Reviewed, UniProtKB/Swiss-Prot Q96B36 (AKTS1_HUMAN)

Names and origin

Protein names

Recommended name:
    Proline-rich AKT1 substrate 1
Alternative name(s):
    40 kDa proline-rich AKT substrate

Gene names

Name:	AKT1S1
Synonyms:	PRAS40

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	256 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. Amino-acid-signaling to mTORC1 is mediated by Rag GTPases, which cause amino-acid-induced relocalization of mTOR within the endomembrane system. 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. 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 proteins. 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.6 Ref.8 Ref.9
Subunit structure	Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains FRAP1, LST8, RAPTOR and AKT1S1. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Interacts directly with RPTOR. The phosphorylated form interacts with 14-3-3 proteins. Ref.8 Ref.5
Subcellular location	Cytoplasm › cytosol By similarity. Note: Found in the cytosolic fraction of the brain By similarity.
Tissue specificity	Widely expressed with highest levels of expression in liver and heart. Expressed at higher levels in cancer cell lines (e.g. A549 and HeLa) than in normal cell lines (e.g. HEK293). Ref.6 Ref.5 Ref.1
Post-translational modification	Phosphorylated by AKT1. Phosphorylation relieves inhibitory function on mTORC1. Ref.5 Ref.7 Ref.10 Ref.11

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	negative regulation of TOR signaling pathway Ref.8 Inferred from direct assay. Source: UniProtKB negative regulation of cell size Ref.8 Inferred from direct assay. Source: UniProtKB negative regulation of protein kinase activity Ref.8 Inferred from direct assay. Source: UniProtKB neuroprotection Inferred from sequence or structural similarity. Source: UniProtKB regulation of survival gene product expression Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosolic part Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 Ref.4 Ref.1 (identifier: Q96B36-1)

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 Ref.4 (identifier: Q96B36-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 256	256	Proline-rich AKT1 substrate 1		PRO_0000253446
Regions
	Compositional bias	35 – 43	9	Poly-Pro
	Compositional bias	77 – 96	20	Pro-rich
Amino acid modifications
	Modified residue	88	1	Phosphoserine Ref.10 Ref.11
	Modified residue	92	1	Phosphoserine Ref.10 Ref.11
	Modified residue	116	1	Phosphoserine By similarity
	Modified residue	183	1	Phosphoserine Ref.7 Ref.11
	Modified residue	198	1	Phosphothreonine
	Modified residue	202	1	Phosphoserine Ref.11
	Modified residue	203	1	Phosphoserine Ref.11
	Modified residue	211	1	Phosphoserine Ref.11
	Modified residue	212	1	Phosphoserine Ref.11
	Modified residue	246	1	Phosphothreonine; by PKB/AKT1 Ref.5 Ref.7 Ref.11
Natural variations
	Alternative sequence	1 – 130	130	Missing in isoform 2. Ref.4		VSP_052182
	Natural variant	47	1	A → P: dbSNP rs17850191. Ref.4		VAR_028239
Experimental info
	Mutagenesis	246	1	T → A: Suppresses S6K1 phosphorylation by mTORC1. Ref.9
	Sequence conflict	108	1	D → G in BAB70937. Ref.1
	Sequence conflict	196	1	K → M in BAB70937. Ref.1
	Sequence conflict	233	1	T → A in BAB70937. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: F6CB195CBB54326C	FASTA	256	27,383
	10 20 30 40 50 60 MASGRPEELW EAVVGAAERF RARTGTELVL LTAAPPPPPR PGPCAYAAHG RGALAEAARR 70 80 90 100 110 120 CLHDIALAHR AATAARPPAP PPAPQPPSPT PSPPRPTLAR EDNEEDEDEP TETETSGEQL 130 140 150 160 170 180 GISDNGGLFV MDEDATLQDL PPFCESDPES TDDGSLSEET PAGPPTCSVP PASALPTQQY 190 200 210 220 230 240 AKSLPVSVPV WGFKEKRTEA RSSDEENGPP SSPDLDRIAA SMRALVLREA EDTQVFGDLP 250 RPRLNTSDFQ KLKRKY
	Isoform 2. Checksum: 2E34744BBEFEC1E9	FASTA	126	13,807
	10 20 30 40 50 60 MDEDATLQDL PPFCESDPES TDDGSLSEET PAGPPTCSVP PASALPTQQY AKSLPVSVPV 70 80 90 100 110 120 WGFKEKRTEA RSSDEENGPP SSPDLDRIAA SMRALVLREA EDTQVFGDLP RPRLNTSDFQ KLKRKY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Prostate and Synovium.
[2]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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].
[4]	"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] (ISOFORMS 1 AND 2), VARIANT PRO-47. Tissue: Brain, Eye and Skin.
[5]	"Identification of a proline-rich Akt substrate as a 14-3-3 binding partner." Kovacina K.S., Park G.Y., Bae S.S., Guzzetta A.W., Schaefer E., Birnbaum M.J., Roth R.A. J. Biol. Chem. 278:10189-10194(2003) [PubMed: 12524439] [Abstract] Cited for: INTERACTION WITH 14-3-3, TISSUE SPECIFICITY, PHOSPHORYLATION AT THR-246.
[6]	"Expression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis." Huang B., Porter G. Acta Pharmacol. Sin. 26:1253-1258(2005) [PubMed: 16174443] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183 AND THR-246, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase." Sancak Y., Thoreen C.C., Peterson T.R., Lindquist R.A., Kang S.A., Spooner E., Carr S.A., Sabatini D.M. Mol. Cell 25:903-915(2007) [PubMed: 17386266] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE TORC1 COMPLEX, INTERACTION WITH RPTOR.
[9]	"Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40." Vander Haar E., Lee S.-I., Bandhakavi S., Griffin T.J., Kim D.-H. Nat. Cell Biol. 9:316-323(2007) [PubMed: 17277771] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE TORC1 COMPLEX, MUTAGENESIS OF THR-246.
[10]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88 AND SER-92, MASS SPECTROMETRY.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183; SER-202; SER-203; SER-211; SER-212 AND THR-246, MASS SPECTROMETRY.
[12]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183; THR-198; SER-202; SER-203; SER-211; SER-212 AND THR-246, MASS SPECTROMETRY.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183; SER-202; SER-212 AND THR-246, MASS SPECTROMETRY. Tissue: T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK055511 mRNA. Translation: BAB70937.1. AK092610 mRNA. Translation: BAG52583.1. AK316603 mRNA. Translation: BAG38190.1. AC118341 Genomic DNA. No translation available. CH471177 Genomic DNA. Translation: EAW52568.1. BC000031 mRNA. Translation: AAH00031.2. Different initiation. BC007416 mRNA. Translation: AAH07416.1. BC015562 mRNA. Translation: AAH15562.1. BC016043 mRNA. Translation: AAH16043.1. BC051844 mRNA. Translation: AAH51844.1.
IPI	IPI00306195. IPI00549786.
RefSeq	NP_001092102.1. NP_001092103.1. NP_115751.2.
UniGene	Hs.515542
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96B36. 5 interactions.
STRING	Q96B36.
PTM databases
PhosphoSite	Q96B36.
Proteomic databases
PRIDE	Q96B36.
Genome annotation databases
Ensembl	ENST00000344175; ENSP00000341698; ENSG00000204673; Homo sapiens. [Genome view] ENST00000391831; ENSP00000375707; ENSG00000204673; Homo sapiens. [Genome view] ENST00000391832; ENSP00000375708; ENSG00000204673; Homo sapiens. [Genome view] ENST00000391833; ENSP00000375709; ENSG00000204673; Homo sapiens. [Genome view] ENST00000391834; ENSP00000375710; ENSG00000204673; Homo sapiens. [Genome view] ENST00000391835; ENSP00000375711; ENSG00000204673; Homo sapiens. [Genome view]
GeneID	84335.
KEGG	hsa:84335.
UCSC	uc002pql.2. human.
Organism-specific databases
CTD	84335.
GeneCards	GC19M055073.
HGNC	HGNC:28426. AKT1S1.
HPA	CAB021903.
MIM	610221. gene.
PharmGKB	PA134943587.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q96B36.
InParanoid	Q96B36.
OrthoDB	EOG94XN2H.
Enzyme and pathway databases
Pathway_Interaction_DB	pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
Reactome	REACT_11061. Signalling by NGF.
Gene expression databases
ArrayExpress	Q96B36.
Bgee	Q96B36.
CleanEx	HS_AKT1S1.
Genevestigator	Q96B36.
GermOnline	ENSG00000204673. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other Resources
NextBio	74105.
SOURCE	Search...

Entry information

Entry name

AKTS1_HUMAN

Accession

Primary (citable) accession number: Q96B36
Secondary accession number(s): A8MTQ1 , B2RE93, Q96BI4, Q96IK7, Q96NG2, Q9BWR5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	December 1, 2001
Last modified:	December 15, 2009
This is version 57 of the entry and version 1 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.