P01857
uniprot
P01857
canonical
amino_acid_sequence
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPELQLEESCAEAQDGELDGLWTTITIFITLFLLSVCYSATVTFFKVKWIFSSVVDLKQTIIPDYRNMIGQGA
uniprot
proteins
disease_involvement
DISEASE: Multiple myeloma (MM) [MIM:254500]: A malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. {ECO:0000269|PubMed:11972529, ECO:0000269|PubMed:8943038}. Note=The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.
uniprot
proteins
function
FUNCTION: Constant region of immunoglobulin (Ig) heavy chains. Igs are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound Igs serve as receptors, which upon binding to a specific antigen trigger the clonal expansion and differentiation of B lymphocytes into Ig-secreting plasma cells. Secreted Igs known as antibodies mediate the effector phase of humoral immunity by blocking the interaction of infectious antigens with cellular receptors (via the antigen-binding region) and eliciting effector mechanisms that lead to pathogen neutralization (via the constant region) (PubMed:17576170, PubMed:20176268, PubMed:22158414). The antigen-binding region is formed by the variable domain of one heavy chain paired with the variable domain of its associated light chain. Each Ig molecule has two antigen-binding sites with remarkable affinity for a particular antigen due to V-(D)-J rearrangement, somatic hypermutations and affinity maturation of the variable domains upon antigen exposure (PubMed:17576170, PubMed:20176268, PubMed:22158414). The constant region defines the Ig isotype that perform distinct sets of effector functions. B cells diversify and rearrange their Ig constant regions through class-switch recombination, a process by which the constant region is switched from one Ig isotype to another, namely from IgM and IgD to IgG, IgA and IgE (PubMed:17576170, PubMed:20176268, PubMed:22158414). The constant region of Ig gamma-1 (IgG1) isotype interacts (via the fragment crystallizable, Fc) with receptors on innate immune cells and the complement system to mediate humoral effector functions, including antibody-dependent cellular cytotoxicity or phagocytosis, complement-dependent cytotoxicity and inflammatory responses. {ECO:0000269|PubMed:11711607, ECO:0000269|PubMed:12427744, ECO:0000269|PubMed:16219319, ECO:0000269|PubMed:18420934, ECO:0000269|PubMed:25561553, ECO:0000269|PubMed:26140596, ECO:0000269|PubMed:28566370, ECO:0000269|PubMed:30061887, ECO:0000269|PubMed:33563762, ECO:0000269|PubMed:36867679, ECO:0000303|PubMed:17576170, ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}.
uniprot
proteins
mass_dalton
43912
uniprot
proteins
mutagenesis
MUTAGEN 117..118; /note="LL->AA: Abolishes binding to FCGR1A, FCGR2A and FCGR3A. Impairs ADCC of virus-infected cells by monocytes."; /evidence="ECO:0000269|PubMed:11711607"; MUTAGEN 117; /note="L->A: Reduces the affinity for FCGR1A about 5-fold. Abolishes binding to FCGR2A and FCGR3A. Impairs ADCC of virus-infected cells by monocytes. Impairs binding to complement component C1q. Impairs complement-dependent cytotoxicity."; /evidence="ECO:0000269|PubMed:11711607"; MUTAGEN 118; /note="L->E: Reduces the affinity for FCGR1A about 40-fold. Abolishes binding to FCGR2A and FCGR3A. Impairs ADCC of virus-infected cells by monocytes. Impairs binding to complement component C1q. Impairs complement-dependent cytotoxicity."; MUTAGEN 120; /note="G->A: Reduces the affinity for FCGR1A about 40-fold. Abolishes binding to FCGR2A and FCGR3A. Impairs ADCC of virus-infected cells by monocytes. Decreases binding to complement component C1q. Decreases complement-dependent cytotoxicity."; /evidence="ECO:0000269|PubMed:11711607"; MUTAGEN 180; /note="N->A: Loss of N-glycosylation. Abolishes binding to FCGR3A, FCGR3B and FCGR2BFc receptors. Decreases FCGR1A receptor binding."; /evidence="ECO:0000269|PubMed:30061887, ECO:0000269|PubMed:36867679"; MUTAGEN 205; /note="K->A: Does not affect binding to FCGR1A. Only slightly affects binding to FCGR2A and FCGR3A. Impairs binding to complement component C1q. Impairs complement-dependent cytotoxicity."; /evidence="ECO:0000269|PubMed:11711607"; MUTAGEN 228; /note="E->R: Spontaneously forms hexameric Ig structures in solution in the absence of antigen; when associated with R-313 and Y-323."; /evidence="ECO:0000269|PubMed:33563762"; MUTAGEN 313; /note="E->R: Spontaneously forms hexameric Ig structures in solution in the absence of antigen; when associated with R-228 and Y-323."; /evidence="ECO:0000269|PubMed:33563762"; MUTAGEN 323; /note="S->Y: Spontaneously forms hexameric Ig structures in solution in the absence of antigen; when associated with R-228 and R-313."; /evidence="ECO:0000269|PubMed:33563762
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. Carries predominantly biantennary complex-type glycans attached at Asn-180 residue on the Fc region of each heavy chain. Unique Fc glycan profiles found in secreted IgGs are induced in an antigen-specific way, likely programmed during B cell priming to mount an appropriate Ig effector response (PubMed:10818239, PubMed:10917521, PubMed:21768335, PubMed:22184099, PubMed:25561553, PubMed:29133956, PubMed:29445378). The core glycan is composed of two sequential N-acetylglucosamine (GlcNAc) moieties followed by a central mannose (Man) from which two additional Man residues branch out (alpha1,3 and alpha1,6 antennae) each capped with a GlcNAc. Additional sugar molecules can be added to generate over 30 possible glycans. Such sugar modifications include the addition of one fucose at the initial GlcNAc, galactose (Gal) and sialic acid (Neu5Ac) residues at antennary GlcNAc or a bisecting GlcNAc to the core Man (PubMed:10818239, PubMed:22184099, PubMed:29133956, PubMed:38383719). Variable addition of sugars account for different IgG functional states associated with antibody-dependent cellular cytotoxicity or phagocytosis and inflammatory responses such as complement activation and cytokine secretion. Fc N-glycan diversity is further enhanced by asymmetric glycan pairing on the heavy chains (PubMed:10818239, PubMed:20357243, PubMed:22184099, PubMed:29133956). Fc N-glycan sialylation is linked to anti-inflammatory effects. It regulates Fc effector functions through conformational changes leading to preferential interaction with type II Fc receptors while reducing binding to type I Fc receptors. During plasmablast response, sialylated Fc domains within immune complexes signal via FCER2/CD23 and drive the selection of B cells with high affinity for antigen (PubMed:18420934, PubMed:22184099, PubMed:25733881, PubMed:26140596). Fc Igs carrying afucosylated N-glycans preferentially activate FCGR3A, antigen-dependent cellular cytotoxicity and antitumor immunity (PubMed:12427744, PubMed:21768335, PubMed:28566370, PubMed:30061887, PubMed:36867679). {ECO:0000269|PubMed:10818239, ECO:0000269|PubMed:10917521, ECO:0000269|PubMed:12427744, ECO:0000269|PubMed:18420934, ECO:0000269|PubMed:20357243, ECO:0000269|PubMed:21768335, ECO:0000269|PubMed:22184099, ECO:0000269|PubMed:25561553, ECO:0000269|PubMed:25733881, ECO:0000269|PubMed:26140596, ECO:0000269|PubMed:28566370, ECO:0000269|PubMed:29133956, ECO:0000269|PubMed:29445378, ECO:0000269|PubMed:30061887, ECO:0000269|PubMed:36867679, ECO:0000303|PubMed:38383719}.; PTM: (Microbial infection) Deglycosylation on Asn-180 by S. pyogenes EndoS or Endos2 endoglucosidases prevents interaction between immunoglobulin-gamma (IgG) and Fc receptors, impairing ability to activate the complement pathway. {ECO:0000269|PubMed:11406581, ECO:0000269|PubMed:20357243, ECO:0000269|PubMed:23865566}.
uniprot
proteins
pubmed
1002129
uniprot
proteins
pubmed
10818239
uniprot
proteins
pubmed
10917521
uniprot
proteins
pubmed
11340299
uniprot
proteins
pubmed
11406581
uniprot
proteins
pubmed
11711607
uniprot
proteins
pubmed
11972529
uniprot
proteins
pubmed
12427744
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
15572068
uniprot
proteins
pubmed
16219319
uniprot
proteins
pubmed
17576170
uniprot
proteins
pubmed
18420934
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19358553
uniprot
proteins
pubmed
20176268
uniprot
proteins
pubmed
2026457
uniprot
proteins
pubmed
20357243
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21768335
uniprot
proteins
pubmed
22158414
uniprot
proteins
pubmed
22184099
uniprot
proteins
pubmed
23865566
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25561553
uniprot
proteins
pubmed
25733881
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26140596
uniprot
proteins
pubmed
28566370
uniprot
proteins
pubmed
29133956
uniprot
proteins
pubmed
29445378
uniprot
proteins
pubmed
30061887
uniprot
proteins
pubmed
33563762
uniprot
proteins
pubmed
36529104
uniprot
proteins
pubmed
36867679
uniprot
proteins
pubmed
37421619
uniprot
proteins
pubmed
38383719
uniprot
proteins
pubmed
39983994
uniprot
proteins
pubmed
4923144
uniprot
proteins
pubmed
5489771
uniprot
proteins
pubmed
5530842
uniprot
proteins
pubmed
6287432
uniprot
proteins
pubmed
6811139
uniprot
proteins
pubmed
6884994
uniprot
proteins
pubmed
7236608
uniprot
proteins
pubmed
826475
uniprot
proteins
pubmed
8943038
uniprot
proteins
sequence_length
399
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Secreted {ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}; Single-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 351..371; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins