Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Na(+)/H(+) exchange regulatory cofactor NHE-RF2

Gene

SLC9A3R2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 cAMP-mediated phosphorylation and inhibition of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the nucleus.3 Publications

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • phosphatase binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • receptor binding Source: UniProtKB

GO - Biological processi

  • protein complex assembly Source: ProtInc
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000065054-MONOMER.

Protein family/group databases

TCDBi8.A.24.1.2. the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Na(+)/H(+) exchange regulatory cofactor NHE-RF2
Short name:
NHERF-2
Alternative name(s):
NHE3 kinase A regulatory protein E3KARP
SRY-interacting protein 1
Short name:
SIP-1
Sodium-hydrogen exchanger regulatory factor 2
Solute carrier family 9 isoform A3 regulatory factor 2
Tyrosine kinase activator protein 1
Short name:
TKA-1
Gene namesi
Name:SLC9A3R2
Synonyms:NHERF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:11076. SLC9A3R2.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • cell-cell adherens junction Source: BHF-UCL
  • endomembrane system Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • nucleus Source: ProtInc
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi9351.
OpenTargetsiENSG00000065054.
PharmGKBiPA35932.

Polymorphism and mutation databases

BioMutaiSLC9A3R2.
DMDMi42559433.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000968051 – 337Na(+)/H(+) exchange regulatory cofactor NHE-RF2Add BLAST337

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei130PhosphoserineBy similarity1
Modified residuei183PhosphoserineCombined sources1
Modified residuei254PhosphoserineCombined sources1
Modified residuei269PhosphoserineBy similarity1
Modified residuei280PhosphoserineCombined sources1
Modified residuei303PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ15599.
MaxQBiQ15599.
PaxDbiQ15599.
PeptideAtlasiQ15599.
PRIDEiQ15599.

PTM databases

iPTMnetiQ15599.
PhosphoSitePlusiQ15599.

Expressioni

Tissue specificityi

Widely expressed.2 Publications

Gene expression databases

BgeeiENSG00000065054.
CleanExiHS_SLC9A3R2.
ExpressionAtlasiQ15599. baseline and differential.
GenevisibleiQ15599. HS.

Organism-specific databases

HPAiHPA001672.

Interactioni

Subunit structurei

Homodimer, and heterodimer with SLC9A3R1. Binds PDZK1. Found in a complex with EZR, PODXL and SLC9A3R2 (By similarity). Interacts (via the PDZ domains) with PODXL (via the C-terminal PDZ-binding motif DTHL); interaction is detected in glomerular epithelium cells (By similarity). Binds ADRB2, SLC9A3, P2RY1, P2YR2, SRY, RDX and LPAR2. Interacts with MCC and PODXL. Interacts with SGK1 and KCNJ1/ROMK1. Interacts (via the PDZ domains) with SLC26A6 isoform 4 and isoform 5.By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CFTRP135697EBI-1149760,EBI-349854
LPAR2Q9HBW02EBI-1149760,EBI-765995
mGluR1aQ9R0W02EBI-1149760,EBI-8505383From a different organism.
PTENP604845EBI-1149760,EBI-696162
SLC26A3P408795EBI-1149760,EBI-8542350

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • phosphatase binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114754. 51 interactors.
DIPiDIP-29093N.
IntActiQ15599. 40 interactors.
MINTiMINT-126664.
STRINGi9606.ENSP00000408005.

Structurei

Secondary structure

1337
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi10 – 15Combined sources6
Beta strandi23 – 27Combined sources5
Beta strandi34 – 39Combined sources6
Helixi44 – 47Combined sources4
Beta strandi55 – 59Combined sources5
Helixi69 – 78Combined sources10
Beta strandi82 – 88Combined sources7
Beta strandi150 – 155Combined sources6
Beta strandi163 – 167Combined sources5
Beta strandi169 – 179Combined sources11
Helixi184 – 188Combined sources5
Beta strandi195 – 199Combined sources5
Helixi209 – 216Combined sources8
Beta strandi219 – 228Combined sources10
Helixi327 – 336Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D11X-ray2.81E/F/G/H310-337[»]
2HE4X-ray1.45A147-228[»]
2OCSX-ray1.50A9-91[»]
4P0CX-ray1.34A9-90[»]
ProteinModelPortaliQ15599.
SMRiQ15599.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15599.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 90PDZ 1PROSITE-ProRule annotationAdd BLAST80
Domaini150 – 230PDZ 2PROSITE-ProRule annotationAdd BLAST81

Sequence similaritiesi

Contains 2 PDZ (DHR) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410ITAC. Eukaryota.
ENOG4111V58. LUCA.
GeneTreeiENSGT00530000062999.
HOGENOMiHOG000089940.
HOVERGENiHBG052616.
InParanoidiQ15599.
KOiK13358.
OMAiNVEQETH.
OrthoDBiEOG091G086H.
PhylomeDBiQ15599.
TreeFamiTF350449.

Family and domain databases

Gene3Di2.30.42.10. 2 hits.
InterProiIPR015098. EBP50_C-term.
IPR017300. NHERF-1/NHERF-2.
IPR031197. NHERF-2.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR14191:SF4. PTHR14191:SF4. 1 hit.
PfamiPF09007. EBP50_C. 2 hits.
PF00595. PDZ. 2 hits.
[Graphical view]
PIRSFiPIRSF037866. EBP50. 1 hit.
ProDomiPD283022. EBP50_C-term. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00228. PDZ. 2 hits.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 2 hits.
PROSITEiPS50106. PDZ. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15599-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAAPEPLRPR LCRLVRGEQG YGFHLHGEKG RRGQFIRRVE PGSPAEAAAL
60 70 80 90 100
RAGDRLVEVN GVNVEGETHH QVVQRIKAVE GQTRLLVVDQ ETDEELRRRQ
110 120 130 140 150
LTCTEEMAQR GLPPAHDPWE PKPDWAHTGS HSSEAGKKDV SGPLRELRPR
160 170 180 190 200
LCHLRKGPQG YGFNLHSDKS RPGQYIRSVD PGSPAARSGL RAQDRLIEVN
210 220 230 240 250
GQNVEGLRHA EVVASIKARE DEARLLVVDP ETDEHFKRLR VTPTEEHVEG
260 270 280 290 300
PLPSPVTNGT SPAQLNGGSA CSSRSDLPGS DKDTEDGSAW KQDPFQESGL
310 320 330
HLSPTAAEAK EKARAMRVNK RAPQMDWNRK REIFSNF
Length:337
Mass (Da):37,414
Last modified:February 16, 2004 - v2
Checksum:i4F5D341590D22ED7
GO
Isoform 2 (identifier: Q15599-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     286-296: Missing.

Show »
Length:326
Mass (Da):36,153
Checksum:i59EB725D61D896DC
GO
Isoform 3 (identifier: Q15599-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MAAPEPLRPRLCRLVRGEQGYGFHLHG → MARSGSATPPARAPGAPPRSPPQRLVQ
     28-138: Missing.

Note: No experimental confirmation available.
Show »
Length:226
Mass (Da):24,718
Checksum:i51D77F534CB2328A
GO

Sequence cautioni

The sequence AAH14513 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAA90511 differs from that shown. Reason: Frameshift at position 309.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51Missing in CAA90511 (PubMed:9314537).Curated1
Sequence conflicti180D → Y in BM920873 (PubMed:15489334).Curated1
Sequence conflicti334 – 336FSN → LQH in BM920873 (PubMed:15489334).Curated3

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0468491 – 27MAAPE…FHLHG → MARSGSATPPARAPGAPPRS PPQRLVQ in isoform 3. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_04685028 – 138Missing in isoform 3. 1 PublicationAdd BLAST111
Alternative sequenceiVSP_009378286 – 296Missing in isoform 2. 1 PublicationAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82108 mRNA. Translation: AAB53042.1.
Z50150 mRNA. Translation: CAA90511.1. Frameshift.
AF004900 mRNA. Translation: AAC63061.1.
AF035771 mRNA. Translation: AAC52090.1.
AB014460 Genomic DNA. Translation: BAA32696.1.
AB016243 Genomic DNA. Translation: BAA33216.1.
AC005600 Genomic DNA. Translation: AAC34208.1.
AC093513 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85563.1.
CH471112 Genomic DNA. Translation: EAW85564.1.
CH471112 Genomic DNA. Translation: EAW85565.1.
CH471112 Genomic DNA. Translation: EAW85566.1.
BC014513 mRNA. Translation: AAH14513.2. Different initiation.
BC106001 mRNA. Translation: AAI06002.1.
BM920873 mRNA. No translation available.
CCDSiCCDS45382.1. [Q15599-1]
CCDS45383.1. [Q15599-2]
CCDS58407.1. [Q15599-3]
PIRiG01158.
RefSeqiNP_001123484.1. NM_001130012.2. [Q15599-1]
NP_001239002.1. NM_001252073.1. [Q15599-3]
NP_004776.3. NM_004785.5. [Q15599-2]
UniGeneiHs.440896.

Genome annotation databases

EnsembliENST00000424542; ENSP00000408005; ENSG00000065054. [Q15599-1]
ENST00000432365; ENSP00000402857; ENSG00000065054. [Q15599-2]
ENST00000566198; ENSP00000456895; ENSG00000065054. [Q15599-3]
GeneIDi9351.
KEGGihsa:9351.
UCSCiuc002coi.3. human. [Q15599-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82108 mRNA. Translation: AAB53042.1.
Z50150 mRNA. Translation: CAA90511.1. Frameshift.
AF004900 mRNA. Translation: AAC63061.1.
AF035771 mRNA. Translation: AAC52090.1.
AB014460 Genomic DNA. Translation: BAA32696.1.
AB016243 Genomic DNA. Translation: BAA33216.1.
AC005600 Genomic DNA. Translation: AAC34208.1.
AC093513 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85563.1.
CH471112 Genomic DNA. Translation: EAW85564.1.
CH471112 Genomic DNA. Translation: EAW85565.1.
CH471112 Genomic DNA. Translation: EAW85566.1.
BC014513 mRNA. Translation: AAH14513.2. Different initiation.
BC106001 mRNA. Translation: AAI06002.1.
BM920873 mRNA. No translation available.
CCDSiCCDS45382.1. [Q15599-1]
CCDS45383.1. [Q15599-2]
CCDS58407.1. [Q15599-3]
PIRiG01158.
RefSeqiNP_001123484.1. NM_001130012.2. [Q15599-1]
NP_001239002.1. NM_001252073.1. [Q15599-3]
NP_004776.3. NM_004785.5. [Q15599-2]
UniGeneiHs.440896.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D11X-ray2.81E/F/G/H310-337[»]
2HE4X-ray1.45A147-228[»]
2OCSX-ray1.50A9-91[»]
4P0CX-ray1.34A9-90[»]
ProteinModelPortaliQ15599.
SMRiQ15599.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114754. 51 interactors.
DIPiDIP-29093N.
IntActiQ15599. 40 interactors.
MINTiMINT-126664.
STRINGi9606.ENSP00000408005.

Protein family/group databases

TCDBi8.A.24.1.2. the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family.

PTM databases

iPTMnetiQ15599.
PhosphoSitePlusiQ15599.

Polymorphism and mutation databases

BioMutaiSLC9A3R2.
DMDMi42559433.

Proteomic databases

EPDiQ15599.
MaxQBiQ15599.
PaxDbiQ15599.
PeptideAtlasiQ15599.
PRIDEiQ15599.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000424542; ENSP00000408005; ENSG00000065054. [Q15599-1]
ENST00000432365; ENSP00000402857; ENSG00000065054. [Q15599-2]
ENST00000566198; ENSP00000456895; ENSG00000065054. [Q15599-3]
GeneIDi9351.
KEGGihsa:9351.
UCSCiuc002coi.3. human. [Q15599-1]

Organism-specific databases

CTDi9351.
DisGeNETi9351.
GeneCardsiSLC9A3R2.
HGNCiHGNC:11076. SLC9A3R2.
HPAiHPA001672.
MIMi606553. gene.
neXtProtiNX_Q15599.
OpenTargetsiENSG00000065054.
PharmGKBiPA35932.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITAC. Eukaryota.
ENOG4111V58. LUCA.
GeneTreeiENSGT00530000062999.
HOGENOMiHOG000089940.
HOVERGENiHBG052616.
InParanoidiQ15599.
KOiK13358.
OMAiNVEQETH.
OrthoDBiEOG091G086H.
PhylomeDBiQ15599.
TreeFamiTF350449.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000065054-MONOMER.

Miscellaneous databases

EvolutionaryTraceiQ15599.
GenomeRNAii9351.
PROiQ15599.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000065054.
CleanExiHS_SLC9A3R2.
ExpressionAtlasiQ15599. baseline and differential.
GenevisibleiQ15599. HS.

Family and domain databases

Gene3Di2.30.42.10. 2 hits.
InterProiIPR015098. EBP50_C-term.
IPR017300. NHERF-1/NHERF-2.
IPR031197. NHERF-2.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR14191:SF4. PTHR14191:SF4. 1 hit.
PfamiPF09007. EBP50_C. 2 hits.
PF00595. PDZ. 2 hits.
[Graphical view]
PIRSFiPIRSF037866. EBP50. 1 hit.
ProDomiPD283022. EBP50_C-term. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00228. PDZ. 2 hits.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 2 hits.
PROSITEiPS50106. PDZ. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNHRF2_HUMAN
AccessioniPrimary (citable) accession number: Q15599
Secondary accession number(s): D3DU84
, D3DU85, H3BSV6, O00272, O00556, Q3KQY7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: February 16, 2004
Last modified: November 30, 2016
This is version 165 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.