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Protein

Immunoglobulin heavy constant mu

Gene

IGHM

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). IgM antibodies play an important role in primary defense mechanisms. They have been shown to be involved in early recognition of external invaders like bacteria and viruses, cellular waste and modified self, as well as in recognition and elimination of precancerous and cancerous lesions. The membrane-bound form is found in the majority of normal B-cells alongside with IgD. Membrane-bound IgM induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. It may cause death of cells by apoptosis. It is also found in soluble form, which represents about 30% of the total serum immunoglobulins where it is found almost exclusively as a homopentamer. After the antigen binds to the B-cell receptor, the secreted form is secreted in large amounts (PubMed:3137579, PubMed:16895553).4 Publications1 Publication

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • antibacterial humoral response Source: UniProtKB
  • B cell receptor signaling pathway Source: GO_Central
  • complement activation, classical pathway Source: GO_Central
  • defense response to Gram-negative bacterium Source: UniProtKB
  • innate immune response Source: UniProtKB
  • leukocyte migration Source: Reactome
  • phagocytosis, engulfment Source: GO_Central
  • phagocytosis, recognition Source: GO_Central
  • positive regulation of B cell activation Source: GO_Central

Keywordsi

Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-202733. Cell surface interactions at the vascular wall.
R-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-DBIGHM.

Names & Taxonomyi

Protein namesi
Recommended name:
Immunoglobulin heavy constant mu2 Publications
Alternative name(s):
Ig mu chain C regionCurated
Ig mu chain C region GAL1 Publication
Ig mu chain C region OU1 Publication
Gene namesi
Name:IGHM2 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:5541. IGHM.

Subcellular locationi

Isoform 1 :
  • Secreted

  • Note: During differentiation, B-lymphocytes switch from expression of membrane-bound IgM to secretion of IgM.

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • cell surface Source: UniProtKB
  • external side of plasma membrane Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
  • hexameric IgM immunoglobulin complex Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • pentameric IgM immunoglobulin complex Source: UniProtKB
  • plasma membrane Source: Reactome

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Agammaglobulinemia 1, autosomal recessive (AGM1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
See also OMIM:601495

Organism-specific databases

DisGeNETi3507.
MalaCardsiIGHM.
MIMi601495. phenotype.
OpenTargetsiENSG00000211899.
Orphaneti33110. Autosomal agammaglobulinemia.

Polymorphism and mutation databases

DMDMi193806374.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000153619‹1 – 453Immunoglobulin heavy constant muAdd BLAST›453

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi14Interchain (with light chain)1 Publication
Disulfide bondi28 ↔ 88PROSITE-ProRule annotation
Glycosylationi46N-linked (GlcNAc...) (complex) asparagine3 Publications1
Disulfide bondi134 ↔ 197PROSITE-ProRule annotation
Glycosylationi209N-linked (GlcNAc...) (complex) asparagine1 Publication1
Disulfide bondi214Interchain (with heavy chain)1 Publication
Disulfide bondi244 ↔ 303PROSITE-ProRule annotation
Glycosylationi272N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi279N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi291Interchain (with heavy chain of another subunit)1 Publication
Disulfide bondi351 ↔ 413PROSITE-ProRule annotation
GlycosylationiCAR_000219440N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi452Interchain (with heavy chain)1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PeptideAtlasiP01871.
PRIDEiP01871.

2D gel databases

UCD-2DPAGEiP01871.

PTM databases

iPTMnetiP01871.
PhosphoSitePlusiP01871.
UniCarbKBiP01871.

Interactioni

Subunit structurei

Immunoglobulins are composed of two identical heavy chains and two identical light chains; disulfide-linked.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CD19P153912EBI-953797,EBI-79902

Protein-protein interaction databases

IntActiP01871. 62 interactors.
MINTiMINT-2860005.

Structurei

Secondary structure

1453
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi178 – 184Combined sources7
Beta strandi196 – 201Combined sources6
Beta strandi206 – 208Combined sources3
Beta strandi210 – 216Combined sources7
Beta strandi223 – 227Combined sources5
Helixi236 – 238Combined sources3
Beta strandi240 – 242Combined sources3
Helixi249 – 251Combined sources3
Beta strandi253 – 258Combined sources6
Turni261 – 264Combined sources4
Beta strandi265 – 272Combined sources8
Helixi275 – 277Combined sources3
Beta strandi279 – 285Combined sources7
Beta strandi287 – 290Combined sources4
Beta strandi300 – 302Combined sources3
Beta strandi316 – 318Combined sources3
Beta strandi345 – 351Combined sources7
Beta strandi354 – 359Combined sources6
Beta strandi363 – 366Combined sources4
Beta strandi386 – 388Combined sources3
Beta strandi391 – 393Combined sources3
Beta strandi396 – 401Combined sources6
Helixi402 – 405Combined sources4
Beta strandi406 – 408Combined sources3
Beta strandi413 – 418Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AGJX-ray2.60H169-428[»]
ProteinModelPortaliP01871.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01871.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 102Ig-like 1PROSITE-ProRule annotationAdd BLAST97
Domaini111 – 211Ig-like 2PROSITE-ProRule annotationAdd BLAST101
Domaini229 – 319Ig-like 3PROSITE-ProRule annotationAdd BLAST91
Domaini329 – 430Ig-like 4PROSITE-ProRule annotationAdd BLAST102

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 105CH1Add BLAST105
Regioni106 – 217CH2Add BLAST112
Regioni218 – 323CH3Add BLAST106
Regioni324 – 452CH4Add BLAST129

Keywords - Domaini

Immunoglobulin C region, Immunoglobulin domain, Transmembrane

Phylogenomic databases

GeneTreeiENSGT00530000063726.
HOGENOMiHOG000202819.
HOVERGENiHBG005814.
InParanoidiP01871.
PhylomeDBiP01871.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
PfamiView protein in Pfam
PF07654. C1-set. 4 hits.
SMARTiView protein in SMART
SM00407. IGc1. 4 hits.
SUPFAMiSSF48726. SSF48726. 4 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 4 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: P01871-1) [UniParc]FASTAAdd to basket
Also known as: Secreted

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
GSASAPTLFP LVSCENSPSD TSSVAVGCLA QDFLPDSITF SWKYKNNSDI
60 70 80 90 100
SSTRGFPSVL RGGKYAATSQ VLLPSKDVMQ GTDEHVVCKV QHPNGNKEKN
110 120 130 140 150
VPLPVIAELP PKVSVFVPPR DGFFGNPRKS KLICQATGFS PRQIQVSWLR
160 170 180 190 200
EGKQVGSGVT TDQVQAEAKE SGPTTYKVTS TLTIKESDWL GQSMFTCRVD
210 220 230 240 250
HRGLTFQQNA SSMCVPDQDT AIRVFAIPPS FASIFLTKST KLTCLVTDLT
260 270 280 290 300
TYDSVTISWT RQNGEAVKTH TNISESHPNA TFSAVGEASI CEDDWNSGER
310 320 330 340 350
FTCTVTHTDL PSPLKQTISR PKGVALHRPD VYLLPPAREQ LNLRESATIT
360 370 380 390 400
CLVTGFSPAD VFVQWMQRGQ PLSPEKYVTS APMPEPQAPG RYFAHSILTV
410 420 430 440 450
SEEEWNTGET YTCVVAHEAL PNRVTERTVD KSTGKPTLYN VSLVMSDTAG

TCY
Length:453
Mass (Da):49,440
Last modified:March 15, 2017 - v4
Checksum:i607CA2FA7BFA0D39
GO
Isoform 2 (identifier: P01871-2) [UniParc]FASTAAdd to basket
Also known as: Membrane-bound

The sequence of this isoform differs from the canonical sequence as follows:
     434-453: GKPTLYNVSLVMSDTAGTCY → EGEVSADEEGFENLWATASTFIVLFLLSLFYSTTVTLFKVK

Show »
Length:474
Mass (Da):51,924
Checksum:i7A66A47C8810BDF1
GO

Sequence cautioni

The sequence CAA33065 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA33069 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA33071 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAA34971 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAE82013 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAE82014 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11
Sequence conflicti128R → RS in CAA34971 (PubMed:2115996).Curated1
Sequence conflicti220T → I in CAB37838 (Ref. 6) Curated1
Isoform 2 (identifier: P01871-2)
Sequence conflicti438S → N in AAB59422 (PubMed:6795593).Curated1
Sequence conflicti440D → E in AAB59422 (PubMed:6795593).Curated1
Sequence conflicti449A → T in AAB59422 (PubMed:6795593).Curated1
Sequence conflicti472 – 474KVK → K in AAB59422 (PubMed:6795593).Curated3
Sequence conflicti472 – 474KVK → K in CAA33065 (PubMed:2505237).Curated3

Polymorphismi

There are several alleles. The sequence shown is that of IMGT allele IGHM*04.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07789340F → L in IMGT allele IGHM*01. 1 Publication1
Natural variantiVAR_003903191G → S in IMGT allele IGHM*03. 1 Publication1
Natural variantiVAR_003904215V → G. Corresponds to variant dbSNP:rs12365Ensembl.1
Natural variantiVAR_077894414Missing in IMGT allele IGHM*01 IMGT allele IGHM*02. 2 Publications1
Natural variantiVAR_077895418E → D in IMGT allele IGHM*02. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_034488434 – 453GKPTL…AGTCY → EGEVSADEEGFENLWATAST FIVLFLLSLFYSTTVTLFKV K in isoform 2. 2 PublicationsAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14940 Genomic DNA. Translation: CAE82013.1. Different initiation.
X14940 Genomic DNA. Translation: CAE82014.1. Different initiation.
X14940 Genomic DNA. Translation: CAA33069.1. Different initiation.
X14940 Genomic DNA. Translation: CAA33070.1.
X14940 Genomic DNA. Translation: CAA33071.1. Sequence problems.
X14939 Genomic DNA. Translation: CAA33065.1. Different initiation.
X17115 mRNA. Translation: CAA34971.1. Different initiation.
X57086 mRNA. Translation: CAB37838.1.
AC244226 Genomic DNA. No translation available.
AC245166 Genomic DNA. No translation available.
AC246787 Genomic DNA. No translation available.
AC247036 Genomic DNA. No translation available.
K01310 Genomic DNA. Translation: AAB59422.1.
PIRiS14683.
S16510. MHHUM.
UniGeneiHs.510635.

Genome annotation databases

EnsembliENST00000390559; ENSP00000375001; ENSG00000211899. [P01871-1]
ENST00000626472; ENSP00000485962; ENSG00000282657. [P01871-1]
ENST00000637539; ENSP00000490253; ENSG00000211899. [P01871-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

IGHMbase

IGHM mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14940 Genomic DNA. Translation: CAE82013.1. Different initiation.
X14940 Genomic DNA. Translation: CAE82014.1. Different initiation.
X14940 Genomic DNA. Translation: CAA33069.1. Different initiation.
X14940 Genomic DNA. Translation: CAA33070.1.
X14940 Genomic DNA. Translation: CAA33071.1. Sequence problems.
X14939 Genomic DNA. Translation: CAA33065.1. Different initiation.
X17115 mRNA. Translation: CAA34971.1. Different initiation.
X57086 mRNA. Translation: CAB37838.1.
AC244226 Genomic DNA. No translation available.
AC245166 Genomic DNA. No translation available.
AC246787 Genomic DNA. No translation available.
AC247036 Genomic DNA. No translation available.
K01310 Genomic DNA. Translation: AAB59422.1.
PIRiS14683.
S16510. MHHUM.
UniGeneiHs.510635.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AGJX-ray2.60H169-428[»]
ProteinModelPortaliP01871.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP01871. 62 interactors.
MINTiMINT-2860005.

Protein family/group databases

IMGT/GENE-DBIGHM.

PTM databases

iPTMnetiP01871.
PhosphoSitePlusiP01871.
UniCarbKBiP01871.

Polymorphism and mutation databases

DMDMi193806374.

2D gel databases

UCD-2DPAGEiP01871.

Proteomic databases

PeptideAtlasiP01871.
PRIDEiP01871.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000390559; ENSP00000375001; ENSG00000211899. [P01871-1]
ENST00000626472; ENSP00000485962; ENSG00000282657. [P01871-1]
ENST00000637539; ENSP00000490253; ENSG00000211899. [P01871-2]

Organism-specific databases

DisGeNETi3507.
GeneCardsiIGHM.
HGNCiHGNC:5541. IGHM.
MalaCardsiIGHM.
MIMi147020. gene.
601495. phenotype.
neXtProtiNX_P01871.
OpenTargetsiENSG00000211899.
Orphaneti33110. Autosomal agammaglobulinemia.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00530000063726.
HOGENOMiHOG000202819.
HOVERGENiHBG005814.
InParanoidiP01871.
PhylomeDBiP01871.

Enzyme and pathway databases

ReactomeiR-HSA-202733. Cell surface interactions at the vascular wall.
R-HSA-5690714. CD22 mediated BCR regulation.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Miscellaneous databases

EvolutionaryTraceiP01871.
PROiPR:P01871.
SOURCEiSearch...

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
PfamiView protein in Pfam
PF07654. C1-set. 4 hits.
SMARTiView protein in SMART
SM00407. IGc1. 4 hits.
SUPFAMiSSF48726. SSF48726. 4 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 4 hits.
PS00290. IG_MHC. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiIGHM_HUMAN
AccessioniPrimary (citable) accession number: P01871
Secondary accession number(s): A0A075B6N9, A0A0G2JQL4, P20769
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 15, 2017
Last modified: May 10, 2017
This is version 172 of the entry and version 4 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 mu heavy chain see AC P0DOX6.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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.