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P01876 (IGHA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ig alpha-1 chain C region
Gene names
Name:IGHA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length353 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Ig alpha is the major immunoglobulin class in body secretions. It may serve both to defend against local infection and to prevent access of foreign antigens to the general immunologic system.

Subunit structure

Monomeric or polymeric.

Post-translational modification

3-Hydroxykynurenine, an oxidized tryptophan metabolite that is common in biological fluids, reacts with alpha-1-microglobulin to form heterogeneous polycyclic chromophores including hydroxanthommatin. The chromophore reacts with accessible cysteines forming non-reducible thioether cross-links with Ig alpha-1 chain C region Cys-352.

N- and O-glycosylated. N-glycan at Asn-144: Hex5HexNAc4. Ref.9 Ref.12

Involvement in disease

A chromosomal aberration involving IGHA1 is found in multiple myeloma (MM) cell lines. Translocation t(1;14)(q21;q32) that forms a FCRL4-IGHA1 fusion protein.

Sequence similarities

Contains 3 Ig-like (immunoglobulin-like) domains.

Sequence caution

The sequence AAC82528.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DomainImmunoglobulin C region
Immunoglobulin domain
Repeat
   LigandChromophore
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processantibacterial humoral response

Inferred from direct assay PubMed 23250751. Source: UniProt

glomerular filtration

Inferred from mutant phenotype PubMed 23398317. Source: UniProt

immune response

Non-traceable author statement Ref.2. Source: UniProtKB

positive regulation of respiratory burst

Inferred from direct assay PubMed 24145934. Source: UniProt

protein-chromophore linkage

Inferred from electronic annotation. Source: UniProtKB-KW

retina homeostasis

Inferred from expression pattern PubMed 23580065. Source: UniProt

   Cellular_componentblood microparticle

Inferred from direct assay PubMed 22516433. Source: UniProt

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 16502470PubMed 22664934PubMed 23398317PubMed 23580065. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337PubMed 23376485. Source: UniProt

monomeric IgA immunoglobulin complex

Inferred from direct assay PubMed 23250751. Source: UniProt

secretory IgA immunoglobulin complex

Inferred from direct assay PubMed 23250751PubMed 24145934. Source: UniProt

secretory dimeric IgA immunoglobulin complex

Inferred from direct assay PubMed 24145934. Source: UniProt

   Molecular_functionantigen binding

Non-traceable author statement Ref.2. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain‹1 – 353›353Ig alpha-1 chain C region
PRO_0000153566

Regions

Domain6 – 9893Ig-like 1
Domain125 – 22096Ig-like 2
Domain228 – 330103Ig-like 3

Sites

Binding site3521Multimeric 3-hydroxykynurenine chromophore (covalent); in form alpha-1-microglobulin complex

Amino acid modifications

Glycosylation1051O-linked (GalNAc...)
Glycosylation1111O-linked (GalNAc...)
Glycosylation1131O-linked (GalNAc...)
Glycosylation1191O-linked (GalNAc...)
Glycosylation1211O-linked (GalNAc...)
Glycosylation1441N-linked (GlcNAc...) (complex) Ref.8 Ref.9 Ref.10 Ref.12
Glycosylation3401N-linked (GlcNAc...) (complex) Ref.9
Disulfide bond14Interchain (with light chain) Ref.2 Ref.4
Disulfide bond26 ↔ 85 Ref.2 Ref.4
Disulfide bond77 ↔ 101 Ref.2 Ref.4
Disulfide bond122Interchain (with heavy chain) Ref.2 Ref.4
Disulfide bond123 ↔ 180Or C-123 with C-182 Ref.2 Ref.4
Disulfide bond147 ↔ 204 Ref.2 Ref.4
Disulfide bond182Interchain (with heavy chain) (or with C-180) Ref.2 Ref.4
Disulfide bond192Interchain (with heavy chain of another subunit) Probable
Disulfide bond250 ↔ 313 Ref.2 Ref.4
Disulfide bond352Interchain (with J chain); in oligomeric form Ref.2 Ref.4

Natural variations

Natural variant1761E → D.
Corresponds to variant rs1407 [ dbSNP | Ensembl ].
VAR_014602

Experimental info

Sequence conflict163 – 1653TPS → PST AA sequence Ref.2
Sequence conflict1761E → B AA sequence Ref.3
Sequence conflict1901P → S AA sequence Ref.3
Sequence conflict2271R → H AA sequence Ref.3
Sequence conflict2311H → R AA sequence Ref.3
Sequence conflict2901T → E AA sequence Ref.3
Non-terminal residue11

Secondary structure

..................................... 353
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01876 [UniParc].

Last modified February 1, 1991. Version 2.
Checksum: EBA11ECB7E85DB21

FASTA35337,655
        10         20         30         40         50         60 
ASPTSPKVFP LSLCSTQPDG NVVIACLVQG FFPQEPLSVT WSESGQGVTA RNFPPSQDAS 

        70         80         90        100        110        120 
GDLYTTSSQL TLPATQCLAG KSVTCHVKHY TNPSQDVTVP CPVPSTPPTP SPSTPPTPSP 

       130        140        150        160        170        180 
SCCHPRLSLH RPALEDLLLG SEANLTCTLT GLRDASGVTF TWTPSSGKSA VQGPPERDLC 

       190        200        210        220        230        240 
GCYSVSSVLP GCAEPWNHGK TFTCTAAYPE SKTPLTATLS KSGNTFRPEV HLLPPPSEEL 

       250        260        270        280        290        300 
ALNELVTLTC LARGFSPKDV LVRWLQGSQE LPREKYLTWA SRQEPSQGTT TFAVTSILRV 

       310        320        330        340        350 
AAEDWKKGDT FSCMVGHEAL PLAFTQKTID RLAGKPTHVN VSVVMAEVDG TCY 

« Hide

References

« Hide 'large scale' references
[1]"Mechanisms of divergence and convergence of the human immunoglobulin alpha 1 and alpha 2 constant region gene sequences."
Flanagan J.G., Lefranc M.-P., Rabbitts T.H.
Cell 36:681-688(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Primary structure of a human IgA1 immunoglobulin. IV. Streptococcal IgA1 protease, digestion, Fab and Fc fragments, and the complete amino acid sequence of the alpha 1 heavy chain."
Putnam F.W., Liu Y.-S.V., Low T.L.K.
J. Biol. Chem. 254:2865-2874(1979) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE (MYELOMA PROTEIN BUR), DISULFIDE BONDS.
[3]"The primary structure of a monoclonal IgA-immunoglobulin (IgA Tro.), II. The amino acid sequence of the H-chain, alpha-type, subgroup III; structure of the complete IgA-molecule."
Kratzin H., Altevogt P., Ruban E., Kortt A., Staroscik K., Hilschmann N.
Hoppe-Seyler's Z. Physiol. Chem. 356:1337-1342(1975) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE (MYELOMA PROTEIN TRO).
[4]"Rule of antibody structure. Primary structure of a human monoclonal IgA-immunoglobulin (myeloma protein Tro). VII. Purification and characterization of the disulfide bridges."
Yang C.-Y., Kratzin H., Gotz H., Hilschmann N.
Hoppe-Seyler's Z. Physiol. Chem. 360:1919-1940(1979) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS.
[5]"Location of a novel type of interpolypeptide chain linkage in the human protein HC-IgA complex (HC-IgA) and identification of a heterogeneous chromophore associated with the complex."
Calero M., Escribano J., Grubb A., Mendez E.
J. Biol. Chem. 269:384-389(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 345-353, BINDING TO CHROMOPHORE.
[6]"The structure and function of human IgA."
Kerr M.A.
Biochem. J. 271:285-296(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[7]"IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy."
Hatzivassiliou G., Miller I., Takizawa J., Palanisamy N., Rao P.H., Iida S., Tagawa S., Taniwaki M., Russo J., Neri A., Cattoretti G., Clynes R., Mendelsohn C., Chaganti R.S.K., Dalla-Favera R.
Immunity 14:277-289(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH FCRL4.
[8]"A proteomic analysis of human bile."
Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.
Mol. Cell. Proteomics 3:715-728(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-144.
Tissue: Bile.
[9]"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-144 AND ASN-340.
[10]"Enrichment of glycopeptides for glycan structure and attachment site identification."
Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G.
Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-144, STRUCTURE OF CARBOHYDRATES.
Tissue: Cerebrospinal fluid.
[11]"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].
[12]"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD."
Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.
Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-144, STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J00220 Genomic DNA. Translation: AAC82528.1. Different initiation.
PIRA1HU. A22360.
UniGeneHs.699841.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IGAX-ray-A/B1-353[»]
1OW0X-ray3.10A/B122-335[»]
2QEJX-ray3.20A/B123-336[»]
3CHNX-ray-A/B/C/D2-353[»]
ProteinModelPortalP01876.
SMRP01876. Positions 1-102, 123-331.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP01876. 43 interactions.
STRING9606.ENSP00000374989.

Protein family/group databases

MEROPSI43.001.
IMGTSearch...

PTM databases

PhosphoSiteP01876.

Polymorphism databases

DMDM113584.

Proteomic databases

PaxDbP01876.
PRIDEP01876.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000390547; ENSP00000374989; ENSG00000211895.
ENST00000604598; ENSP00000474960; ENSG00000271189.

Organism-specific databases

GeneCardsGC14M106171.
HGNCHGNC:5478. IGHA1.
MIM146900. gene.
neXtProtNX_P01876.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG27314.
HOVERGENHBG005814.
InParanoidP01876.
OMAEVDGTCY.
PhylomeDBP01876.
TreeFamTF334176.

Enzyme and pathway databases

ReactomeREACT_160300. Binding and Uptake of Ligands by Scavenger Receptors.

Gene expression databases

BgeeP01876.
GenevestigatorP01876.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
[Graphical view]
PfamPF07654. C1-set. 2 hits.
[Graphical view]
SMARTSM00407. IGc1. 2 hits.
[Graphical view]
PROSITEPS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01876.
PROP01876.
SOURCESearch...

Entry information

Entry nameIGHA1_HUMAN
AccessionPrimary (citable) accession number: P01876
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1991
Last modified: July 9, 2014
This is version 147 of the entry and version 2 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

SIMILARITY comments

Index of protein domains and families

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