CPLM-000289

Genbank Nucleotide ID

Na(+)/H(+) exchange regulatory cofactor NHE-RF1

Protein Synonyms/Alias

NHERF-1; Ezrin-radixin-moesin-binding phosphoprotein 50; EBP50; Regulatory cofactor of Na(+)/H(+) exchanger; Sodium-hydrogen exchanger regulatory factor 1; Solute carrier family 9 isoform A3 regulatory factor 1

Homo sapiens (Human)

Position	Peptide	Type	References
32	GFHLHGEKGKLGQYI	acetylation	[1]
50	EPGSPAEKAGLLAGD	ubiquitination	[2]
101	ETDEQLQKLGVQVRE	ubiquitination	[2, 3, 4, 5]
158	RPRLCTMKKGPSGYG	ubiquitination	[5]
159	PRLCTMKKGPSGYGF	ubiquitination	[5]
351	PQMDWSKKNELFSNL	ubiquitination	[4]

[1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]

Functional Description

Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules.

DOMAIN 14 94 PDZ 1.
DOMAIN 154 234 PDZ 2.
MOD_RES 2 2 N-acetylserine.
MOD_RES 46 46 Phosphoserine.
MOD_RES 162 162 Phosphoserine.
MOD_RES 269 269 Phosphoserine.
MOD_RES 280 280 Phosphoserine.
MOD_RES 288 288 Phosphoserine (By similarity).
MOD_RES 290 290 Phosphoserine.
MOD_RES 291 291 Phosphoserine.
MOD_RES 293 293 Phosphothreonine.
MOD_RES 294 294 Phosphoserine (By similarity).
MOD_RES 302 302 Phosphoserine (By similarity).

3D-structure; Acetylation; Cell membrane; Cell projection; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Membrane; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Wnt signaling pathway.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
GO:0031526; C:brush border membrane; IEA:Compara.
GO:0005813; C:centrosome; IDA:HPA.
GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
GO:0031528; C:microvillus membrane; ISS:UniProtKB.
GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
GO:0017081; F:chloride channel regulator activity; IDA:UniProtKB.
GO:0043621; F:protein self-association; IDA:UniProtKB.
GO:0030036; P:actin cytoskeleton organization; IEA:Compara.
GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; IEA:Compara.
GO:0006915; P:apoptotic process; IDA:UniProtKB.
GO:0032782; P:bile acid secretion; ISS:UniProtKB.
GO:0030643; P:cellular phosphate ion homeostasis; IEA:Compara.
GO:0034613; P:cellular protein localization; IEA:Compara.
GO:0034635; P:glutathione transport; ISS:UniProtKB.
GO:0030033; P:microvillus assembly; IMP:UniProtKB.
GO:0030336; P:negative regulation of cell migration; IEA:Compara.
GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB.
GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase cascade; ISS:UniProtKB.
GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB.
GO:0051898; P:negative regulation of protein kinase B signaling cascade; IMP:UniProtKB.
GO:0010766; P:negative regulation of sodium ion transport; IEA:Compara.
GO:0032416; P:negative regulation of sodium:hydrogen antiporter activity; IEA:Compara.
GO:0060158; P:phospholipase C-activating dopamine receptor signaling pathway; IEA:Compara.
GO:0006461; P:protein complex assembly; TAS:ProtInc.
GO:0044062; P:regulation of excretion; IEA:Compara.
GO:0045859; P:regulation of protein kinase activity; ISS:UniProtKB.
GO:0032415; P:regulation of sodium:hydrogen antiporter activity; NAS:UniProtKB.
GO:0097291; P:renal phosphate ion absorption; IMP:UniProtKB.
GO:0003096; P:renal sodium ion transport; IEA:Compara.
GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW.

IPR015098; EBP50_C-term.
IPR017300; NaH_exchngr_reg_CF_NHE-RF.
IPR001478; PDZ.

PF09007; EBP50_C-term
PF00595; PDZ