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P01871 (IGHM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ig mu chain C region
Gene names
Name:IGHM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length452 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9

Subunit structure

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 IgM molecule contains thus a mu heavy chain combined with either a kappa or a lambda light chains. It is found almost exclusively as a homopentamer in the serum. Membrane-bound IgM molecules are non-covalently associated with heterodimer of CD79A and CD79B.

Subcellular location

Isoform 1: Secreted. Note: During differentiation, B-lymphocytes switch from expression of membrane-bound IgM to secretion of IgM.

Isoform 2: Cell membrane; Single-pass type I membrane protein.

Polymorphism

All 4 combinations of the S/G and V/G polymorphisms at positions 191 and 215 have been observed in human mu chains.

Involvement in disease

Agammaglobulinemia 1, autosomal recessive (AGM1) [MIM:601495]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence caution

The sequence CAA33071.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAA34971.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P01871-1)

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.
Isoform 2 (identifier: P01871-2)

Also known as: Membrane-bound;

The sequence of this isoform differs from the canonical sequence as follows:
     433-452: GKPTLYNVSLVMSDTAGTCY → EGEVSADEEGFENLWATASTFIVLFLLSLFYSTTVTLFKVK

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain‹1 – 452›452Ig mu chain C region
PRO_0000153619

Regions

Region1 – 105105CH1
Region106 – 217112CH2
Region218 – 323106CH3
Region324 – 452129CH4

Amino acid modifications

Glycosylation461N-linked (GlcNAc...) (complex) Ref.12 Ref.13 Ref.14
Glycosylation2091N-linked (GlcNAc...) (complex) Ref.14
Glycosylation2721N-linked (GlcNAc...)
Glycosylation2791N-linked (GlcNAc...)
Glycosylation4391N-linked (GlcNAc...)
CAR_000219
Disulfide bond14Interchain (with light chain) Ref.6
Disulfide bond28 ↔ 88 Ref.6
Disulfide bond134 ↔ 197 Ref.6
Disulfide bond214Interchain (with heavy chain) Ref.6
Disulfide bond244 ↔ 303 Ref.6
Disulfide bond291Interchain (with heavy chain of another subunit) Ref.6
Disulfide bond351 ↔ 413 Ref.6
Disulfide bond451Interchain (with heavy chain) Ref.6

Natural variations

Alternative sequence433 – 45220GKPTL…AGTCY → EGEVSADEEGFENLWATAST FIVLFLLSLFYSTTVTLFKV K in isoform 2.
VSP_034488
Natural variant1911G → S. Ref.2
VAR_003903
Natural variant2151V → G.
Corresponds to variant rs12365 [ dbSNP | Ensembl ].
VAR_003904

Experimental info

Sequence conflict401L → F in CAA34971. Ref.2
Sequence conflict401L → F in CAB37838. Ref.3
Sequence conflict1281R → RS in CAA34971. Ref.2
Sequence conflict2201T → I in CAB37838. Ref.3
Sequence conflict4141V → VV in CAA34971. Ref.2
Sequence conflict4141V → VV in CAB37838. Ref.3
Sequence conflict4171E → D in AAB59422. Ref.8
Non-terminal residue11
Isoform 2:
Sequence conflict4371S → N in AAB59422. Ref.8
Sequence conflict4391D → E in AAB59422. Ref.8
Sequence conflict4481A → T in AAB59422. Ref.8
Sequence conflict471 – 4733KVK → K in AAB59422. Ref.8

Secondary structure

................................................ 452
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Secreted) [UniParc].

Last modified July 1, 2008. Version 3.
Checksum: 83E7603C8526CB7A

FASTA45249,307
        10         20         30         40         50         60 
GSASAPTLFP LVSCENSPSD TSSVAVGCLA QDFLPDSITL SWKYKNNSDI SSTRGFPSVL 

        70         80         90        100        110        120 
RGGKYAATSQ VLLPSKDVMQ GTDEHVVCKV QHPNGNKEKN VPLPVIAELP PKVSVFVPPR 

       130        140        150        160        170        180 
DGFFGNPRKS KLICQATGFS PRQIQVSWLR EGKQVGSGVT TDQVQAEAKE SGPTTYKVTS 

       190        200        210        220        230        240 
TLTIKESDWL GQSMFTCRVD HRGLTFQQNA SSMCVPDQDT AIRVFAIPPS FASIFLTKST 

       250        260        270        280        290        300 
KLTCLVTDLT TYDSVTISWT RQNGEAVKTH TNISESHPNA TFSAVGEASI CEDDWNSGER 

       310        320        330        340        350        360 
FTCTVTHTDL PSPLKQTISR PKGVALHRPD VYLLPPAREQ LNLRESATIT CLVTGFSPAD 

       370        380        390        400        410        420 
VFVQWMQRGQ PLSPEKYVTS APMPEPQAPG RYFAHSILTV SEEEWNTGET YTCVAHEALP 

       430        440        450 
NRVTERTVDK STGKPTLYNV SLVMSDTAGT CY 

« Hide

Isoform 2 (Membrane-bound) [UniParc].

Checksum: 878EB62603593D37
Show »

FASTA47351,790

References

« Hide 'large scale' references
[1]"The complete nucleotide sequence of a human immunoglobulin genomic C mu gene."
Dorai H., Gillies S.D.
Nucleic Acids Res. 17:6412-6412(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Complete nucleotide sequence of the membrane form of the human IgM heavy chain."
Friedlander R.M., Nussenzweig M.C., Leder P.
Nucleic Acids Res. 18:4278-4278(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT SER-191.
[3]"Complete nucleotide sequence of a cDNA encoding human IgM heavy chain constant domains."
Calvo B.F., Schlom J., Kashmiri S.
Submitted (DEC-1990) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"The primary structure of a monoclonal IgM-immunoglobulin (macroglobulin Gal.), II: the amino acid sequence of the H-chain (mu-type), subgroup H III. Architecture of the complete IgM-molecule."
Watanabe S., Barnikol H.U., Horn J., Bertram J., Hilschmann N.
Hoppe-Seyler's Z. Physiol. Chem. 354:1505-1509(1973) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE (WALDENSTROM'S MACROGLOBULIN GAL).
[5]"The primary structure of the constant part of mu-chain-disease protein BOT."
Mihaesco E., Barnikol-Watanabe S., Barnikol H.U., Mihaesco C., Hilschmann N.
Eur. J. Biochem. 111:275-286(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION (GAL).
[6]"Complete amino acid sequence of the Mu heavy chain of a human IgM immunoglobulin."
Putnam F.W., Florent G., Paul C., Shinoda T., Shimizu A.
Science 182:287-291(1973) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE (WALDENSTROM'S OU), DISULFIDE BONDS, GLYCOSYLATION.
[7]"Cloning and partial nucleotide sequence of human immunoglobulin mu chain cDNA from B cells and mouse-human hybridomas."
Dolby T.W., Devuono J., Croce C.M.
Proc. Natl. Acad. Sci. U.S.A. 77:6027-6031(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 298-386 AND 436-452.
[8]"Human immunoglobulin heavy chain genes: evolutionary comparisons of C mu, C delta and C gamma genes and associated switch sequences."
Rabbitts T.H., Forster A., Milstein C.P.
Nucleic Acids Res. 9:4509-4524(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 339-452.
[9]"Functional differences between immunoglobulins M and D expressed on the surface of an immature B-cell line."
Tisch R., Roifman C.M., Hozumi N.
Proc. Natl. Acad. Sci. U.S.A. 85:6914-6918(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Mutations in the mu heavy-chain gene in patients with agammaglobulinemia."
Yel L., Minegishi Y., Coustan-Smith E., Buckley R.H., Trubel H., Pachman L.M., Kitchingman G.R., Campana D., Rohrer J., Conley M.E.
N. Engl. J. Med. 335:1486-1493(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN AGM1.
[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]"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.
Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-46.
Tissue: Plasma.
[13]"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-46.
Tissue: Liver.
[14]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-46 AND ASN-209.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

IGHMbase

IGHM mutation db

IMGT/GENE-DB

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14940 Genomic DNA. Translation: CAE82013.1.
X14940 Genomic DNA. Translation: CAE82014.1.
X14940 Genomic DNA. Translation: CAA33069.1.
X14940 Genomic DNA. Translation: CAA33070.1.
X14940 Genomic DNA. Translation: CAA33071.1. Different initiation.
X14939 Genomic DNA. Translation: CAA33065.1.
X17115 mRNA. Translation: CAA34971.1. Different initiation.
X57086 mRNA. Translation: CAB37838.1.
K01310 Genomic DNA. Translation: AAB59422.1.
PIRS14683.
MHHUM. S16510.
UniGeneHs.510635.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AGJX-ray2.60H1-183[»]
ProteinModelPortalP01871.
SMRP01871. Positions 1-433.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP01871. 60 interactions.
MINTMINT-2860005.
STRING9606.ENSP00000418294.

Protein family/group databases

MEROPSI43.001.
IMGTSearch...
Search...
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PTM databases

UniCarbKBP01871.

Polymorphism databases

DMDM193806374.

2D gel databases

UCD-2DPAGEP01871.

Proteomic databases

PaxDbP01871.
PRIDEP01871.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

GeneCardsGC14M106318.
HGNCHGNC:5541. IGHM.
MIM147020. gene.
601495. phenotype.
neXtProtNX_P01871.
Orphanet33110. Autosomal agammaglobulinemia.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47782.
HOGENOMHOG000202819.
HOVERGENHBG005814.
PhylomeDBP01871.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

GenevestigatorP01871.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
[Graphical view]
PfamPF07654. C1-set. 4 hits.
[Graphical view]
SMARTSM00407. IGc1. 3 hits.
[Graphical view]
PROSITEPS50835. IG_LIKE. 4 hits.
PS00290. IG_MHC. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01871.
PROP01871.
SOURCESearch...

Entry information

Entry nameIGHM_HUMAN
AccessionPrimary (citable) accession number: P01871
Secondary accession number(s): P20769
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 2008
Last modified: June 11, 2014
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM