Reviewed, UniProtKB/Swiss-Prot Q13155 (AIMP2_HUMAN)

Names and origin

Protein names

Recommended name:
    Aminoacyl tRNA synthetase complex-interacting multifunctional protein 2
Alternative name(s):
    Multisynthetase complex auxiliary component p38
    Protein JTV-1

Gene names

Name:	AIMP2
Synonyms:	JTV1
ORF Names:	PRO0992

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	320 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for assembly and stability of the aminoacyl-tRNA synthetase complex. Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation. Blocks MDM2-mediated ubiquitination and degradation of TP53/p53. Functions as a proapoptotic factor. Ref.8
Subunit structure	Component of the aminoacyl-tRNA synthetase complex which is comprised of a bifunctional glutamyl-prolyl-tRNA synthetase, the monospecific isoleucyl, leucyl, glutaminyl, methionyl, lysyl, arginyl and aspartyl-tRNA synthetases, and three auxiliary proteins, EEF1E1/p18, AIMP2/p38 and AIMP1/p43. Binds FUBP1 (via C-terminus). Interacts in both its unphosphorylated and phosphorylated forms with TP53/p53 (via N-terminus) in the nucleus following UV irradiation. Interacts (via N-terminus) with PARK2/parkin (via first RING-type domain). Ref.8 Ref.7 Ref.9
Subcellular location	Cytoplasm › cytosol By similarity. Nucleus By similarity. Note: Following DNA damage, dissociates from the aminoacyl-tRNA synthetase complex and translocates from the cytoplasm to the nucleus By similarity.
Post-translational modification	Phosphorylated on serine residues in response to UV irradiation By similarity. Ubiquitinated by PARK2, leading to its degradation by the proteasome. Mutant PARK2 fails to ubiquitinate AIMP2 efficiently, allowing its accumulation which may contribute to neurodegeneration associated with Parkinson disease. Ref.8
Miscellaneous	Accumulates in brains affected by autosomal-recessive juvenile parkinsonism, idiopathic Parkinson disease and diffuse Lewy body disease.
Sequence similarities	Contains 1 GST C-terminal domain.
Sequence caution	The sequence AAC50391.1 differs from that shown. Reason: Frameshift at position 312.

Ontologies

Keywords
Biological process	Apoptosis Differentiation Protein biosynthesis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW translation Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
C19orf57	Q0VDD7	3	EBI-745226,EBI-741210

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 320	320	Aminoacyl tRNA synthetase complex-interacting multifunctional protein 2		PRO_0000221129
Regions
	Domain	220 – 317	98	GST C-terminal
	Region	82 – 162	81	Interaction with PARK2
	Region	162 – 225	64	Interaction with TP53
Natural variations
	Natural variant	92	1	I → V in a lung cancer cell line; reduced interaction with TP53, loss of TP53 activation and loss of proapoptotic activity. Ref.9		VAR_058392
	Natural variant	97 – 99	3	EPT → DLS in a lung cancer cell line; no effect on proapoptotic activity.		VAR_058393
	Natural variant	129	1	A → G: dbSNP rs17855441. Ref.5		VAR_025521
	Natural variant	166	1	L → I: dbSNP rs34525431.		VAR_050125
	Natural variant	209	1	G → S in a lung cancer cell line; no effect on proapoptotic activity. Ref.9		VAR_058394
Experimental info
	Mutagenesis	163 – 164	2	EN → AA: Reduced interaction with TP53, loss of TP53 activation and loss of proapoptotic activity. Ref.9
	Mutagenesis	172 – 173	2	QN → AA: Reduced interaction with TP53, loss of TP53 activation and loss of proapoptotic activity. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Q13155-1 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: F253726B63C12BAB	FASTA	320	35,349
	10 20 30 40 50 60 MPMYQVKPYH GGGAPLRVEL PTCMYRLPNV HGRSYGPAPG AGHVQEESNL SLQALESRQD 70 80 90 100 110 120 DILKRLYELK AAVDGLSKMI QTPDADLDVT NIIQADEPTT LTTNALDLNS VLGKDYGALK 130 140 150 160 170 180 DIVINANPAS PPLSLLVLHR LLCEHFRVLS TVHTHSSVKS VPENLLKCFG EQNKKQPRQD 190 200 210 220 230 240 YQLGFTLIWK NVPKTQMKFS IQTMCPIEGE GNIARFLFSL FGQKHNAVNA TLIDSWVDIA 250 260 270 280 290 300 IFQLKEGSSK EKAAVFRSMN SALGKSPWLA GNELTVADVV LWSVLQQIGG CSVTVPANVQ 310 320 RWMRSCENLA PFNTALKLLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Analysis of the 5' region of PMS2 reveals heterogeneous transcripts and a novel overlapping gene." Nicolaides N.C., Kinzler K.W., Vogelstein B. Genomics 29:329-334(1995) [PubMed: 8666379] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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], VARIANT GLY-129. Tissue: Lymph and Placenta.
[6]	"Functional prediction of the coding sequences of 121 new genes deduced by analysis of cDNA clones from human fetal liver." Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J., Liu M., He F. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 197-320. Tissue: Fetal liver.
[7]	"Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation." Kim M.J., Park B.-J., Kang Y.-S., Kim H.J., Park J.-H., Kang J.W., Lee S.W., Han J.M., Lee H.-W., Kim S. Nat. Genet. 34:330-336(2003) [PubMed: 12819782] [Abstract] Cited for: INTERACTION WITH FUBP1.
[8]	"Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death." Ko H.S., von Coelln R., Sriram S.R., Kim S.W., Chung K.K.K., Pletnikova O., Troncoso J., Johnson B., Saffary R., Goh E.L., Song H., Park B.-J., Kim M.J., Kim S., Dawson V.L., Dawson T.M. J. Neurosci. 25:7968-7978(2005) [PubMed: 16135753] [Abstract] Cited for: FUNCTION, INTERACTION WITH PARK2, UBIQUITINATION.
[9]	"AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53." Han J.M., Park B.-J., Park S.G., Oh Y.S., Choi S.J., Lee S.W., Hwang S.-K., Chang S.-H., Cho M.-H., Kim S. Proc. Natl. Acad. Sci. U.S.A. 105:11206-11211(2008) [PubMed: 18695251] [Abstract] Cited for: INTERACTION WITH TP53, VARIANTS VAL-92; 97-ASP--SER-99 AND SER-209, MUTAGENESIS OF 163-GLU-ASN-164 AND 172-GLN-ASN-173.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U24169 mRNA. Translation: AAC50391.1. Frameshift. AC005995 Genomic DNA. Translation: AAS00389.1. CH236963 Genomic DNA. Translation: EAL23713.1. CH878731 Genomic DNA. Translation: EAW55053.1. BC002853 mRNA. Translation: AAH02853.1. BC010156 mRNA. Translation: AAH10156.1. BC013630 mRNA. Translation: AAH13630.1. AF116615 mRNA. Translation: AAF71039.1.
IPI	IPI00011916.
RefSeq	NP_006294.2.
UniGene	Hs.301613 Hs.520205 Hs.632637
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13155. 10 interactions.
STRING	Q13155.
PTM databases
PhosphoSite	Q13155.
Proteomic databases
PeptideAtlas	Q13155.
PRIDE	Q13155.
Genome annotation databases
Ensembl	ENST00000223029; ENSP00000223029; ENSG00000106305; Homo sapiens. [Genome view]
GeneID	7965.
KEGG	hsa:7965.
UCSC	uc003spo.1. human.
Organism-specific databases
CTD	7965.
GeneCards	GC07P006015.
H-InvDB	HIX0006460.
HGNC	HGNC:20609. AIMP2.
HPA	HPA019098. HPA020057.
MIM	600859. gene.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q13155.
HOVERGEN	Q13155.
OMA	LFGQKHN
OrthoDB	EOG9QJV6T
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q13155.
Bgee	Q13155.
Genevestigator	Q13155.
GermOnline	ENSG00000106305. Homo sapiens.
Family and domain databases
InterPro	IPR010987. Glutathione-S-Trfase_C-like. [Graphical view]
Gene3D	G3DSA:1.20.1050.10. GST_C_like. 1 hit.
PROSITE	PS50405. GST_CTER. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	30485.
SOURCE	Search...

Entry information

Entry name

AIMP2_HUMAN

Accession

Primary (citable) accession number: Q13155
Secondary accession number(s): Q75MR1, Q96CZ5, Q9P1L2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 11, 2001
Last modified:	November 24, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.