ID HV102_HUMAN Reviewed; 117 AA. AC P23083; A0A087WSX2; P01744; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 07-SEP-2016, sequence version 2. DT 27-MAR-2024, entry version 151. DE RecName: Full=Immunoglobulin heavy variable 1-2 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.7}; DE AltName: Full=Ig heavy chain V-I region ND {ECO:0000305|PubMed:6815656}; DE AltName: Full=Ig heavy chain V-I region V35 {ECO:0000305|PubMed:2841108}; DE Flags: Precursor; GN Name=IGHV1-2 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.7}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (IMGT ALLELE IGHV1-2*01), AND VARIANTS RP ARG-69; ARG-86; SER-89 AND VAL-111. RX PubMed=2841108; DOI=10.1002/j.1460-2075.1988.tb02912.x; RA Matsuda F., Lee K.H., Nakai S., Sato T., Kodaira M., Zong S.Q., Ohno H., RA Fukuhara S., Honjo T.; RT "Dispersed localization of D segments in the human immunoglobulin heavy- RT chain locus."; RL EMBO J. 7:1047-1051(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE IGHV1-2*04). 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., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., 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., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA 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 NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-86. RX PubMed=6815656; DOI=10.1073/pnas.79.21.6661; RA Kenten J.H., Molgaard H.V., Houghton M., Derbyshire R.B., Viney J., RA Bell L.O., Gould H.J.; RT "Cloning and sequence determination of the gene for the human RT immunoglobulin epsilon chain expressed in a myeloma cell line."; RL Proc. Natl. Acad. Sci. U.S.A. 79:6661-6665(1982). RN [4] RP PROTEIN SEQUENCE OF 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20. RA Bennich H.H., Johansson S.G.O., von Bahr-Lindstrom H.; RL (In) Bach M.K. (eds.); RL Immediate hypersensitivity: modern concepts and developments, pp.1-36, RL Marcel Dekker, New York (1978). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-116 (IMGT ALLELE IGHV1-2*01), AND RP VARIANTS ARG-69; ARG-86; SER-89 AND VAL-111. RX PubMed=7681398; DOI=10.1002/eji.1830230412; RA Mariette X., Tsapis A., Brouet J.C.; RT "Nucleotidic sequence analysis of the variable domains of four human RT monoclonal IgM with an antibody activity to myelin-associated RT glycoprotein."; RL Eur. J. Immunol. 23:846-851(1993). RN [6] RP NOMENCLATURE. RX PubMed=11340299; DOI=10.1159/000049189; RA Lefranc M.P.; RT "Nomenclature of the human immunoglobulin heavy (IGH) genes."; RL Exp. Clin. Immunogenet. 18:100-116(2001). RN [7] 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. (2001). RN [8] 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 [9] 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 [10] 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 [11] 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 Rise RT of Immunoinformatics."; RL Front. Immunol. 5:22-22(2014). RN [12] 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 (PubMed:24600447). CC Immunoglobulins, also known as antibodies, are membrane-bound or CC secreted glycoproteins produced by B lymphocytes. In the recognition CC phase of humoral immunity, the membrane-bound immunoglobulins serve as CC receptors which, upon binding of a specific antigen, trigger the clonal CC expansion and differentiation of B lymphocytes into immunoglobulins- CC secreting plasma cells. Secreted immunoglobulins mediate the effector CC phase of humoral immunity, which results in the elimination of bound CC antigens (PubMed:22158414, PubMed:20176268). The antigen binding site CC is formed by the variable domain of one heavy chain, together with that CC of its associated light chain. Thus, each immunoglobulin has two CC antigen binding sites with remarkable affinity for a particular CC antigen. The variable domains are assembled by a process called V-(D)-J CC rearrangement and can then be subjected to somatic hypermutations CC which, after exposure to antigen and selection, allow affinity CC maturation for a particular antigen (PubMed:20176268, PubMed:17576170). CC {ECO:0000303|PubMed:17576170, ECO:0000303|PubMed:20176268, CC ECO:0000303|PubMed:22158414, ECO:0000303|PubMed:24600447}. CC -!- SUBUNIT: Immunoglobulins are composed of two identical heavy chains and CC 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 that of CC IMGT allele IGHV1-2*04. {ECO:0000305}. CC -!- CAUTION: For examples of full-length immunoglobulin heavy chains (of CC different isotypes) see AC P0DOX2, AC P0DOX3, AC P0DOX4, AC P0DOX5 and CC 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; X07448; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC246787; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A93933; E1HUND. DR PIR; S00476; HVHU35. DR PDB; 1WT5; X-ray; 2.10 A; A=20-117. DR PDBsum; 1WT5; -. DR AlphaFoldDB; P23083; -. DR SMR; P23083; -. DR DrugBank; DB08294; 2-(4-HYDROXY-3-NITROPHENYL)ACETIC ACID. DR DrugBank; DB08295; 4-HYDROXY-3-NITROPHENYLACETYL-EPSILON-AMINOCAPROIC ACID ANION. DR DrugBank; DB08273; 4-HYDROXY-5-IODO-3-NITROPHENYLACETYL-EPSILON-AMINOCAPROIC ACID ANION. DR IMGT_GENE-DB; IGHV1-2; -. DR CarbonylDB; P23083; -. DR BioMuta; IGHV1-2; -. DR DMDM; 123808; -. DR jPOST; P23083; -. DR MassIVE; P23083; -. DR PeptideAtlas; P23083; -. DR Ensembl; ENST00000390594.3; ENSP00000375003.2; ENSG00000211934.3. DR Ensembl; ENST00000633350.1; ENSP00000488290.1; ENSG00000282550.1. DR UCSC; uc059gfn.1; human. DR AGR; HGNC:5550; -. DR GeneCards; IGHV1-2; -. DR HGNC; HGNC:5550; IGHV1-2. DR HPA; ENSG00000211934; Tissue enhanced (intestine, lymphoid tissue). DR neXtProt; NX_P23083; -. DR OpenTargets; ENSG00000211934; -. DR VEuPathDB; HostDB:ENSG00000211934; -. DR GeneTree; ENSGT00950000183013; -. DR InParanoid; P23083; -. DR OMA; DLTHSCV; -. DR PhylomeDB; P23083; -. DR PathwayCommons; P23083; -. 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-9664323; FCGR3A-mediated IL10 synthesis. DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. 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 SignaLink; P23083; -. DR ChiTaRS; IGHV1-2; human. DR EvolutionaryTrace; P23083; -. DR Pharos; P23083; Tdark. DR PRO; PR:P23083; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P23083; Protein. DR Bgee; ENSG00000211934; Expressed in vermiform appendix and 87 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0019814; C:immunoglobulin complex; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0003823; F:antigen binding; IBA:GO_Central. DR GO; GO:0006955; P:immune response; NAS:UniProtKB. DR GO; GO:0016064; P:immunoglobulin mediated immune response; IBA:GO_Central. DR CDD; cd04981; IgV_H; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 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 PANTHER; PTHR23266; IMMUNOGLOBULIN HEAVY CHAIN; 1. DR PANTHER; PTHR23266:SF272; IMMUNOGLOBULIN HEAVY VARIABLE 1-2; 1. DR Pfam; PF07686; V-set; 1. DR SMART; SM00406; IGv; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR PROSITE; PS50835; IG_LIKE; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Cell membrane; Direct protein sequencing; KW Disulfide bond; Immunity; Immunoglobulin; Immunoglobulin domain; Membrane; KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000269|Ref.4" FT CHAIN 20..117 FT /note="Immunoglobulin heavy variable 1-2" FT /evidence="ECO:0000269|Ref.4" FT /id="PRO_0000015245" FT DOMAIN 20..>117 FT /note="Ig-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT MOD_RES 20 FT /note="Pyrrolidone carboxylic acid" FT /evidence="ECO:0000269|Ref.4" FT DISULFID 41..115 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17947238, ECO:0007744|PDB:1WT5" FT VARIANT 69 FT /note="W -> R (in IMGT allele IGHV1-2*01)" FT /evidence="ECO:0000269|PubMed:2841108, FT ECO:0000269|PubMed:7681398" FT /id="VAR_076173" FT VARIANT 86 FT /note="W -> R (in IMGT allele IGHV1-2*01)" FT /evidence="ECO:0000269|PubMed:2841108, FT ECO:0000269|PubMed:7681398" FT /id="VAR_076174" FT VARIANT 89 FT /note="M -> S (in IMGT allele IGHV1-2*01; requires 2 FT nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:2841108, FT ECO:0000269|PubMed:7681398" FT /id="VAR_076175" FT VARIANT 111 FT /note="A -> V (in IMGT allele IGHV1-2*01)" FT /evidence="ECO:0000269|PubMed:2841108, FT ECO:0000269|PubMed:7681398" FT /id="VAR_076176" FT CONFLICT 16..21 FT /note="GAHSQV -> RVHSQT (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 31 FT /note="K -> R (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 38 FT /note="K -> R (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 49..56 FT /note="TGYYMHWV -> IDSYIHWI (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 53..54 FT /note="MH -> HI (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 62 FT /note="Q -> H (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 67..68 FT /note="MG -> GV (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 67 FT /note="M -> V (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 81..82 FT /note="QK -> PR (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 93..95 FT /note="TSI -> ASF (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 101..104 FT /note="ELSR -> DLRS (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 110..117 FT /note="TAVYYCAR -> SAVFYCAK (in Ref. 3)" FT /evidence="ECO:0000305" FT NON_TER 117 SQ SEQUENCE 117 AA; 13085 MW; CFCC08BE572F76A8 CRC64; MDWTWRILFL VAAATGAHSQ VQLVQSGAEV KKPGASVKVS CKASGYTFTG YYMHWVRQAP GQGLEWMGWI NPNSGGTNYA QKFQGWVTMT RDTSISTAYM ELSRLRSDDT AVYYCAR //