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Protein

Immunoglobulin heavy constant alpha 1

Gene

IGHA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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). Ig alpha is the major immunoglobulin class in body secretions (PubMed:2241915).4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei352Multimeric 3-hydroxykynurenine chromophore (covalent); in form alpha-1-microglobulin complex1

GO - Molecular functioni

  • antigen binding Source: UniProtKB

GO - Biological processi

  • antibacterial humoral response Source: UniProtKB
  • B cell receptor signaling pathway Source: GO_Central
  • complement activation, classical pathway Source: GO_Central
  • glomerular filtration Source: UniProtKB
  • immune response Source: UniProtKB
  • innate immune response Source: GO_Central
  • leukocyte migration Source: Reactome
  • phagocytosis, engulfment Source: GO_Central
  • phagocytosis, recognition Source: GO_Central
  • positive regulation of B cell activation Source: GO_Central
  • positive regulation of respiratory burst Source: UniProtKB
  • protein-chromophore linkage Source: UniProtKB-KW
  • receptor-mediated endocytosis Source: Reactome
  • retina homeostasis Source: UniProtKB

Keywordsi

Biological processAdaptive immunity, Immunity
LigandChromophore

Enzyme and pathway databases

ReactomeiR-HSA-202733. Cell surface interactions at the vascular wall.
R-HSA-2168880. Scavenging of heme from plasma.

Protein family/group databases

IMGT/GENE-DBIGHA1.

Names & Taxonomyi

Protein namesi
Recommended name:
Immunoglobulin heavy constant alpha 12 Publications
Alternative name(s):
Ig alpha-1 chain C regionCurated
Ig alpha-1 chain C region BUR1 Publication
Ig alpha-1 chain C region TRO1 Publication
Gene namesi
Name:IGHA12 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:5478. IGHA1.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • external side of plasma membrane Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • monomeric IgA immunoglobulin complex Source: UniProtKB
  • secretory dimeric IgA immunoglobulin complex Source: UniProtKB
  • secretory IgA immunoglobulin complex Source: UniProtKB

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

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.1 Publication

Organism-specific databases

DisGeNETi3493.
OpenTargetsiENSG00000211895.

Polymorphism and mutation databases

DMDMi113584.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000153566‹1 – 353Immunoglobulin heavy constant alpha 1Add BLAST›353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi14Interchain (with light chain)1 Publication
Disulfide bondi26 ↔ 85PROSITE-ProRule annotation
Disulfide bondi77 ↔ 101
Glycosylationi105O-linked (GalNAc...)1
Glycosylationi111O-linked (GalNAc...)1
Glycosylationi113O-linked (GalNAc...)1
Glycosylationi119O-linked (GalNAc...)1
Glycosylationi121O-linked (GalNAc...)1
Disulfide bondi122Interchain (with heavy chain)1 Publication
Disulfide bondi123 ↔ 180Or C-123 with C-1821 Publication
Glycosylationi144N-linked (GlcNAc...) (complex)4 Publications1
Disulfide bondi147 ↔ 204PROSITE-ProRule annotation
Disulfide bondi182Interchain (with heavy chain) (or with C-180)1 Publication
Disulfide bondi192Interchain (with heavy chain of another subunit)1 Publication
Disulfide bondi250 ↔ 313PROSITE-ProRule annotation
Glycosylationi340N-linked (GlcNAc...) (complex)1 Publication1
Disulfide bondi352Interchain (with J chain); in oligomeric form1 Publication

Post-translational modificationi

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-352.1 Publication
N- and O-glycosylated. N-glycan at Asn-144: Hex5HexNAc4.4 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP01876.
PeptideAtlasiP01876.
PRIDEiP01876.

PTM databases

iPTMnetiP01876.
PhosphoSitePlusiP01876.
UniCarbKBiP01876.

Expressioni

Gene expression databases

BgeeiENSG00000211895.
GenevisibleiP01876. HS.

Interactioni

Subunit structurei

Immunoglobulins are composed of two identical heavy chains and two identical light chains; disulfide-linked (PubMed:20176268). Monomeric or polymeric (PubMed:2241915).2 Publications

Protein-protein interaction databases

IntActiP01876. 47 interactors.

Structurei

Secondary structure

1353
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi128 – 130Combined sources3
Helixi134 – 139Combined sources6
Beta strandi146 – 149Combined sources4
Beta strandi162 – 164Combined sources3
Beta strandi185 – 188Combined sources4
Turni190 – 192Combined sources3
Helixi193 – 198Combined sources6
Beta strandi201 – 206Combined sources6
Beta strandi215 – 220Combined sources6
Beta strandi229 – 233Combined sources5
Turni237 – 241Combined sources5
Beta strandi242 – 258Combined sources17
Beta strandi261 – 266Combined sources6
Helixi273 – 275Combined sources3
Beta strandi276 – 278Combined sources3
Beta strandi287 – 289Combined sources3
Beta strandi292 – 301Combined sources10
Helixi302 – 307Combined sources6
Beta strandi311 – 316Combined sources6
Beta strandi323 – 325Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP01876.
SMRiP01876.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01876.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 98Ig-like 1PROSITE-ProRule annotationAdd BLAST93
Domaini125 – 220Ig-like 2PROSITE-ProRule annotationAdd BLAST96
Domaini228 – 330Ig-like 3PROSITE-ProRule annotationAdd BLAST103

Keywords - Domaini

Immunoglobulin C region, Immunoglobulin domain

Phylogenomic databases

GeneTreeiENSGT00530000063726.
HOVERGENiHBG005814.
InParanoidiP01876.
OMAiHGKTFTC.
PhylomeDBiP01876.
TreeFamiTF334176.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
PfamiView protein in Pfam
PF07654. C1-set. 2 hits.
SMARTiView protein in SMART
SM00407. IGc1. 2 hits.
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.

Sequencei

Sequence statusi: Complete.

P01876-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
ASPTSPKVFP LSLCSTQPDG NVVIACLVQG FFPQEPLSVT WSESGQGVTA
60 70 80 90 100
RNFPPSQDAS GDLYTTSSQL TLPATQCLAG KSVTCHVKHY TNPSQDVTVP
110 120 130 140 150
CPVPSTPPTP SPSTPPTPSP SCCHPRLSLH RPALEDLLLG SEANLTCTLT
160 170 180 190 200
GLRDASGVTF TWTPSSGKSA VQGPPERDLC GCYSVSSVLP GCAEPWNHGK
210 220 230 240 250
TFTCTAAYPE SKTPLTATLS KSGNTFRPEV HLLPPPSEEL ALNELVTLTC
260 270 280 290 300
LARGFSPKDV LVRWLQGSQE LPREKYLTWA SRQEPSQGTT TFAVTSILRV
310 320 330 340 350
AAEDWKKGDT FSCMVGHEAL PLAFTQKTID RLAGKPTHVN VSVVMAEVDG

TCY
Length:353
Mass (Da):37,655
Last modified:February 1, 1991 - v2
Checksum:iEBA11ECB7E85DB21
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11
Sequence conflicti163 – 165TPS → PST AA sequence (PubMed:107164).Curated3
Sequence conflicti176E → B AA sequence (PubMed:809331).Curated1
Sequence conflicti190P → S AA sequence (PubMed:809331).Curated1
Sequence conflicti227R → H AA sequence (PubMed:809331).Curated1
Sequence conflicti231H → R AA sequence (PubMed:809331).Curated1
Sequence conflicti290T → E AA sequence (PubMed:809331).Curated1

Polymorphismi

There are several alleles. The sequence shown is that of IMGT allele IGHA1*02.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014602176E → D. Corresponds to variant dbSNP:rs1407Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J00220 Genomic DNA. Translation: AAC82528.1. Different initiation.
AL901608 Genomic DNA. No translation available.
AL928768 Genomic DNA. No translation available.
PIRiA22360. A1HU.
UniGeneiHs.699841.

Genome annotation databases

EnsembliENST00000390547; ENSP00000374989; ENSG00000211895.
ENST00000633714; ENSP00000488021; ENSG00000282633.
UCSCiuc059gcy.1. human.

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J00220 Genomic DNA. Translation: AAC82528.1. Different initiation.
AL901608 Genomic DNA. No translation available.
AL928768 Genomic DNA. No translation available.
PIRiA22360. A1HU.
UniGeneiHs.699841.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP01876.
SMRiP01876.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP01876. 47 interactors.

Protein family/group databases

IMGT/GENE-DBIGHA1.

PTM databases

iPTMnetiP01876.
PhosphoSitePlusiP01876.
UniCarbKBiP01876.

Polymorphism and mutation databases

DMDMi113584.

Proteomic databases

EPDiP01876.
PeptideAtlasiP01876.
PRIDEiP01876.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000390547; ENSP00000374989; ENSG00000211895.
ENST00000633714; ENSP00000488021; ENSG00000282633.
UCSCiuc059gcy.1. human.

Organism-specific databases

DisGeNETi3493.
GeneCardsiIGHA1.
HGNCiHGNC:5478. IGHA1.
MIMi146900. gene.
neXtProtiNX_P01876.
OpenTargetsiENSG00000211895.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00530000063726.
HOVERGENiHBG005814.
InParanoidiP01876.
OMAiHGKTFTC.
PhylomeDBiP01876.
TreeFamiTF334176.

Enzyme and pathway databases

ReactomeiR-HSA-202733. Cell surface interactions at the vascular wall.
R-HSA-2168880. Scavenging of heme from plasma.

Miscellaneous databases

EvolutionaryTraceiP01876.
PROiPR:P01876.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000211895.
GenevisibleiP01876. HS.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
PfamiView protein in Pfam
PF07654. C1-set. 2 hits.
SMARTiView protein in SMART
SM00407. IGc1. 2 hits.
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiIGHA1_HUMAN
AccessioniPrimary (citable) accession number: P01876
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1991
Last modified: April 12, 2017
This is version 172 of the entry and version 2 of the sequence. See 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

Caution

For an example of a full length immunoglobulin alpha heavy chain see AC P0DOX2.Curated

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.