PRR7_HUMAN
ID PRR7_HUMAN Reviewed; 274 AA.
AC Q8TB68; Q8WU53; Q9BTA7;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Proline-rich protein 7;
DE AltName: Full=Synaptic proline-rich membrane protein;
GN Name=PRR7;
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 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP HIS-127.
RC TISSUE=Skin, Testis, and 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 [3]
RP FUNCTION, INTERACTION WITH SRC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP INDUCTION, PALMITOYLATION, TYROSINE PHOSPHORYLATION, AND MUTAGENESIS OF
RP TYR-139; TYR-153; TYR-166; TYR-177; TYR-201 AND TYR-210.
RX PubMed=21460222; DOI=10.1074/jbc.m110.175117;
RA Hrdinka M., Draber P., Stepanek O., Ormsby T., Otahal P., Angelisova P.,
RA Brdicka T., Paces J., Horejsi V., Drbal K.;
RT "PRR7 is a transmembrane adaptor protein expressed in activated T cells
RT involved in regulation of T cell receptor signaling and apoptosis.";
RL J. Biol. Chem. 286:19617-19629(2011).
RN [4]
RP FUNCTION, IDENTIFICATION IN COMPLEX WITH JUN AND FBXW7, IDENTIFICATION IN A
RP COMPLEX WITH GRIN1 AND GRIN2B, INTERACTION WITH JUN; FBXW7; GRIN1 AND
RP GRIN2B, AND SUBCELLULAR LOCATION.
RX PubMed=27458189; DOI=10.15252/embj.201593070;
RA Kravchick D.O., Karpova A., Hrdinka M., Lopez-Rojas J., Iacobas S.,
RA Carbonell A.U., Iacobas D.A., Kreutz M.R., Jordan B.A.;
RT "Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates
RT NMDA-mediated excitotoxicity.";
RL EMBO J. 35:1923-1934(2016).
CC -!- FUNCTION: Acts as a synapse-to-nucleus messenger to promote NMDA
CC receptor-mediated excitotoxicity in neurons in a JUN-dependent manner
CC (By similarity). Inhibits ubiquitination-mediated degradation and
CC promotes phosphorylation and transcriptional activity of transcription
CC factor JUN (PubMed:27458189). Might play a redundant role in the
CC regulation of T cell receptor signaling (PubMed:21460222). Might
CC promote apoptosis in T cells (PubMed:21460222).
CC {ECO:0000250|UniProtKB:P0C6T3, ECO:0000250|UniProtKB:Q3V0I2,
CC ECO:0000269|PubMed:21460222, ECO:0000269|PubMed:27458189}.
CC -!- SUBUNIT: Forms a complex with NMDA receptor zeta subunit GRIN1 and
CC epsilon subunit GRIN2B (PubMed:27458189). Interacts with GRIN1 and
CC GRIN2B (PubMed:27458189). The interaction with GRIN1 is reduced upon
CC NMDA receptor activity (By similarity). Found in a postsynaptic
CC membrane complex with DLG4 and GRIN1 (By similarity). Interacts with
CC DLG4 (via PDZ3 domain and to lesser degree via PDZ2 domain) (By
CC similarity). Found in a complex with JUN and FBXW7 (PubMed:27458189).
CC Interacts with JUN and FBXW7; the interaction inhibits ubiquitination-
CC mediated JUN degradation promoting its phosphorylation and
CC transcriptional activity (PubMed:27458189). Interacts with SRC
CC (PubMed:21460222). {ECO:0000250|UniProtKB:P0C6T3,
CC ECO:0000269|PubMed:21460222, ECO:0000269|PubMed:27458189}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21460222};
CC Single-pass type III membrane protein {ECO:0000305}. Postsynaptic cell
CC membrane {ECO:0000250|UniProtKB:P0C6T3}; Single-pass type III membrane
CC protein {ECO:0000305}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:P0C6T3}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:21460222}. Synapse {ECO:0000269|PubMed:27458189}.
CC Cell projection, dendrite {ECO:0000269|PubMed:27458189}. Nucleus
CC {ECO:0000269|PubMed:27458189}. Note=Enriched in postsynaptic plasma
CC membrane and postsynaptic densities (PSD). Accumulates in spines along
CC with synapse maturation and colocalizes with DLG4 in a punctate
CC pattern. Translocates from synapses to nuclei following NMDA receptor
CC activity (By similarity). {ECO:0000250|UniProtKB:P0C6T3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TB68-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TB68-2; Sequence=VSP_032750;
CC -!- TISSUE SPECIFICITY: Strongly expressed in brain tissue including the
CC hippocampus, and moderately expressed in esophagus, trachea, lung,
CC ovary, cervix, prostate, testes, thyroid, thymus, lymph nodes and
CC peripheral blood lymphocytes. {ECO:0000269|PubMed:21460222}.
CC -!- INDUCTION: Up-regulated in peripheral blood leukocytes in response to
CC T-cell receptor stimulation. {ECO:0000269|PubMed:21460222}.
CC -!- PTM: Palmitoylated. {ECO:0000269|PubMed:21460222}.
CC -!- PTM: Tyrosine phosphorylated, possibly by SRC.
CC {ECO:0000269|PubMed:21460222}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CH471195; EAW84994.1; -; Genomic_DNA.
DR EMBL; BC004261; AAH04261.1; -; mRNA.
DR EMBL; BC021240; AAH21240.1; -; mRNA.
DR EMBL; BC024233; AAH24233.2; -; mRNA.
DR EMBL; BC033649; AAH33649.1; -; mRNA.
DR CCDS; CCDS4419.1; -. [Q8TB68-1]
DR RefSeq; NP_001167572.1; NM_001174101.1. [Q8TB68-1]
DR RefSeq; NP_001167573.1; NM_001174102.2. [Q8TB68-1]
DR RefSeq; NP_085044.2; NM_030567.4. [Q8TB68-1]
DR RefSeq; XP_011532964.1; XM_011534662.1.
DR RefSeq; XP_011532965.1; XM_011534663.2.
DR RefSeq; XP_016865385.1; XM_017009896.1. [Q8TB68-1]
DR RefSeq; XP_016865386.1; XM_017009897.1.
DR AlphaFoldDB; Q8TB68; -.
DR BioGRID; 123292; 3.
DR CORUM; Q8TB68; -.
DR IntAct; Q8TB68; 3.
DR STRING; 9606.ENSP00000327168; -.
DR iPTMnet; Q8TB68; -.
DR PhosphoSitePlus; Q8TB68; -.
DR SwissPalm; Q8TB68; -.
DR BioMuta; PRR7; -.
DR DMDM; 74730435; -.
DR MassIVE; Q8TB68; -.
DR MaxQB; Q8TB68; -.
DR PaxDb; Q8TB68; -.
DR PeptideAtlas; Q8TB68; -.
DR PRIDE; Q8TB68; -.
DR ProteomicsDB; 73966; -. [Q8TB68-1]
DR ProteomicsDB; 73967; -. [Q8TB68-2]
DR Antibodypedia; 29296; 144 antibodies from 22 providers.
DR DNASU; 80758; -.
DR Ensembl; ENST00000323249.8; ENSP00000327168.3; ENSG00000131188.12. [Q8TB68-1]
DR Ensembl; ENST00000502922.5; ENSP00000420872.1; ENSG00000131188.12. [Q8TB68-1]
DR Ensembl; ENST00000510492.1; ENSP00000421039.1; ENSG00000131188.12. [Q8TB68-1]
DR GeneID; 80758; -.
DR KEGG; hsa:80758; -.
DR MANE-Select; ENST00000323249.8; ENSP00000327168.3; NM_030567.5; NP_085044.2.
DR UCSC; uc003mgu.2; human. [Q8TB68-1]
DR CTD; 80758; -.
DR DisGeNET; 80758; -.
DR GeneCards; PRR7; -.
DR HGNC; HGNC:28130; PRR7.
DR HPA; ENSG00000131188; Tissue enhanced (brain).
DR MIM; 618306; gene.
DR neXtProt; NX_Q8TB68; -.
DR OpenTargets; ENSG00000131188; -.
DR PharmGKB; PA134939770; -.
DR VEuPathDB; HostDB:ENSG00000131188; -.
DR eggNOG; ENOG502RA5T; Eukaryota.
DR GeneTree; ENSGT00950000183109; -.
DR HOGENOM; CLU_081607_0_0_1; -.
DR InParanoid; Q8TB68; -.
DR OMA; FCSYLRR; -.
DR PhylomeDB; Q8TB68; -.
DR TreeFam; TF332076; -.
DR PathwayCommons; Q8TB68; -.
DR SignaLink; Q8TB68; -.
DR BioGRID-ORCS; 80758; 28 hits in 1075 CRISPR screens.
DR ChiTaRS; PRR7; human.
DR GenomeRNAi; 80758; -.
DR Pharos; Q8TB68; Tbio.
DR PRO; PR:Q8TB68; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8TB68; protein.
DR Bgee; ENSG00000131188; Expressed in nucleus accumbens and 94 other tissues.
DR ExpressionAtlas; Q8TB68; baseline and differential.
DR Genevisible; Q8TB68; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IEA:Ensembl.
DR GO; GO:0036041; F:long-chain fatty acid binding; IMP:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0046632; P:alpha-beta T cell differentiation; IEA:Ensembl.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:UniProtKB.
DR GO; GO:2001269; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0099527; P:postsynapse to nucleus signaling pathway; IEA:Ensembl.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Immunity; Lipoprotein; Membrane; Nucleus; Palmitate;
KW Phosphoprotein; Postsynaptic cell membrane; Reference proteome;
KW Signal-anchor; Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1..274
FT /note="Proline-rich protein 7"
FT /id="PRO_0000328649"
FT TOPO_DOM 1..9
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..44
FT /note="Required for interaction with NMDA receptors"
FT /evidence="ECO:0000269|PubMed:27458189"
FT REGION 2..39
FT /note="Required for membrane localization"
FT /evidence="ECO:0000269|PubMed:21460222"
FT REGION 63..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 151..274
FT /note="Required for apoptosis induction"
FT /evidence="ECO:0000269|PubMed:21460222"
FT REGION 151..171
FT /note="Required for internalization"
FT /evidence="ECO:0000269|PubMed:21460222"
FT MOTIF 272..274
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 109..123
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V0I2"
FT VAR_SEQ 89..109
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032750"
FT VARIANT 127
FT /note="P -> H (in dbSNP:rs17851889)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_042437"
FT MUTAGEN 139
FT /note="Y->F: Reduced induction of apoptosis; when
FT associated with F-153; F-166; F-177; F-201 and F-210."
FT /evidence="ECO:0000269|PubMed:21460222"
FT MUTAGEN 153
FT /note="Y->F: Reduced induction of apoptosis; when
FT associated with F-139; F-166; F-177; F-201 and F-210."
FT /evidence="ECO:0000269|PubMed:21460222"
FT MUTAGEN 166
FT /note="Y->F: Reduced induction of apoptosis; when
FT associated with F-139; F-153; F-177; F-201 and F-210."
FT /evidence="ECO:0000269|PubMed:21460222"
FT MUTAGEN 177
FT /note="Y->F: Reduced induction of apoptosis; when
FT associated with F-139; F-153; F-166; F-201 and F-210."
FT /evidence="ECO:0000269|PubMed:21460222"
FT MUTAGEN 201
FT /note="Y->F: Reduced induction of apoptosis; when
FT associated with F-139; F-153; F-166; F-177 and F-210."
FT /evidence="ECO:0000269|PubMed:21460222"
FT MUTAGEN 210
FT /note="Y->F: Reduced induction of apoptosis; when
FT associated with F-139; F-153; F-166; F-177 and F-201."
FT /evidence="ECO:0000269|PubMed:21460222"
SQ SEQUENCE 274 AA; 30930 MW; 3F83198AD2F8032B CRC64;
MVMSQGTYTF LTCFAGFWLI WGLIVLLCCF CSFLRRRLKR RQEERLREQN LRALELEPLE
LEGSLAGSPP GLAPPQPPPH RSRLEAPAHA HSHPHVHVHP LLHHGPAQPH AHAHPHPHHH
ALPHPPPTHL SVPPRPWSYP RQAESDMSKP PCYEEAVLMA EPPPPYSEVL TDTRGLYRKI
VTPFLSRRDS AEKQEQPPPS YKPLFLDRGY TSALHLPSAP RPAPPCPALC LQADRGRRVF
PSWTDSELSS REPLEHGAWR LPVSIPLFGR TTAV
