Q13155 (AIMP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aminoacyl tRNA synthase complex-interacting multifunctional protein 2

Alternative name(s):
Multisynthase complex auxiliary component p38
Protein JTV-1

Gene names

Name:	AIMP2
Synonyms:	JTV1
ORF Names:	PRO0992

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

General annotation (Comments)

Function	Required for assembly and stability of the aminoacyl-tRNA synthase 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 p53/TP53. Functions as a proapoptotic factor. Ref.10
Subunit structure	Component of the aminoacyl-tRNA synthase complex which is comprised of a bifunctional glutamyl-prolyl-tRNA synthase, the monospecific isoleucyl, leucyl, glutaminyl, methionyl, lysyl, arginyl and aspartyl-tRNA synthases, 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 p53/TP53 (via N-terminus) in the nucleus following UV irradiation. Interacts (via N-terminus) with KARS and PARK2/parkin (via first RING-type domain). Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location	Cytoplasm › cytosol By similarity. Nucleus By similarity. Note: Following DNA damage, dissociates from the aminoacyl-tRNA synthase 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.10
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Type II pneumocyte differentiation Inferred from electronic annotation. Source: Compara apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of protein ubiquitination Inferred from electronic annotation. Source: Compara tRNA aminoacylation for protein translation Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
C19orf57	Q0VDD7	4	EBI-745226,EBI-741210
gag	P04591	3	EBI-745226,EBI-6179719	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 320	320	Aminoacyl tRNA synthase 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.12		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. Ref.5 Corresponds to variant rs17855441 [ dbSNP | Ensembl ].		VAR_025521
	Natural variant	166	1	L → I. Corresponds to variant rs34525431 [ dbSNP | Ensembl ].		VAR_050125
	Natural variant	209	1	G → S in a lung cancer cell line; no effect on proapoptotic activity. Ref.12		VAR_058394
Experimental info
	Mutagenesis	163 – 164	2	EN → AA: Reduced interaction with TP53, loss of TP53 activation and loss of proapoptotic activity. Ref.12
	Mutagenesis	172 – 173	2	QN → AA: Reduced interaction with TP53, loss of TP53 activation and loss of proapoptotic activity. Ref.12

Sequences

	Sequence		Length	Mass (Da)
	Q13155 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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]	"Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein." Quevillon S., Robinson J.-C., Berthonneau E., Siatecka M., Mirande M. J. Mol. Biol. 285:183-195(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KARS.
[8]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FUBP1.
[9]	"Cellular distribution of Lysyl-tRNA synthetase and its interaction with Gag during human immunodeficiency virus type 1 assembly." Halwani R., Cen S., Javanbakht H., Saadatmand J., Kim S., Shiba K., Kleiman L. J. Virol. 78:7553-7564(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KARS.
[10]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PARK2, UBIQUITINATION.
[11]	"Lysyl-tRNA synthetase interacts with EF1alpha, aspartyl-tRNA synthetase and p38 in vitro." Guzzo C.M., Yang D.C.H. Biochem. Biophys. Res. Commun. 365:718-723(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KARS.
[12]	"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] [Europe PMC] [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.
[13]	"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

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. NM_006303.3.

UniGene

Hs.301613.
Hs.520205.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4DPG	X-ray	2.84	I/J/K/L	1-48	[»]

ProteinModelPortal

Q13155.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34421N.

IntAct

Q13155. 16 interactions.

MINT

MINT-5002775.

STRING

9606.ENSP00000223029.

PTM databases

PhosphoSite

Q13155.

Polymorphism databases

DMDM

12644405.

Proteomic databases

PaxDb

Q13155.

PeptideAtlas

Q13155.

PRIDE

Q13155.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000223029; ENSP00000223029; ENSG00000106305.

GeneID

7965.

KEGG

hsa:7965.

UCSC

uc003spo.3. human.

Organism-specific databases

CTD

7965.

GeneCards

GC07P006016.

HGNC

HGNC:20609. AIMP2.

HPA

HPA019098.
HPA020057.

MIM

600859. gene.

neXtProt

NX_Q13155.

PharmGKB

PA165617609.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG72943.

HOGENOM

HOG000233491.

InParanoid

Q13155.

KO

K15438.

OMA

IIQADEP.

OrthoDB

EOG44TP8P.

PhylomeDB

Q13155.

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

Gene3D

1.20.1050.10. 1 hit.

InterPro

IPR010987. Glutathione-S-Trfase_C-like.
[Graphical view]

SUPFAM

SSF47616. GST_C_like. 1 hit.

PROSITE

PS50405. GST_CTER. False negative.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

7965.

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:	April 3, 2013
This is version 111 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.