ID TMIG2_HUMAN Reviewed; 282 AA.
AC Q96BF3; Q6UW59;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 24-JAN-2024, entry version 163.
DE RecName: Full=Transmembrane and immunoglobulin domain-containing protein 2;
DE AltName: Full=CD28 homolog;
DE AltName: Full=Immunoglobulin and proline-rich receptor 1;
DE Short=IGPR-1;
DE Flags: Precursor;
GN Name=TMIGD2; Synonyms=CD28H, IGPR1; ORFNames=UNQ3059/PRO9879;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-202.
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 23-37.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-220, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [5]
RP FUNCTION, INTERACTION WITH CACNB2; DST; MIA AND NCKIPSD, SUBCELLULAR
RP LOCATION, HOMOPHILIC INTERACTION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=22419821; DOI=10.1091/mbc.e11-11-0934;
RA Rahimi N., Rezazadeh K., Mahoney J.E., Hartsough E., Meyer R.D.;
RT "Identification of IGPR-1 as a novel adhesion molecule involved in
RT angiogenesis.";
RL Mol. Biol. Cell 23:1646-1656(2012).
RN [6]
RP FUNCTION IN T-CELL COSTIMULATION, INTERACTION WITH HHLA2, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, PROBABLE PHOSPHORYLATION AT TYR-192 AND
RP TYR-222, AND MUTAGENESIS OF TYR-192; TYR-197 AND TYR-222.
RX PubMed=23784006; DOI=10.1038/ncomms3043;
RA Zhu Y., Yao S., Iliopoulou B.P., Han X., Augustine M.M., Xu H.,
RA Phennicie R.T., Flies S.J., Broadwater M., Ruff W., Taube J.M., Zheng L.,
RA Luo L., Zhu G., Chen J., Chen L.;
RT "B7-H5 costimulates human T cells via CD28H.";
RL Nat. Commun. 4:2043-2043(2013).
CC -!- FUNCTION: Plays a role in cell-cell interaction, cell migration, and
CC angiogenesis. Through interaction with HHLA2, costimulates T-cells in
CC the context of TCR-mediated activation. Enhances T-cell proliferation
CC and cytokine production via an AKT-dependent signaling cascade.
CC {ECO:0000269|PubMed:22419821, ECO:0000269|PubMed:23784006}.
CC -!- SUBUNIT: May form homophilic interactions that could regulate cell-cell
CC interaction. Interacts with CACNB2, DST, MIA and NCKIPSD. Interacts
CC with HHLA2. {ECO:0000269|PubMed:22419821, ECO:0000269|PubMed:23784006}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22419821};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:22419821}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96BF3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96BF3-2; Sequence=VSP_022967;
CC -!- TISSUE SPECIFICITY: Widely expressed, mainly by epithelial and
CC endothelial cells, including bronchial epithelial cells of lung, breast
CC glandular and lobular epithelia cells, urothelium of the bladder, skin
CC epidermis, epithelium of gastrointestinal, rectum, endometrial glands
CC of the uterus, ureter, fallopian tube epithelium, colonic epithelium,
CC small bowl epithelium, stomach epithelium, including both chief and
CC parietal cells, trophoblastic epithelium of placenta, and pancreatic
CC acinar cells (at protein level). Consistently expressed in veins and
CC arteries (at protein level). Not detected in thyroid, cerebellum,
CC cerebral cortex and thymus (at protein level). Expressed in lymphoid
CC organs, with highest levels in thymus, spleen, peripheral blood
CC lymphocytes and liver. In the thymus, expressed in CD4+ and CD8+
CC single- and double-positive cells, but not in immature CD4- and
CC CD8- double-negative cells (at protein level). In peripheral blood
CC mononuclear cells, highly expressed on CD56+ or CD16+ natural killer
CC cells and CD3+ T-cells(at protein level). Not detected on B-cells(at
CC protein level). Expressed in tonsils (at protein level).
CC {ECO:0000269|PubMed:22419821, ECO:0000269|PubMed:23784006}.
CC -!- DEVELOPMENTAL STAGE: Repetitive stimulation of naive T-cells, including
CC with IL2 and antibodies against CD3 and CD28 or repetitive antigenic
CC exposure, leads to progressive and irreversible loss of expression.
CC {ECO:0000269|PubMed:23784006}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:22419821}.
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DR EMBL; AY358964; AAQ89323.1; -; mRNA.
DR EMBL; BC015655; AAH15655.1; -; mRNA.
DR CCDS; CCDS12126.1; -. [Q96BF3-1]
DR CCDS; CCDS59334.1; -. [Q96BF3-2]
DR RefSeq; NP_001162597.1; NM_001169126.1. [Q96BF3-2]
DR RefSeq; NP_001295161.1; NM_001308232.1.
DR RefSeq; NP_653216.2; NM_144615.2. [Q96BF3-1]
DR AlphaFoldDB; Q96BF3; -.
DR SMR; Q96BF3; -.
DR BioGRID; 125971; 2.
DR STRING; 9606.ENSP00000301272; -.
DR GlyCosmos; Q96BF3; 3 sites, No reported glycans.
DR GlyGen; Q96BF3; 3 sites.
DR iPTMnet; Q96BF3; -.
DR PhosphoSitePlus; Q96BF3; -.
DR SwissPalm; Q96BF3; -.
DR BioMuta; TMIGD2; -.
DR DMDM; 125991218; -.
DR MassIVE; Q96BF3; -.
DR PaxDb; 9606-ENSP00000301272; -.
DR PeptideAtlas; Q96BF3; -.
DR ProteomicsDB; 76072; -. [Q96BF3-1]
DR ProteomicsDB; 76073; -. [Q96BF3-2]
DR ABCD; Q96BF3; 15 sequenced antibodies.
DR Antibodypedia; 2599; 230 antibodies from 25 providers.
DR DNASU; 126259; -.
DR Ensembl; ENST00000301272.6; ENSP00000301272.1; ENSG00000167664.9. [Q96BF3-1]
DR Ensembl; ENST00000595645.6; ENSP00000470561.1; ENSG00000167664.9. [Q96BF3-2]
DR GeneID; 126259; -.
DR KEGG; hsa:126259; -.
DR MANE-Select; ENST00000595645.6; ENSP00000470561.1; NM_001169126.2; NP_001162597.1. [Q96BF3-2]
DR UCSC; uc002lzx.3; human. [Q96BF3-1]
DR AGR; HGNC:28324; -.
DR CTD; 126259; -.
DR DisGeNET; 126259; -.
DR GeneCards; TMIGD2; -.
DR HGNC; HGNC:28324; TMIGD2.
DR HPA; ENSG00000167664; Tissue enriched (lymphoid).
DR MIM; 614715; gene.
DR neXtProt; NX_Q96BF3; -.
DR OpenTargets; ENSG00000167664; -.
DR PharmGKB; PA145148047; -.
DR VEuPathDB; HostDB:ENSG00000167664; -.
DR eggNOG; ENOG502SX6X; Eukaryota.
DR GeneTree; ENSGT00390000007100; -.
DR HOGENOM; CLU_1008198_0_0_1; -.
DR InParanoid; Q96BF3; -.
DR OMA; SWQPPGN; -.
DR OrthoDB; 4611673at2759; -.
DR PhylomeDB; Q96BF3; -.
DR TreeFam; TF341425; -.
DR PathwayCommons; Q96BF3; -.
DR SignaLink; Q96BF3; -.
DR SIGNOR; Q96BF3; -.
DR BioGRID-ORCS; 126259; 20 hits in 1148 CRISPR screens.
DR GenomeRNAi; 126259; -.
DR Pharos; Q96BF3; Tbio.
DR PRO; PR:Q96BF3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96BF3; Protein.
DR Bgee; ENSG00000167664; Expressed in left ventricle myocardium and 175 other cell types or tissues.
DR ExpressionAtlas; Q96BF3; baseline and differential.
DR Genevisible; Q96BF3; HS.
DR GO; GO:0019815; C:B cell receptor complex; IEA:InterPro.
DR GO; GO:0015026; F:coreceptor activity; IDA:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:InterPro.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:CACAO.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0031295; P:T cell costimulation; IDA:UniProtKB.
DR CDD; cd00096; Ig; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR InterPro; IPR039695; CD79a/CD79b.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR PANTHER; PTHR14334; B-CELL ANTIGEN RECEPTOR COMPLEX-ASSOCIATED PROTEIN; 1.
DR PANTHER; PTHR14334:SF3; IG-LIKE DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 23..282
FT /note="Transmembrane and immunoglobulin domain-containing
FT protein 2"
FT /id="PRO_0000275870"
FT TOPO_DOM 23..150
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 172..282
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 23..129
FT /note="Ig-like"
FT REGION 201..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..231
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 233..253
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 192
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 222
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..112
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 186..189
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_022967"
FT VARIANT 168
FT /note="W -> L (in dbSNP:rs58237134)"
FT /id="VAR_061328"
FT VARIANT 202
FT /note="A -> P (in dbSNP:rs28477168)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030469"
FT MUTAGEN 192
FT /note="Y->F: Partial loss of phosphorylation; when
FT associated with F-197. Complete loss of phosphorylation;
FT when associated with F-222."
FT /evidence="ECO:0000269|PubMed:23784006"
FT MUTAGEN 197
FT /note="Y->F: Partial loss of phosphorylation; when
FT associated with F-192 or with F-222."
FT /evidence="ECO:0000269|PubMed:23784006"
FT MUTAGEN 222
FT /note="Y->F: Partial loss of phosphorylation; when tested
FT individually or when associated with F-197. Complete loss
FT of phosphorylation; when associated with F-192."
FT /evidence="ECO:0000269|PubMed:23784006"
SQ SEQUENCE 282 AA; 30675 MW; AABB3FFD840B44DC CRC64;
MGSPGMVLGL LVQIWALQEA SSLSVQQGPN LLQVRQGSQA TLVCQVDQAT AWERLRVKWT
KDGAILCQPY ITNGSLSLGV CGPQGRLSWQ APSHLTLQLD PVSLNHSGAY VCWAAVEIPE
LEEAEGNITR LFVDPDDPTQ NRNRIASFPG FLFVLLGVGS MGVAAIVWGA WFWGRRSCQQ
RDSGNSPGNA FYSNVLYRPR GAPKKSEDCS GEGKDQRGQS IYSTSFPQPA PRQPHLASRP
CPSPRPCPSP RPGHPVSMVR VSPRPSPTQQ PRPKGFPKVG EE
//
