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Protein

Immunoglobulin heavy constant delta

Gene

IGHD

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

Functioni

Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268). 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 (PubMed:8774350, PubMed:10702483, PubMed:11282392).5 Publications1 Publication

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.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processAdaptive immunity, Immunity

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.

Protein family/group databases

IMGT/GENE-DBIGHD.

Names & Taxonomyi

Protein namesi
Recommended name:
Immunoglobulin heavy constant delta2 Publications
Alternative name(s):
Ig delta chain C regionCurated
Ig delta chain C region NIG-652 Publications
Ig delta chain C region WAH2 Publications
Gene namesi
Name:IGHD2 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:5480. IGHD.

Subcellular locationi

Isoform 1 :
Isoform 2 :

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

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3495.
OpenTargetsiENSG00000211898.

Polymorphism and mutation databases

DMDMi193806360.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000153570‹1 – 384Immunoglobulin heavy constant deltaAdd BLAST›384

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi15Interchain (with light chain)PROSITE-ProRule annotation1 Publication
Disulfide bondi28 ↔ 84PROSITE-ProRule annotation1 Publication
Glycosylationi109O-linked (GalNAc...) serine1 Publication1
Glycosylationi110O-linked (GalNAc...) serine1 Publication1
Glycosylationi113O-linked (GalNAc...) threonine1 Publication1
Glycosylationi126O-linked (GalNAc...) threonine1 Publication1
Glycosylationi127O-linked (GalNAc...) threonine1 Publication1
Glycosylationi131O-linked (GalNAc...) threonine1 Publication1
Glycosylationi132O-linked (GalNAc...) threonine1 Publication1
Disulfide bondi161Interchain (with heavy chain)1 Publication
Disulfide bondi190 ↔ 249PROSITE-ProRule annotation
Glycosylationi225N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi294 ↔ 355PROSITE-ProRule annotation
Glycosylationi316N-linked (GlcNAc...) asparagine4 Publications1
Glycosylationi367N-linked (GlcNAc...) asparagine2 Publications1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PeptideAtlasiP01880.
PRIDEiP01880.

PTM databases

iPTMnetiP01880.
PhosphoSitePlusiP01880.

Interactioni

Subunit structurei

Immunoglobulins are composed of two identical heavy chains and two identical light chains; disulfide-linked (PubMed:20176268). 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 (PubMed:11282392).2 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiP01880. 2 interactors.
MINTiMINT-4657766.

Structurei

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP01880.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 98Ig-like 1PROSITE-ProRule annotationAdd BLAST93
Domaini175 – 263Ig-like 2PROSITE-ProRule annotationAdd BLAST89
Domaini267 – 373Ig-like 3PROSITE-ProRule annotationAdd BLAST107

Keywords - Domaini

Immunoglobulin C region, Immunoglobulin domain, Transmembrane

Phylogenomic databases

GeneTreeiENSGT00730000112949.
HOVERGENiHBG107994.
InParanoidiP01880.
PhylomeDBiP01880.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR013151. Immunoglobulin.
PfamiView protein in Pfam
PF07654. C1-set. 2 hits.
PF00047. ig. 1 hit.
SMARTiView protein in SMART
SM00407. IGc1. 3 hits.
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 2 hits.

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, sIgD1 Publication

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 APARPPPQPR STTFWAWSVL RVPAPPSPQP
360 370 380
ATYTCVVSHE DSRTLLNASR SLEVSYVTDH GPMK
Length:384
Mass (Da):42,353
Last modified:March 15, 2017 - v3
Checksum:i726F08E73519DDDC
GO
Isoform 2 (identifier: P01880-2) [UniParc]FASTAAdd to basket
Also known as: Membrane-bound, mIgD1 Publication

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

Show »
Length:430
Mass (Da):47,500
Checksum:iE1F53C43C5AF144B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11
Sequence conflicti247V → I in BC063384 (PubMed:15489334).Curated1
Sequence conflicti330R → G AA sequence (PubMed:6787589).1
Sequence conflicti330R → G AA sequence (PubMed:6785754).1

Polymorphismi

There are several alleles. The sequence shown is that of IMGT allele IGHD*02.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_034489377 – 384VTDHGPMK → LAMTPLIPQSKDENSDDYTT FDDVGSLWTTLSTFVALFIL TLLYSGIVTFIKVK in isoform 2. 1 Publication8

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.
AC246787 Genomic DNA. No translation available.
BC021276 mRNA. No translation available.
BC063384 mRNA. No translation available.
PIRiA02175. DHHU.
S21205.
S30532.
UniGeneiHs.510635.

Genome annotation databases

EnsembliENST00000613640; ENSP00000478893; ENSG00000211898. [P01880-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

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.
AC246787 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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZVOX-ray-C/D1-383[»]
ProteinModelPortaliP01880.
SMRiP01880.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP01880. 2 interactors.
MINTiMINT-4657766.

Protein family/group databases

IMGT/GENE-DBIGHD.

PTM databases

iPTMnetiP01880.
PhosphoSitePlusiP01880.

Polymorphism and mutation databases

DMDMi193806360.

Proteomic databases

PeptideAtlasiP01880.
PRIDEiP01880.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000613640; ENSP00000478893; ENSG00000211898. [P01880-1]

Organism-specific databases

DisGeNETi3495.
GeneCardsiIGHD.
HGNCiHGNC:5480. IGHD.
MIMi147170. gene.
neXtProtiNX_P01880.
OpenTargetsiENSG00000211898.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00730000112949.
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.
PROiPR:P01880.
SOURCEiSearch...

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR013151. Immunoglobulin.
PfamiView protein in Pfam
PF07654. C1-set. 2 hits.
PF00047. ig. 1 hit.
SMARTiView protein in SMART
SM00407. IGc1. 3 hits.
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiIGHD_HUMAN
AccessioniPrimary (citable) accession number: P01880
Secondary accession number(s): A0A087WUS7, Q6P4I8, Q8WU38
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 15, 2017
Last modified: June 7, 2017
This is version 138 of the entry and version 3 of the sequence. See 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

Caution

For an example of a full length immunoglobulin delta heavy chain see AC P0DOX3.Curated

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

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.