UniProtKB - P01871 (IGHM_HUMAN)
Protein
Immunoglobulin heavy constant mu
Gene
IGHM
Organism
Homo sapiens (Human)
Status
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
Caution
For an example of a full-length immunoglobulin mu heavy chain see AC P0DOX6.Curated
GO - Molecular functioni
- antigen binding Source: GO_Central
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 bacterium 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 process | Adaptive immunity, Immunity |
Enzyme and pathway databases
PathwayCommonsi | P01871 |
Reactomei | R-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-DB | IGHM |
Names & Taxonomyi
Protein namesi | Recommended name: Immunoglobulin heavy constant mu2 PublicationsAlternative name(s): Ig mu chain C regionCurated Ig mu chain C region BOT1 Publication Ig mu chain C region GAL1 Publication Ig mu chain C region OU1 Publication |
Gene namesi | Name:IGHM2 Publications |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5541, IGHM |
MIMi | 147020, gene |
neXtProti | NX_P01871 |
VEuPathDBi | HostDB:ENSG00000211899.8 |
Subcellular locationi
Extracellular region or secreted
Note: During differentiation, B-lymphocytes switch from expression of membrane-bound IgM to secretion of IgM.
Plasma membrane
Extracellular region or secreted
- blood microparticle Source: UniProtKB
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
- hexameric IgM immunoglobulin complex Source: UniProtKB
- immunoglobulin complex, circulating Source: GO_Central
- pentameric IgM immunoglobulin complex Source: UniProtKB
Plasma Membrane
- external side of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Other locations
- cell surface Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
Keywords - Cellular componenti
Cell membrane, Immunoglobulin, Membrane, SecretedPathology & Biotechi
Involvement in diseasei
Agammaglobulinemia 1, autosomal recessive (AGM1)1 Publication
The disease is caused by variants 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.
Related information in OMIMOrganism-specific databases
MalaCardsi | IGHM |
MIMi | 601495, phenotype |
OpenTargetsi | ENSG00000211899 |
Orphaneti | 33110, Autosomal agammaglobulinemia |
Miscellaneous databases
Pharosi | P01871, Tbio |
Chemistry databases
DrugBanki | DB01593, Zinc DB14487, Zinc acetate |
Genetic variation databases
BioMutai | IGHM |
DMDMi | 127506 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000153619 | ‹1 – 453 | Immunoglobulin heavy constant muAdd BLAST | ›453 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 14 | Interchain (with light chain)1 Publication | ||
Disulfide bondi | 28 ↔ 88 | Combined sources2 Publications | ||
Glycosylationi | 46 | N-linked (GlcNAc...) (complex) asparagineCombined sources4 Publications | 1 | |
Disulfide bondi | 134 ↔ 197 | PROSITE-ProRule annotation | ||
Glycosylationi | 209 | N-linked (GlcNAc...) (complex) asparagine1 Publication | 1 | |
Disulfide bondi | 214 | Interchain (with heavy chain)1 Publication | ||
Disulfide bondi | 244 ↔ 303 | PROSITE-ProRule annotation | ||
Glycosylationi | 272 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 279 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 291 | Interchain (with heavy chain of another subunit)1 Publication | ||
Disulfide bondi | 351 ↔ 413 | PROSITE-ProRule annotation | ||
GlycosylationiCAR_000219 | 440 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 452 | Interchain (with heavy chain)1 Publication |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
CPTACi | non-CPTAC-2676 |
jPOSTi | P01871 |
MassIVEi | P01871 |
PeptideAtlasi | P01871 |
PRIDEi | P01871 |
ProteomicsDBi | 51498 [P01871-1] 51499 [P01871-2] 51686 |
2D gel databases
UCD-2DPAGEi | P01871 |
PTM databases
CarbonylDBi | P01871 |
GlyConnecti | 280, 122 N-Linked glycans (5 sites) |
GlyGeni | P01871, 6 sites, 83 N-linked glycans (5 sites) |
iPTMneti | P01871 |
PhosphoSitePlusi | P01871 |
SwissPalmi | P01871 |
Expressioni
Gene expression databases
Bgeei | ENSG00000211899, Expressed in lymph node and 191 other tissues |
ExpressionAtlasi | P01871, baseline and differential |
Interactioni
Subunit structurei
Immunoglobulins are composed of two identical heavy chains and two identical light chains; disulfide-linked.
1 PublicationProtein-protein interaction databases
CORUMi | P01871 |
IntActi | P01871, 67 interactors |
MINTi | P01871 |
Miscellaneous databases
RNActi | P01871, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P01871 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P01871 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 6 – 102 | Ig-like 1PROSITE-ProRule annotationAdd BLAST | 97 | |
Domaini | 111 – 211 | Ig-like 2PROSITE-ProRule annotationAdd BLAST | 101 | |
Domaini | 229 – 319 | Ig-like 3PROSITE-ProRule annotationAdd BLAST | 91 | |
Domaini | 329 – 430 | Ig-like 4PROSITE-ProRule annotationAdd BLAST | 102 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 105 | CH1Add BLAST | 105 | |
Regioni | 106 – 217 | CH2Add BLAST | 112 | |
Regioni | 218 – 323 | CH3Add BLAST | 106 | |
Regioni | 324 – 452 | CH4Add BLAST | 129 |
Keywords - Domaini
Immunoglobulin domain, TransmembranePhylogenomic databases
GeneTreei | ENSGT00940000161491 |
InParanoidi | P01871 |
OMAi | MVTERSV |
PhylomeDBi | P01871 |
Family and domain databases
Gene3Di | 2.60.40.10, 4 hits |
InterProi | View protein in InterPro IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003006, Ig/MHC_CS IPR003597, Ig_C1-set |
Pfami | View protein in Pfam PF07654, C1-set, 4 hits |
SMARTi | View protein in SMART SM00407, IGc1, 4 hits |
SUPFAMi | SSF48726, SSF48726, 4 hits |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 4 hits PS00290, IG_MHC, 3 hits |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: P01871-1) [UniParc]FASTAAdd to basket
Also known as: Secreted
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Sequence cautioni
The sequence CAA33065 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence CAA33069 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence CAA33071 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAA34971 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence CAE82013 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence CAE82014 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Non-terminal residuei | 1 | 1 | |||
Sequence conflicti | 128 | R → RS in CAA34971 (PubMed:2115996).Curated | 1 | ||
Sequence conflicti | 145 | Q → E AA sequence (PubMed:6425189).Curated | 1 | ||
Sequence conflicti | 163 – 165 | QVQ → EVE AA sequence (PubMed:6425189).Curated | 3 | ||
Sequence conflicti | 220 | T → I in CAB37838 (Ref. 6) Curated | 1 | ||
Sequence conflicti | 263 | N → D AA sequence (PubMed:6425189).Curated | 1 | ||
Sequence conflicti | 296 | N → D AA sequence (PubMed:6425189).Curated | 1 | ||
Isoform 2 (identifier: P01871-2) | |||||
Sequence conflicti | 438 | S → N in AAB59422 (PubMed:6795593).Curated | 1 | ||
Sequence conflicti | 440 | D → E in AAB59422 (PubMed:6795593).Curated | 1 | ||
Sequence conflicti | 449 | A → T in AAB59422 (PubMed:6795593).Curated | 1 | ||
Sequence conflicti | 472 – 474 | KVK → K in AAB59422 (PubMed:6795593).Curated | 3 | ||
Sequence conflicti | 472 – 474 | KVK → K in CAA33065 (PubMed:2505237).Curated | 3 |
Polymorphismi
There are several alleles. The sequence shown is that of IMGT allele IGHM*04.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077893 | 40 | F → L in IMGT allele IGHM*01. 1 Publication | 1 | |
Natural variantiVAR_003903 | 191 | G → S in IMGT allele IGHM*03. 1 Publication | 1 | |
Natural variantiVAR_003904 | 215 | V → G1 PublicationCorresponds to variant dbSNP:rs12365Ensembl. | 1 | |
Natural variantiVAR_077894 | 414 | Missing in IMGT allele IGHM*01 IMGT allele IGHM*02. 2 Publications | 1 | |
Natural variantiVAR_077895 | 418 | E → D in IMGT allele IGHM*02. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_034488 | 434 – 453 | GKPTL…AGTCY → EGEVSADEEGFENLWATAST FIVLFLLSLFYSTTVTLFKV K in isoform 2. 2 PublicationsAdd BLAST | 20 |
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 |
PIRi | A02163, MHHUBT S14683 S16510, MHHUM |
Genome annotation databases
Ensembli | ENST00000390559; ENSP00000375001; ENSG00000211899 [P01871-1] ENST00000626472; ENSP00000485962; ENSG00000282657 [P01871-1] ENST00000637539; ENSP00000490253; ENSG00000211899 [P01871-2] |
UCSCi | uc059gdp.1, human |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
PIRi | A02163, MHHUBT S14683 S16510, MHHUM |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1HEZ | X-ray | 2.70 | B/D | 1-104 | [»] | |
2AGJ | X-ray | 2.60 | H | 1-105 | [»] | |
2RCJ | X-ray | - | C/D/G/H/K/L/O/P/S/T | 1-326 | [»] | |
6KXS | electron microscopy | 3.40 | A/B/C/D/E/F/G/H/K/L | 106-453 | [»] | |
SMRi | P01871 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
CORUMi | P01871 |
IntActi | P01871, 67 interactors |
MINTi | P01871 |
Chemistry databases
DrugBanki | DB01593, Zinc DB14487, Zinc acetate |
Protein family/group databases
IMGT/GENE-DB | IGHM |
PTM databases
CarbonylDBi | P01871 |
GlyConnecti | 280, 122 N-Linked glycans (5 sites) |
GlyGeni | P01871, 6 sites, 83 N-linked glycans (5 sites) |
iPTMneti | P01871 |
PhosphoSitePlusi | P01871 |
SwissPalmi | P01871 |
Genetic variation databases
BioMutai | IGHM |
DMDMi | 127506 |
2D gel databases
UCD-2DPAGEi | P01871 |
Proteomic databases
CPTACi | non-CPTAC-2676 |
jPOSTi | P01871 |
MassIVEi | P01871 |
PeptideAtlasi | P01871 |
PRIDEi | P01871 |
ProteomicsDBi | 51498 [P01871-1] 51499 [P01871-2] 51686 |
Protocols and materials databases
ABCDi | P01871, 1 sequenced antibody |
Genome annotation databases
Ensembli | ENST00000390559; ENSP00000375001; ENSG00000211899 [P01871-1] ENST00000626472; ENSP00000485962; ENSG00000282657 [P01871-1] ENST00000637539; ENSP00000490253; ENSG00000211899 [P01871-2] |
UCSCi | uc059gdp.1, human |
Organism-specific databases
GeneCardsi | IGHM |
HGNCi | HGNC:5541, IGHM |
MalaCardsi | IGHM |
MIMi | 147020, gene 601495, phenotype |
neXtProti | NX_P01871 |
OpenTargetsi | ENSG00000211899 |
Orphaneti | 33110, Autosomal agammaglobulinemia |
VEuPathDBi | HostDB:ENSG00000211899.8 |
GenAtlasi | Search... |
Phylogenomic databases
GeneTreei | ENSGT00940000161491 |
InParanoidi | P01871 |
OMAi | MVTERSV |
PhylomeDBi | P01871 |
Enzyme and pathway databases
PathwayCommonsi | P01871 |
Reactomei | R-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
ChiTaRSi | IGHM, human |
EvolutionaryTracei | P01871 |
Pharosi | P01871, Tbio |
PROi | PR:P01871 |
RNActi | P01871, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000211899, Expressed in lymph node and 191 other tissues |
ExpressionAtlasi | P01871, baseline and differential |
Family and domain databases
Gene3Di | 2.60.40.10, 4 hits |
InterProi | View protein in InterPro IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003006, Ig/MHC_CS IPR003597, Ig_C1-set |
Pfami | View protein in Pfam PF07654, C1-set, 4 hits |
SMARTi | View protein in SMART SM00407, IGc1, 4 hits |
SUPFAMi | SSF48726, SSF48726, 4 hits |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 4 hits PS00290, IG_MHC, 3 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IGHM_HUMAN | |
Accessioni | P01871Primary (citable) accession number: P01871 Secondary accession number(s): A0A075B6N9 P20769 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | March 15, 2017 | |
Last modified: | April 7, 2021 | |
This is version 200 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references