NHRF1_CAEEL
ID NHRF1_CAEEL Reviewed; 467 AA.
AC G5EDM4; G5EC64; G5EE55; G5EFP7; I2HAG6; I2HAI6; Q27GP2; X5LQ26; X5LVA5;
AC X5MBG4;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor-like protein nrfl-1 {ECO:0000305};
DE Short=NHERF-1 {ECO:0000305};
DE AltName: Full=Regulatory cofactor of Na(+)/H(+) exchanger {ECO:0000305};
DE AltName: Full=Sodium-hydrogen exchanger regulatory factor 1 {ECO:0000305};
GN Name=nrfl-1 {ECO:0000312|WormBase:C01F6.6a};
GN Synonyms=mpz-2 {ECO:0000312|WormBase:C01F6.6a},
GN tag-60 {ECO:0000312|WormBase:C01F6.6a};
GN ORFNames=C01F6.6 {ECO:0000312|WormBase:C01F6.6a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, INTERACTION WITH AAT-6, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, DOMAIN, PHOSPHORYLATION, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF 26-GLY-TYR-27 AND 154-GLU-PHE-155.
RX PubMed=22916205; DOI=10.1371/journal.pone.0043050;
RA Hagiwara K., Nagamori S., Umemura Y.M., Ohgaki R., Tanaka H., Murata D.,
RA Nakagomi S., Nomura K.H., Kage-Nakadai E., Mitani S., Nomura K., Kanai Y.;
RT "NRFL-1, the C. elegans NHERF orthologue, interacts with amino acid
RT transporter 6 (AAT-6) for age-dependent maintenance of AAT-6 on the
RT membrane.";
RL PLoS ONE 7:E43050-E43050(2012).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30560135; DOI=10.3389/fmolb.2018.00109;
RA Spanier B., Wallwitz J., Zapoglou D., Idrissou B.M.G., Fischer C.,
RA Troll M., Petzold K., Daniel H.;
RT "The Reproduction Rate of Peptide Transporter PEPT-1 Deficient C. elegans
RT Is Dependent on Dietary Glutamate Supply.";
RL Front. Mol. Biosci. 5:109-109(2018).
CC -!- FUNCTION: Scaffold protein that connects plasma membrane proteins with
CC members of the ezrin/moesin/radixin family and thereby helps to link
CC them to the actin cytoskeleton and to regulate their surface expression
CC (By similarity). Anchors the amino acid transporter protein aat-6 to
CC the apical cell membrane of intestinal cells, particularly in older
CC animals, in order to maintain amino acid homeostasis (PubMed:22916205).
CC May play a role in promoting fertility (PubMed:30560135).
CC {ECO:0000250|UniProtKB:O14745, ECO:0000269|PubMed:22916205,
CC ECO:0000269|PubMed:30560135}.
CC -!- SUBUNIT: Interacts (via PDZ 2 domain) with aat-6 (via PDZ-binding
CC motif); the interaction sequesters aat-6 to the apical cell membrane of
CC intestinal cells. {ECO:0000269|PubMed:22916205}.
CC -!- INTERACTION:
CC G5EDM4; G5EBK3: erm-1; NbExp=2; IntAct=EBI-313674, EBI-313664;
CC G5EDM4-1; Q22397: aat-6; NbExp=2; IntAct=EBI-25423624, EBI-21449230;
CC -!- SUBCELLULAR LOCATION: Cell projection, microvillus membrane
CC {ECO:0000269|PubMed:22916205}. Apical cell membrane
CC {ECO:0000269|PubMed:22916205}. Note=Co-localizes with aat-6 at the
CC apical cell membrane of intestinal cells.
CC {ECO:0000269|PubMed:22916205}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Name=a {ECO:0000312|WormBase:C01F6.6a};
CC IsoId=G5EDM4-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C01F6.6b};
CC IsoId=G5EDM4-2; Sequence=VSP_060380;
CC Name=c {ECO:0000312|WormBase:C01F6.6c};
CC IsoId=G5EDM4-3; Sequence=VSP_060383, VSP_060384;
CC Name=d {ECO:0000312|WormBase:C01F6.6d};
CC IsoId=G5EDM4-4; Sequence=VSP_060383, VSP_060385;
CC Name=e {ECO:0000312|WormBase:C01F6.6e};
CC IsoId=G5EDM4-5; Sequence=VSP_060379;
CC Name=f {ECO:0000312|WormBase:C01F6.6f};
CC IsoId=G5EDM4-6; Sequence=VSP_060381;
CC Name=g {ECO:0000312|WormBase:C01F6.6g};
CC IsoId=G5EDM4-7; Sequence=VSP_060382;
CC Name=h {ECO:0000312|WormBase:C01F6.6h};
CC IsoId=G5EDM4-8; Sequence=VSP_060383;
CC Name=i {ECO:0000312|WormBase:C01F6.6i};
CC IsoId=G5EDM4-9; Sequence=VSP_060384;
CC Name=j {ECO:0000312|WormBase:C01F6.6j};
CC IsoId=G5EDM4-10; Sequence=VSP_060379, VSP_060384;
CC -!- TISSUE SPECIFICITY: Expressed in the excretory canal and intestine
CC (PubMed:22916205). Expressed on the apical cell membrane of intestinal
CC cells (at protein level) (PubMed:22916205).
CC {ECO:0000269|PubMed:22916205}.
CC -!- DEVELOPMENTAL STAGE: Expressed in larval and adult stages.
CC {ECO:0000269|PubMed:22916205}.
CC -!- DOMAIN: The PDZ 2 domain is required for the interaction with the amino
CC acid transporter protein aat-6. {ECO:0000269|PubMed:22916205}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:22916205}.
CC -!- DISRUPTION PHENOTYPE: Viable, with no gross anatomy or growth defects
CC observed (PubMed:22916205). Localization of aat-6 at the intestinal
CC apical cell membrane diminishes as animals age, and eventually aat-6
CC becomes diffusely dispersed in the cytoplasm (PubMed:22916205). RNAi-
CC mediated knockdown in a pept-1 (lg601) mutant background results in a
CC reduced number of progeny (PubMed:30560135).
CC {ECO:0000269|PubMed:22916205, ECO:0000269|PubMed:30560135}.
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DR EMBL; BX284604; CAA92439.3; -; Genomic_DNA.
DR EMBL; BX284604; CAD37352.1; -; Genomic_DNA.
DR EMBL; BX284604; CAJ80811.1; -; Genomic_DNA.
DR EMBL; BX284604; CAJ80816.1; -; Genomic_DNA.
DR EMBL; BX284604; CAJ80817.1; -; Genomic_DNA.
DR EMBL; BX284604; CCH63894.1; -; Genomic_DNA.
DR EMBL; BX284604; CCH63914.1; -; Genomic_DNA.
DR EMBL; BX284604; CDO41140.1; -; Genomic_DNA.
DR EMBL; BX284604; CDO41141.1; -; Genomic_DNA.
DR EMBL; BX284604; CDO50111.1; -; Genomic_DNA.
DR PIR; T18808; T18808.
DR PIR; T21299; T21299.
DR RefSeq; NP_001040908.1; NM_001047443.3. [G5EDM4-3]
DR RefSeq; NP_001040909.1; NM_001047444.4. [G5EDM4-4]
DR RefSeq; NP_001040910.1; NM_001047445.4. [G5EDM4-5]
DR RefSeq; NP_001263761.1; NM_001276832.1. [G5EDM4-6]
DR RefSeq; NP_001263762.1; NM_001276833.1. [G5EDM4-7]
DR RefSeq; NP_001294067.1; NM_001307138.1.
DR RefSeq; NP_001294068.1; NM_001307139.1. [G5EDM4-9]
DR RefSeq; NP_001294128.1; NM_001307199.1.
DR RefSeq; NP_741478.1; NM_171410.4. [G5EDM4-1]
DR RefSeq; NP_741479.1; NM_171411.5. [G5EDM4-2]
DR AlphaFoldDB; G5EDM4; -.
DR SMR; G5EDM4; -.
DR ComplexPortal; CPX-4311; nrfl-1-aat-6 complex.
DR IntAct; G5EDM4; 10.
DR STRING; 6239.C01F6.6b; -.
DR EPD; G5EDM4; -.
DR PeptideAtlas; G5EDM4; -.
DR EnsemblMetazoa; C01F6.6a.1; C01F6.6a.1; WBGene00006438. [G5EDM4-1]
DR EnsemblMetazoa; C01F6.6b.1; C01F6.6b.1; WBGene00006438. [G5EDM4-2]
DR EnsemblMetazoa; C01F6.6c.1; C01F6.6c.1; WBGene00006438. [G5EDM4-3]
DR EnsemblMetazoa; C01F6.6d.1; C01F6.6d.1; WBGene00006438. [G5EDM4-4]
DR EnsemblMetazoa; C01F6.6e.1; C01F6.6e.1; WBGene00006438. [G5EDM4-5]
DR EnsemblMetazoa; C01F6.6f.1; C01F6.6f.1; WBGene00006438. [G5EDM4-6]
DR EnsemblMetazoa; C01F6.6g.1; C01F6.6g.1; WBGene00006438. [G5EDM4-7]
DR EnsemblMetazoa; C01F6.6h.1; C01F6.6h.1; WBGene00006438. [G5EDM4-8]
DR EnsemblMetazoa; C01F6.6i.1; C01F6.6i.1; WBGene00006438. [G5EDM4-9]
DR EnsemblMetazoa; C01F6.6j.1; C01F6.6j.1; WBGene00006438. [G5EDM4-10]
DR GeneID; 177736; -.
DR KEGG; cel:CELE_C01F6.6; -.
DR UCSC; C01F6.6a; c. elegans.
DR CTD; 177736; -.
DR WormBase; C01F6.6a; CE30847; WBGene00006438; nrfl-1. [G5EDM4-1]
DR WormBase; C01F6.6b; CE30848; WBGene00006438; nrfl-1. [G5EDM4-2]
DR WormBase; C01F6.6c; CE39888; WBGene00006438; nrfl-1. [G5EDM4-3]
DR WormBase; C01F6.6d; CE39889; WBGene00006438; nrfl-1. [G5EDM4-4]
DR WormBase; C01F6.6e; CE39890; WBGene00006438; nrfl-1. [G5EDM4-5]
DR WormBase; C01F6.6f; CE47486; WBGene00006438; nrfl-1. [G5EDM4-6]
DR WormBase; C01F6.6g; CE47559; WBGene00006438; nrfl-1. [G5EDM4-7]
DR WormBase; C01F6.6h; CE49694; WBGene00006438; nrfl-1. [G5EDM4-8]
DR WormBase; C01F6.6i; CE49735; WBGene00006438; nrfl-1. [G5EDM4-9]
DR WormBase; C01F6.6j; CE49636; WBGene00006438; nrfl-1. [G5EDM4-10]
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00950000182849; -.
DR HOGENOM; CLU_057921_0_0_1; -.
DR OMA; THEATTE; -.
DR OrthoDB; 880632at2759; -.
DR PRO; PR:G5EDM4; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00006438; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:1990184; C:amino acid transport complex; IC:ComplexPortal.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IDA:UniProtKB.
DR GO; GO:0080144; P:amino acid homeostasis; IC:ComplexPortal.
DR GO; GO:0015807; P:L-amino acid transport; IC:ComplexPortal.
DR Gene3D; 2.30.42.10; -; 2.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR Pfam; PF17820; PDZ_6; 2.
DR SMART; SM00228; PDZ; 2.
DR SUPFAM; SSF50156; SSF50156; 2.
DR PROSITE; PS50106; PDZ; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Membrane;
KW Reference proteome; Repeat.
FT CHAIN 1..467
FT /note="Na(+)/H(+) exchange regulatory cofactor-like protein
FT nrfl-1"
FT /id="PRO_0000448295"
FT DOMAIN 12..94
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 143..225
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 344..429
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 344..371
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 406..422
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..136
FT /note="Missing (in isoform e and isoform j)"
FT /evidence="ECO:0000305"
FT /id="VSP_060379"
FT VAR_SEQ 1..119
FT /note="MVHIPSDVTPPRLCVVEKLNGENEYGYNLHAEKGRGQFVGTVDPDSPAERGG
FT LITGDRIFAVNGHSIIGENHKKVVERIKANPNRCEMLVISEEGAKWYNENNVQITLDLP
FT NIERVSPM -> MDRNPSEPERIDWKNPITWISYLYTSFVYYLWLISSHLPHLPQPQRI
FT TDDKSTEQITRDAGIPRTEIVTRGDATQTVRQVAGLGDPAPKDSSLLPPSSSFVYCNNC
FT LTPHSSQRTCSPAYVSTLSRQKSLTLLKKLKKPSSSASSTTTTTSSTVSFRAPSRASST
FT ISDASTIRPSELIAIVPSGSHVLLRVPKLDWKTESIRIKRTRMSDWMDAEQRDVMRQFD
FT EVIRSEEEDERTSRKRNGIFKDGSVRSIESLESRSR (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060380"
FT VAR_SEQ 1..119
FT /note="MVHIPSDVTPPRLCVVEKLNGENEYGYNLHAEKGRGQFVGTVDPDSPAERGG
FT LITGDRIFAVNGHSIIGENHKKVVERIKANPNRCEMLVISEEGAKWYNENNVQITLDLP
FT NIERVSPM -> MHFIDK (in isoform f)"
FT /evidence="ECO:0000305"
FT /id="VSP_060381"
FT VAR_SEQ 1..119
FT /note="MVHIPSDVTPPRLCVVEKLNGENEYGYNLHAEKGRGQFVGTVDPDSPAERGG
FT LITGDRIFAVNGHSIIGENHKKVVERIKANPNRCEMLVISEEGAKWYNENNVQITLDLP
FT NIERVSPM -> MRRNFCSLLIQGCSKSCK (in isoform g)"
FT /evidence="ECO:0000305"
FT /id="VSP_060382"
FT VAR_SEQ 119
FT /note="M -> MRNSCHPSNNSPPPSSWYAPTSYSQ (in isoform c,
FT isoform d and isoform h)"
FT /evidence="ECO:0000305"
FT /id="VSP_060383"
FT VAR_SEQ 311..378
FT /note="Missing (in isoform c, isoform i and isoform j)"
FT /evidence="ECO:0000305"
FT /id="VSP_060384"
FT VAR_SEQ 311..378
FT /note="ESSTAYDAYATPPVDSNDLMDEVFGRVNLPGVTMSSHTEVLPPTDDISSVSS
FT LSSHRESAVDVPVSHQ -> VSQNNENYGDNQTIVITTCSFLK (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_060385"
FT MUTAGEN 26..27
FT /note="GY->AA: Does not impair binding to aat-6. Abolishes
FT binding to aat-6; when associated with A-154 and A-155."
FT /evidence="ECO:0000269|PubMed:22916205"
FT MUTAGEN 154..155
FT /note="EF->AA: Highly reduces binding to aat-6. Abolishes
FT binding to aat-6; when associated with A-26 and A-27."
FT /evidence="ECO:0000269|PubMed:22916205"
SQ SEQUENCE 467 AA; 52066 MW; 68FCB98A33515930 CRC64;
MVHIPSDVTP PRLCVVEKLN GENEYGYNLH AEKGRGQFVG TVDPDSPAER GGLITGDRIF
AVNGHSIIGE NHKKVVERIK ANPNRCEMLV ISEEGAKWYN ENNVQITLDL PNIERVSPMS
KETPVFVPPP PPPTDAMPYL PRLAELNKGT PDQEFGFNLH AERGRGHFIG TVDAGGIGEK
AGLEAGQRIV GVNGQLIYPT TGHKEVVALI KKDTMKTTLL VASEDVDKYH KDHNIAYSWD
NVERVDTRPV INVETHHHHE EVSVPKSNGY DVPPLNPHSI QVNEEREISK MTTTTRTETI
TNSNSAYQYK ESSTAYDAYA TPPVDSNDLM DEVFGRVNLP GVTMSSHTEV LPPTDDISSV
SSLSSHRESA VDVPVSHQYV PSYATESHQK HEQHSQTHHH HHQHQQPSPL SNGSSHGYAA
SSTSGYDDDD IYHLSAREAR ERLRMKNRKH HLHEMSLNEK YQLVSNM
