Q3ZCQ8 (TIM50_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	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: 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 Transmembrane helix
Ligand	RNA-binding
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	mitochondrial membrane organization Inferred from mutant phenotype Ref.1. Source: UniProtKB protein targeting to mitochondrion Traceable author statement. Source: Reactome release of cytochrome c from mitochondria Inferred from direct assay Ref.1. Source: MGI
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane presequence translocase complex Inferred from physical interaction Ref.1. Source: UniProtKB nuclear speck Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW interleukin-2 receptor binding Inferred from direct assay Ref.1. Source: MGI protein serine/threonine phosphatase activity Inferred from direct assay Ref.1. Source: UniProtKB protein tyrosine phosphatase activity Inferred from direct assay Ref.1. Source: UniProtKB ribonucleoprotein complex binding Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	3	EBI-355175,EBI-365961
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

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	Helical; 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) [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 2), RNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH COIL.
[7]	"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	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. NM_001001563.1.
UniGene	Hs.590956. Hs.597106.
3D structure databases
ProteinModelPortal	Q3ZCQ8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q3ZCQ8. 18 interactions.
MINT	MINT-1148586.
STRING	9606.ENSP00000318115.
PTM databases
PhosphoSite	Q3ZCQ8.
Polymorphism databases
DMDM	83305924.
Proteomic databases
PaxDb	Q3ZCQ8.
PRIDE	Q3ZCQ8.
Protocols and materials databases
DNASU	92609.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000314349; ENSP00000318115; ENSG00000105197.
GeneID	92609.
KEGG	hsa:92609.
UCSC	uc002olu.1. human.
Organism-specific databases
CTD	92609.
GeneCards	GC19P039971.
H-InvDB	HIX0040029.
HGNC	HGNC:23656. TIMM50.
MIM	607381. gene.
neXtProt	NX_Q3ZCQ8.
PharmGKB	PA134902846.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5190.
HOVERGEN	HBG084157.
InParanoid	Q3ZCQ8.
OMA	MEGHHVK.
OrthoDB	EOG42RD84.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins.
Gene expression databases
ArrayExpress	Q3ZCQ8.
Bgee	Q3ZCQ8.
CleanEx	HS_TIMM50.
Genevestigator	Q3ZCQ8.
GermOnline	ENSG00000105197. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.1000. 1 hit.
InterPro	IPR023214. HAD-like_dom. IPR004274. NIF. IPR027111. Tim50. [Graphical view]
PANTHER	PTHR12210:SF3. PTHR12210:SF3. 1 hit.
Pfam	PF03031. NIF. 1 hit. [Graphical view]
SMART	SM00577. CPDc. 1 hit. [Graphical view]
SUPFAM	SSF56784. HAD-like_dom. 1 hit.
PROSITE	PS50969. FCP1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	92609.
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:	May 1, 2013
This is version 82 of the entry and version 2 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.