HV459_HUMAN
ID HV459_HUMAN Reviewed; 116 AA.
AC P01825; A0A0C4DH40; A0A0G2JPU1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2016, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Immunoglobulin heavy variable 4-59 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.4};
DE AltName: Full=Ig heavy chain V-II region NEWM {ECO:0000305|PubMed:407927};
DE Flags: Precursor;
GN Name=IGHV4-59 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.4};
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 IGHV4-59*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 [2]
RP PROTEIN SEQUENCE OF 20-116, AND PYROGLUTAMATE FORMATION AT GLN-20.
RX PubMed=407927; DOI=10.1021/bi00634a019;
RA Poljak R.J., Nakashima Y., Chen B.L., Konigsberg W.;
RT "Amino acid sequence of the VH region of a human myeloma immunoglobulin
RT (IgG New).";
RL Biochemistry 16:3412-3420(1977).
RN [3]
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 [4]
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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF FAB FRAGMENT.
RX PubMed=618887; DOI=10.1016/s0021-9258(17)38249-2;
RA Saul F.A., Amzel L.M., Poljak R.J.;
RT "Preliminary refinement and structural analysis of the Fab fragment from
RT human immunoglobulin new at 2.0-A resolution.";
RL J. Biol. Chem. 253:585-597(1978).
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 IGHV4-59*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; AC244452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A90404; G1HUNM.
DR PDB; 7CZP; EM; 3.00 A; H/J=24-116.
DR PDB; 7CZX; EM; 2.80 A; H/I/J=50-115.
DR PDB; 7FAB; X-ray; 2.00 A; H=21-116.
DR PDBsum; 7CZP; -.
DR PDBsum; 7CZX; -.
DR PDBsum; 7FAB; -.
DR AlphaFoldDB; P01825; -.
DR SMR; P01825; -.
DR IMGT_GENE-DB; IGHV4-59; -.
DR BioMuta; IGHV4-59; -.
DR DMDM; 123828; -.
DR jPOST; P01825; -.
DR MassIVE; P01825; -.
DR PeptideAtlas; P01825; -.
DR PRIDE; P01825; -.
DR Ensembl; ENST00000390629.3; ENSP00000375038.2; ENSG00000224373.3.
DR Ensembl; ENST00000619078.2; ENSP00000484250.2; ENSG00000282691.1.
DR GeneCards; IGHV4-59; -.
DR HGNC; HGNC:5654; IGHV4-59.
DR HPA; ENSG00000224373; Tissue enhanced (intestine, lymphoid tissue, urinary bladder).
DR neXtProt; NX_P01825; -.
DR OpenTargets; ENSG00000224373; -.
DR VEuPathDB; HostDB:ENSG00000224373; -.
DR GeneTree; ENSGT01030000234536; -.
DR OMA; CYLARNT; -.
DR PathwayCommons; P01825; -.
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; IGHV4-59; human.
DR EvolutionaryTrace; P01825; -.
DR Pharos; P01825; Tdark.
DR PRO; PR:P01825; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P01825; protein.
DR Bgee; ENSG00000224373; Expressed in rectum and 93 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 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|PubMed:407927"
FT CHAIN 20..116
FT /note="Immunoglobulin heavy variable 4-59"
FT /evidence="ECO:0000269|PubMed:407927"
FT /id="PRO_0000059913"
FT DOMAIN 20..>116
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:407927"
FT DISULFID 41..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 24..25
FT /note="QE -> EQ (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 32
FT /note="K -> R (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="E -> Q (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 46..56
FT /note="GSISSYYWSWI -> STFSNDYYTWV (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="K -> R (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 70..83
FT /note="IYYSGSTNYNPSLK -> VFYHGTSDDTTPLR (in Ref. 2; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 88..89
FT /note="IS -> ML (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 100
FT /note="K -> R (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT NON_TER 116
FT STRAND 22..26
FT /evidence="ECO:0007829|PDB:7FAB"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:7FAB"
FT STRAND 37..46
FT /evidence="ECO:0007829|PDB:7FAB"
FT STRAND 51..58
FT /evidence="ECO:0007829|PDB:7FAB"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:7FAB"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:7CZP"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:7FAB"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:7FAB"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:7FAB"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:7FAB"
FT TURN 92..95
FT /evidence="ECO:0007829|PDB:7FAB"
FT STRAND 96..101
FT /evidence="ECO:0007829|PDB:7FAB"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:7FAB"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:7FAB"
SQ SEQUENCE 116 AA; 12936 MW; 09C37EE35E4918D5 CRC64;
MKHLWFFLLL VAAPRWVLSQ VQLQESGPGL VKPSETLSLT CTVSGGSISS YYWSWIRQPP
GKGLEWIGYI YYSGSTNYNP SLKSRVTISV DTSKNQFSLK LSSVTAADTA VYYCAR
