IGD_HUMAN
ID IGD_HUMAN Reviewed; 512 AA.
AC P0DOX3;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=Immunoglobulin delta heavy chain {ECO:0000305};
DE AltName: Full=Immunoglobulin delta heavy chain WAH {ECO:0000305|PubMed:6806818};
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 PROTEIN SEQUENCE, DISULFIDE BOND, AND GLYCOSYLATION AT ASN-354; ASN-445 AND
RP ASN-496.
RX PubMed=6806818; DOI=10.1073/pnas.79.9.2850;
RA Takahashi N., Tetaert D., Debuire B., Lin L.-C., Putnam F.W.;
RT "Complete amino acid sequence of the delta heavy chain of human
RT immunoglobulin D.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:2850-2854(1982).
RN [2]
RP GLYCOSYLATION AT SER-238; THR-255; THR-256; THR-260 AND THR-261.
RA Takahashi N., Tetaert D., Putnam F.W.;
RT "Separation of hinge glycopeptides of human IgD by HPLC.";
RL (In) Elzinga M. (eds.);
RL Methods in protein sequence analysis, pp.463-470, Humana Press, Clifton.
RL (1982).
RN [3]
RP FUNCTION.
RX PubMed=8774350; DOI=10.1046/j.1365-2567.1996.d01-672.x;
RA Drenth J.P., Goertz J., Daha M.R., van der Meer J.W.;
RT "Immunoglobulin D enhances the release of tumor necrosis factor-alpha, and
RT interleukin-1 beta as well as interleukin-1 receptor antagonist from human
RT mononuclear cells.";
RL Immunology 88:355-362(1996).
RN [4]
RP REVIEW ON FUNCTION.
RX PubMed=10702483; DOI=10.1128/cdli.7.2.131-140.2000;
RA Vladutiu A.O.;
RT "Immunoglobulin D: properties, measurement, and clinical relevance.";
RL Clin. Diagn. Lab. Immunol. 7:131-140(2000).
RN [5]
RP REVIEW ON FUNCTION; SUBCELLULAR LOCATION AND SUBUNIT.
RX PubMed=11282392; DOI=10.1016/s0161-5890(01)00006-2;
RA Preud'homme J.L., Petit I., Barra A., Morel F., Lecron J.C., Lelievre E.;
RT "Structural and functional properties of membrane and secreted IgD.";
RL Mol. Immunol. 37:871-887(2000).
RN [6]
RP REVIEW.
RX PubMed=16895553; DOI=10.1111/j.1365-2567.2006.02386.x;
RA Geisberger R., Lamers M., Achatz G.;
RT "The riddle of the dual expression of IgM and IgD.";
RL Immunology 118:429-437(2006).
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).
CC -!- FUNCTION: Immunoglobulins, also known as antibodies, are membrane-bound
CC or 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 IgD is the major antigen receptor isotype on the surface of most
CC peripheral B cells, where it is coexpressed with IgM. The membrane-
CC bound IgD (mIgD) induces the phosphorylation of CD79A and CD79B by the
CC Src family of protein tyrosine kinases. Soluble IgD (sIgD)
CC concentration in serum is below those of IgG, IgA, and IgM but much
CC higher than that of IgE. IgM and IgD molecules present on B cells have
CC identical V regions and antigen-binding sites. After the antigen binds
CC to the B cell receptor, the secreted form sIgD is shut off. IgD is a
CC potent inducer of TNF, IL1B, and IL1RN. IgD also induces release of
CC IL6, IL10, and LIF from peripheral blood mononuclear cells. Monocytes
CC seem to be the main producers of cytokines in vitro in the presence of
CC IgD (PubMed:8774350, PubMed:11282392, PubMed:10702483,
CC PubMed:16895553). {ECO:0000269|PubMed:8774350,
CC ECO:0000303|PubMed:10702483, ECO:0000303|PubMed:11282392,
CC ECO:0000303|PubMed:16895553, ECO:0000303|PubMed:17576170,
CC ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}.
CC -!- SUBUNIT: Immunoglobulins are composed of two identical heavy chains and
CC two identical light chains; disulfide-linked (PubMed:20176268). An IgD
CC molecule contains thus a delta heavy chain combined with either a kappa
CC or a lambda light chains. Kappa light chains are found predominantly on
CC the membrane IgD (mIgD) form and lambda on the secreted IgD (sIgD)
CC form, this fact is poorly understood. Membrane-bound IgD molecules are
CC non-covalently associated with a heterodimer of CD79A and CD79B
CC (PubMed:11282392, PubMed:16895553). {ECO:0000303|PubMed:11282392,
CC ECO:0000303|PubMed:16895553, ECO:0000303|PubMed:20176268}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000303|PubMed:11282392,
CC ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}. Cell
CC membrane {ECO:0000303|PubMed:11282392, ECO:0000303|PubMed:20176268,
CC ECO:0000303|PubMed:22158414}.
CC -!- CAUTION: This sequence is an example of a full-length immunoglobulin
CC delta heavy chain. {ECO:0000305}.
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DR PDB; 1ZVO; X-ray; -; C/D=1-512.
DR PDBsum; 1ZVO; -.
DR AlphaFoldDB; P0DOX3; -.
DR SMR; P0DOX3; -.
DR iPTMnet; P0DOX3; -.
DR jPOST; P0DOX3; -.
DR PRIDE; P0DOX3; -.
DR SIGNOR; P0DOX3; -.
DR Pharos; P0DOX3; Tbio.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0019814; C:immunoglobulin complex; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0042117; P:monocyte activation; IDA:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR GO; GO:0032732; P:positive regulation of interleukin-1 production; IDA:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 4.
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 InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR013151; Immunoglobulin.
DR Pfam; PF07654; C1-set; 2.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00407; IGc1; 3.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 4.
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; Secreted.
FT CHAIN 1..512
FT /note="Immunoglobulin delta heavy chain"
FT /id="PRO_0000439284"
FT DOMAIN 1..97
FT /note="Ig-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 135..227
FT /note="Ig-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 304..392
FT /note="Ig-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 396..502
FT /note="Ig-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 1..129
FT /note="Variable (V) domain, involved in antigen
FT recognition"
FT /evidence="ECO:0000305|PubMed:6806818"
FT REGION 130..512
FT /note="Constant (C) domain"
FT /evidence="ECO:0000305|PubMed:6806818"
FT REGION 225..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 235..263
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..289
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 238
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|Ref.2"
FT CARBOHYD 255
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.2"
FT CARBOHYD 256
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.2"
FT CARBOHYD 260
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.2"
FT CARBOHYD 261
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|Ref.2"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6806818"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6806818"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6806818"
FT DISULFID 22..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000303|PubMed:6806818"
FT DISULFID 144
FT /note="Interchain (with light chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000303|PubMed:6806818"
FT DISULFID 157..213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000303|PubMed:6806818"
FT DISULFID 290
FT /note="Interchain (with heavy chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000303|PubMed:6806818"
FT DISULFID 319..378
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000303|PubMed:6806818"
FT DISULFID 423..484
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000303|PubMed:6806818"
SQ SEQUENCE 512 AA; 56224 MW; 74FBAD9F87EDE94C CRC64;
RLQLQESGPG LVKPSETLSL TCIVSGGPIR RTGYYWGWIR QPPGKGLEWI GGVYYTGSIY
YNPSLRGRVT ISVDTSRNQF SLNLRSMSAA DTAMYYCARG NPPPYYDIGT GSDDGIDVWG
QGTTVHVSSA PTKAPDVFPI ISGCRHPKDN SPVVLACLIT GYHPTSVTVT WYMGTQSQPQ
RTFPEIQRRD SYYMTSSQLS TPLQQWRQGE YKCVVQHTAS KSKKEIFRWP ESPKAQASSV
PTAQPQAEGS LAKATTAPAT TRNTGRGGEE KKKEKEKEEQ EERETKTPEC PSHTQPLGVY
LLTPAVQDLW LRDKATFTCF VVGSDLKDAH LTWEVAGKVP TGGVEEGLLE RHSNGSQSQH
SRLTLPRSLW NAGTSVTCTL NHPSLPPQRL MALREPAAQA PVKLSLNLLA SSDPPEAASW
LLCEVSGFSP PNILLMWLED QREVNTSGFA PARPPPQPGS TTFWAWSVLR VPAPPSPQPA
TYTCVVSHED SRTLLNASRS LEVSYVTDHG PM
