Reviewed, UniProtKB/Swiss-Prot Q3ZCQ8 (TIM50_HUMAN)

Names and origin

Protein names

Recommended name:
    Mitochondrial import inner membrane translocase subunit TIM50

Gene names

Name:	TIMM50
Synonyms:	TIM50
ORF Names:	PRO1512

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	353 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	Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Has some phosphatase activity in vitro; however such activity may not be relevant in vivo. Isoform 2 may participate in the release of snRNPs and SMN from the Cajal body. Ref.1
Subunit structure	Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50. Interacts directly with TIMM23. Isoform 2 interacts with COIL and snRNPs. Ref.1 Ref.6
Subcellular location	Mitochondrion inner membrane; Single-pass membrane protein. Ref.1 Ref.6 Isoform 2: Nucleus speckle. Note: Nuclear and enriched in speckles with snRNPs. Ref.1 Ref.6
Tissue specificity	Widely expressed. Expressed at higher level in brain, kidney and liver (at protein level). Ref.1 Ref.6
Domain	The FCP1 homology domain does not contain the canonical D-x-D-x-[TV] active site, suggesting that it probably does not display phosphatase activity in vivo.
Sequence similarities	Belongs to the TIM50 family. Contains 1 FCP1 homology domain.
Sequence caution	The sequence AAG35534.1 differs from that shown. Reason: Miscellaneous discrepancy. Chimera.

Ontologies

Keywords
Biological process	Protein transport Translocation Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Transit peptide Transmembrane
Ligand	RNA-binding
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	intracellular protein transmembrane transport Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial membrane organization Ref.1 Inferred from mutant phenotype. Source: UniProtKB protein amino acid dephosphorylation Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane presequence translocase complex Ref.1 Inferred from physical interaction. Source: UniProtKB nuclear speck Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.1 Inferred from physical interaction. Source: UniProtKB protein serine/threonine phosphatase activity Ref.1 Inferred from direct assay. Source: UniProtKB protein tyrosine phosphatase activity Ref.1 Inferred from direct assay. Source: UniProtKB ribonucleoprotein binding Ref.6 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AKTIP	Q9H8T0	1	EBI-355175,EBI-711399
ARAF	P10398	2	EBI-355175,EBI-365961
MAGED1	Q9Y5V3	1	EBI-355175,EBI-716006
PELO	Q9BRX2	1	EBI-355175,EBI-1043580
PHB2	Q99623	1	EBI-355175,EBI-358348
RAF1	P04049	3	EBI-355175,EBI-365996

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q3ZCQ8-1)

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: Q3ZCQ8-2)

Also known as: Tim50a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MASALSLGNK...GGAAWRQRKM

Note: Nuclear and enriched in speckles with snRNPs. Ref.1 Ref.6

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 44	44	Mitochondrion Potential
	Chain	45 – 353	309	Mitochondrial import inner membrane translocase subunit TIM50		PRO_0000043115
Regions
	Topological domain	45 – 65	21	Mitochondrial matrix Potential
	Transmembrane	66 – 86	21	Potential
	Topological domain	87 – 353	267	Mitochondrial intermembrane Potential
	Domain	143 – 286	144	FCP1 homology
Natural variations
	Alternative sequence	1	1	M → MASALSLGNKCDPFLRCVLC RGGGALQGPRGRGPDDFESQ LSPPGSARRLVRSKRACGNP PDAFGLSRASVHPPLPRVSI GCSSGPGRAKRERVGGAAWR QRKM in isoform 2.		VSP_016389

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 6, 2005. Version 2. Checksum: 524EB9989BBF6988	FASTA	353	39,646
	10 20 30 40 50 60 MAASAAVFSR LRSGLRLGSR GLCTRLATPP RRAPDQAAEI GSRGSTKAQG PQQQPGSEGP 70 80 90 100 110 120 SYAKKVALWL AGLLGAGGTV SVVYIFGNNP VDENGAKIPD EFDNDPILVQ QLRRTYKYFK 130 140 150 160 170 180 DYRQMIIEPT SPCLLPDPLQ EPYYQPPYTL VLELTGVLLH PEWSLATGWR FKKRPGIETL 190 200 210 220 230 240 FQQLAPLYEI VIFTSETGMT AFPLIDSVDP HGFISYRLFR DATRYMDGHH VKDISCLNRD 250 260 270 280 290 300 PARVVVVDCK KEAFRLQPYN GVALRPWDGN SDDRVLLDLS AFLKTIALNG VEDVRTVLEH 310 320 330 340 350 YALEDDPLAA FKQRQSRLEQ EEQQRLAELS KSNKQNLFLG SLTSRLWPRS KQP
	Isoform 2 (Tim50a). Checksum: 870E81E2A0289BC4	FASTA	456	50,465
	10 20 30 40 50 60 MASALSLGNK CDPFLRCVLC RGGGALQGPR GRGPDDFESQ LSPPGSARRL VRSKRACGNP 70 80 90 100 110 120 PDAFGLSRAS VHPPLPRVSI GCSSGPGRAK RERVGGAAWR QRKMAASAAV FSRLRSGLRL 130 140 150 160 170 180 GSRGLCTRLA TPPRRAPDQA AEIGSRGSTK AQGPQQQPGS EGPSYAKKVA LWLAGLLGAG 190 200 210 220 230 240 GTVSVVYIFG NNPVDENGAK IPDEFDNDPI LVQQLRRTYK YFKDYRQMII EPTSPCLLPD 250 260 270 280 290 300 PLQEPYYQPP YTLVLELTGV LLHPEWSLAT GWRFKKRPGI ETLFQQLAPL YEIVIFTSET 310 320 330 340 350 360 GMTAFPLIDS VDPHGFISYR LFRDATRYMD GHHVKDISCL NRDPARVVVV DCKKEAFRLQ 370 380 390 400 410 420 PYNGVALRPW DGNSDDRVLL DLSAFLKTIA LNGVEDVRTV LEHYALEDDP LAAFKQRQSR 430 440 450 LEQEEQQRLA ELSKSNKQNL FLGSLTSRLW PRSKQP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death." Guo Y., Cheong N., Zhang Z., De Rose R., Deng Y., Farber S.A., Fernandes-Alnemri T., Alnemri E.S. J. Biol. Chem. 279:24813-24825(2004) [PubMed: 15044455] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH TIMM23.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain, Eye and Pancreas.
[3]	"Functional prediction of the coding sequences of 75 new genes deduced by analysis of cDNA clones from human fetal liver." Zhang C., Yu Y., Zhang S., Wei H., Bi J., Zhou G., Dong C., Zai Y., Xu W., Gao F., Liu M., He F. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-353. Tissue: Fetal liver.
[4]	Bienvenut W.V. Submitted (JUN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 98-113; 275-284; 285-295 AND 335-345, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[5]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 98-113, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[6]	"Tim50a, a nuclear isoform of the mitochondrial Tim50, interacts with proteins involved in snRNP biogenesis." Xu H., Somers Z.B., Robinson M.L. II, Hebert M.D. BMC Cell Biol. 6:29-29(2005) [PubMed: 16008839] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 2), RNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH COIL.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY551341 mRNA. Translation: AAT01208.1. BC009072 mRNA. Translation: AAH09072.1. BC010736 mRNA. Translation: AAH10736.1. BC050082 mRNA. Translation: AAH50082.1. AF130109 mRNA. Translation: AAG35534.1. Sequence problems.
IPI	IPI00418497. IPI00656071.
RefSeq	NP_001001563.1.
UniGene	Hs.590956 Hs.597106
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q3ZCQ8. 30 interactions.
PTM databases
PhosphoSite	Q3ZCQ8.
Proteomic databases
PRIDE	Q3ZCQ8.
Genome annotation databases
Ensembl	ENSG00000105197. Homo sapiens. [Contig view]
GeneID	92609.
KEGG	hsa:92609.
UCSC	uc002olu.1. human.
Organism-specific databases
GeneCards	GC19P044663.
H-InvDB	HIX0040029.
HGNC	HGNC:23656. TIMM50.
MIM	607381. gene.
PharmGKB	PA134902846.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q3ZCQ8.
OMA	Q3ZCQ8. PVDENGA.
Gene expression databases
ArrayExpress	Q3ZCQ8.
Bgee	Q3ZCQ8.
CleanEx	HS_TIMM50.
GermOnline	ENSG00000105197. Homo sapiens.
Family and domain databases
InterPro	IPR004274. NIF. [Graphical view]
Pfam	PF03031. NIF. 1 hit. [Graphical view]
SMART	SM00577. CPDc. 1 hit. [Graphical view]
PROSITE	PS50969. FCP1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	77819.
SOURCE	Search...

Entry information

Entry name

TIM50_HUMAN

Accession

Primary (citable) accession number: Q3ZCQ8
Secondary accession number(s): Q6QA00 , Q96FJ5, Q96GY2, Q9H370

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	December 6, 2005
Last modified:	July 7, 2009
This is version 43 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)