O95202 (LETM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
LETM1 and EF-hand domain-containing protein 1, mitochondrial

Alternative name(s):
Leucine zipper-EF-hand-containing transmembrane protein 1

Gene names

Name:

LETM1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	739 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Crucial for the maintenance of mitochondrial tubular networks and for the assembly of the supercomplexes of the respiratory chain. Required for the maintenance of the tubular shape and cristae organization. Ref.7
Subunit structure	Can form 2 complexes: a major (300 kDa) and a minor complex (500-600 kDa). Interacts with BCS1L. Ref.7
Subcellular location	Mitochondrion inner membrane; Single-pass membrane protein Ref.5 Ref.6 Ref.7.
Sequence similarities	Contains 1 EF-hand domain. Contains 1 LETM1 domain.
Sequence caution	The sequence CAB63769.2 differs from that shown. Reason: Erroneous translation. Incomplete prediction of CDS at the C-terminus.

Ontologies

Keywords
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Transit peptide Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cristae formation Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	calcium ion binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95202-1)

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.

Isoform 2 (identifier: O95202-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: MASILLRSCRGRAPARLPPPPRYTVPRGSPGDPAHLSCASTLGLRNCL → MRHTWPFR
     292-294: KIR → QVL
     295-739: Missing.

Note: May be due to intron retention. No experimental confirmation available.

Isoform 3 (identifier: O95202-3)

The sequence of this isoform differs from the canonical sequence as follows:
     292-294: KIR → QVL
     295-739: Missing.

Note: May be due to intron retention.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 115	115	Mitochondrion Potential
	Chain	116 – 739	624	LETM1 and EF-hand domain-containing protein 1, mitochondrial		PRO_0000017694
Regions
	Topological domain	116 – 208	93	Mitochondrial intermembrane Potential
	Transmembrane	209 – 229	21	Helical; Potential
	Topological domain	230 – 739	510	Mitochondrial matrix Potential
	Domain	150 – 418	269	LETM1
	Domain	663 – 698	36	EF-hand
	Calcium binding	676 – 688	13	Potential
	Coiled coil	115 – 136	22	Potential
	Coiled coil	462 – 490	29	Potential
	Coiled coil	537 – 627	91	Potential
	Coiled coil	708 – 739	32	Potential
	Compositional bias	18 – 21	4	Poly-Pro
Amino acid modifications
	Modified residue	597	1	N6-acetyllysine Ref.8
Natural variations
	Alternative sequence	1 – 48	48	MASIL…LRNCL → MRHTWPFR in isoform 2.		VSP_037814
	Alternative sequence	292 – 294	3	KIR → QVL in isoform 2 and isoform 3.		VSP_037815
	Alternative sequence	295 – 739	445	Missing in isoform 2 and isoform 3.		VSP_037816

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 942E9138F299D94F	FASTA	739	83,354
	10 20 30 40 50 60 MASILLRSCR GRAPARLPPP PRYTVPRGSP GDPAHLSCAS TLGLRNCLNV PFGCCTPIHP 70 80 90 100 110 120 VYTSSRGDHL GCWALRPECL RIVSRAPWTS TSVGFVAVGP QCLPVRGWHS SRPVRDDSVV 130 140 150 160 170 180 EKSLKSLKDK NKKLEEGGPV YSPPAEVVVK KSLGQRVLDE LKHYYHGFRL LWIDTKIAAR 190 200 210 220 230 240 MLWRILNGHS LTRRERRQFL RICADLFRLV PFLVFVVVPF MEFLLPVAVK LFPNMLPSTF 250 260 270 280 290 300 ETQSLKEERL KKELRVKLEL AKFLQDTIEE MALKNKAAKG SATKDFSVFF QKIRETGERP 310 320 330 340 350 360 SNEEIMRFSK LFEDELTLDN LTRPQLVALC KLLELQSIGT NNFLRFQLTM RLRSIKADDK 370 380 390 400 410 420 LIAEEGVDSL NVKELQAACR ARGMRALGVT EDRLRGQLKQ WLDLHLHQEI PTSLLILSRA 430 440 450 460 470 480 MYLPDTLSPA DQLKSTLQTL PEIVAKEAQV KVAEVEGEQV DNKAKLEATL QEEAAIQQEH 490 500 510 520 530 540 REKELQKRSE VAKDFEPERV VAAPQRPGTE PQPEMPDTVL QSETLKDTAP VLEGLKEEEI 550 560 570 580 590 600 TKEEIDILSD ACSKLQEQKK SLTKEKEELE LLKEDVQDYS EDLQEIKKEL SKTGEEKYVE 610 620 630 640 650 660 ESKASKRLTK RVQQMIGQID GLISQLEMDQ QAGKLAPANG MPTGENVISV AELINAMKQV 670 680 690 700 710 720 KHIPESKLTS LAAALDENKD GKVNIDDLVK VIELVDKEDV HISTSQVAEI VATLEKEEKV 730 EEKEKAKEKA EKEVAEVKS
	Isoform 2 [UniParc]. Checksum: 5510CB4D93FFDDDE	FASTA	254	29,291
	10 20 30 40 50 60 MRHTWPFRNV PFGCCTPIHP VYTSSRGDHL GCWALRPECL RIVSRAPWTS TSVGFVAVGP 70 80 90 100 110 120 QCLPVRGWHS SRPVRDDSVV EKSLKSLKDK NKKLEEGGPV YSPPAEVVVK KSLGQRVLDE 130 140 150 160 170 180 LKHYYHGFRL LWIDTKIAAR MLWRILNGHS LTRRERRQFL RICADLFRLV PFLVFVVVPF 190 200 210 220 230 240 MEFLLPVAVK LFPNMLPSTF ETQSLKEERL KKELRVKLEL AKFLQDTIEE MALKNKAAKG 250 SATKDFSVFF QQVL
	Isoform 3 [UniParc]. Checksum: 5C8B98ECA4D20E42	FASTA	294	33,245
	10 20 30 40 50 60 MASILLRSCR GRAPARLPPP PRYTVPRGSP GDPAHLSCAS TLGLRNCLNV PFGCCTPIHP 70 80 90 100 110 120 VYTSSRGDHL GCWALRPECL RIVSRAPWTS TSVGFVAVGP QCLPVRGWHS SRPVRDDSVV 130 140 150 160 170 180 EKSLKSLKDK NKKLEEGGPV YSPPAEVVVK KSLGQRVLDE LKHYYHGFRL LWIDTKIAAR 190 200 210 220 230 240 MLWRILNGHS LTRRERRQFL RICADLFRLV PFLVFVVVPF MEFLLPVAVK LFPNMLPSTF 250 260 270 280 290 ETQSLKEERL KKELRVKLEL AKFLQDTIEE MALKNKAAKG SATKDFSVFF QQVL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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., Fuhry M., Pak S.-J., Zabel B.U., Winterpacht A. Genomics 60:218-225(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Cerebellum and Thymus.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Skin.
[5]	"LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily conserved mitochondrial protein." Schlickum S., Moghekar A., Simpson J.C., Steglich C., O'Brien R.J., Winterpacht A., Endele S.U. Genomics 83:254-261(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[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., Froschauer E.M., Zsurka G., Samaj J., Reipert S., Kolisek M., Wiesenberger G., Schweyen R.J. J. Biol. Chem. 279:30307-30315(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	"Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L." Tamai S., Iida H., Yokota S., Sayano T., Kiguchiya S., Ishihara N., Hayashi J., Mihara K., Oka T. J. Cell Sci. 121:2588-2600(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH BCS1L.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-597, MASS SPECTROMETRY.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF061025 mRNA. Translation: AAD13138.1. AK293572 mRNA. Translation: BAG57043.1. AK310563 mRNA. No translation available. AL133650 mRNA. Translation: CAB63769.2. Sequence problems. BC014500 mRNA. Translation: AAH14500.1. BC021208 mRNA. Translation: AAH21208.1.
IPI	IPI00017592. IPI00941510. IPI00941879.
PIR	T43494.
RefSeq	NP_036450.1. NM_012318.2.
UniGene	Hs.120165.
3D structure databases
ProteinModelPortal	O95202.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95202. 4 interactions.
STRING	9606.ENSP00000305653.
Protein family/group databases
TCDB	2.A.97.1.1. mitochondrial inner membrane K+/H+ and Ca2+/H+ exchanger (LetM1) family.
PTM databases
PhosphoSite	O95202.
Proteomic databases
PaxDb	O95202.
PeptideAtlas	O95202.
PRIDE	O95202.
Protocols and materials databases
DNASU	3954.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000302787; ENSP00000305653; ENSG00000168924.
GeneID	3954.
KEGG	hsa:3954.
UCSC	uc003gdv.3. human. uc011bvg.2. human.
Organism-specific databases
CTD	3954.
GeneCards	GC04M001781.
HGNC	HGNC:6556. LETM1.
HPA	HPA011029. HPA011100.
MIM	604407. gene.
neXtProt	NX_O95202.
Orphanet	280. Wolf-Hirschhorn syndrome.
PharmGKB	PA30335.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG243495.
HOGENOM	HOG000290246.
HOVERGEN	HBG052322.
InParanoid	O95202.
OMA	DKEDVHI.
OrthoDB	EOG4RFKSF.
PhylomeDB	O95202.
Gene expression databases
ArrayExpress	O95202.
Bgee	O95202.
CleanEx	HS_LETM1.
Genevestigator	O95202.
GermOnline	ENSG00000168924. Homo sapiens.
Family and domain databases
Gene3D	1.10.238.10. 1 hit.
InterPro	IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR002048. EF_hand_dom. IPR011685. LETM1. [Graphical view]
Pfam	PF07766. LETM1. 1 hit. [Graphical view]
PROSITE	PS00018. EF_HAND_1. 1 hit. PS50222. EF_HAND_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	LETM1. human.
GenomeRNAi	3954.
NextBio	15513.
SOURCE	Search...

Entry information

Entry name

LETM1_HUMAN

Accession

Primary (citable) accession number: O95202
Secondary accession number(s): B4DED2, Q9UF65

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.