Reviewed, UniProtKB/Swiss-Prot P01876 (IGHA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Ig alpha-1 chain C region

Gene names

Name:

IGHA1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	353 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.
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.

Ontologies

Keywords
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Domain	Immunoglobulin C region Immunoglobulin domain Repeat
Ligand	Chromophore
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	immune response Ref.2 Non-traceable author statement. Source: UniProtKB protein-chromophore linkage Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	antigen binding Ref.2 Non-traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK2AP1	O14519	1	EBI-727651,EBI-1052532
CDK5RAP3	Q96JB5	1	EBI-727651,EBI-718818

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

‹1 – 353

›353

Ig alpha-1 chain C region

PRO_0000153566

Regions

Domain

6 – 98

93

Ig-like 1

Domain

125 – 220

96

Ig-like 2

Domain

228 – 330

103

Ig-like 3

Sites

Binding site

352

1

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

Amino acid modifications

Glycosylation

105

1

O-linked (GalNAc...)

Glycosylation

111

1

O-linked (GalNAc...)

Glycosylation

113

1

O-linked (GalNAc...)

Glycosylation

119

1

O-linked (GalNAc...)

Glycosylation

121

1

O-linked (GalNAc...)

Glycosylation

144

1

N-linked (GlcNAc...) Ref.8

Glycosylation

340

1

N-linked (GlcNAc...)

Disulfide bond

14

Interchain (with light chain) Ref.2 Ref.4

Disulfide bond

26 ↔ 85

Ref.2 Ref.4

Disulfide bond

77 ↔ 101

Ref.2 Ref.4

Disulfide bond

122

Interchain (with heavy chain) Ref.2 Ref.4

Disulfide bond

123 ↔ 180

Or C-123 with C-182 Ref.2 Ref.4

Disulfide bond

147 ↔ 204

Ref.2 Ref.4

Disulfide bond

182

Interchain (with heavy chain) (or with C-180) Ref.2 Ref.4

Disulfide bond

192

Interchain (with heavy chain of another subunit) Probable

Disulfide bond

250 ↔ 313

Ref.2 Ref.4

Disulfide bond

352

Interchain (with J chain); in oligomeric form Ref.2 Ref.4

Natural variations

Natural variant

176

1

E → D: dbSNP rs1407.

VAR_014602

Experimental info

Sequence conflict

163 – 165

3

TPS → PST AA sequence Ref.2

Sequence conflict

176

1

E → B AA sequence Ref.3

Sequence conflict

190

1

P → S AA sequence Ref.3

Sequence conflict

227

1

R → H AA sequence Ref.3

Sequence conflict

231

1

H → R AA sequence Ref.3

Sequence conflict

290

1

T → E AA sequence Ref.3

Non-terminal residue

1

1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

353

Helix Strand Turn

Details...

Beta strand

128 – 130

3

Helix

134 – 139

6

Beta strand

146 – 149

4

Beta strand

162 – 164

3

Beta strand

185 – 188

4

Turn

190 – 192

3

Helix

193 – 198

6

Beta strand

201 – 206

6

Beta strand

215 – 220

6

Beta strand

229 – 233

5

Turn

237 – 241

5

Beta strand

242 – 258

17

Beta strand

261 – 266

6

Helix

273 – 275

3

Beta strand

276 – 278

3

Beta strand

287 – 289

3

Beta strand

292 – 301

10

Helix

302 – 307

6

Beta strand

311 – 316

6

Beta strand

323 – 325

3

Sequences

	Sequence		Length	Mass (Da)
	P01876-1 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: EBA11ECB7E85DB21	FASTA	353	37,655
	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

References

	« Hide 'large scale' referencesShow '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: 6421489] [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: 107164] [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: 809331] [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: 393607] [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: 7506257] [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: 2241915] [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: 11290337] [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: 15084671] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-144, MASS SPECTROMETRY. Tissue: Bile.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

J00220 Genomic DNA. Translation: AAC82528.1. Different initiation.

IPI

IPI00449920.

PIR

A1HU. A22360.

UniGene

Hs.510635

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IGA	X-ray	-	A/B	1-353	[»]
1OW0	X-ray	3.10	A/B	123-335	[»]
2QEJ	X-ray	3.20	A/B	123-336	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P01876. 43 interactions.

Protein family/group databases

IMGT

Search...

Proteomic databases

PRIDE

P01876.

Genome annotation databases

Ensembl

ENSG00000211895. Homo sapiens. [Contig view]

Organism-specific databases

GeneCards

GC14M105250.

HGNC

HGNC:5478. IGHA1.

MIM

146900. gene.

PharmGKB

PA29710.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P01876.

Enzyme and pathway databases

Pathway_Interaction_DB

smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.

Gene expression databases

ArrayExpress

P01876.

Bgee

P01876.

GermOnline

ENSG00000130076. Homo sapiens.

Family and domain databases

InterPro

IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 3 hits.

Pfam

PF07654. C1-set. 2 hits.
[Graphical view]

SMART

SM00407. IGc1. 2 hits.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

IGHA1_HUMAN

Accession

Primary (citable) accession number: P01876

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 1, 1991
Last modified:	July 7, 2009
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)