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2.A.97.1.1
The leucine zipper-EF band transmembrane protein 1, LetM1.  Reduces mitochondrial Ca2+ uptake in response to cytoplasmic Ca2+entry in pancreatic beta cells (Alam et al. 2012).  LetM1 is a cation/Ca2+ transporter, with apparent affinities of cations in the order Ca2+ = Mn2+ > Gd3+ = La3+ > Sr2+ >> Ba2+, Mg2+, K+, Na+ (Shao et al. 2016). The LetM1 turnover rate is only 2 Ca2+/sec with a Km of ~ 25 microM. LetM1 mediates electroneutral 1 Ca2+/2 H+ antiport (Tsai et al. 2013).  However, NCLX (2.A.19.4.4), rather than LetM1, may mediate miltochondrial Ca2+ extrusion (De Marchi et al. 2014).  Letm1 is associated with seizure attacks in Wolf-Hirschhorn syndrome, and its inhibition and mitochondrial dysfunctions contribute to the development of epileptic seizures. An appropriate LetM1 level may be critical for maintaining normal neuronal functions (Zhang et al. 2014).  Glu221 in the mouse orthologue is essential. The protein is a hexamer with a central cavity and exhibits two different conformational states (Shao et al. 2016).

Accession Number:O95202
Protein Name:LETM1 and EF-hand domain-containing protein 1, mitochondrial
Length:739
Molecular Weight:83354.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Mitochondrion inner membrane1 / Single-pass membrane protein2
Substrate Ca2+, Mn2+, Gd3+, La3+, Sr2+, Ba2+, Mg2+, K+, Na+

Cross database links:

Genevestigator: O95202
eggNOG: prNOG06402
HEGENOM: HBG386452
RefSeq: NP_036450.1   
Entrez Gene ID: 3954   
Pfam: PF07766   
OMIM: 604407  gene
KEGG: hsa:3954   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005743 C:mitochondrial inner membrane
GO:0005509 F:calcium ion binding
GO:0005515 F:protein binding
GO:0042407 P:cristae formation

References (9)

[1] “LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients.”  Endele S.et.al.   10486213
[2] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[3] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily conserved mitochondrial protein.”  Schlickum S.et.al.   14706454
[6] “The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome.”  Nowikovsky K.et.al.   15138253
[7] “Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L.”  Tamai S.et.al.   18628306
[8] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[9] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MASILLRSCR GRAPARLPPP PRYTVPRGSP GDPAHLSCAS TLGLRNCLNV PFGCCTPIHP 
61:	VYTSSRGDHL GCWALRPECL RIVSRAPWTS TSVGFVAVGP QCLPVRGWHS SRPVRDDSVV 
121:	EKSLKSLKDK NKKLEEGGPV YSPPAEVVVK KSLGQRVLDE LKHYYHGFRL LWIDTKIAAR 
181:	MLWRILNGHS LTRRERRQFL RICADLFRLV PFLVFVVVPF MEFLLPVAVK LFPNMLPSTF 
241:	ETQSLKEERL KKELRVKLEL AKFLQDTIEE MALKNKAAKG SATKDFSVFF QKIRETGERP 
301:	SNEEIMRFSK LFEDELTLDN LTRPQLVALC KLLELQSIGT NNFLRFQLTM RLRSIKADDK 
361:	LIAEEGVDSL NVKELQAACR ARGMRALGVT EDRLRGQLKQ WLDLHLHQEI PTSLLILSRA 
421:	MYLPDTLSPA DQLKSTLQTL PEIVAKEAQV KVAEVEGEQV DNKAKLEATL QEEAAIQQEH 
481:	REKELQKRSE VAKDFEPERV VAAPQRPGTE PQPEMPDTVL QSETLKDTAP VLEGLKEEEI 
541:	TKEEIDILSD ACSKLQEQKK SLTKEKEELE LLKEDVQDYS EDLQEIKKEL SKTGEEKYVE 
601:	ESKASKRLTK RVQQMIGQID GLISQLEMDQ QAGKLAPANG MPTGENVISV AELINAMKQV 
661:	KHIPESKLTS LAAALDENKD GKVNIDDLVK VIELVDKEDV HISTSQVAEI VATLEKEEKV 
721:	EEKEKAKEKA EKEVAEVKS