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Protein

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

Gene

SLC9A3R2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 Source: BHF-UCL
  • phosphatase binding Source: UniProtKB
  • protein-containing complex scaffold activity Source: InterPro
  • protein C-terminus binding Source: UniProtKB
  • signaling receptor binding Source: UniProtKB

GO - Biological processi

  • protein-containing complex assembly Source: ProtInc

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

EuPathDBiHostDB:ENSG00000065054.13
HGNCiHGNC:11076 SLC9A3R2
MIMi606553 gene
neXtProtiNX_Q15599

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi60650
60651 [Q15599-2]

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
HPA066520

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

Show more details

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • cadherin binding Source: BHF-UCL
  • phosphatase binding Source: UniProtKB
  • protein-containing complex scaffold activity Source: InterPro
  • protein C-terminus binding Source: UniProtKB
  • signaling receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114754, 127 interactors
CORUMiQ15599
DIPiDIP-29093N
ELMiQ15599
IntActiQ15599, 52 interactors
MINTiQ15599
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

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

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR015098 EBP50_C-term
IPR017300 NHERF-1/NHERF-2
IPR031197 NHERF-2
IPR001478 PDZ
IPR036034 PDZ_sf
PANTHERiPTHR14191:SF4 PTHR14191:SF4, 1 hit
PfamiView protein in Pfam
PF09007 EBP50_C, 2 hits
PF00595 PDZ, 2 hits
PIRSFiPIRSF037866 EBP50, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD283022 EBP50_C-term, 1 hit
SMARTiView protein in SMART
SM00228 PDZ, 2 hits
SUPFAMiSSF50156 SSF50156, 2 hits
PROSITEiView protein in PROSITE
PS50106 PDZ, 2 hits

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

Similar proteinsi

Entry informationi

Entry nameiNHRF2_HUMAN
AccessioniPrimary (citable) accession number: Q15599
Secondary accession number(s): D3DU84
, D3DU85, H3BSV6, O00272, O00556, Q3KQY7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: February 16, 2004
Last modified: July 18, 2018
This is version 179 of the entry and version 2 of the sequence. See 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

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