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Protein

T-cell immunoglobulin and mucin domain-containing protein 4

Gene

Timd4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Involved in regulating T-cell proliferation and lymphotoxin signaling. Ligand for HAVCR1/TIMD1.3 Publications

GO - Molecular functioni

  • phosphatidylserine binding Source: MGI
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell immunoglobulin and mucin domain-containing protein 4
Short name:
TIMD-4
Alternative name(s):
Spleen, mucin-containing, knockout of lymphotoxin protein
Short name:
SMUCKLER
T-cell immunoglobulin mucin receptor 4
Short name:
TIM-4
T-cell membrane protein 4
Gene namesi
Name:Timd4
Synonyms:Tim4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:2445125. Timd4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 279257ExtracellularSequence analysisAdd
BLAST
Transmembranei280 – 30021HelicalSequence analysisAdd
BLAST
Topological domaini301 – 34343CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Chaini23 – 343321T-cell immunoglobulin and mucin domain-containing protein 4PRO_0000042104Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi40 ↔ 112PROSITE-ProRule annotation1 Publication
Disulfide bondi53 ↔ 64PROSITE-ProRule annotation1 Publication
Disulfide bondi59 ↔ 111PROSITE-ProRule annotation1 Publication
Glycosylationi220 – 2201N-linked (GlcNAc...)Sequence analysis
Modified residuei323 – 3231PhosphoserineCombined sources
Modified residuei325 – 3251PhosphoserineCombined sources
Modified residuei331 – 3311PhosphoserineCombined sources

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ6U7R4.
PRIDEiQ6U7R4.

PTM databases

PhosphoSiteiQ6U7R4.

Expressioni

Tissue specificityi

Predominantly expressed in lymphoid tissues, such as spleen, lymph nodes, and Peyer patches. Also expressed in fetal liver, salivary gland, and spleen stromal cells, predominantly in the marginal zone and to a lesser extent throughout the white pulp. Not expressed by bone marrow-derived cells. In spleen, expressed mostly by stromal cells in T- and B-cell areas, but not by T or B-lymphocytes.2 Publications

Inductioni

Down-regulated in lymphotoxin deficient mice.1 Publication

Gene expression databases

BgeeiQ6U7R4.
GenevisibleiQ6U7R4. MM.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000069456.

Structurei

Secondary structure

1
343
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi26 – 316Combined sources
Beta strandi36 – 383Combined sources
Turni47 – 493Combined sources
Beta strandi51 – 588Combined sources
Beta strandi61 – 633Combined sources
Beta strandi67 – 715Combined sources
Beta strandi73 – 819Combined sources
Beta strandi84 – 863Combined sources
Helixi90 – 923Combined sources
Beta strandi97 – 993Combined sources
Helixi104 – 1063Combined sources
Beta strandi108 – 1158Combined sources
Beta strandi117 – 1204Combined sources
Beta strandi123 – 13210Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3BI9X-ray2.95X24-134[»]
3BIAX-ray2.20X24-134[»]
3BIBX-ray2.50X24-134[»]
ProteinModelPortaliQ6U7R4.
SMRiQ6U7R4. Positions 25-134.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ6U7R4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini23 – 128106Ig-like V-typeAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi135 – 269135Thr-richAdd
BLAST

Sequence similaritiesi

Belongs to the immunoglobulin superfamily. TIM family.Curated

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IYS0. Eukaryota.
ENOG4111VB0. LUCA.
GeneTreeiENSGT00440000039800.
HOGENOMiHOG000074110.
HOVERGENiHBG083934.
InParanoidiQ6U7R4.
OMAiKINVRLN.
OrthoDBiEOG7R2BK4.
PhylomeDBiQ6U7R4.
TreeFamiTF336163.

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]

Sequencei

Sequence statusi: Complete.

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

Q6U7R4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSKGLLLLWL VTELWWLYLT PAASEDTIIG FLGQPVTLPC HYLSWSQSRN
60 70 80 90 100
SMCWGKGSCP NSKCNAELLR TDGTRIISRK STKYTLLGKV QFGEVSLTIS
110 120 130 140 150
NTNRGDSGVY CCRIEVPGWF NDVKKNVRLE LRRATTTKKP TTTTRPTTTP
160 170 180 190 200
YVTTTTPELL PTTVMTTSVL PTTTPPQTLA TTAFSTAVTT CPSTTPGSFS
210 220 230 240 250
QETTKGSAFT TESETLPASN HSQRSMMTIS TDIAVLRPTG SNPGILPSTS
260 270 280 290 300
QLTTQKTTLT TSESLQKTTK SHQINSRQTI LIIACCVGFV LMVLLFLAFL
310 320 330 340
LRGKVTGANC LQRHKRPDNT EDSDSVLNDM SHGRDDEDGI FTL
Length:343
Mass (Da):37,548
Last modified:September 27, 2005 - v2
Checksum:iD2D5539A7CDB8290
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121T → M in strain: C57BL/6. 1 Publication
Natural varianti209 – 2091F → I in strain: C57BL/6.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY376717 mRNA. Translation: AAR23484.1.
AY376716 mRNA. Translation: AAR23483.1.
CCDSiCCDS36137.1.
RefSeqiNP_848874.3. NM_178759.4.
UniGeneiMm.69002.

Genome annotation databases

EnsembliENSMUST00000068877; ENSMUSP00000069456; ENSMUSG00000055546.
GeneIDi276891.
KEGGimmu:276891.
UCSCiuc007iox.1. mouse.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY376717 mRNA. Translation: AAR23484.1.
AY376716 mRNA. Translation: AAR23483.1.
CCDSiCCDS36137.1.
RefSeqiNP_848874.3. NM_178759.4.
UniGeneiMm.69002.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3BI9X-ray2.95X24-134[»]
3BIAX-ray2.20X24-134[»]
3BIBX-ray2.50X24-134[»]
ProteinModelPortaliQ6U7R4.
SMRiQ6U7R4. Positions 25-134.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000069456.

PTM databases

PhosphoSiteiQ6U7R4.

Proteomic databases

PaxDbiQ6U7R4.
PRIDEiQ6U7R4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000068877; ENSMUSP00000069456; ENSMUSG00000055546.
GeneIDi276891.
KEGGimmu:276891.
UCSCiuc007iox.1. mouse.

Organism-specific databases

CTDi91937.
MGIiMGI:2445125. Timd4.

Phylogenomic databases

eggNOGiENOG410IYS0. Eukaryota.
ENOG4111VB0. LUCA.
GeneTreeiENSGT00440000039800.
HOGENOMiHOG000074110.
HOVERGENiHBG083934.
InParanoidiQ6U7R4.
OMAiKINVRLN.
OrthoDBiEOG7R2BK4.
PhylomeDBiQ6U7R4.
TreeFamiTF336163.

Miscellaneous databases

EvolutionaryTraceiQ6U7R4.
NextBioi393675.
PROiQ6U7R4.
SOURCEiSearch...

Gene expression databases

BgeeiQ6U7R4.
GenevisibleiQ6U7R4. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "SMUCKLER/TIM4 is a distinct member of TIM family expressed by stromal cells of secondary lymphoid tissues and associated with lymphotoxin signaling."
    Shakhov A.N., Rybtsov S., Tumanov A.V., Shulenin S., Dean M., Kuprash D.V., Nedospasov S.A.
    Eur. J. Immunol. 34:494-503(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MET-12 AND 209-ILE, FUNCTION, INDUCTION, TISSUE SPECIFICITY.
    Strain: BALB/cJ and C57BL/6.
  2. "TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation."
    Meyers J.H., Chakravarti S., Schlesinger D., Illes Z., Waldner H., Umetsu S.E., Kenny J., Zheng X.X., Umetsu D.T., DeKruyff R.H., Strom T.B., Kuchroo V.K.
    Nat. Immunol. 6:455-464(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HAVCR1/TIM1.
  3. "Identification of Tim4 as a phosphatidylserine receptor."
    Miyanishi M., Tada K., Koike M., Uchiyama Y., Kitamura T., Nagata S.
    Nature 450:435-439(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBUNIT.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323; SER-325 AND SER-331, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Spleen.
  5. "Structures of T cell immunoglobulin mucin protein 4 show a metal-ion-dependent ligand binding site where phosphatidylserine binds."
    Santiago C., Ballesteros A., Martinez-Munoz L., Mellado M., Kaplan G.G., Freeman G.J., Casasnovas J.M.
    Immunity 27:941-951(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-134 IN COMPLEX WITH PHOSPHATIDYLSERINE, DISULFIDE BONDS.

Entry informationi

Entry nameiTIMD4_MOUSE
AccessioniPrimary (citable) accession number: Q6U7R4
Secondary accession number(s): Q6U7R3, Q8CIC7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: September 27, 2005
Last modified: January 20, 2016
This is version 91 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Belongs to the T-cell and airway phenotype regulator (Tapr) locus, a single chromosomal region that confers reduced T-helper type 2 responsiveness and protects against airway hyperactivity (AHR), the hallmark of human asthma.
Low expression of Timd4 is associated with lymphotoxin deficiency.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.