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P01871

- IGHM_HUMAN

UniProt

P01871 - IGHM_HUMAN

Protein

Ig mu chain C region

Gene

IGHM

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 148 (01 Oct 2014)
      Sequence version 3 (01 Jul 2008)
      Previous versions | rss
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    Functioni

    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.1 Publication

    GO - Molecular functioni

    1. antigen binding Source: UniProtKB-KW

    GO - Biological processi

    1. adaptive immune response Source: UniProt
    2. antibacterial humoral response Source: UniProt
    3. defense response to Gram-negative bacterium Source: UniProt
    4. innate immune response Source: UniProt

    Enzyme and pathway databases

    ReactomeiREACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

    Protein family/group databases

    MEROPSiI43.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ig mu chain C region
    Gene namesi
    Name:IGHM
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Unplaced

    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

    1. blood microparticle Source: UniProt
    2. cell surface Source: UniProt
    3. extracellular space Source: UniProt
    4. extracellular vesicular exosome Source: UniProt
    5. hexameric IgM immunoglobulin complex Source: UniProt
    6. integral component of membrane Source: UniProtKB-KW
    7. pentameric IgM immunoglobulin complex Source: UniProt
    8. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Organism-specific databases

    MIMi601495. phenotype.
    Orphaneti33110. Autosomal agammaglobulinemia.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini‹1 – 452›452Ig mu chain C regionPRO_0000153619Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi14 – 14Interchain (with light chain)1 PublicationPROSITE-ProRule annotation
    Disulfide bondi28 ↔ 881 PublicationPROSITE-ProRule annotation
    Glycosylationi46 – 461N-linked (GlcNAc...) (complex)4 Publications
    Disulfide bondi134 ↔ 1971 PublicationPROSITE-ProRule annotation
    Glycosylationi209 – 2091N-linked (GlcNAc...) (complex)2 Publications
    Disulfide bondi214 – 214Interchain (with heavy chain)1 PublicationPROSITE-ProRule annotation
    Disulfide bondi244 ↔ 3031 PublicationPROSITE-ProRule annotation
    Glycosylationi272 – 2721N-linked (GlcNAc...)1 Publication
    Glycosylationi279 – 2791N-linked (GlcNAc...)1 Publication
    Disulfide bondi291 – 291Interchain (with heavy chain of another subunit)1 PublicationPROSITE-ProRule annotation
    Disulfide bondi351 ↔ 4131 PublicationPROSITE-ProRule annotation
    Glycosylationi439 – 4391N-linked (GlcNAc...)1 PublicationCAR_000219
    Disulfide bondi451 – 451Interchain (with heavy chain)1 PublicationPROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP01871.
    PRIDEiP01871.

    2D gel databases

    UCD-2DPAGEP01871.

    PTM databases

    UniCarbKBiP01871.

    Expressioni

    Gene expression databases

    GenevestigatoriP01871.

    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 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.

    Protein-protein interaction databases

    IntActiP01871. 60 interactions.
    MINTiMINT-2860005.
    STRINGi9606.ENSP00000418294.

    Structurei

    Secondary structure

    1
    452
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi178 – 1847
    Beta strandi196 – 2016
    Beta strandi206 – 2083
    Beta strandi210 – 2167
    Beta strandi223 – 2275
    Helixi236 – 2383
    Beta strandi240 – 2423
    Helixi249 – 2513
    Beta strandi253 – 2586
    Turni261 – 2644
    Beta strandi265 – 2728
    Helixi275 – 2773
    Beta strandi279 – 2857
    Beta strandi287 – 2904
    Beta strandi300 – 3023
    Beta strandi316 – 3183
    Beta strandi345 – 3517
    Beta strandi354 – 3596
    Beta strandi363 – 3664
    Beta strandi386 – 3883
    Beta strandi391 – 3933
    Beta strandi396 – 4016
    Helixi402 – 4054
    Beta strandi406 – 4094
    Beta strandi412 – 4176

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2AGJX-ray2.60H1-183[»]
    ProteinModelPortaliP01871.
    SMRiP01871. Positions 1-433.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP01871.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 105105CH1Add
    BLAST
    Regioni106 – 217112CH2Add
    BLAST
    Regioni218 – 323106CH3Add
    BLAST
    Regioni324 – 452129CH4Add
    BLAST

    Keywords - Domaini

    Immunoglobulin C region, Immunoglobulin domain, Transmembrane

    Phylogenomic databases

    eggNOGiNOG47782.
    HOGENOMiHOG000202819.
    HOVERGENiHBG005814.
    PhylomeDBiP01871.

    Family and domain databases

    Gene3Di2.60.40.10. 4 hits.
    InterProiIPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR003006. Ig/MHC_CS.
    IPR003597. Ig_C1-set.
    [Graphical view]
    PfamiPF07654. C1-set. 4 hits.
    [Graphical view]
    SMARTiSM00407. IGc1. 3 hits.
    [Graphical view]
    PROSITEiPS50835. IG_LIKE. 4 hits.
    PS00290. IG_MHC. 2 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    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

    GSASAPTLFP LVSCENSPSD TSSVAVGCLA QDFLPDSITL SWKYKNNSDI    50
    SSTRGFPSVL RGGKYAATSQ VLLPSKDVMQ GTDEHVVCKV QHPNGNKEKN 100
    VPLPVIAELP PKVSVFVPPR DGFFGNPRKS KLICQATGFS PRQIQVSWLR 150
    EGKQVGSGVT TDQVQAEAKE SGPTTYKVTS TLTIKESDWL GQSMFTCRVD 200
    HRGLTFQQNA SSMCVPDQDT AIRVFAIPPS FASIFLTKST KLTCLVTDLT 250
    TYDSVTISWT RQNGEAVKTH TNISESHPNA TFSAVGEASI CEDDWNSGER 300
    FTCTVTHTDL PSPLKQTISR PKGVALHRPD VYLLPPAREQ LNLRESATIT 350
    CLVTGFSPAD VFVQWMQRGQ PLSPEKYVTS APMPEPQAPG RYFAHSILTV 400
    SEEEWNTGET YTCVAHEALP NRVTERTVDK STGKPTLYNV SLVMSDTAGT 450
    CY 452
    Length:452
    Mass (Da):49,307
    Last modified:July 1, 2008 - v3
    Checksum:i83E7603C8526CB7A
    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:
         433-452: GKPTLYNVSLVMSDTAGTCY → EGEVSADEEGFENLWATASTFIVLFLLSLFYSTTVTLFKVK

    Show »
    Length:473
    Mass (Da):51,790
    Checksum:i878EB62603593D37
    GO

    Sequence cautioni

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Non-terminal residuei1 – 11
    Sequence conflicti40 – 401L → F in CAA34971. (PubMed:2115996)Curated
    Sequence conflicti40 – 401L → F in CAB37838. 1 PublicationCurated
    Sequence conflicti128 – 1281R → RS in CAA34971. (PubMed:2115996)Curated
    Sequence conflicti220 – 2201T → I in CAB37838. 1 PublicationCurated
    Sequence conflicti414 – 4141V → VV in CAA34971. (PubMed:2115996)Curated
    Sequence conflicti414 – 4141V → VV in CAB37838. 1 PublicationCurated
    Sequence conflicti417 – 4171E → D in AAB59422. (PubMed:6795593)Curated
    Isoform 2 (identifier: P01871-2)
    Sequence conflicti437 – 4371S → N in AAB59422. (PubMed:6795593)Curated
    Sequence conflicti439 – 4391D → E in AAB59422. (PubMed:6795593)Curated
    Sequence conflicti448 – 4481A → T in AAB59422. (PubMed:6795593)Curated
    Sequence conflicti471 – 4733KVK → K in AAB59422. (PubMed:6795593)Curated

    Polymorphismi

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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti191 – 1911G → S.1 Publication
    VAR_003903
    Natural varianti215 – 2151V → G.
    Corresponds to variant rs12365 [ dbSNP | Ensembl ].
    VAR_003904

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei433 – 45220GKPTL…AGTCY → EGEVSADEEGFENLWATAST FIVLFLLSLFYSTTVTLFKV K in isoform 2. 1 PublicationVSP_034488Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    PIRiS14683.
    S16510. MHHUM.
    UniGeneiHs.510635.

    Polymorphism databases

    DMDMi193806374.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    IGHMbase

    IGHM mutation db

    IMGT/GENE-DB

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    PIRi S14683.
    S16510. MHHUM.
    UniGenei Hs.510635.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2AGJ X-ray 2.60 H 1-183 [» ]
    ProteinModelPortali P01871.
    SMRi P01871. Positions 1-433.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P01871. 60 interactions.
    MINTi MINT-2860005.
    STRINGi 9606.ENSP00000418294.

    Protein family/group databases

    MEROPSi I43.001.
    IMGTi Search...
    Search...
    Search...
    Search...
    Search...
    Search...
    Search...
    Search...
    Search...

    PTM databases

    UniCarbKBi P01871.

    Polymorphism databases

    DMDMi 193806374.

    2D gel databases

    UCD-2DPAGE P01871.

    Proteomic databases

    PaxDbi P01871.
    PRIDEi P01871.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    GeneCardsi GC14M106318.
    HGNCi HGNC:5541. IGHM.
    MIMi 147020. gene.
    601495. phenotype.
    neXtProti NX_P01871.
    Orphaneti 33110. Autosomal agammaglobulinemia.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG47782.
    HOGENOMi HOG000202819.
    HOVERGENi HBG005814.
    PhylomeDBi P01871.

    Enzyme and pathway databases

    Reactomei REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

    Miscellaneous databases

    EvolutionaryTracei P01871.
    PROi P01871.
    SOURCEi Search...

    Gene expression databases

    Genevestigatori P01871.

    Family and domain databases

    Gene3Di 2.60.40.10. 4 hits.
    InterProi IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR003006. Ig/MHC_CS.
    IPR003597. Ig_C1-set.
    [Graphical view ]
    Pfami PF07654. C1-set. 4 hits.
    [Graphical view ]
    SMARTi SM00407. IGc1. 3 hits.
    [Graphical view ]
    PROSITEi PS50835. IG_LIKE. 4 hits.
    PS00290. IG_MHC. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. Cited for: GLYCOSYLATION AT ASN-46 AND ASN-209.
    15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiIGHM_HUMAN
    AccessioniPrimary (citable) accession number: P01871
    Secondary accession number(s): P20769
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 1, 2008
    Last modified: October 1, 2014
    This is version 148 of the entry and version 3 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

    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

    External Data

    Dasty 3