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Protein

Transmembrane and immunoglobulin domain-containing protein 2

Gene

TMIGD2

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

Functioni

Plays a role in cell-cell interaction, cell migration, and angiogenesis. Through interaction with HHLA2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade.2 Publications

GO - Molecular functioni

  • coreceptor activity Source: UniProtKB

GO - Biological processi

  • immune response Source: GO_Central
  • immunoglobulin production Source: GO_Central
  • positive regulation of activated T cell proliferation Source: UniProtKB
  • positive regulation of angiogenesis Source: CACAO
  • positive regulation of cytokine production Source: UniProtKB
  • T cell costimulation Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane and immunoglobulin domain-containing protein 2
Alternative name(s):
CD28 homolog
Immunoglobulin and proline-rich receptor 1
Short name:
IGPR-1
Gene namesi
Name:TMIGD2
Synonyms:CD28H, IGPR1
ORF Names:UNQ3059/PRO9879
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:28324. TMIGD2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 150128ExtracellularSequence analysisAdd
BLAST
Transmembranei151 – 17121HelicalSequence analysisAdd
BLAST
Topological domaini172 – 282111CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi192 – 1921Y → F: Partial loss of phosphorylation; when associated with F-197. Complete loss of phosphorylation; when associated with F-222. 1 Publication
Mutagenesisi197 – 1971Y → F: Partial loss of phosphorylation; when associated with F-192 or with F-222. 1 Publication
Mutagenesisi222 – 2221Y → F: Partial loss of phosphorylation; when tested individually or when associated with F-197. Complete loss of phosphorylation; when associated with F-192. 1 Publication

Organism-specific databases

PharmGKBiPA145148047.

Polymorphism and mutation databases

BioMutaiTMIGD2.
DMDMi125991218.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 22221 PublicationAdd
BLAST
Chaini23 – 282260Transmembrane and immunoglobulin domain-containing protein 2PRO_0000275870Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi44 ↔ 112PROSITE-ProRule annotation
Glycosylationi73 – 731N-linked (GlcNAc...)Sequence analysis
Glycosylationi105 – 1051N-linked (GlcNAc...)Sequence analysis
Glycosylationi127 – 1271N-linked (GlcNAc...)Sequence analysis
Modified residuei192 – 1921PhosphotyrosineCurated
Modified residuei220 – 2201PhosphoserineCombined sources
Modified residuei222 – 2221PhosphotyrosineCurated

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ96BF3.
PeptideAtlasiQ96BF3.
PRIDEiQ96BF3.

PTM databases

iPTMnetiQ96BF3.
PhosphoSiteiQ96BF3.
SwissPalmiQ96BF3.

Expressioni

Tissue specificityi

Widely expressed, mainly by epithelial and endothelial cells, including bronchial epithelial cells of lung, breast glandular and lobular epithelia cells, urothelium of the bladder, skin epidermis, epithelium of gastrointestinal, rectum, endometrial glands of the uterus, ureter, fallopian tube epithelium, colonic epithelium, small bowl epithelium, stomach epithelium, including both chief and parietal cells, trophoblastic epithelium of placenta, and pancreatic acinar cells (at protein level). Consistently expressed in veins and arteries (at protein level). Not detected in thyroid, cerebellum, cerebral cortex and thymus (at protein level). Expressed in lymphoid organs, with highest levels in thymus, spleen, peripheral blood lymphocytes and liver. In the thymus, expressed in CD4+ and CD8+ single- and double-positive cells, but not in immature CD4- and CD8- double-negative cells (at protein level). In peripheral blood mononuclear cells, highly expressed on CD56+ or CD16+ natural killer cells and CD3+ T-cells(at protein level). Not detected on B-cells(at protein level). Expressed in tonsils (at protein level).2 Publications

Developmental stagei

Repetitive stimulation of naive T-cells, including with IL2 and antibodies against CD3 and CD28 or repetitive antigenic exposure, leads to progressive and irreversible loss of expression.1 Publication

Gene expression databases

BgeeiENSG00000167664.
CleanExiHS_TMIGD2.
ExpressionAtlasiQ96BF3. baseline and differential.
GenevisibleiQ96BF3. HS.

Organism-specific databases

HPAiHPA011081.

Interactioni

Subunit structurei

May form homophilic interactions that could regulate cell-cell interaction. Interacts with CACNB2, DST, MIA and NCKIPSD. Interacts with HHLA2.2 Publications

Protein-protein interaction databases

BioGridi125971. 1 interaction.
STRINGi9606.ENSP00000301272.

Structurei

3D structure databases

ProteinModelPortaliQ96BF3.
SMRiQ96BF3. Positions 27-119.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini23 – 129107Ig-likeAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi227 – 27751Pro-richAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J9M6. Eukaryota.
ENOG41118HW. LUCA.
GeneTreeiENSGT00390000007100.
HOGENOMiHOG000154641.
InParanoidiQ96BF3.
KOiK16668.
OMAiYSNVLYR.
OrthoDBiEOG091G0MZN.
PhylomeDBiQ96BF3.
TreeFamiTF341425.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96BF3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGSPGMVLGL LVQIWALQEA SSLSVQQGPN LLQVRQGSQA TLVCQVDQAT
60 70 80 90 100
AWERLRVKWT KDGAILCQPY ITNGSLSLGV CGPQGRLSWQ APSHLTLQLD
110 120 130 140 150
PVSLNHSGAY VCWAAVEIPE LEEAEGNITR LFVDPDDPTQ NRNRIASFPG
160 170 180 190 200
FLFVLLGVGS MGVAAIVWGA WFWGRRSCQQ RDSGNSPGNA FYSNVLYRPR
210 220 230 240 250
GAPKKSEDCS GEGKDQRGQS IYSTSFPQPA PRQPHLASRP CPSPRPCPSP
260 270 280
RPGHPVSMVR VSPRPSPTQQ PRPKGFPKVG EE
Note: No experimental confirmation available.
Length:282
Mass (Da):30,675
Last modified:February 6, 2007 - v2
Checksum:iAABB3FFD840B44DC
GO
Isoform 2 (identifier: Q96BF3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     186-189: Missing.

Note: No experimental confirmation available.
Show »
Length:278
Mass (Da):30,319
Checksum:iD9E74C79AF4BBAE0
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti168 – 1681W → L.
Corresponds to variant rs58237134 [ dbSNP | Ensembl ].
VAR_061328
Natural varianti202 – 2021A → P.1 Publication
Corresponds to variant rs28477168 [ dbSNP | Ensembl ].
VAR_030469

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei186 – 1894Missing in isoform 2. 1 PublicationVSP_022967

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358964 mRNA. Translation: AAQ89323.1.
BC015655 mRNA. Translation: AAH15655.1.
CCDSiCCDS12126.1. [Q96BF3-1]
CCDS59334.1. [Q96BF3-2]
RefSeqiNP_001162597.1. NM_001169126.1. [Q96BF3-2]
NP_001295161.1. NM_001308232.1.
NP_653216.2. NM_144615.2. [Q96BF3-1]
UniGeneiHs.263928.

Genome annotation databases

EnsembliENST00000301272; ENSP00000301272; ENSG00000167664. [Q96BF3-1]
ENST00000595645; ENSP00000470561; ENSG00000167664. [Q96BF3-2]
GeneIDi126259.
KEGGihsa:126259.
UCSCiuc002lzx.3. human. [Q96BF3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358964 mRNA. Translation: AAQ89323.1.
BC015655 mRNA. Translation: AAH15655.1.
CCDSiCCDS12126.1. [Q96BF3-1]
CCDS59334.1. [Q96BF3-2]
RefSeqiNP_001162597.1. NM_001169126.1. [Q96BF3-2]
NP_001295161.1. NM_001308232.1.
NP_653216.2. NM_144615.2. [Q96BF3-1]
UniGeneiHs.263928.

3D structure databases

ProteinModelPortaliQ96BF3.
SMRiQ96BF3. Positions 27-119.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125971. 1 interaction.
STRINGi9606.ENSP00000301272.

PTM databases

iPTMnetiQ96BF3.
PhosphoSiteiQ96BF3.
SwissPalmiQ96BF3.

Polymorphism and mutation databases

BioMutaiTMIGD2.
DMDMi125991218.

Proteomic databases

PaxDbiQ96BF3.
PeptideAtlasiQ96BF3.
PRIDEiQ96BF3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301272; ENSP00000301272; ENSG00000167664. [Q96BF3-1]
ENST00000595645; ENSP00000470561; ENSG00000167664. [Q96BF3-2]
GeneIDi126259.
KEGGihsa:126259.
UCSCiuc002lzx.3. human. [Q96BF3-1]

Organism-specific databases

CTDi126259.
GeneCardsiTMIGD2.
H-InvDBHIX0014660.
HGNCiHGNC:28324. TMIGD2.
HPAiHPA011081.
MIMi614715. gene.
neXtProtiNX_Q96BF3.
PharmGKBiPA145148047.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J9M6. Eukaryota.
ENOG41118HW. LUCA.
GeneTreeiENSGT00390000007100.
HOGENOMiHOG000154641.
InParanoidiQ96BF3.
KOiK16668.
OMAiYSNVLYR.
OrthoDBiEOG091G0MZN.
PhylomeDBiQ96BF3.
TreeFamiTF341425.

Miscellaneous databases

GenomeRNAii126259.
PROiQ96BF3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167664.
CleanExiHS_TMIGD2.
ExpressionAtlasiQ96BF3. baseline and differential.
GenevisibleiQ96BF3. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTMIG2_HUMAN
AccessioniPrimary (citable) accession number: Q96BF3
Secondary accession number(s): Q6UW59
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: September 7, 2016
This is version 118 of the entry and version 2 of the sequence. [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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. SIMILARITY comments
    Index of protein domains and families

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.