IGHG4_HUMAN
ID IGHG4_HUMAN Reviewed; 327 AA.
AC P01861;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Immunoglobulin heavy constant gamma 4 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.5};
DE AltName: Full=Ig gamma-4 chain C region {ECO:0000305};
GN Name=IGHG4 {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.5};
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 IGHG4*01).
RX PubMed=6299662; DOI=10.1089/dna.1.1981.1.11;
RA Ellison J.W., Buxbaum J.N., Hood L.E.;
RT "Nucleotide sequence of a human immunoglobulin C gamma 4 gene.";
RL DNA 1:11-18(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE IGHG4*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 PROTEIN SEQUENCE OF 1-30 AND 81-326.
RX PubMed=4192699; DOI=10.1042/bj1170033;
RA Pink J.R.L., Buttery S.H., de Vries G.M., Milstein C.;
RT "Human immunoglobulin subclasses. Partial amino acid sequence of the
RT constant region of a gamma 4 chain.";
RL Biochem. J. 117:33-47(1970).
RN [4]
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 [5]
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 [6]
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 [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-177.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [8]
RP GLYCOSYLATION AT ASN-177.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Constant region of immunoglobulin heavy chains.
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:17576170, PubMed:20176268).
CC {ECO:0000303|PubMed:17576170, ECO:0000303|PubMed:20176268,
CC ECO:0000303|PubMed:22158414}.
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 IGHG4*04. {ECO:0000305}.
CC -!- CAUTION: For an example of a full-length immunoglobulin gamma heavy
CC chain see AC P0DOX5. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB59394.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; K01316; AAB59394.1; ALT_INIT; Genomic_DNA.
DR EMBL; AL928742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A90933; G4HU.
DR PDB; 1ADQ; X-ray; 3.15 A; A=118-323.
DR PDB; 1BBJ; X-ray; 3.10 A; B/H=1-98.
DR PDB; 2FL5; X-ray; 3.00 A; B/D/F/H=1-99.
DR PDB; 3EO1; X-ray; 3.10 A; B/E/H/K=1-105.
DR PDB; 4B53; X-ray; 1.80 A; A/B=223-327.
DR PDB; 4C54; X-ray; 1.90 A; A/B=114-327.
DR PDB; 4C55; X-ray; 2.35 A; A/B=110-327.
DR PDB; 4D2N; X-ray; 2.70 A; A/B/C/D=102-327.
DR PDB; 5HVW; X-ray; 1.95 A; A=115-324.
DR PDB; 5LG1; X-ray; 2.70 A; A/B=114-327.
DR PDB; 5W5M; X-ray; 1.90 A; A/B=106-327.
DR PDB; 5W5N; X-ray; 1.85 A; A/B=106-327.
DR PDB; 6WIB; X-ray; 2.55 A; A=115-325.
DR PDB; 6WMH; X-ray; 2.30 A; A/H=118-324.
DR PDB; 6WNA; X-ray; 2.40 A; H=118-324.
DR PDB; 6WOL; X-ray; 2.49 A; H=117-326.
DR PDBsum; 1ADQ; -.
DR PDBsum; 1BBJ; -.
DR PDBsum; 2FL5; -.
DR PDBsum; 3EO1; -.
DR PDBsum; 4B53; -.
DR PDBsum; 4C54; -.
DR PDBsum; 4C55; -.
DR PDBsum; 4D2N; -.
DR PDBsum; 5HVW; -.
DR PDBsum; 5LG1; -.
DR PDBsum; 5W5M; -.
DR PDBsum; 5W5N; -.
DR PDBsum; 6WIB; -.
DR PDBsum; 6WMH; -.
DR PDBsum; 6WNA; -.
DR PDBsum; 6WOL; -.
DR AlphaFoldDB; P01861; -.
DR SMR; P01861; -.
DR ComplexPortal; CPX-6949; IgG4 - Ig kappa immunoglobulin complex, constant regions.
DR ComplexPortal; CPX-6950; IgG4 - Ig lambda 1 immunoglobulin complex, constant regions.
DR ComplexPortal; CPX-6951; IgG4 - Ig lambda 2 immunoglobulin complex, constant regions.
DR ComplexPortal; CPX-6952; IgG4 - Ig lambda 3 immunoglobulin complex, constant regions.
DR ComplexPortal; CPX-6953; IgG4 - Ig lambda 6 immunoglobulin complex, constant regions.
DR ComplexPortal; CPX-6954; IgG4 - Ig lambda 7 immunoglobulin complex, constant regions.
DR IntAct; P01861; 6.
DR MINT; P01861; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB15258; Imlifidase.
DR IMGT_GENE-DB; IGHG4; -.
DR GlyConnect; 233; 111 N-Linked glycans.
DR GlyConnect; 770; 43 N-Linked glycans (1 site).
DR GlyGen; P01861; 2 sites, 141 N-linked glycans (2 sites).
DR iPTMnet; P01861; -.
DR PhosphoSitePlus; P01861; -.
DR BioMuta; IGHG4; -.
DR DMDM; 121047; -.
DR CPTAC; CPTAC-673; -.
DR jPOST; P01861; -.
DR MassIVE; P01861; -.
DR MaxQB; P01861; -.
DR PeptideAtlas; P01861; -.
DR PRIDE; P01861; -.
DR ProteomicsDB; 51497; -.
DR ABCD; P01861; 1 sequenced antibody.
DR Ensembl; ENST00000390543.3; ENSP00000374985.2; ENSG00000211892.4.
DR Ensembl; ENST00000618981.2; ENSP00000483393.2; ENSG00000277016.2.
DR UCSC; uc059gcs.1; human.
DR GeneCards; IGHG4; -.
DR HGNC; HGNC:5528; IGHG4.
DR HPA; ENSG00000211892; Tissue enriched (lymphoid).
DR MIM; 147130; gene.
DR neXtProt; NX_P01861; -.
DR OpenTargets; ENSG00000211892; -.
DR VEuPathDB; HostDB:ENSG00000211892; -.
DR GeneTree; ENSGT00940000162793; -.
DR HOGENOM; CLU_030625_0_2_1; -.
DR InParanoid; P01861; -.
DR PhylomeDB; P01861; -.
DR TreeFam; TF334176; -.
DR PathwayCommons; P01861; -.
DR Reactome; R-HSA-166663; Initial triggering of complement.
DR Reactome; R-HSA-173623; Classical antibody-mediated complement activation.
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-6785807; Interleukin-4 and Interleukin-13 signaling.
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 SignaLink; P01861; -.
DR ChiTaRS; IGHG4; human.
DR EvolutionaryTrace; P01861; -.
DR Pharos; P01861; Tclin.
DR PRO; PR:P01861; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P01861; protein.
DR Bgee; ENSG00000211892; Expressed in vermiform appendix and 90 other tissues.
DR ExpressionAtlas; P01861; baseline and differential.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0071735; C:IgG immunoglobulin complex; IC:ComplexPortal.
DR GO; GO:0042571; C:immunoglobulin complex, circulating; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0003823; F:antigen binding; IBA:GO_Central.
DR GO; GO:0034987; F:immunoglobulin receptor binding; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IC:ComplexPortal.
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: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; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003597; Ig_C1-set.
DR Pfam; PF07654; C1-set; 3.
DR SMART; SM00407; IGc1; 3.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00290; IG_MHC; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Immunity; Immunoglobulin;
KW Immunoglobulin domain; Membrane; Reference proteome; Secreted.
FT CHAIN <1..327
FT /note="Immunoglobulin heavy constant gamma 4"
FT /id="PRO_0000153581"
FT DOMAIN 6..99
FT /note="Ig-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 118..217
FT /note="Ig-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 226..322
FT /note="Ig-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 1..98
FT /note="CH1"
FT REGION 99..110
FT /note="Hinge"
FT REGION 111..220
FT /note="CH2"
FT REGION 221..327
FT /note="CH3"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19139490,
FT ECO:0000269|PubMed:19159218"
FT DISULFID 14
FT /note="Interchain (with a light chain)"
FT DISULFID 27..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 106
FT /note="Interchain (with a heavy chain)"
FT DISULFID 109
FT /note="Interchain (with a heavy chain)"
FT DISULFID 141..201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 247..305
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT NON_TER 1
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 23..35
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:1BBJ"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 63..71
FT /evidence="ECO:0007829|PDB:1BBJ"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:1BBJ"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 92..98
FT /evidence="ECO:0007829|PDB:1BBJ"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:5W5N"
FT HELIX 127..131
FT /evidence="ECO:0007829|PDB:5W5N"
FT STRAND 138..146
FT /evidence="ECO:0007829|PDB:5W5N"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:5HVW"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:5W5N"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:5W5N"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:5LG1"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:4C54"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:4C54"
FT STRAND 180..187
FT /evidence="ECO:0007829|PDB:5W5N"
FT HELIX 190..194
FT /evidence="ECO:0007829|PDB:5W5N"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:5W5N"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:6WOL"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:5W5N"
FT STRAND 227..231
FT /evidence="ECO:0007829|PDB:4B53"
FT HELIX 235..239
FT /evidence="ECO:0007829|PDB:4B53"
FT STRAND 240..255
FT /evidence="ECO:0007829|PDB:4B53"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:4B53"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:5HVW"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:4B53"
FT STRAND 284..293
FT /evidence="ECO:0007829|PDB:4B53"
FT HELIX 294..298
FT /evidence="ECO:0007829|PDB:4B53"
FT STRAND 303..308
FT /evidence="ECO:0007829|PDB:4B53"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:4B53"
FT STRAND 316..321
FT /evidence="ECO:0007829|PDB:4B53"
SQ SEQUENCE 327 AA; 35941 MW; 3EDBD811EF208E7A CRC64;
ASTKGPSVFP LAPCSRSTSE STAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS
GLYSLSSVVT VPSSSLGTKT YTCNVDHKPS NTKVDKRVES KYGPPCPSCP APEFLGGPSV
FLFPPKPKDT LMISRTPEVT CVVVDVSQED PEVQFNWYVD GVEVHNAKTK PREEQFNSTY
RVVSVLTVLH QDWLNGKEYK CKVSNKGLPS SIEKTISKAK GQPREPQVYT LPPSQEEMTK
NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSRL TVDKSRWQEG
NVFSCSVMHE ALHNHYTQKS LSLSLGK
