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Database: UniProt
Entry: P01825
LinkDB: P01825
Original site: P01825 
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   24-JAN-2024, entry version 148.
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   Ensembl; ENST00000390629.3; ENSP00000375038.2; ENSG00000224373.3.
DR   Ensembl; ENST00000619078.2; ENSP00000484250.2; ENSG00000282691.1.
DR   AGR; HGNC:5654; -.
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   InParanoid; P01825; -.
DR   OMA; ISSDYWW; -.
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-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   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 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   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:SF323; IMMUNOGLOBULIN HEAVY VARIABLE 4-30-2-RELATED; 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|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
//
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