Immunoglobulin supergene family
The immunoglobulin supergene family is "the group of proteins that have immunoglobulin-like domains, including histocompatibility antigens, the T-cell antigen receptor, poly-IgR, and other proteins involved in the vertebrate immune response (17)."

# Immunoglobulin supergenes
Each family within the immunoglobulin supergene family has its share of human genes:
- ATP-binding cassette (ABC) transporters : 23, 6890, 6891,
- Carcinoembryonic antigen genes : 634, 1048, 1084, 1087, 1088, 1089, 4680, 56971, 90273, 125931, 388551, 729767,
- Cell adhesion molecule genes : 214, 914, 1826, 3897, 4059, 4162, 4684, 4685, 4897, 4978, 5175, 7412, 8174, 10752, 23705, 51148, 57453, 57863, 90952, 199731, 220296, 221935, 253559,
- Cell adhesion-related genes : 50937,
- Immunoglobulin domain genes : 915, 916, 917, 3492, 3493, 3494, 3495, 3496, 3497, 3500, 3501, 3502, 3503, 3507, 3514, 3515, 3519, 3535, 3537, 3538, 3539, 3543, 3546, 6405, 6696, 7075, 7842, 7869, 8217, 8482, 9037, 9723, 9860, 10371, 10500, 10501, 10505, 10507, 10509, 10512, 11317, 11326, 23584, 26018, 26103, 28299, 28385, 28386, 28388, 28389, 28391, 28392, 28394, 28395, 28396, 28397, 28398, 28399, 28400, 28401, 28406, 28408, 28409, 28410, 28412, 28414, 28420, 28423, 28424, 28426, 28434, 28439, 28442, 28444, 28445, 28448, 28449, 28450, 28451, 28452, 28454, 28455, 28457, 28458, 28461, 28464, 28465, 28466, 28467, 28468, 28472, 28473, 28474, 28475, 28476, 28477, 28479, 28481, 28483, 28484, 28485, 28486, 28487, 28488, 28490, 28491, 28492, 28494, 28496, 28497, 28498, 28499, 28500, 28501, 28502, 28503, 28504, 28505, 28506, 28507, 28509, 28510, 28772, 28773, 28774, 28775, 28776, 28778, 28779, 28781, 28782, 28783, 28784, 28785, 28786, 28791, 28793, 28795, 28796, 28797, 28799, 28802, 28803, 28804, 28809, 28813, 28814, 28815, 28816, 28817, 28820, 28822, 28823, 28825, 28826, 28827, 28828, 28831, 28832, 28833, 28834, 28874, 28875, 28876, 28877, 28878, 28881, 28882, 28883, 28891, 28893, 28896, 28900, 28901, 28902, 28903, 28904, 28907, 28908, 28912, 28913, 28914, 28916, 28919, 28921, 28923, 28930, 28933, 28935, 28937, 28938, 28939, 28940, 28941, 28942, 28943, 28946, 28947, 28948, 28949, 28950, 50802, 54437, 54841, 54910, 56920, 57289, 57290, 57556, 57715, 59307, 64218, 79037, 80031, 89770, 126259, 158038, 223117, 339398, 340745, 345193,
- Immunoglobulin like domain smart00410 : 176, 558, 925, 926, 2260, 2261, 3570, 3791, 3815, 4916, 5133, 91937, 388364, 391123,
- Immunoglobulin like domain pfam13895 : 942, 962, 2324, 3339,
- Immunoglobulin like domain cd05751 : 9437, 10859, 11006, 11024, 11025, 11026, 51206, 79168, 353514, 102725035, 107987425, 107987462,
- Immunoglobulin domain cl11960 : 920, 930, 2263, 2321, 3084, 5156, 5159, 7273, 29126,
- Immunoglobulin receptor superfamily : 973, 974, 1630, 2208, 2209, 2212, 2213, 2214, 3802, 3803, 3804, 3805, 3806, 3808, 3809, 3810, 3811, 3812, 3813, 3903, 3904, 5284, 10288, 10990, 11027, 23547, 26762, 57292, 79368, 83416, 83417, 84868, 115350, 115352, 115653, 126014, 286676, 343413, 391123, 553128, 100132285,
- Immunoglobulin superfamily genes : 682, 2204, 3321, 3476, 3547, 3671, 9398, 9543, 10261, 10871, 11314, 22997, 57549, 57611, 57722, 65978, 83953, 84966, 93185, 117166, 121227, 124857, 140885, 146722, 147710, 150084, 152404, 283284, 285313, 492311,
- Immunoglobulin supergenes : 1, 7441, 29802,
- Intercellular adhesion molecule genes : 3383, 3384, 3385, 3386, 7087,
- Junction adhesion molecule genes : 50848, 58494, 83700, 120425, 340547,
- Major histocompatibility complex class I gene family : 563, 567, 696, 821, 909, 910, 911, 912, 913, 2217, 2794, 3077, 3105, 3106, 3107, 3133, 3134, 3135, 3140, 4277, 6992, 7726, 10107, 10384, 10385, 11118, 11119, 11120, 79692, 222698, 282890, 353219, 100507436,
- Major histocompatibility complex class II gene family : 972, 1302, 1388, 1616, 2968, 3108, 3109, 3111, 3112, 3113, 3115, 3117, 3118, 3119, 3120, 3121, 3122, 3123, 3125, 3126, 3127, 3833, 4261, 4904, 5089, 5252, 5696, 5698, 5863, 6015, 6046, 6048, 6222, 6257, 6293, 7922, 7923, 8705, 8831, 9277, 9278, 9374, 10471,
- Major histocompatibility complex class III gene family : 177, 578, 629, 717, 720, 721, 780, 1041, 1192, 1432, 1460, 1589, 1797, 2289, 2914, 4295, 4439, 4736, 4758, 4855, 5460, 5514, 5603, 6204, 6631, 6732, 6882, 6941, 6954, 7148, 7287, 7407, 7629, 7936, 7940, 8449, 8859, 8870, 9656, 10211, 259197,
- Major histocompatibility complex class IV gene family : 199, 3303, 3304, 3305, 3309, 6892, 23640,
- Major histocompatibility complex class V gene family : 534, 7916, 7917, 7918, 7919, 7920,
- Major histocompatibility complex class VI gene family : 4049, 4050, 7124,
- ZAS family : 3096,
- for a total of 517 genes.
The human gene sequence is 1, 23, 176, 177, 199, 214, 534, 558, 563, 567, 578, 629, 634, 682, 696, 717, 720, 721, 780, 821, 909, 910, 911, 912, 913, 914, 915, 916, 917, 920, 925, 926, 930, 942, 962, 972, 973, 974, 1041, 1048, 1084, 1087, 1088, 1089, 1192, 1302, 1388, 1432, 1460, 1589, 1616, 1630, 1797, 1826, 2204, 2208, 2209, 2212, 2213, 2214, 2217, 2260, 2261, 2263, 2289, 2321, 2324, 2794, 2914, 2968, 3077, 3084, 3096, 3105, 3106, 3107, 3108, 3109, 3111, 3112, 3113, 3115, 3117, 3118, 3119, 3120, 3121, 3122, 3123, 3125, 3126, 3127, 3133, 3134, 3135, 3140, 3303, 3304, 3305, 3309, 3321, 3339, 3383, 3384, 3385, 3386, 3476, 3492, 3493, 3494, 3495, 3496, 3497, 3500, 3501, 3502, 3503, 3507, 3514, 3515, 3519, 3535, 3537, 3538, 3539, 3543, 3546, 3547, 3570, 3671, 3791, 3802, 3803, 3804, 3805, 3806, 3808, 3809, 3810, 3811, 3812, 3813, 3815, 3833, 3897, 3903, 3904, 4049, 4050, 4059, 4162, 4261, 4277, 4295, 4439, 4680, 4684, 4685, 4736, 4758, 4855, 4897, 4904, 4916, 4978, 5089, 5133, 5156, 5159, 5175, 5252, 5284, 5460, 5514, 5603, 5696, 5698, 5863, 6015, 6046, 6048, 6204, 6222, 6257, 6293, 6405, 6631, 6696, 6732, 6882, 6890, 6891, 6892, 6941, 6954, 6992, 7075, 7087, 7124, 7148, 7273, 7287, 7407, 7412, 7441, 7629, 7726, 7842, 7869, 7916, 7917, 7918, 7919, 7920, 7922, 7923, 7936, 7940, 8174, 8217, 8449, 8482, 8705, 8831, 8859, 8870, 9037, 9277, 9278, 9374, 9398, 9437, 9543, 9656, 9723, 9860, 10107, 10211, 10261, 10288, 10371, 10384, 10385, 10471, 10500, 10501, 10505, 10507, 10509, 10512, 10752, 10859, 10871, 10990, 11006, 11024, 11025, 11026, 11027, 11118, 11119, 11120, 11314, 11317, 11326, 11314, 22997, 23547, 23584, 23640, 23705, 26018, 26103, 26762, 28299, 28385, 28386, 28388, 28389, 28391, 28392, 28394, 28395, 28396, 28397, 28398, 28399, 28400, 28401, 28406, 28408, 28409, 28410, 28412, 28414, 28420, 28423, 28424, 28426, 28434, 28439, 28442, 28444, 28445, 28448, 28449, 28450, 28451, 28452, 28454, 28455, 28457, 28458, 28461, 28464, 28465, 28466, 28467, 28468, 28472, 28473, 28474, 28475, 28476, 28477, 28479, 28481, 28483, 28484, 28485, 28486, 28487, 28488, 28490, 28491, 28492, 28494, 28496, 28497, 28498, 28499, 28500, 28501, 28502, 28503, 28504, 28505, 28506, 28507, 28509, 28510, 28772, 28773, 28774, 28775, 28776, 28778, 28779, 28781, 28782, 28783, 28784, 28785, 28786, 28791, 28793, 28795, 28796, 28797, 28799, 28802, 28803, 28804, 28809, 28813, 28814, 28815, 28816, 28817, 28820, 28822, 28823, 28825, 28826, 28827, 28828, 28831, 28832, 28833, 28834, 28874, 28875, 28876, 28877, 28878, 28881, 28882, 28883, 28891, 28893, 28896, 28900, 28901, 28902, 28903, 28904, 28907, 28908, 28912, 28913, 28914, 28916, 28919, 28921, 28923, 28930, 28933, 28935, 28937, 28938, 28939, 28940, 28941, 28942, 28943, 28946, 28947, 28948, 28949, 28950, 29126, 29802, 50802, 50848, 50937, 51148, 51206, 54437, 54910, 54841, 56920, 56971, 57289, 57290, 57292, 57453, 57549, 57556, 57611, 57715, 57722, 57863, 58494, 59307, 64218, 65978, 79037, 79168, 79368, 79692, 80031, 83416, 83417, 83700, 83953, 84868, 84966, 89770, 90273, 90952, 91937, 93185, 115350, 115352, 115653, 117166, 120425, 121227, 124857, 125931, 126014, 126259, 140885, 146722, 147710, 150084, 152404, 158038, 199731, 220296, 221935, 222698, 223117, 253559, 259197, 282890, 283284, 285313, 286676, 339398, 340547, 340745, 343413, 345193, 353219, 353514, 388364, 388551, 391123, 492311, 553128, 729767, 100132285, 100507436, 102725035, 107987425, 107987462.
Gene ID: 1 A1BG alpha-1-B glycoprotein on 19q13.43: "The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins."
- NP_570602.2  alpha-1B-glycoprotein precursor, Conserved Domains (4) summary: cd05751 Location: 401  493 Ig1_LILRB1_like; First immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILR)B1 (also known as LIR-1) and similar proteins, smart00410 Location: 218  280 IG_like; Immunoglobulin like, pfam13895 Location: 210  301 Ig_2; Immunoglobulin domain and cl11960 Location: 28  110 Ig; Immunoglobulin domain.
A1BG contains the immunoglobulin domain: cl11960 and three immunoglobulin-like domains: pfam13895, cd05751 and smart00410.
"Immunoglobulin (Ig) domain  found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond."
"This domain  contains immunoglobulin-like domains."
"Ig1_LILR_KIR_like:  domain similar to the first immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILRs) and Natural killer inhibitory receptors (KIRs). This group includes LILRB1 (or LIR-1), LILRA5 (or LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (or CD89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3,and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1 (LIR-1), LILRB2 (LIR-2), and LILRB3 (LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LIR-1 (LILRB1), and LIR-2 (LILRB2), show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1 (LIR-1), and LILRB2 (LIR-2), and two in the case of LILRB4 (LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst."
"IG domains  that cannot be classified into one of IGv1, IGc1, IGc2, IG."
"1B-glycoprotein(1B)  consists of a single polypeptide chain N-linked to four
glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues.  1B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond.  several domains of 1B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 1B  exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."
"Some of the domains of 1B show significant homology to variable (V) and constant (C) regions of certain immunoglobulins. Likewise, there is statistically significant homology between 1B and the secretory component (SC) of human IgA (15) and also with the extracellular portion of the rabbit receptor for transepithelial transport of polymeric immunoglobulins (IgA and IgM). Mostov et al. (16) have called the later protein the poly-Ig receptor or poly-IgR and have shown that it is the precursor of SC."
Gene ID: 7441 is VPREB1 V-set pre-B cell surrogate light chain 1 on 22q11.22: "The protein encoded by this gene belongs to the immunoglobulin superfamily and is expressed selectively at the early stages of B cell development, namely, in proB and early preB cells. This gene encodes the iota polypeptide chain that is associated with the Ig-mu chain to form a molecular complex which is expressed on the surface of pre-B cells. The complex is thought to regulate Ig gene rearrangements in the early steps of B-cell differentiation. Alternative splicing results in multiple transcript variants."
- NP_001290438.1 immunoglobulin iota chain isoform 2: "Transcript Variant: This variant (2) uses an alternate splice site in the coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1." Conserved Domains summary: smart00410 Location: 25  115 IG_like; Immunoglobulin like and cl11960 Location: 29  117 Ig; Immunoglobulin domain.
- NP_009059.1 immunoglobulin iota chain isoform 1 precursor: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)." Conserved Domains summary: smart00410 Location: 26  116 IG_like; Immunoglobulin like and cl11960 Location: 30  118 Ig; Immunoglobulin domain.
Gene ID: 29802 is VPREB3 V-set pre-B cell surrogate light chain 3 on 22q11.23; 22q11: "The protein encoded by this gene is the human ortholog of the mouse VpreB3 (8HS20) protein, is thought to be involved in B-cell maturation, and may play a role in assembly of the pre-B cell receptor (pre-BCR). While the role of this protein in B-cell development has not yet been elucidated, studies with the chicken ortholog of this protein have found that when overexpressed, this protein localizes to the endoplasmic reticulum. The mouse ortholog of this protein has been shown to associate with membrane mu heavy chains early in the course of pre-B cell receptor biosynthesis. Expression of this gene has been observed in some lymphomas."
- NP_037510.1  pre-B lymphocyte protein 3 precursor, Conserved Domains summary: cl11960 Location: 30  122 Ig; Immunoglobulin domain.

# Carcinoembryonic antigen gene family

# Immunoglobulin superfamily genes

# Major histocompatibility complex genes

## Class I

## Class II

## Class III

## Class IV
Several "genes have been described that are encoded in the telomeric end of the Class III region and that appear to be involved in both global and specific inflammatory responses. Due to this commonality of function this gene-rich region was dubbed Class IV, and includes the TNF family, AIF1, and HSP70."
The B144/LST1 protein  is expressed in T cell, monocytic, and macrophage cell lines, and is also substantially expressed in both murine and human dendritic cells in culture."
"The 1C7 gene  is located immediately adjacent to the B144 gene. RNA for B144 and 1C7 are transcribed in convergent directions such that there is a slight overlap between the 3' ends of the two mRNAs.  1C7 also shows multiple splice forms with 9 forms of the human mRNA reported so far.(21) The major forms encode proteins containing a leader sequence, a probable trans-membrane segment, an external sequence including an immunoglobulin-like domain, and at least three alternative forms of the putative intracellular segment of the protein. One alternative splice modifies the structure of the immunoglobulin-like domain, changing it from a sequence more closely resembling those of the V regions of Ig molecules to one that is more similar to IgC2 regions. Of the three alternative putative intracellular domains, one encodes multiple proline repeats suggestive of SH3 binding domains."
"The existence of the G1 gene was initially noted as a part of a screen of MHC cosmids for embedded genes. The G1 and AIF1 transcripts appear to be derived by alternative splicing from partially overlapping genomic templates. A third human interferon gamma-responsive transcript, IRT-1, has been noted that shares some internal sequences with both G1 and AIF1, but on the basis of the predicted open reading frame it shares only limited amino acid sequences with G1."
Gene ID: 199 is AIF1 allograft inflammatory factor 1 on 6p21.33: "This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain."
- NP_001305899.1 allograft inflammatory factor 1 isoform 1: "Transcript Variant: This variant (4) uses an alternate splice site in the 5' region and initiates translation at a downstream start codon compared to variant 3. The encoded isoform (1) has a shorter N-terminus than isoform 3. Variants 1 and 4 encode the same isoform (1)."
- NP_001614.3 allograft inflammatory factor 1 isoform 3: "Transcript Variant: This variant (3) encodes the longest isoform (3)."
- NP_116573.1 allograft inflammatory factor 1 isoform 1: "Transcript Variant: This variant (1, also known as G1) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon compared to variant 3. The encoded isoform (1) has a shorter N-terminus than isoform 3. Variants 1 and 4 encode the same isoform (1)."
"AIF-1 (allograft inflammatory factor-1) is a Ca2+ binding protein predominantly expressed by activated monocytes, originally identified in rat cardiac allografts with chronic rejection.(22) The human cDNA homologue is 86% identical to the rat (90% identical to the amino acid sequence) and was identified by reverse transcriptase-PCR of endomyocardial biopsy specimens from human heart transplants and in macrophage cell lines.(23)"
Gene ID: 3303 is HSPA1A heat shock protein family A (Hsp70) member 1A on 6p21.33: "This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins."
Gene ID: 3304 is HSPA1B heat shock protein family A (Hsp70) member 1B on 6p21.33: "This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins."
Gene ID: 3305 is HSPA1L heat shock protein family A (Hsp70) member 1 like on 6p21.33: "This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein."
Gene ID: 3309 is HSPA5 heat shock protein family A (Hsp70) member 5 on 9q33.3: "The protein encoded by this gene is a member of the heat shock protein 70 (HSP70) family. It is localized in the lumen of the endoplasmic reticulum (ER), and is involved in the folding and assembly of proteins in the ER. As this protein interacts with many ER proteins, it may play a key role in monitoring protein transport through the cell."
- NP_005338.1 endoplasmic reticulum chaperone BiP precursor.
Gene ID: 6892 is TAPBP TAP binding protein on 6p21.32: "This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms."
- NP_003181.3 tapasin isoform 1 precursor: "Transcript Variant: This variant (1) represents the longest transcript and encodes isoform 1.  Ig; Immunoglobulin domain"
- NP_757345.2 tapasin isoform 2 precursor: "Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is longer than isoform 1."
- NP_757346.2 tapasin isoform 3 precursor: "Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1."
Gene ID: 23640 is HSPBP1 HSPA (Hsp70) binding protein 1 on 19q13.42.
- NP_001123578.1 hsp70-binding protein 1 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 3. Variants 1 and 2 encode the same isoform (2), which has a shorter N-terminus, compared to isoform 1."
- NP_001284529.1 hsp70-binding protein 1 isoform 1: "Transcript Variant: This variant (3) encodes the longer isoform (1)."
- NP_036399.3 hsp70-binding protein 1 isoform 2: "Transcript Variant: This variant (1) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 3. Variants 1 and 2 encode the same isoform (2), which has a shorter N-terminus, compared to isoform 1."

## Class V
"Vacuolar ATPase is a multi-subunit protein complex that transports H+ ions. It functions in general to mediate acidification of cellular vacuoles, and consequently in receptor recycling, lysosome formation, and cellular pH control.  centromeric to the BAT1 gene  encode exons of a gene, ATP6G, homologous to the G subunit of the vacuolar H+ ATPase of a number of species.(26) The mRNA for this gene had two alternative splice forms, with the shorter form removing the presumptive translation initiation codon of the longer form and therefore removing an amino terminal region of high homology to other G subunits. The longer splice form was selectively expressed in some B and T cell lines as compared with myelomonocytic lines. Vacuolar ATPase subunit G is up-regulated in neutrophils exposed to non-pathogenic bacteria (Yeramilli and Weissman, unpublished). The ATPase is also up-regulated in neutrophils by GM-CSF or phorbol myristic acid. Up-regulation of the ATPase is one of the mechanisms that may delay apoptosis in activated neutrophils. However a specific role for the ATP6G in inflammation remains to be established by more specific means."
Gene ID: 534 is ATP6V1G2 ATPase H+ transporting V1 subunit G2 on 6p21.33: "This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of three V1 domain G subunit proteins. This gene had previous gene symbols of ATP6G and ATP6G2. Alternatively spliced transcript variants encoding different isoforms have been described. Read-through transcription also exists between this gene and the downstream DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) gene."
- NP_001191007.1 V-type proton ATPase subunit G 2 isoform c.
- NP_569730.1 V-type proton ATPase subunit G 2 isoform a.
- NP_612139.1 V-type proton ATPase subunit G 2 isoform b.
Gene ID: 7916 is PRRC2A proline rich coiled-coil 2A aka G2; BAT2; D6S51; D6S51E on 6p21.33: "A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene."
- NP_004629.3 protein PRRC2A: "Transcript Variant: This variant (2) represents the longer transcript. Variants 1 and 2 both encode the same protein."
- NP_542417.2 protein PRRC2A: "Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 2. Variants 1 and 2 both encode the same protein."
Gene ID: 7917 is BAG6 BAG cochaperone 6 aka G3; BAT3 on 6p21.33: "This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene."
- NP_001092004.1 large proline-rich protein BAG6 isoform b: "Transcript Variant: This variant (4) differs in the 5' UTR and utilizes an alternative in-frame splice site in the 5' coding region, compared to variant 1. Variants 2, 3, and 4 encode the same isoform (b), which is 6 aa shorter than isoform a."
- NP_001186626.1 large proline-rich protein BAG6 isoform c: "Transcript Variant: This variant (5) differs in the 5' UTR and lacks three alternate in-frame segments compared to variant 1. The resulting isoform (c) has the same N- and C-termini but is shorter compared to isoform a."
- NP_001186627.1 large proline-rich protein BAG6 isoform d: "Transcript Variant: This variant (6) differs in the 5' UTR and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (d) has the same N- and C-termini but is shorter compared to isoform a."
- NP_542433.1 large proline-rich protein BAG6 isoform b: "Transcript Variant: This variant (2) differs in the 5' UTR and utilizes an alternative in-frame splice site in the 5' coding region, compared to variant 1. Variants 2, 3, and 4 encode the same isoform (b), which is 6 aa shorter than isoform a."
- NP_542434.1 large proline-rich protein BAG6 isoform b: "Transcript Variant: This variant (3) utilizes an alternative in-frame splice site in the 5' coding region, compared to variant 1. Variants 2, 3, and 4 encode the same isoform (b), which is 6 aa shorter than isoform a."
Gene ID: 7918 is GPANK1 G-patch domain and ankyrin repeats 1 aka G5; BAT4, on 6p21.33: "This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified."
- NP_001186166.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (1) represents the longest transcript."
- NP_001186167.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."
- NP_001186168.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."
- NP_001186169.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."
- NP_149417.1 G patch domain and ankyrin repeat-containing protein 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4, and 5 encode the same protein."
Gene ID: 7919 is DDX39B DExD-box helicase 39B aka BAT1 on 6p21.33: "This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene."
- NP_004631.1 spliceosome RNA helicase DDX39B: "Transcript Variant: This variant (1) represents the longest transcript. Both variants 1 and 2 encode the same protein."
- NP_542165.1 spliceosome RNA helicase DDX39B: "Transcript Variant: This variant (2) uses an alternative splice site in the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same protein."
Gene ID: 7920 is ABHD16A abhydrolase domain containing 16A, phospholipase, aka BAT5 on 6p21.33: "A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. The protein encoded by this gene is thought to be involved in some aspects of immunity. Alternatively spliced transcript variants have been described."
- NP_001170986.1 phosphatidylserine lipase ABHD16A isoform b: "Transcript Variant: This variant (2) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at an alternate AUG and result in an isoform (b) with a shorter, distinct N-terminus, compared to isoform 1."
- NP_066983.1 phosphatidylserine lipase ABHD16A isoform a: "Transcript Variant: This variant (1) encodes the longer isoform (a)."

## Class VI
"A cluster of genes for three related cytokines/cytokine receptors, tumor necrosis factor (TNF, formerly known as TNF-alpha or cachectin), lymphotoxin alpha (LTA), and lymphotoxin beta (LTB), lies in the Class IV region shortly before the most centromeric Class I related genes. TNF has been very extensively studied(5) and plays an important role in inflammation, bacterial(6) and viral infection,(7) tumor cachexia and the immune response. It is produced by a variety of cells including prominently monocytes, macrophages, and some T cell subsets."
"LTB (also called TNF C) is a membrane bound molecule that forms a heterotrimer with LTA.(12) This LTA-LTB complex can then induce activation of NF kappa B in certain cell lines by binding with the LTB receptor, a member of the TNF receptor family.(13) (14) NF kappa B is a pleiotropic transcription factor capable of activating the expression of a great variety of genes critical for the Immunoin flammatory response.(14)"
The region within the MHC class III gene cluster that contains genes for TNFs is also known as MHC class VI or the inflammatory region.
Gene ID: 4049 is LTA lymphotoxin alpha on 6p21.33: "The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene."
- NP_000586.2 lymphotoxin-alpha precursor: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein."
- NP_001153212.1 lymphotoxin-alpha precursor: "Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein."
Gene ID: 4050 is LTB lymphotoxin beta on 6p21.33: "Lymphotoxin beta is a type II membrane protein of the TNF family. It anchors lymphotoxin-alpha to the cell surface through heterotrimer formation. The predominant form on the lymphocyte surface is the lymphotoxin-alpha 1/beta 2 complex (e.g. 1 molecule alpha/2 molecules beta) and this complex is the primary ligand for the lymphotoxin-beta receptor. The minor complex is lymphotoxin-alpha 2/beta 1. LTB is an inducer of the inflammatory response system and involved in normal development of lymphoid tissue. Lymphotoxin-beta isoform b is unable to complex with lymphotoxin-alpha suggesting a function for lymphotoxin-beta which is independent of lympyhotoxin-alpha. Alternative splicing results in multiple transcript variants encoding different isoforms."
- NP_002332.1 lymphotoxin-beta isoform a: "Transcript Variant: This variant (1) represents the longer transcript, encodes the longer isoform (a), and can form the heterotrimeric complex with lymphotoxin-alpha."
- NP_033666.1 lymphotoxin-beta isoform b: "Transcript Variant: This splice variant (2) lacks an exon in the coding region, compared to variant 1. The encoded protein (isoform b) has a premature stop codon and lacks the majority of the extracellular domain, compared to isoform a. This loss impairs its ability to complex with lympytoxin-alpha."
Gene ID: 7124 is TNF tumor necrosis factor on 6p21.33: "This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine."

## ATP-binding cassette (ABC) transporters
Gene ID: 23 is ABCF1 ATP binding cassette subfamily F member 1, on 6p21.33: "The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the GCN20 subfamily. Unlike other members of the superfamily, this protein lacks the transmembrane domains which are characteristic of most ABC transporters. This protein may be regulated by tumor necrosis factor-alpha and play a role in enhancement of protein synthesis and the inflammation process." No immunoglobulins.
- NP_001020262.1 ATP-binding cassette sub-family F member 1 isoform a: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a)."
- NP_001081.1 ATP-binding cassette sub-family F member 1 isoform b: "Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1. The resulting protein (isoform b) is shorter than isoform a."
Gene ID: 6890 is TAP1 transporter 1, ATP binding cassette subfamily B member aka transporter, ATP-binding cassette, major histocompatibility complex, 1 on 6p21.32: "The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene." No immunoglobulins.
- NP_000584.3 antigen peptide transporter 1 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."
- NP_001278951.1 antigen peptide transporter 1 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1."
Gene ID: 6891 is TAP2 transporter 2, ATP binding cassette subfamily B member on 6p21.32: "The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules." No immunoglobulins.
- NP_000535.3 antigen peptide transporter 2 isoform 1: "Transcript Variant: This variant (1, B allele) represents the longer transcript and encodes the longest isoform (1). An allele (variant 1, A allele) exists in which a single nt change creates an internal stop codon, leading to a protein that is 17 aa shorter at the C-terminus."
- NP_001276972.1 antigen peptide transporter 2 isoform 3: "Transcript Variant: This variant (1, A allele) differs at 3 nt positions compared to variant 1, B allele. The resulting isoform (3) is shorter at the C-terminus compared to isoform 1."
- NP_061313.2 antigen peptide transporter 2 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting isoform (2) is shorter and has a distinct C-terminus compared to isoform 1."

## Immunoglobulin domain genes

## Immunoglobulin receptor superfamily

## ZAS family
Gene ID: 3096 is HIVEP1 HIVEP zinc finger 1 aka major histocompatibility complex binding protein 1 on 6p24.1: "This gene encodes a transcription factor belonging to the ZAS family, members of which are large proteins that contain a ZAS domain - a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine-rich sequence. These proteins bind specifically to the DNA sequence motif, GGGACTTTCC, found in the enhancer elements of several viral promoters, including human immunodeficiency virus (HIV), and to related sequences found in the enhancer elements of a number of cellular promoters. This protein binds to this sequence motif, suggesting a role in the transcriptional regulation of both viral and cellular genes."
- NP_002105.3 zinc finger protein 40.

# Hypotheses
- Downstream core promoters may work as transcription factors even as their complements or inverses.
- In addition to the DNA binding sequences listed above, the transcription factors that can open up and attach through the local epigenome need to be known and specified.