Q9D1F4 (AKTS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proline-rich AKT1 substrate 1
Short name=Proline-rich AKT substrate

Gene names

Name:	Akt1s1
Synonyms:	Pras

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	257 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Subunit of mTORC1, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection. Ref.3 Ref.5
Subunit structure	Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Interacts directly with RPTOR. The phosphorylated form interacts with 14-3-3 proteins and with phosphorylated AKT1 following transient focal cerebral ischemia in vivo. Ref.3
Subcellular location	Cytoplasm › cytosol. Note: Found in the cytosolic fraction of the brain. Colocalizes with cortical neurons following ischemic/reperfusion injury. Ref.3

Ontologies

Keywords
Cellular component	Cytoplasm
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Inferred from sequence alignment PubMed 12163404. Source: MGI negative regulation of TOR signaling cascade Inferred from electronic annotation. Source: Compara negative regulation of cell size Inferred from electronic annotation. Source: Compara negative regulation of protein kinase activity Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Inferred from electronic annotation. Source: InterPro regulation of neuron apoptotic process Inferred from direct assay Ref.3. Source: UniProtKB
Cellular_component	TORC1 complex Inferred from electronic annotation. Source: Compara cytosolic part Inferred from direct assay Ref.3. Source: UniProtKB nucleus Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 257	257	Proline-rich AKT1 substrate 1		PRO_0000253447
Regions
	Compositional bias	35 – 43	9	Poly-Pro
	Compositional bias	77 – 97	21	Pro-rich
Amino acid modifications
	Modified residue	88	1	Phosphoserine Ref.7
	Modified residue	92	1	Phosphoserine Ref.7
	Modified residue	117	1	Phosphoserine Ref.6
	Modified residue	184	1	Phosphoserine By similarity
	Modified residue	203	1	Phosphoserine Ref.4 Ref.6 Ref.7
	Modified residue	204	1	Phosphoserine Ref.4 Ref.6 Ref.7
	Modified residue	212	1	Phosphoserine Ref.6
	Modified residue	213	1	Phosphoserine Ref.4 Ref.6
	Modified residue	247	1	Phosphothreonine; by PKB/AKT1 By similarity UniProtKB Q96B36

Sequences

	Sequence		Length	Mass (Da)
	Q9D1F4 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 4BFFC8630DBBA5EC	FASTA	257	27,483
	10 20 30 40 50 60 MASGRPEELW EAVVGAAERF QARTGTELVL LTAAPPPPPR PGPCAYAAHG RGALAEAARR 70 80 90 100 110 120 CLHDIAQAHR AATATRPPGP PPAPQPPSPA PSPPPRPALA REDEEEDEDE PTETETSGER 130 140 150 160 170 180 LGGSDNGGLF MMDEDATLQD LPPFCESDPE STDDGSLSEE TPAGPTACPQ PPATALPTQQ 190 200 210 220 230 240 YAKSLPVSVP VWAFKEKRTE ARSSDEENGP PSSPDLDRIA ASMRALVLRE AEDTQVFGDL 250 PRPRLNTSDF QKLKRKY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Embryo.
[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]. Tissue: Lung.
[3]	"Neuroprotective role of a proline-rich Akt substrate in apoptotic neuronal cell death after stroke: relationships with nerve growth factor." Saito A., Narasimhan P., Hayashi T., Okuno S., Ferrand-Drake M., Chan P.H. J. Neurosci. 24:1584-1593(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
[4]	"Phosphoproteomic analysis of the developing mouse brain." Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P. Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203; SER-204 AND SER-213, MASS SPECTROMETRY. Tissue: Embryonic brain.
[5]	"Modulation of proline-rich akt substrate survival signaling pathways by oxidative stress in mouse brains after transient focal cerebral ischemia." Saito A., Hayashi T., Okuno S., Nishi T., Chan P.H. Stroke 37:513-517(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117; SER-203; SER-204; SER-212 AND SER-213, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-203 AND SER-204, MASS SPECTROMETRY. Tissue: Melanoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK003638 mRNA. Translation: BAB22905.1. AK141771 mRNA. Translation: BAE24829.1. AK154110 mRNA. Translation: BAE32383.1. BC132372 mRNA. Translation: AAI32373.1. BC132374 mRNA. Translation: AAI32375.1.
IPI	IPI00133685.
RefSeq	NP_001240849.1. NM_001253920.1. NP_080546.1. NM_026270.4.
UniGene	Mm.148007. Mm.431538. Mm.490268.
3D structure databases
ProteinModelPortal	Q9D1F4.
ModBase	Search...
PTM databases
PhosphoSite	Q9D1F4.
Proteomic databases
PaxDb	Q9D1F4.
PRIDE	Q9D1F4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000054343; ENSMUSP00000049764; ENSMUSG00000011096. ENSMUST00000107880; ENSMUSP00000103512; ENSMUSG00000011096.
GeneID	67605.
KEGG	mmu:67605.
UCSC	uc009grd.1. mouse.
Organism-specific databases
CTD	84335.
MGI	MGI:1914855. Akt1s1.
Phylogenomic databases
eggNOG	NOG40718.
GeneTree	ENSGT00390000017397.
HOGENOM	HOG000236322.
HOVERGEN	HBG059465.
InParanoid	A2RT52.
KO	K16184.
OrthoDB	EOG4V6ZHQ.
Gene expression databases
ArrayExpress	Q9D1F4.
Bgee	Q9D1F4.
CleanEx	MM_AKT1S1.
Genevestigator	Q9D1F4.
GermOnline	ENSMUSG00000011096. Mus musculus.
Family and domain databases
InterPro	IPR026682. AKT1S1. [Graphical view]
PANTHER	PTHR21844. PTHR21844. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	AKT1S1. mouse.
NextBio	325025.
SOURCE	Search...

Entry information

Entry name

AKTS1_MOUSE

Accession

Primary (citable) accession number: Q9D1F4
Secondary accession number(s): A2RT52

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	June 1, 2001
Last modified:	April 3, 2013
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program