Sequence information
Variant position: 66 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 230 The length of the canonical sequence.
Location on the sequence:
RRKAWCRQLGEKGPCQRVVS
T HNLWLLSFLRRWNGSTAITD
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human RRKAWCRQLGEKGPCQRVVST HNLWLLSFLRRWNGSTAITD
Mouse RRKAWCRQLGEEGPCQRVVST HGVWLLAFLKKRNGSTVIAD
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:Type: the type of sequence feature. Positions: endpoints of the sequence feature. Description: contains additional information about the feature.
Type Positions Description
Chain
19 – 230
Triggering receptor expressed on myeloid cells 2
Topological domain
19 – 174
Extracellular
Domain
29 – 112
Ig-like V-type
Binding site
67 – 67
Phospholipid
Binding site
68 – 68
Phospholipid; via amide nitrogen
Binding site
77 – 77
Phospholipid
Glycosylation
79 – 79
N-linked (GlcNAc...) asparagine
Disulfide bond
36 – 110
Mutagenesis
48 – 48
K -> M. Loss of LDL, CLU and APOE binding.
Mutagenesis
60 – 60
C -> A. Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization.
Mutagenesis
68 – 68
N -> K. No effect on cell membrane localization.
Mutagenesis
76 – 76
R -> D. Decreases binding to THP-1 cells.
Mutagenesis
77 – 77
R -> D. Decreases binding to THP-1 cells.
Beta strand
60 – 66
Literature citations
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis.
Kleinberger G.; Yamanishi Y.; Suarez-Calvet M.; Czirr E.; Lohmann E.; Cuyvers E.; Struyfs H.; Pettkus N.; Wenninger-Weinzierl A.; Mazaheri F.; Tahirovic S.; Lleo A.; Alcolea D.; Fortea J.; Willem M.; Lammich S.; Molinuevo J.L.; Sanchez-Valle R.; Antonell A.; Ramirez A.; Heneka M.T.; Sleegers K.; van der Zee J.; Martin J.J.; Engelborghs S.; Demirtas-Tatlidede A.; Zetterberg H.; Van Broeckhoven C.; Gurvit H.; Wyss-Coray T.; Hardy J.; Colonna M.; Haass C.;
Sci. Transl. Med. 6:243RA86-243RA86(2014)
Cited for: FUNCTION; SUBCELLULAR LOCATION; PROTEOLYTIC PROCESSING; CHARACTERIZATION OF VARIANTS CYS-38; HIS-47 AND MET-66; MUTAGENESIS OF CYS-36 AND CYS-60;
TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia.
Yeh F.L.; Wang Y.; Tom I.; Gonzalez L.C.; Sheng M.;
Neuron 91:328-340(2016)
Cited for: FUNCTION; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87; MUTAGENESIS OF LYS-48;
Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the ER and ER-Golgi intermediate compartment.
Sirkis D.W.; Aparicio R.E.; Schekman R.;
Mol. Biol. Cell 28:2723-2733(2017)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS CYS-38 AND MET-66; CHARACTERIZATION OF VARIANTS PLOSL2 GLY-126; GLY-134 AND ASN-186;
Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms.
Kober D.L.; Alexander-Brett J.M.; Karch C.M.; Cruchaga C.; Colonna M.; Holtzman M.J.; Brett T.J.;
Elife 5:E20391-E20391(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 19-133; DISULFIDE BONDS; SUBUNIT; SUBCELLULAR LOCATION; MUTAGENESIS OF ASN-68; ARG-76 AND ARG-77; GLYCOSYLATION AT ASN-79; CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66; ASN-87 AND LYS-96; CHARACTERIZATION OF VARIANT PLOSL2 GLY-126;
Disease-associated mutations of TREM2 alter the processing of N-linked oligosaccharides in the Golgi apparatus.
Park J.S.; Ji I.J.; An H.J.; Kang M.J.; Kang S.W.; Kim D.H.; Yoon S.Y.;
Traffic 16:510-518(2015)
Cited for: CHARACTERIZATION OF VARIANT PLOSL2 33-GLN--THR-230 DEL; CHARACTERIZATION OF VARIANTS CYS-38; HIS-47 AND MET-66; SUBCELLULAR LOCATION;
Disclaimer:
Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.