HV169_HUMAN
ID HV169_HUMAN Reviewed; 117 AA.
AC P01742; A0A0B4J1V5; P01760; P01761;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2016, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Immunoglobulin heavy variable 1-69 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.6};
DE AltName: Full=Ig heavy chain V-I region EU {ECO:0000305|PubMed:5489771};
DE AltName: Full=Ig heavy chain V-I region SIE {ECO:0000305|PubMed:7028111};
DE AltName: Full=Ig heavy chain V-I region WOL {ECO:0000305|PubMed:7028111};
DE Flags: Precursor;
GN Name=IGHV1-69 {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 [LARGE SCALE GENOMIC DNA] (IMGT ALLELE IGHV1-69*06).
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 [2]
RP PROTEIN SEQUENCE OF 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20.
RX PubMed=5489771; DOI=10.1021/bi00818a008;
RA Cunningham B.A., Rutishauser U., Gall W.E., Gottlieb P.D., Waxdal M.J.,
RA Edelman G.M.;
RT "The covalent structure of a human gamma G-immunoglobulin. VII. Amino acid
RT sequence of heavy-chain cyanogen bromide fragments H1-H4.";
RL Biochemistry 9:3161-3170(1970).
RN [3]
RP PROTEIN SEQUENCE OF 20-117, AND PYROGLUTAMATE FORMATION AT GLN-20.
RX PubMed=7028111; DOI=10.1021/bi00523a027;
RA Andrews D.W., Capra J.D.;
RT "Amino acid sequence of the variable regions of heavy chains from two
RT idiotypically cross-reactive human IgM anti-gamma-globulins of the Wa
RT group.";
RL Biochemistry 20:5822-5830(1981).
RN [4]
RP DISULFIDE BOND.
RX PubMed=4923144; DOI=10.1021/bi00818a011;
RA Gall W.E., Edelman G.M.;
RT "The covalent structure of a human gamma G-immunoglobulin. X. Intrachain
RT disulfide bonds.";
RL Biochemistry 9:3188-3196(1970).
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 IGHV1-69*06. {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; AC245369; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A02043; M1HUWL.
DR PIR; A02044; M1HUSI.
DR PIR; A90563; G1HUEU.
DR AlphaFoldDB; P01742; -.
DR SMR; P01742; -.
DR IntAct; P01742; 1.
DR IMGT_GENE-DB; IGHV1-69; -.
DR iPTMnet; P01742; -.
DR PhosphoSitePlus; P01742; -.
DR BioMuta; IGHV1-69; -.
DR jPOST; P01742; -.
DR MassIVE; P01742; -.
DR PeptideAtlas; P01742; -.
DR PRIDE; P01742; -.
DR Ensembl; ENST00000390633.2; ENSP00000375042.2; ENSG00000211973.2.
DR Ensembl; ENST00000632882.1; ENSP00000488090.1; ENSG00000282350.1.
DR GeneCards; IGHV1-69; -.
DR HGNC; HGNC:5558; IGHV1-69.
DR HPA; ENSG00000211973; Tissue enhanced (intestine, lymphoid tissue, urinary bladder).
DR neXtProt; NX_P01742; -.
DR OpenTargets; ENSG00000211973; -.
DR VEuPathDB; HostDB:ENSG00000211973; -.
DR GeneTree; ENSGT00950000183013; -.
DR OMA; TTAYMEL; -.
DR PhylomeDB; P01742; -.
DR PathwayCommons; P01742; -.
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; IGHV1-69; human.
DR Pharos; P01742; Tdark.
DR PRO; PR:P01742; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P01742; protein.
DR Bgee; ENSG00000211973; Expressed in vermiform appendix and 82 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 Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:5489771,
FT ECO:0000269|PubMed:7028111"
FT CHAIN 20..117
FT /note="Immunoglobulin heavy variable 1-69"
FT /evidence="ECO:0000269|PubMed:5489771,
FT ECO:0000269|PubMed:7028111"
FT /id="PRO_0000059902"
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|PubMed:5489771,
FT ECO:0000269|PubMed:7028111"
FT DISULFID 41..115
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:4923144"
FT CONFLICT 24
FT /note="V -> M (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 38
FT /note="K -> R (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="S -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="A -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 49..50
FT /note="SS -> VD (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 50..51
FT /note="SY -> RS (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="S -> G (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 52..54
FT /note="AIS -> KGL (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="A -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 54
FT /note="S -> I (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="Q -> K (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="Q -> R (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="M -> V (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 69..76
FT /note="GIIPIFGT -> SP (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 69
FT /note="G -> Q (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 71..77
FT /note="IPIFGTA -> VPMFGPP (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 71..73
FT /note="IPI -> PLR (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 75..85
FT /note="GTANYAQKFQG -> NGEVKNPGSVV (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 78..82
FT /note="NYAQK -> KWTDP (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="G -> GVYIKWE (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="T -> S (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 89..93
FT /note="ITADK -> VSLKP (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 93..96
FT /note="KSTS -> ESTN (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 95..97
FT /note="TST -> FNQ (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="Y -> H (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 103..104
FT /note="SS -> VN (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="R -> F (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 107
FT /note="S -> N (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="T -> G (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 112..117
FT /note="VYYCAR -> FYFCAG (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT NON_TER 117
SQ SEQUENCE 117 AA; 12659 MW; 89671FD4910590DD CRC64;
MDWTWRFLFV VAAATGVQSQ VQLVQSGAEV KKPGSSVKVS CKASGGTFSS YAISWVRQAP
GQGLEWMGGI IPIFGTANYA QKFQGRVTIT ADKSTSTAYM ELSSLRSEDT AVYYCAR
