PRR5L_HUMAN
ID PRR5L_HUMAN Reviewed; 368 AA.
AC Q6MZQ0; A4QN22; E9PKY1; Q96H46; Q9H7V4;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Proline-rich protein 5-like;
DE AltName: Full=Protein observed with Rictor-2;
DE Short=Protor-2;
GN Name=PRR5L; Synonyms=PROTOR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT THR-41.
RC TISSUE=Fetal brain;
RA Birkett C., Cho J., Gau Y., Hamer R., Kelly S., Kovacs K., Liu L., Liu X.,
RA Porter J., Sachs A., Shu Y., Sun Z., Wong J., Wu M., Zhang X., Jay G.,
RA He W.;
RT "High-throughput cloning of full-length human cDNAs directly from cDNA
RT libraries optimized for large and rare transcripts.";
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-41.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP IDENTIFICATION, FUNCTION, AND SUBUNIT.
RX PubMed=17461779; DOI=10.1042/bj20070540;
RA Pearce L.R., Huang X., Boudeau J., Pawlowski R., Wullschleger S., Deak M.,
RA Ibrahim A.F.M., Gourlay R., Magnuson M.A., Alessi D.R.;
RT "Identification of Protor as a novel Rictor-binding component of mTOR
RT complex-2.";
RL Biochem. J. 405:513-522(2007).
RN [8]
RP FUNCTION, AND INTERACTION WITH ZFP36 AND RICTOR.
RX PubMed=21964062; DOI=10.1016/j.cellsig.2011.09.015;
RA Holmes B., Artinian N., Anderson L., Martin J., Masri J., Cloninger C.,
RA Bernath A., Bashir T., Benavides-Serrato A., Gera J.;
RT "Protor-2 interacts with tristetraprolin to regulate mRNA stability during
RT stress.";
RL Cell. Signal. 24:309-315(2012).
RN [9]
RP FUNCTION IN MTORC2 SIGNALING, INTERACTION WITH MTORC2 COMPLEX AND RFFL, AND
RP UBIQUITINATION BY RFFL.
RX PubMed=22609986; DOI=10.1038/ncb2507;
RA Gan X., Wang J., Wang C., Sommer E., Kozasa T., Srinivasula S., Alessi D.,
RA Offermanns S., Simon M.I., Wu D.;
RT "PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and
RT cell migration downstream of Galpha12.";
RL Nat. Cell Biol. 14:686-696(2012).
CC -!- FUNCTION: Associates with the mTORC2 complex that regulates cellular
CC processes including survival and organization of the cytoskeleton
CC (PubMed:17461779). Regulates the activity of the mTORC2 complex in a
CC substrate-specific manner preventing for instance the specific
CC phosphorylation of PKCs and thereby controlling cell migration
CC (PubMed:22609986). Plays a role in the stimulation of ZFP36-mediated
CC mRNA decay of several ZFP36-associated mRNAs, such as TNF-alpha and GM-
CC CSF, in response to stress (PubMed:21964062). Required for ZFP36
CC localization to cytoplasmic stress granule (SG) and P-body (PB) in
CC response to stress (PubMed:21964062). {ECO:0000269|PubMed:17461779,
CC ECO:0000269|PubMed:21964062, ECO:0000269|PubMed:22609986}.
CC -!- SUBUNIT: Interacts with the mammalian target of rapamycin complex 2
CC (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR
CC (PubMed:17461779). Interacts with RFFL (PubMed:22609986). Interacts
CC (via C-terminus) with ZFP36 (via C-terminus); this interaction may
CC accelerate ZFP36-mediated mRNA decay during stress (PubMed:21964062).
CC Interacts with RICTOR (PubMed:21964062). {ECO:0000269|PubMed:17461779,
CC ECO:0000269|PubMed:21964062, ECO:0000269|PubMed:22609986}.
CC -!- INTERACTION:
CC Q6MZQ0; Q7Z6B0-2: CCDC91; NbExp=3; IntAct=EBI-1567866, EBI-12012082;
CC Q6MZQ0; Q5JVL4: EFHC1; NbExp=3; IntAct=EBI-1567866, EBI-743105;
CC Q6MZQ0; Q14192: FHL2; NbExp=3; IntAct=EBI-1567866, EBI-701903;
CC Q6MZQ0; Q13643: FHL3; NbExp=3; IntAct=EBI-1567866, EBI-741101;
CC Q6MZQ0; O75031: HSF2BP; NbExp=3; IntAct=EBI-1567866, EBI-7116203;
CC Q6MZQ0; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-1567866, EBI-2556193;
CC Q6MZQ0; Q9UI95: MAD2L2; NbExp=3; IntAct=EBI-1567866, EBI-77889;
CC Q6MZQ0; Q8IVT2: MISP; NbExp=3; IntAct=EBI-1567866, EBI-2555085;
CC Q6MZQ0; P40692: MLH1; NbExp=3; IntAct=EBI-1567866, EBI-744248;
CC Q6MZQ0; Q6PF18: MORN3; NbExp=3; IntAct=EBI-1567866, EBI-9675802;
CC Q6MZQ0; Q9BSU1: PHAF1; NbExp=3; IntAct=EBI-1567866, EBI-946080;
CC Q6MZQ0; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-1567866, EBI-748391;
CC Q6MZQ0; O75604: USP2; NbExp=3; IntAct=EBI-1567866, EBI-743272;
CC Q6MZQ0; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-1567866, EBI-12030590;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6MZQ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6MZQ0-2; Sequence=VSP_033375, VSP_033379;
CC Name=3;
CC IsoId=Q6MZQ0-3; Sequence=VSP_033376, VSP_033377, VSP_033378;
CC Name=4;
CC IsoId=Q6MZQ0-4; Sequence=VSP_044981, VSP_044982;
CC -!- PTM: Ubiquitinated. Ubiquitination by RFFL promotes proteasomal
CC degradation of PRR5L thereby modifying the substrate-specific activity
CC of the mTORC2 complex. Ubiquitination by RFFL is stimulated by
CC LPA/lysophosphatidic acid. {ECO:0000269|PubMed:22609986}.
CC -!- SIMILARITY: Belongs to the PROTOR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI25123.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK024275; BAB14870.1; -; mRNA.
DR EMBL; DR001466; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BX640959; CAE45978.1; -; mRNA.
DR EMBL; AC009656; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087277; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68124.1; -; Genomic_DNA.
DR EMBL; BC008922; AAH08922.1; -; mRNA.
DR EMBL; BC125122; AAI25123.1; ALT_INIT; mRNA.
DR CCDS; CCDS31463.1; -. [Q6MZQ0-1]
DR CCDS; CCDS53617.1; -. [Q6MZQ0-4]
DR RefSeq; NP_001153639.1; NM_001160167.1. [Q6MZQ0-1]
DR RefSeq; NP_001153640.1; NM_001160168.1. [Q6MZQ0-3]
DR RefSeq; NP_001153641.1; NM_001160169.1. [Q6MZQ0-4]
DR RefSeq; NP_079117.3; NM_024841.4. [Q6MZQ0-1]
DR AlphaFoldDB; Q6MZQ0; -.
DR BioGRID; 122983; 19.
DR IntAct; Q6MZQ0; 18.
DR STRING; 9606.ENSP00000368144; -.
DR iPTMnet; Q6MZQ0; -.
DR PhosphoSitePlus; Q6MZQ0; -.
DR BioMuta; PRR5L; -.
DR DMDM; 296452872; -.
DR EPD; Q6MZQ0; -.
DR jPOST; Q6MZQ0; -.
DR MassIVE; Q6MZQ0; -.
DR MaxQB; Q6MZQ0; -.
DR PaxDb; Q6MZQ0; -.
DR PeptideAtlas; Q6MZQ0; -.
DR PRIDE; Q6MZQ0; -.
DR ProteomicsDB; 21616; -.
DR ProteomicsDB; 66581; -. [Q6MZQ0-1]
DR ProteomicsDB; 66582; -. [Q6MZQ0-2]
DR ProteomicsDB; 66583; -. [Q6MZQ0-3]
DR Antibodypedia; 13120; 82 antibodies from 25 providers.
DR DNASU; 79899; -.
DR Ensembl; ENST00000378867.7; ENSP00000368144.3; ENSG00000135362.14. [Q6MZQ0-1]
DR Ensembl; ENST00000527487.1; ENSP00000435241.1; ENSG00000135362.14. [Q6MZQ0-4]
DR Ensembl; ENST00000530639.6; ENSP00000435050.1; ENSG00000135362.14. [Q6MZQ0-1]
DR GeneID; 79899; -.
DR KEGG; hsa:79899; -.
DR MANE-Select; ENST00000530639.6; ENSP00000435050.1; NM_001160167.2; NP_001153639.1.
DR UCSC; uc001mwo.5; human. [Q6MZQ0-1]
DR CTD; 79899; -.
DR DisGeNET; 79899; -.
DR GeneCards; PRR5L; -.
DR HGNC; HGNC:25878; PRR5L.
DR HPA; ENSG00000135362; Tissue enhanced (brain, intestine, lymphoid tissue).
DR MIM; 611728; gene.
DR neXtProt; NX_Q6MZQ0; -.
DR OpenTargets; ENSG00000135362; -.
DR PharmGKB; PA165543593; -.
DR VEuPathDB; HostDB:ENSG00000135362; -.
DR eggNOG; ENOG502QSM7; Eukaryota.
DR GeneTree; ENSGT00530000063981; -.
DR HOGENOM; CLU_046146_1_0_1; -.
DR InParanoid; Q6MZQ0; -.
DR OMA; MASMMHS; -.
DR OrthoDB; 1260193at2759; -.
DR PhylomeDB; Q6MZQ0; -.
DR TreeFam; TF314826; -.
DR PathwayCommons; Q6MZQ0; -.
DR SignaLink; Q6MZQ0; -.
DR BioGRID-ORCS; 79899; 8 hits in 1071 CRISPR screens.
DR ChiTaRS; PRR5L; human.
DR GenomeRNAi; 79899; -.
DR Pharos; Q6MZQ0; Tbio.
DR PRO; PR:Q6MZQ0; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6MZQ0; protein.
DR Bgee; ENSG00000135362; Expressed in mucosa of transverse colon and 125 other tissues.
DR ExpressionAtlas; Q6MZQ0; baseline and differential.
DR Genevisible; Q6MZQ0; HS.
DR GO; GO:0031932; C:TORC2 complex; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0009968; P:negative regulation of signal transduction; IEA:UniProtKB-KW.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IMP:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0010762; P:regulation of fibroblast migration; IMP:UniProtKB.
DR GO; GO:0038203; P:TORC2 signaling; IDA:UniProtKB.
DR InterPro; IPR013745; Bit61/PRR5.
DR PANTHER; PTHR32428; PTHR32428; 1.
DR Pfam; PF08539; HbrB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Phosphoprotein; Reference proteome;
KW Signal transduction inhibitor; Ubl conjugation.
FT CHAIN 1..368
FT /note="Proline-rich protein 5-like"
FT /id="PRO_0000332709"
FT REGION 327..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2AVJ5"
FT VAR_SEQ 1..229
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033375"
FT VAR_SEQ 1..81
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033376"
FT VAR_SEQ 82
FT /note="R -> M (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033377"
FT VAR_SEQ 149..195
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033378"
FT VAR_SEQ 196..205
FT /note="SVHEPTGPSE -> PGGTPGSGPR (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_044981"
FT VAR_SEQ 206..368
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_044982"
FT VAR_SEQ 230..237
FT /note="FSGPTYTL -> MPVFSRAP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033379"
FT VARIANT 41
FT /note="A -> T (in dbSNP:rs330261)"
FT /evidence="ECO:0000269|PubMed:17974005, ECO:0000269|Ref.2"
FT /id="VAR_043006"
FT VARIANT 330
FT /note="P -> S (in dbSNP:rs11033639)"
FT /id="VAR_043007"
FT CONFLICT 368
FT /note="S -> T (in Ref. 5; AAI25123)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 368 AA; 40836 MW; E54122E27B9CDC68 CRC64;
MTRGFAPILP VEFHKMGSFR RPRPRFMSSP VLSDLPRFQA ARQALQLSSS SAWNSVQTAV
INVFKGGGLQ SNELYALNEN IRRLLKSELG SFITDYFQNQ LLAKGLFFVE EKIKLCEGEN
RIEVLAEVWD HFFTETLPTL QAIFYPVQGQ ELTIRQISLL GFRDLVLLKV KLGDLLLLAQ
SKLPSSIVQM LLILQSVHEP TGPSESYLQL EELVKQVVSP FLGISGDRSF SGPTYTLARR
HSRVRPKVTV LNYASPITAV SRPLNEMVLT PLTEQEGEAY LEKCGSVRRH TVANAHSDIQ
LLAMATMMHS GLGEEASSEN KCLLLPPSFP PPHRQCSSEP NITDNPDGLE EGARGSQEGS
ELNCASLS
