Q8IXI1 (MIRO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial Rho GTPase 2
Short name=MIRO-2
Short name=hMiro-2
EC=3.6.5.-

Alternative name(s):
Ras homolog gene family member T2

Gene names

Name:	RHOT2
Synonyms:	ARHT2, C16orf39

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	618 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution By similarity. Ref.10
Subunit structure	Interacts with the kinesin-binding proteins TRAK1/OIP106 and TRAK2/GRIF1, forming a link between mitochondria and the trafficking apparatus of the microtubules By similarity. Ref.10
Subcellular location	Mitochondrion outer membrane; Single-pass type IV membrane protein. Note: Colocalizes with MGARP and RHOT2 at the mitochondria. Ref.1 Ref.11
Tissue specificity	Ubiquitously expressed. Highly expressed in heart, liver, skeletal muscle, kidney and pancreas. Ref.1 Ref.2
Sequence similarities	Belongs to the mitochondrial Rho GTPase family. Contains 2 EF-hand domains. Contains 2 Miro domains.
Sequence caution	The sequence AAK61240.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence BAB15740.1 differs from that shown. Reason: Erroneous initiation. The sequence BAC03407.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Calcium GTP-binding Metal-binding Nucleotide-binding
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	GTP catabolic process Inferred from electronic annotation. Source: GOC apoptotic process Inferred from mutant phenotype Ref.1. Source: UniProtKB cellular homeostasis Inferred from mutant phenotype Ref.1. Source: UniProtKB mitochondrion transport along microtubule Inferred from mutant phenotype Ref.10. Source: UniProtKB regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome integral to mitochondrial outer membrane Inferred from direct assay Ref.1Ref.11. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Inferred from electronic annotation. Source: InterPro calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8IXI1-1)

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: Q8IXI1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.
     251-340: FLFLNTLFIQ...SLFSVFPAAP → EAGCPPVPGE...PWLPVCAESV
     341-618: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 618	618	Mitochondrial Rho GTPase 2		PRO_0000239318
Regions
	Topological domain	1 – 592	592	Mitochondrial intermembrane Potential
	Transmembrane	593 – 615	23	Helical; Anchor for type IV membrane protein; Potential
	Topological domain	616 – 618	3	Cytoplasmic Potential
	Domain	1 – 142	142	Miro 1
	Domain	184 – 219	36	EF-hand 1
	Domain	304 – 339	36	EF-hand 2
	Domain	410 – 618	209	Miro 2
	Nucleotide binding	11 – 18	8	GTP 1 Potential
	Nucleotide binding	57 – 61	5	GTP 1 Potential
	Nucleotide binding	118 – 121	4	GTP 1 Potential
	Calcium binding	197 – 208	12	1 Potential
	Calcium binding	317 – 328	12	2 Potential
	Nucleotide binding	423 – 430	8	GTP 2 Potential
	Nucleotide binding	459 – 463	5	GTP 2 Potential
	Nucleotide binding	524 – 527	4	GTP 2 Potential
Natural variations
	Alternative sequence	1 – 127	127	Missing in isoform 2.		VSP_019162
	Alternative sequence	251 – 340	90	FLFLN…FPAAP → EAGCPPVPGECGEGAVPGAP PALSRCRFPLPEHALHPARP ARDHLDHPAALRLQRCPGAD CGLSLPSDPRAPRLQHGAQP PWLPVCAESV in isoform 2.		VSP_019163
	Alternative sequence	341 – 618	278	Missing in isoform 2.		VSP_019164
	Natural variant	245	1	R → Q. Ref.1 Corresponds to variant rs1139897 [ dbSNP | Ensembl ].		VAR_026637
	Natural variant	425	1	R → C. Ref.1 Corresponds to variant rs3177338 [ dbSNP | Ensembl ].		VAR_026638
Experimental info
	Mutagenesis	13	1	A → V: Causes constitutive activation inducing an aggregation of the mitochondrial network. Ref.9 Ref.10
	Mutagenesis	18	1	T → N: Induces an aggregation of the mitochondrial network. Ref.10
	Sequence conflict	139	1	P → S in CAD56957. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 13, 2006. Version 2. Checksum: C72ECBCA33D04B6B	FASTA	618	68,118
	10 20 30 40 50 60 MRRDVRILLL GEAQVGKTSL ILSLVGEEFP EEVPPRAEEI TIPADVTPEK VPTHIVDYSE 70 80 90 100 110 120 AEQTDEELRE EIHKANVVCV VYDVSEEATI EKIRTKWIPL VNGGTTQGPR VPIILVGNKS 130 140 150 160 170 180 DLRSGSSMEA VLPIMSQFPE IETCVECSAK NLRNISELFY YAQKAVLHPT APLYDPEAKQ 190 200 210 220 230 240 LRPACAQALT RIFRLSDQDL DQALSDEELN AFQKSCFGHP LAPQALEDVK TVVCRNVAGG 250 260 270 280 290 300 VREDRLTLDG FLFLNTLFIQ RGRHETTWTI LRRFGYSDAL ELTADYLSPL IHVPPGCSTE 310 320 330 340 350 360 LNHLGYQFVQ RVFEKHDQDR DGALSPVELQ SLFSVFPAAP WGPELPRTVR TEAGRLPLHG 370 380 390 400 410 420 YLCQWTLVTY LDVRSCLGHL GYLGYPTLCE QDQAHAITVT REKRLDQEKG QTQRSVLLCK 430 440 450 460 470 480 VVGARGVGKS AFLQAFLGRG LGHQDTREQP PGYAIDTVQV NGQEKYLILC EVGTDGLLAT 490 500 510 520 530 540 SLDATCDVAC LMFDGSDPKS FAHCASVYKH HYMDGQTPCL FVSSKADLPE GVAVSGPSPA 550 560 570 580 590 600 EFCRKHRLPA PVPFSCAGPA EPSTTIFTQL ATMAAFPHLV HAELHPSSFW LRGLLGVVGA 610 AVAAVLSFSL YRVLVKSQ
	Isoform 2 [UniParc]. Checksum: 76722819B54E29DE	FASTA	213	23,077
	10 20 30 40 50 60 MEAVLPIMSQ FPEIETCVEC SAKNLRNISE LFYYAQKAVL HPTAPLYDPE AKQLRPACAQ 70 80 90 100 110 120 ALTRIFRLSD QDLDQALSDE ELNAFQKSCF GHPLAPQALE DVKTVVCRNV AGGVREDRLT 130 140 150 160 170 180 LDGEAGCPPV PGECGEGAVP GAPPALSRCR FPLPEHALHP ARPARDHLDH PAALRLQRCP 190 200 210 GADCGLSLPS DPRAPRLQHG AQPPWLPVCA ESV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis." Fransson A., Ruusala A., Aspenstroem P. J. Biol. Chem. 278:6495-6502(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS GLN-245 AND CYS-425.
[2]	"Cloning and characterization of the mouse Arht2 gene which encodes a putative atypical GTPase." Shan Y., Hexige S., Guo Z., Wan B., Chen K., Chen X., Ma L., Huang C., Zhao S., Yu L. Cytogenet. Genome Res. 106:91-97(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]	"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] (ISOFORM 2). Tissue: Spleen.
[4]	"The nucleotide sequence of a long cDNA clone isolated from human spleen." Jikuya H., Takano J., Kikuno R., Nagase T., Ohara O. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Spleen.
[5]	"Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16." Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R. Hum. Mol. Genet. 10:339-352(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: Placenta and Skin.
[9]	"Rho GTPases have diverse effects on the organization of the actin filament system." Aspenstroem P., Fransson A., Saras J. Biochem. J. 377:327-337(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ALA-13.
[10]	"The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking." Fransson S., Ruusala A., Aspenstroem P. Biochem. Biophys. Res. Commun. 344:500-510(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TRAK1 AND TRAK2, MUTAGENESIS OF ALA-13 AND THR-18.
[11]	"HUMMR, a hypoxia- and HIF-1alpha-inducible protein, alters mitochondrial distribution and transport." Li Y., Lim S., Hoffman D., Aspenstrom P., Federoff H.J., Rempe D.A. J. Cell Biol. 185:1065-1081(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"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	AJ517413 mRNA. Translation: CAD56957.1. AY207375 mRNA. Translation: AAP46090.1. AK024450 mRNA. Translation: BAB15740.1. Different initiation. AK090426 mRNA. Translation: BAC03407.1. Different initiation. AE006464 Genomic DNA. Translation: AAK61240.1. Sequence problems. Z92544 Genomic DNA. Translation: CAM26351.1. CH471112 Genomic DNA. Translation: EAW85763.1. BC004327 mRNA. Translation: AAH04327.1. BC014942 mRNA. Translation: AAH14942.1.
IPI	IPI00465059. IPI00759537.
RefSeq	NP_620124.1. NM_138769.2.
UniGene	Hs.513242.
3D structure databases
ProteinModelPortal	Q8IXI1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IXI1. 4 interactions.
MINT	MINT-1191538.
STRING	9606.ENSP00000321971.
PTM databases
PhosphoSite	Q8IXI1.
Polymorphism databases
DMDM	108860798.
Proteomic databases
PaxDb	Q8IXI1.
PRIDE	Q8IXI1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000315082; ENSP00000321971; ENSG00000140983.
GeneID	89941.
KEGG	hsa:89941.
UCSC	uc002cip.3. human.
Organism-specific databases
CTD	89941.
GeneCards	GC16P000727.
HGNC	HGNC:21169. RHOT2.
HPA	HPA012624. HPA012895.
MIM	613889. gene.
neXtProt	NX_Q8IXI1.
PharmGKB	PA134889674.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1100.
HOVERGEN	HBG079778.
InParanoid	Q8IXI1.
KO	K07871.
OMA	RIFYISD.
OrthoDB	EOG4CJVGR.
PhylomeDB	Q8IXI1.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q8IXI1.
Bgee	Q8IXI1.
CleanEx	HS_RHOT2.
Genevestigator	Q8IXI1.
GermOnline	ENSG00000140983. Homo sapiens.
Family and domain databases
Gene3D	1.10.238.10. 2 hits.
InterPro	IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR013566. EF_hand_assoc_1. IPR013567. EF_hand_assoc_2. IPR002048. EF_hand_dom. IPR020860. MIRO. IPR013684. MIRO-like. IPR001806. Small_GTPase. IPR021181. Small_GTPase_Miro. [Graphical view]
Pfam	PF08355. EF_assoc_1. 1 hit. PF08356. EF_assoc_2. 1 hit. PF08477. Miro. 1 hit. PF00071. Ras. 1 hit. [Graphical view]
PIRSF	PIRSF037488. Mt_Rho_GTPase. 1 hit.
PRINTS	PR00449. RASTRNSFRMNG.
SMART	SM00054. EFh. 2 hits. [Graphical view]
PROSITE	PS00018. EF_HAND_1. 1 hit. PS50222. EF_HAND_2. 2 hits. PS51423. MIRO. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	89941.
NextBio	76445.
SOURCE	Search...

Entry information

Entry name

MIRO2_HUMAN

Accession

Primary (citable) accession number: Q8IXI1
Secondary accession number(s): A2IDC2 , Q8NF53, Q96C13, Q96S17, Q9BT60, Q9H7M8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 13, 2006
Last sequence update:	June 13, 2006
Last modified:	May 1, 2013
This is version 98 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.