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Protein

Ig delta chain C region

Gene

IGHD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

IgD is the major antigen receptor isotype on the surface of most peripheral B-cells, where it is coexpressed with IgM. The membrane-bound IgD (mIgD) induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. Soluble IgD (sIgD) concentration in serum below those of IgG, IgA, and IgM but much higher than that of IgE. IgM and IgD molecules present on B cells have identical V regions and antigen-binding sites. After the antigen binds to the B-cell receptor, the secreted form sIgD is shut off. IgD is a potent inducer of TNF, IL1B, and IL1RN. IgD also induces release of IL6, IL10, and LIF from peripheral blood mononuclear cells. Monocytes seem to be the main producers of cytokines in vitro in the presence of IgD.1 Publication

GO - Molecular functioni

  • antigen binding Source: UniProtKB
  • immunoglobulin receptor binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-5690714. CD22 mediated BCR regulation.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Names & Taxonomyi

Protein namesi
Recommended name:
Ig delta chain C region
Gene namesi
Name:IGHD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:5480. IGHD.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • external side of plasma membrane Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • immunoglobulin complex, circulating Source: GO_Central
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Polymorphism and mutation databases

DMDMi193806360.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – 384›384Ig delta chain C regionPRO_0000153570Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi15 – 15Interchain (with light chain)PROSITE-ProRule annotation1 Publication
Disulfide bondi28 ↔ 84PROSITE-ProRule annotation1 Publication
Glycosylationi109 – 1091O-linked (GalNAc...)1 Publication
Glycosylationi110 – 1101O-linked (GalNAc...)1 Publication
Glycosylationi113 – 1131O-linked (GalNAc...)1 Publication
Glycosylationi126 – 1261O-linked (GalNAc...)1 Publication
Glycosylationi127 – 1271O-linked (GalNAc...)1 Publication
Glycosylationi131 – 1311O-linked (GalNAc...)1 Publication
Glycosylationi132 – 1321O-linked (GalNAc...)1 Publication
Disulfide bondi161 – 161Interchain (with heavy chain)PROSITE-ProRule annotation1 Publication
Disulfide bondi190 ↔ 249PROSITE-ProRule annotation
Glycosylationi225 – 2251N-linked (GlcNAc...)3 Publications
Disulfide bondi294 ↔ 355PROSITE-ProRule annotation
Glycosylationi316 – 3161N-linked (GlcNAc...)4 Publications
Glycosylationi367 – 3671N-linked (GlcNAc...)2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP01880.

PTM databases

iPTMnetiP01880.

Interactioni

Subunit structurei

Immunoglobulin (Ig) molecules consist of two chains, one heavy chain (which can be alpha, delta, epsilon, gamma or mu) and one light chain (which can be kappa or lambda) each consisting of a variable and a constant region. An IgD molecule contains thus a delta heavy chain combined with either a kappa or a lambda light chains. Kappa light chains are found predominantly on the membrane IgD (mIgD) form and lambda on the secreted IgD (sIgD) form, this fact is poorly understood. Membrane-bound IgD molecules are non-covalently associated with a heterodimer of CD79A and CD79B.

GO - Molecular functioni

Protein-protein interaction databases

IntActiP01880. 2 interactions.
MINTiMINT-4657766.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZVOX-ray-C/D1-383[»]
ProteinModelPortaliP01880.
SMRiP01880. Positions 1-375.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01880.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 9893Ig-like 1Add
BLAST
Domaini175 – 26389Ig-like 2Add
BLAST
Domaini267 – 373107Ig-like 3Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin C region, Immunoglobulin domain, Repeat, Transmembrane

Phylogenomic databases

HOVERGENiHBG107994.
InParanoidiP01880.
PhylomeDBiP01880.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamiPF07654. C1-set. 2 hits.
PF00047. ig. 1 hit.
[Graphical view]
SMARTiSM00407. IGc1. 3 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P01880-1) [UniParc]FASTAAdd to basket

Also known as: Secreted, sIgD

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
APTKAPDVFP IISGCRHPKD NSPVVLACLI TGYHPTSVTV TWYMGTQSQP
60 70 80 90 100
QRTFPEIQRR DSYYMTSSQL STPLQQWRQG EYKCVVQHTA SKSKKEIFRW
110 120 130 140 150
PESPKAQASS VPTAQPQAEG SLAKATTAPA TTRNTGRGGE EKKKEKEKEE
160 170 180 190 200
QEERETKTPE CPSHTQPLGV YLLTPAVQDL WLRDKATFTC FVVGSDLKDA
210 220 230 240 250
HLTWEVAGKV PTGGVEEGLL ERHSNGSQSQ HSRLTLPRSL WNAGTSVTCT
260 270 280 290 300
LNHPSLPPQR LMALREPAAQ APVKLSLNLL ASSDPPEAAS WLLCEVSGFS
310 320 330 340 350
PPNILLMWLE DQREVNTSGF APARPPPQPG STTFWAWSVL RVPAPPSPQP
360 370 380
ATYTCVVSHE DSRTLLNASR SLEVSYVTDH GPMK
Length:384
Mass (Da):42,254
Last modified:July 1, 2008 - v2
Checksum:i727A1DE73519C76C
GO
Isoform 2 (identifier: P01880-2) [UniParc]FASTAAdd to basket

Also known as: Membrane-bound, mIgD

The sequence of this isoform differs from the canonical sequence as follows:
     377-384: VTDHGPMK → LAMTPLIPQSKDENSDDYTTFDDVGSLWTTLSTFVALFILTLLYSGIVTFIKVK

Show »
Length:430
Mass (Da):47,401
Checksum:i41F52D52D80479FD
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11
Sequence conflicti247 – 2471V → I in BC063384 (PubMed:15489334).Curated
Sequence conflicti330 – 3301G → R in AAA52770 (PubMed:3922054).Curated
Sequence conflicti330 – 3301G → R in X57331 (PubMed:2518659).Curated

Polymorphismi

The following alleles of IGHD are known: IGHD*01 and IGHD*02. They are identical at protein level.2 Publications

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei377 – 3848VTDHGPMK → LAMTPLIPQSKDENSDDYTT FDDVGSLWTTLSTFVALFIL TLLYSGIVTFIKVK in isoform 2. 1 PublicationVSP_034489

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02880
, K02875, K02876, K02877, K02878, K02879 Genomic DNA. Translation: AAA52770.1.
X57331 Genomic DNA. No translation available.
BC021276 mRNA. No translation available.
BC063384 mRNA. No translation available.
PIRiA02175. DHHU.
S21205.
S30532.
UniGeneiHs.510635.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

IMGT/GENE-DB

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02880
, K02875, K02876, K02877, K02878, K02879 Genomic DNA. Translation: AAA52770.1.
X57331 Genomic DNA. No translation available.
BC021276 mRNA. No translation available.
BC063384 mRNA. No translation available.
PIRiA02175. DHHU.
S21205.
S30532.
UniGeneiHs.510635.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZVOX-ray-C/D1-383[»]
ProteinModelPortaliP01880.
SMRiP01880. Positions 1-375.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP01880. 2 interactions.
MINTiMINT-4657766.

Protein family/group databases

IMGTiSearch...
Search...
Search...
Search...
Search...
Search...
Search...
Search...
Search...

PTM databases

iPTMnetiP01880.

Polymorphism and mutation databases

DMDMi193806360.

Proteomic databases

PRIDEiP01880.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

GeneCardsiIGHD.
HGNCiHGNC:5480. IGHD.
MIMi147170. gene.
neXtProtiNX_P01880.
GenAtlasiSearch...

Phylogenomic databases

HOVERGENiHBG107994.
InParanoidiP01880.
PhylomeDBiP01880.

Enzyme and pathway databases

ReactomeiR-HSA-5690714. CD22 mediated BCR regulation.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Miscellaneous databases

EvolutionaryTraceiP01880.
PROiP01880.
SOURCEiSearch...

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamiPF07654. C1-set. 2 hits.
PF00047. ig. 1 hit.
[Graphical view]
SMARTiSM00407. IGc1. 3 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Human immunoglobulin D: genomic sequence of the delta heavy chain."
    White M.B., Shen A.L., Word C.J., Tucker P.W., Blattner F.R.
    Science 228:733-737(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE IGHD*01).
  2. "The human immunoglobulin C mu-C delta locus: complete nucleotide sequence and structural analysis."
    Word C.J., White M.B., Kuziel W.A., Shen A.L., Blattner F.R., Tucker P.W.
    Int. Immunol. 1:296-309(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE IGHD*02).
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: B-cell.
  4. "Amino acid sequence of the first constant region domain and the hinge region of the delta heavy chain of human IgD."
    Putnam F.W., Takahashi N., Tetaert D., Debuire B., Lin L.-C.
    Proc. Natl. Acad. Sci. U.S.A. 78:6168-6172(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-162 (MYELOMA PROTEIN WAH).
  5. "Primary structure of the Fc region of human immunoglobulin D: implications for evolutionary origin and biological function."
    Lin L.-C., Putnam F.W.
    Proc. Natl. Acad. Sci. U.S.A. 78:504-508(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 158-383 (MYELOMA PROTEIN WAH).
  6. "Amino acid sequence of galactosamine-containing glycopeptides in the hinge region of a human immunoglobulin D."
    Takayasu T., Suzuki S., Kametani F., Takahashi N., Shinoda T., Okuyama T., Munekata E.
    Biochem. Biophys. Res. Commun. 105:1066-1071(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 103-137 (MYELOMA PROTEIN NIG-65), GLYCOSYLATION.
  7. "Complete amino acid sequence of the Fc region of a human delta chain."
    Shinoda T., Takahashi N., Takayasu T., Okuyama T., Shimizu A.
    Proc. Natl. Acad. Sci. U.S.A. 78:785-789(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 158-383 (MYELOMA PROTEIN NIG-65).
  8. "Immunoglobulin D enhances the release of tumor necrosis factor-alpha, and interleukin-1 beta as well as interleukin-1 receptor antagonist from human mononuclear cells."
    Drenth J.P., Goertz J., Daha M.R., van der Meer J.W.
    Immunology 88:355-362(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Immunoglobulin D: properties, measurement, and clinical relevance."
    Vladutiu A.O.
    Clin. Diagn. Lab. Immunol. 7:131-140(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  10. "Structural and functional properties of membrane and secreted IgD."
    Preud'homme J.L., Petit I., Barra A., Morel F., Lecron J.C., Lelievre E.
    Mol. Immunol. 37:871-887(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  11. "The riddle of the dual expression of IgM and IgD."
    Geisberger R., Lamers M., Achatz G.
    Immunology 118:429-437(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  12. "Amino acid sequence and location of the three glycopeptides in the Fc region of human immunoglobulin D."
    Takayasu T., Takahashi N., Shinoda T.
    Biochem. Biophys. Res. Commun. 97:635-641(1980) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT ASN-225; ASN-316 AND ASN-367.
  13. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
    Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
    J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-225 AND ASN-316.
    Tissue: Plasma.
  14. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-316.
    Tissue: Liver.

Entry informationi

Entry nameiIGHD_HUMAN
AccessioniPrimary (citable) accession number: P01880
Secondary accession number(s): Q6P4I8, Q8WU38
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 2008
Last modified: June 8, 2016
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

IgD is not present in every species and this does not relate to phylogeny and evolution. IgD is present in primates, dog, mouse and rat whereas it is undetectable in rabbit, guinea pig, swine, cattle, sheep and Xenopus.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.