HV146_HUMAN
ID HV146_HUMAN Reviewed; 117 AA.
AC P01743; A0A0B4J1V4; P06326; P80421;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2016, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Immunoglobulin heavy variable 1-46 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.6};
DE AltName: Full=Ig heavy chain V-I region DOT {ECO:0000305|PubMed:7737190};
DE AltName: Full=Ig heavy chain V-I region HG3 {ECO:0000305|PubMed:6298778};
DE AltName: Full=Ig heavy chain V-I region Mot {ECO:0000305|PubMed:3084950};
DE Flags: Precursor;
GN Name=IGHV1-46 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.6};
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 IGHV1-46*02), AND VARIANT
RP ASN-49.
RX PubMed=6298778; DOI=10.1073/pnas.80.3.855;
RA Rechavi G., Ram D., Glazer L., Zakut R., Givol D.;
RT "Evolutionary aspects of immunoglobulin heavy chain variable region (VH)
RT gene subgroups.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:855-859(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE IGHV1-46*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., 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 PROTEIN SEQUENCE OF 20-117, AND VARIANT ASN-49.
RX PubMed=3084950; DOI=10.1016/0161-5890(86)90039-8;
RA Kojima M., Koide T., Odani S., Ono T.;
RT "Amino acid sequence of the variable region of heavy chain in
RT immunoglobulin (Mot) having unusual papain cleavage sites.";
RL Mol. Immunol. 23:169-174(1986).
RN [4]
RP PROTEIN SEQUENCE OF 20-117.
RX PubMed=7737190; DOI=10.1111/j.1432-1033.1995.tb20336.x;
RA Stoppini M., Bellotti V., Negri A., Merlini G., Garver F., Ferri G.;
RT "Characterization of the two unique human anti-flavin monoclonal
RT immunoglobulins.";
RL Eur. J. Biochem. 228:886-893(1995).
RN [5]
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 [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. (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 Rise
RT 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 (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 IGHV1-46*01. {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}.
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DR EMBL; J00240; AAA52988.1; -; Genomic_DNA.
DR EMBL; AC244452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A02024; HVHUHG.
DR PIR; A02025; HVHUMO.
DR AlphaFoldDB; P01743; -.
DR SMR; P01743; -.
DR IntAct; P01743; 2.
DR MINT; P01743; -.
DR IMGT_GENE-DB; IGHV1-46; -.
DR iPTMnet; P01743; -.
DR PhosphoSitePlus; P01743; -.
DR BioMuta; IGHV1-46; -.
DR DMDM; 123799; -.
DR jPOST; P01743; -.
DR MassIVE; P01743; -.
DR PeptideAtlas; P01743; -.
DR PRIDE; P01743; -.
DR Ensembl; ENST00000390622.2; ENSP00000375031.2; ENSG00000211962.2.
DR Ensembl; ENST00000632105.1; ENSP00000488713.1; ENSG00000282131.1.
DR GeneCards; IGHV1-46; -.
DR HGNC; HGNC:5554; IGHV1-46.
DR HPA; ENSG00000211962; Tissue enhanced (intestine, lymphoid tissue, salivary gland).
DR neXtProt; NX_P01743; -.
DR OpenTargets; ENSG00000211962; -.
DR VEuPathDB; HostDB:ENSG00000211962; -.
DR GeneTree; ENSGT00950000183013; -.
DR OMA; EWMGIIN; -.
DR PhylomeDB; P01743; -.
DR PathwayCommons; P01743; -.
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-977606; Regulation of Complement cascade.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR ChiTaRS; IGHV1-46; human.
DR Pharos; P01743; Tdark.
DR PRO; PR:P01743; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P01743; protein.
DR Bgee; ENSG00000211962; Expressed in lymph node and 83 other tissues.
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:0050853; P:B cell receptor signaling pathway; IBA:GO_Central.
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:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
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 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; Direct protein sequencing;
KW Disulfide bond; Immunity; Immunoglobulin; Immunoglobulin domain; Membrane;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:3084950,
FT ECO:0000269|PubMed:7737190"
FT CHAIN 20..117
FT /note="Immunoglobulin heavy variable 1-46"
FT /evidence="ECO:0000269|PubMed:3084950,
FT ECO:0000269|PubMed:7737190"
FT /id="PRO_0000015244"
FT DOMAIN 20..>117
FT /note="Ig-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 41..115
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VARIANT 49
FT /note="T -> N (in IMGT allele IGHV1-46*02)"
FT /id="VAR_076712"
FT CONFLICT 20
FT /note="Q -> A (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 28..32
FT /note="AEVKK -> VERKV (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="A -> S (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 37..39
FT /note="VKV -> ARL (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 38..39
FT /note="KV -> RI (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="A -> V (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 46..47
FT /note="YT -> DD (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 47..50
FT /note="TFTS -> AFEN (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="S -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 52..53
FT /note="YM -> DI (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 53
FT /note="M -> I (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="Q -> L (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="Q -> R (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 68..71
FT /note="GIIN -> AVVH (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="I -> F (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 73..81
FT /note="SGGSTSYAQ -> VAGAVSSE (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 74..76
FT /note="GGS -> DDR (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="S -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 80..83
FT /note="AQKF -> GPRS (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 84..91
FT /note="QGRVTMTR -> RDRLVMSS (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="G -> A (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="V -> F (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="M -> V (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 93
FT /note="T -> S (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 95..96
FT /note="TS -> AN (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="S -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 99..104
FT /note="YMELSS -> SMQLRN (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 103..104
FT /note="SS -> TA (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="R -> I (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="E -> A (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="E -> D (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 111..114
FT /note="AVYY -> GRYF (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="V -> I (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT NON_TER 117
SQ SEQUENCE 117 AA; 12933 MW; B3CD92FC7538FFF2 CRC64;
MDWTWRVFCL LAVAPGAHSQ VQLVQSGAEV KKPGASVKVS CKASGYTFTS YYMHWVRQAP
GQGLEWMGII NPSGGSTSYA QKFQGRVTMT RDTSTSTVYM ELSSLRSEDT AVYYCAR
