TIMD2_MOUSE
ID TIMD2_MOUSE Reviewed; 305 AA.
AC Q8R183; Q8VBW0;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 25-MAY-2022, entry version 125.
DE RecName: Full=T-cell immunoglobulin and mucin domain-containing protein 2;
DE Short=TIMD-2;
DE AltName: Full=T-cell immunoglobulin mucin receptor 2;
DE Short=TIM-2;
DE AltName: Full=T-cell membrane protein 2;
DE Flags: Precursor;
GN Name=Timd2; Synonyms=Tim2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ, and DBA/2J; TISSUE=Spleen;
RX PubMed=11725301; DOI=10.1038/ni739;
RA McIntire J.J., Umetsu S.E., Akbari O., Potter M., Kuchroo V.K., Barsh G.S.,
RA Freeman G.J., Umetsu D.T., DeKruyff R.H.;
RT "Identification of Tapr (an airway hyperreactivity regulatory locus) and
RT the linked Tim gene family.";
RL Nat. Immunol. 2:1109-1116(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 FUNCTION AS A RECEPTOR FOR SEMA4A.
RX PubMed=12374982; DOI=10.1038/nature01037;
RA Kumanogoh A., Marukawa S., Suzuki K., Takegahara N., Watanabe C., Ch'ng E.,
RA Ishida I., Fujimura H., Sakoda S., Yoshida K., Kikutani H.;
RT "Class IV semaphorin Sema4A enhances T-cell activation and interacts with
RT Tim-2.";
RL Nature 419:629-633(2002).
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16043519; DOI=10.1084/jem.20050308;
RA Chakravarti S., Sabatos C.A., Xiao S., Illes Z., Cha E.K., Sobel R.A.,
RA Zheng X.X., Strom T.B., Kuchroo V.K.;
RT "Tim-2 regulates T helper type 2 responses and autoimmunity.";
RL J. Exp. Med. 202:437-444(2005).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16203866; DOI=10.1084/jem.20042433;
RA Chen T.T., Li L., Chung D.H., Allen C.D., Torti S.V., Torti F.M.,
RA Cyster J.G., Chen C.Y., Brodsky F.M., Niemi E.C., Nakamura M.C.,
RA Seaman W.E., Daws M.R.;
RT "TIM-2 is expressed on B cells and in liver and kidney and is a receptor
RT for H-ferritin endocytosis.";
RL J. Exp. Med. 202:955-965(2005).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21886823; DOI=10.1371/journal.pone.0023800;
RA Han J., Seaman W.E., Di X., Wang W., Willingham M., Torti F.M., Torti S.V.;
RT "Iron uptake mediated by binding of H-ferritin to the TIM-2 receptor in
RT mouse cells.";
RL PLoS ONE 6:e23800-e23800(2011).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=33065090; DOI=10.1016/j.exer.2020.108292;
RA Valenca A., Mendes-Jorge L., Bonet A., Catita J., Ramos D.,
RA Jose-Cunilleras E., Garcia M., Carretero A., Nacher V., Navarro M.,
RA Ruberte J.;
RT "TIM2 modulates retinal iron levels and is involved in blood-retinal
RT barrier breakdown.";
RL Exp. Eye Res. 202:108292-108292(2021).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 19-130, SUBUNIT, DISULFIDE BONDS,
RP AND SUBCELLULAR LOCATION.
RX PubMed=17363299; DOI=10.1016/j.immuni.2007.01.014;
RA Santiago C., Ballesteros A., Tami C., Martinez-Munoz L., Kaplan G.G.,
RA Casasnovas J.M.;
RT "Structures of T Cell immunoglobulin mucin receptors 1 and 2 reveal
RT mechanisms for regulation of immune responses by the TIM receptor family.";
RL Immunity 26:299-310(2007).
CC -!- FUNCTION: Cell surface glycoprotein that participates in iron
CC homeostasis in the liver, the kidney, the retina and oligodendrocytes
CC by acting as a receptor of H-ferritin (PubMed:16203866,
CC PubMed:33065090). Mechanistically, mediates iron-containing ferritin
CC uptake via an endocytic pathway, trafficking to endosomes and
CC subsequently to lysosomes (PubMed:16043519, PubMed:21886823). Plays
CC also an important role in the regulation of Th2 immunity
CC (PubMed:16043519). Receptor for SEMA4A involved in the regulation of T-
CC cell function, enhancing T-cell activation (PubMed:12374982).
CC {ECO:0000269|PubMed:12374982, ECO:0000269|PubMed:16043519,
CC ECO:0000269|PubMed:16203866, ECO:0000269|PubMed:21886823,
CC ECO:0000269|PubMed:33065090}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17363299}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17363299,
CC ECO:0000269|PubMed:21886823}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:17363299}.
CC -!- TISSUE SPECIFICITY: Expressed on late differentiated Th2 cells
CC (PubMed:16043519). Expressed also on all splenic B-cells, with
CC increased levels on germinal center B-cells, in the liver, especially
CC in bile duct epithelial cells, and in renal tubule cells
CC (PubMed:16203866). Within retina, mainly expressed in Mueller cells
CC (PubMed:33065090). {ECO:0000269|PubMed:16043519,
CC ECO:0000269|PubMed:16203866, ECO:0000269|PubMed:33065090}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutants lead to ferritin accumulation
CC and iron overload in the retina leading to retinal lesions.
CC {ECO:0000269|PubMed:33065090}.
CC -!- MISCELLANEOUS: Belongs to the T-cell and airway phenotype regulator
CC (Tapr) locus, a single chromosomal region that confers reduced T-helper
CC type 2 responsiveness and protects against airway hyperactivity (AHR),
CC the hallmark of human asthma. The human genomic locus appears to lack
CC the Timd2 gene.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. TIM family.
CC {ECO:0000305}.
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DR EMBL; AF399827; AAL35772.1; -; mRNA.
DR EMBL; AF399828; AAL35773.1; -; mRNA.
DR EMBL; BC025096; AAH25096.1; -; mRNA.
DR CCDS; CCDS24582.1; -.
DR RefSeq; NP_001154827.1; NM_001161355.1.
DR RefSeq; NP_001154828.1; NM_001161356.1.
DR RefSeq; NP_599010.4; NM_134249.5.
DR PDB; 2OR7; X-ray; 1.50 A; A/B=20-129.
DR PDBsum; 2OR7; -.
DR AlphaFoldDB; Q8R183; -.
DR SMR; Q8R183; -.
DR STRING; 10090.ENSMUSP00000104848; -.
DR GlyGen; Q8R183; 2 sites.
DR iPTMnet; Q8R183; -.
DR PhosphoSitePlus; Q8R183; -.
DR PaxDb; Q8R183; -.
DR PRIDE; Q8R183; -.
DR ProteomicsDB; 259393; -.
DR ABCD; Q8R183; 1 sequenced antibody.
DR DNASU; 171284; -.
DR GeneID; 171284; -.
DR KEGG; mmu:171284; -.
DR CTD; 171284; -.
DR MGI; MGI:2159681; Timd2.
DR eggNOG; ENOG502S454; Eukaryota.
DR InParanoid; Q8R183; -.
DR OrthoDB; 1147868at2759; -.
DR PhylomeDB; Q8R183; -.
DR BioGRID-ORCS; 171284; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Timd2; mouse.
DR EvolutionaryTrace; Q8R183; -.
DR PRO; PR:Q8R183; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8R183; protein.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031514; C:motile cilium; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070287; F:ferritin receptor activity; IDA:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0001618; F:virus receptor activity; ISO:MGI.
DR GO; GO:0006826; P:iron ion transport; IDA:MGI.
DR GO; GO:0006911; P:phagocytosis, engulfment; IBA:GO_Central.
DR GO; GO:0033005; P:positive regulation of mast cell activation; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 1.
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 Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Receptor; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..305
FT /note="T-cell immunoglobulin and mucin domain-containing
FT protein 2"
FT /id="PRO_0000042099"
FT TOPO_DOM 22..231
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 253..305
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..125
FT /note="Ig-like V-type"
FT REGION 130..174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 132..174
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 37..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:17363299"
FT DISULFID 50..61
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:17363299"
FT DISULFID 56..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:17363299"
FT CONFLICT 80
FT /note="L -> R (in Ref. 1; AAL35772/AAL35773)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="D -> S (in Ref. 1; AAL35772/AAL35773)"
FT /evidence="ECO:0000305"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:2OR7"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2OR7"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:2OR7"
FT STRAND 49..54
FT /evidence="ECO:0007829|PDB:2OR7"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:2OR7"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:2OR7"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:2OR7"
FT STRAND 70..78
FT /evidence="ECO:0007829|PDB:2OR7"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:2OR7"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:2OR7"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:2OR7"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:2OR7"
FT STRAND 118..128
FT /evidence="ECO:0007829|PDB:2OR7"
SQ SEQUENCE 305 AA; 33504 MW; 4105D75D99F541AB CRC64;
MNQIQVFISG LILLLPGAVE SHTAVQGLAG HPVTLPCIYS THLGGIVPMC WGLGECRHSY
CIRSLIWTNG YTVTHQRNSL YQLKGNISEG NVSLTIENTV VGDGGPYCCV VEIPGAFHFV
DYMLEVKPEI STSPPTRPTA TGRPTTISTR STHVPTSTRV STSTSPTPAH TETYKPEATT
FYPDQTTAEV TETLPDTPAD WHNTVTSSDD PWDDNTEVIP PQKPQKNLNK GFYVGISIAA
LLILMLLSTM VITRYVVMKR KSESLSFVAF PISKIGASPK KVVERTRCED QVYIIEDTPY
PEEES
