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P01871

- IGHM_HUMAN

UniProt

P01871 - IGHM_HUMAN

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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

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
Complete GO annotation...

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: UniProtKB
  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
Complete GO annotation...

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)3 Publications
Disulfide bondi134 ↔ 1971 PublicationPROSITE-ProRule annotation
Glycosylationi209 – 2091N-linked (GlcNAc...) (complex)1 Publication
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.
InParanoidiP01871.
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

        10         20         30         40         50
GSASAPTLFP LVSCENSPSD TSSVAVGCLA QDFLPDSITL 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 YTCVAHEALP NRVTERTVDK STGKPTLYNV SLVMSDTAGT

CY
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.
InParanoidi P01871.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 149 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