWVRQAP GKGLEWVAVI SYDGSNKYYA DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCAK //