ID HV333_HUMAN Reviewed; 117 AA. AC P01772; A0A0B4J1V3; P01771; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2016, sequence version 2. DT 16-JAN-2019, entry version 123. DE RecName: Full=Immunoglobulin heavy variable 3-33 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.5}; DE AltName: Full=Ig heavy chain V-III region HIL {ECO:0000305|PubMed:420800}; DE AltName: Full=Ig heavy chain V-III region KOL {ECO:0000305|PubMed:6884994}; DE Flags: Precursor; GN Name=IGHV3-33 {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 IGHV3-33*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 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20. RX PubMed=420800; DOI=10.1021/bi00571a001; RA Chiu Y.-Y.H., Lopez de Castro J.A., Poljak R.J.; RT "Amino acid sequence of the VH region of human myeloma RT cryoimmunoglobulin IgG Hil."; RL Biochemistry 18:553-560(1979). RN [3] RP PROTEIN SEQUENCE OF 20-117, PYROGLUTAMATE FORMATION AT GLN-20, AND RP DISULFIDE BONDS. RX PubMed=6884994; RA Schmidt W.E., Jung H.-D., Palm W., Hilschmann N.; RT "Three-dimensional structure determination of antibodies. Primary RT structure of crystallized monoclonal immunoglobulin IgG1 KOL, I."; RL Hoppe-Seyler's Z. Physiol. Chem. 364:713-747(1983). 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). RN [10] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS). RX PubMed=7441755; DOI=10.1016/0022-2836(80)90252-1; RA Marquart M., Deisenhofer J., Huber R., Palm W.; RT "Crystallographic refinement and atomic models of the intact RT immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 A RT and 1.0-A resolution."; RL J. Mol. Biol. 141:369-391(1980). 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 IGHV3-33*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; AC245166; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A02054; G1HUHL. DR PIR; A02055; G1HUKL. DR PDB; 2FB4; X-ray; 1.90 A; H=21-117. DR PDB; 2IG2; X-ray; 3.00 A; H=21-117. DR PDB; 2RCJ; X-ray; -; A/B/E/F/I/J/M/N/Q/R=20-117. DR PDBsum; 2FB4; -. DR PDBsum; 2IG2; -. DR PDBsum; 2RCJ; -. DR ProteinModelPortal; P01772; -. DR SMR; P01772; -. DR MINT; P01772; -. DR IMGT_GENE-DB; IGHV3-33; -. DR BioMuta; IGHV3-33; -. DR DMDM; 123851; -. DR jPOST; P01772; -. DR PeptideAtlas; P01772; -. DR PRIDE; P01772; -. DR ProteomicsDB; 51470; -. DR ProteomicsDB; 51471; -. DR Ensembl; ENST00000390615; ENSP00000375024; ENSG00000211955. DR DisGeNET; 28434; -. DR EuPathDB; HostDB:ENSG00000211955.2; -. DR GeneCards; IGHV3-33; -. DR HGNC; HGNC:5596; IGHV3-33. DR neXtProt; NX_P01772; -. DR OpenTargets; ENSG00000211955; -. DR GeneTree; ENSGT00940000153134; -. DR HOVERGEN; HBG018013; -. DR OMA; FVTGGHI; -. DR PhylomeDB; P01772; -. 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; IGHV3-33; human. DR EvolutionaryTrace; P01772; -. DR PRO; PR:P01772; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000211955; Expressed in 80 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:420800, FT ECO:0000269|PubMed:6884994}. FT CHAIN 20 117 Immunoglobulin heavy variable 3-33. FT {ECO:0000269|PubMed:420800, FT ECO:0000269|PubMed:6884994}. FT /FTId=PRO_0000059923. FT DOMAIN 20 >117 Ig-like. {ECO:0000255|PROSITE- FT ProRule:PRU00114}. FT MOD_RES 20 20 Pyrrolidone carboxylic acid. FT {ECO:0000269|PubMed:420800, FT ECO:0000269|PubMed:6884994}. FT DISULFID 41 115 {ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:6884994}. FT CONFLICT 22 22 Q -> K (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 25 26 ES -> QA (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 42 43 AA -> SS (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 42 42 A -> I (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 47 47 T -> I (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 50 50 S -> N (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 52 54 GMH -> AMY (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 69 69 V -> I (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 72 72 Y -> D (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 73 73 D -> N (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 76 78 NKY -> DQH (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 76 77 NK -> RT (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 80 80 A -> G (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 96 96 N -> R (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 99 99 Y -> F (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 100 100 L -> M (in Ref. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 103 103 N -> D (in Ref. 3; 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. 2; AA sequence). FT {ECO:0000305}. FT CONFLICT 111 111 A -> G (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 114 114 Y -> F (in Ref. 3; AA sequence). FT {ECO:0000305}. FT NON_TER 117 117 FT STRAND 22 26 {ECO:0000244|PDB:2FB4}. FT STRAND 37 46 {ECO:0000244|PDB:2FB4}. FT HELIX 48 50 {ECO:0000244|PDB:2FB4}. FT STRAND 53 58 {ECO:0000244|PDB:2FB4}. FT STRAND 64 70 {ECO:0000244|PDB:2FB4}. FT STRAND 77 79 {ECO:0000244|PDB:2FB4}. FT HELIX 81 83 {ECO:0000244|PDB:2FB4}. FT STRAND 87 92 {ECO:0000244|PDB:2FB4}. FT TURN 93 96 {ECO:0000244|PDB:2FB4}. FT STRAND 97 102 {ECO:0000244|PDB:2FB4}. FT HELIX 107 109 {ECO:0000244|PDB:2FB4}. FT STRAND 111 117 {ECO:0000244|PDB:2FB4}. SQ SEQUENCE 117 AA; 13074 MW; C00B376424DC474D CRC64; MEFGLSWVFL VALLRGVQCQ VQLVESGGGV VQPGRSLRLS CAASGFTFSS YGMHWVRQAP GKGLEWVAVI WYDGSNKYYA DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCAR //