Reviewed,
UniProtKB/Swiss-Prot Q15599 (NHRF2_HUMAN)
Last modified
November 25, 2008.
Version 82.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Na(+)/H(+) exchange regulatory cofactor NHE-RF2 Short name=NHERF-2 Alternative name(s): Tyrosine kinase activator protein 1 Short name=TKA-1 SRY-interacting protein 1 Short name=SIP-1 Solute carrier family 9 isoform A3 regulatory factor 2 NHE3 kinase A regulatory protein E3KARP Sodium-hydrogen exchanger regulatory factor 2 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 337 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | 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. May also act as scaffold protein in the nucleus. |
| Subunit structure | Homodimer, and heterodimer with SLC9A3R1. Binds PODXL and PDZK1 By similarity. Binds ADRB2, SLC9A3, P2RY1, P2YR2, SRY, RDX and LPAR2. |
| Subcellular location | Intracytoplasmic membrane; Peripheral membrane protein. Nucleus. Note= Nuclear, in a punctate pattern. |
| Tissue specificity | Widely expressed. |
| Sequence similarities | Contains 2 PDZ (DHR) domains. |
| Sequence caution | The sequence CAA90511.1 differs from that shown. Reason: Frameshift at position 309. |
Ontologies
Keywords | |
|---|---|
| Cellular component | Membrane Nucleus |
| Coding sequence diversity | Alternative splicing |
| Domain | Repeat |
| PTM | Phosphoprotein |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Biological process | protein complex assembly Traceable author statement. Source: ProtInc |
| Cellular component | cytoplasm Inferred from direct assay. Source: HPA endomembrane systemInferred from electronic annotation. Source: UniProtKB-SubCell nucleus Ref.1Traceable author statement. Source: ProtInc plasma membraneInferred from direct assay. Source: UniProtKB |
| Molecular function | protein C-terminus binding Inferred from physical interaction. Source: UniProtKB |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CFTR | P13569 | 1 | EBI-1149760,EBI-349854 | |
| LPAR2 | Q9HBW0 | 1 | EBI-1149760,EBI-765995 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q15599-1) 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. | ||||||
| Isoform 2 (identifier: Q15599-2) The sequence of this isoform differs from the canonical sequence as follows: 285-295: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 337 | 337 | Na(+)/H(+) exchange regulatory cofactor NHE-RF2 | PRO_0000096805 | |||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||
| Domain | 11 – 90 | 80 | PDZ 1 | ||||||||||||||||||||||||||||||||||
| Domain | 150 – 230 | 81 | PDZ 2 | ||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||
| Modified residue | 183 | 1 | Phosphoserine | ||||||||||||||||||||||||||||||||||
| Modified residue | 254 | 1 | Phosphoserine | ||||||||||||||||||||||||||||||||||
| Modified residue | 272 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||||||||||||
| Modified residue | 275 | 1 | Phosphoserine | ||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||
| Alternative sequence | 285 – 295 | 11 | Missing in isoform 2. | VSP_009378 | |||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||||
| Sequence conflict | 51 | 1 | Missing in CAA90511. Ref.2 | ||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||
| Beta strand | 10 – 15 | 6 | |||||||||||||||||||||||||||||||||||
| Beta strand | 23 – 27 | 5 | |||||||||||||||||||||||||||||||||||
| Beta strand | 34 – 39 | 6 | |||||||||||||||||||||||||||||||||||
| Helix | 44 – 47 | 4 | |||||||||||||||||||||||||||||||||||
| Beta strand | 54 – 59 | 6 | |||||||||||||||||||||||||||||||||||
| Helix | 69 – 77 | 9 | |||||||||||||||||||||||||||||||||||
| Beta strand | 82 – 89 | 8 | |||||||||||||||||||||||||||||||||||
| Beta strand | 150 – 155 | 6 | |||||||||||||||||||||||||||||||||||
| Beta strand | 163 – 167 | 5 | |||||||||||||||||||||||||||||||||||
| Beta strand | 169 – 179 | 11 | |||||||||||||||||||||||||||||||||||
| Helix | 184 – 188 | 5 | |||||||||||||||||||||||||||||||||||
| Beta strand | 195 – 199 | 5 | |||||||||||||||||||||||||||||||||||
| Helix | 209 – 216 | 8 | |||||||||||||||||||||||||||||||||||
| Beta strand | 219 – 228 | 10 | |||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains." Poulat F., de Santa Barbara P., Desclozeaux M., Soullier S., Moniot B., Bonneaud N., Boizet B., Berta P. J. Biol. Chem. 272:7167-7172(1997) [PubMed: 9054412] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH SRY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION. Tissue: Cervix carcinoma, Fetal brain and Testis. |
| [2] | "Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family." Reczek D., Berryman M., Bretscher A. J. Cell Biol. 139:169-179(1997) [PubMed: 9314537] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta. |
| [3] | "cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein." Yun C.H.C., Oh S., Zizak M., Steplock D., Tsao S., Tse C.-M., Weinman E.J., Donowitz M. Proc. Natl. Acad. Sci. U.S.A. 94:3010-3015(1997) [PubMed: 9096337] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH SLC9A3, TISSUE SPECIFICITY. Tissue: Embryo. |
| [4] | "Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes." Imai K., Sarker A.H., Akiyama K., Ikeda S., Yao M., Tsutsui K., Shohmori T., Seki S. Gene 222:287-295(1998) [PubMed: 9831664] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [5] | "A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins." Hall R.A., Ostedgaard L.S., Premont R.T., Blitzer J.T., Rahman N., Welsh M.J., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 95:8496-8501(1998) [PubMed: 9671706] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH ADRB2; P2RY1 AND P2YR2. Tissue: Lung. |
| [6] | "The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. Pennacchio L.A.Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney and Testis. |
| [8] | "cAMP-induced phosphorylation and inhibition of Na(+)/H(+) exchanger 3 (NHE3) are dependent on the presence but not the phosphorylation of NHE regulatory factor." Zizak M., Lamprecht G., Steplock D., Tariq N., Shenolikar S., Donowitz M., Yun C.H.C., Weinman E.J. J. Biol. Chem. 274:24753-24758(1999) [PubMed: 10455146] [Abstract] Cited for: FUNCTION, INTERACTION WITH SLC9A3. |
| [9] | "NHERF2 specifically interacts with LPA2 receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-beta3 activation." Oh Y.-S., Jo N.W., Choi J.W., Kim H.S., Seo S.-W., Kang K.-O., Hwang J.-I., Heo K., Kim S.-H., Kim Y.-H., Kim I.-H., Kim J.H., Banno Y., Ryu S.H., Suh P.-G. Mol. Cell. Biol. 24:5069-5079(2004) [PubMed: 15143197] [Abstract] Cited for: INTERACTION WITH LPAR2. |
| [10] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275, MASS SPECTROMETRY. Tissue: Epithelium. |
| [11] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183 AND SER-254, MASS SPECTROMETRY. |
| [12] | "Structural basis for NHERF recognition by ERM proteins." Terawaki S., Maesaki R., Hakoshima T. Structure 14:777-789(2006) [PubMed: 16615918] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 310-337 IN COMPLEX WITH RDX. |
| [13] | "The crystal structure of the first and second PDZ domain of human NHERF-2 (SLC9A3R2) interacting with a mode 1 PDZ binding motif." Structural genomics consortium (SGC) Submitted (JAN-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 9-232. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. BC014513 mRNA. Translation: AAH14513.2. Different initiation. BC106001 mRNA. Translation: AAI06002.1. | |||||||||||||||||||||||||
| PIR | G01158. | ||||||||||||||||||||||||
| RefSeq | NP_001123484.1. NP_004776.3. | ||||||||||||||||||||||||
| UniGene | Hs.440896 | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
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| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| DIP | DIP:29093N. | ||||||||||||||||||||||||
| IntAct | Q15599. | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | Q15599. | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENSG00000065054. Homo sapiens. [Contig view] | ||||||||||||||||||||||||
| GeneID | 9351. | ||||||||||||||||||||||||
| KEGG | hsa:9351. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| H-InvDB | HIX0012710. | ||||||||||||||||||||||||
| HGNC | HGNC:11076. SLC9A3R2. | ||||||||||||||||||||||||
| HPA | HPA001672. | ||||||||||||||||||||||||
| MIM | 606553. gene. | ||||||||||||||||||||||||
| PharmGKB | PA35932. | ||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||
| GeneCards | Search... | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| HOVERGEN | Q15599. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| CleanEx | HS_SLC9A3R2. | ||||||||||||||||||||||||
| GermOnline | ENSG00000065054. Homo sapiens. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR015098. EBP50_C-term. IPR017300. NaH_exchngr_reg_CF_NHE-RF. IPR001478. PDZ. [Graphical view] | ||||||||||||||||||||||||
| Pfam | PF09007. EBP50_C-term. 1 hit. PF00595. PDZ. 2 hits. [Graphical view] | ||||||||||||||||||||||||
| PIRSF | PIRSF037866. EBP50. 1 hit. | ||||||||||||||||||||||||
| SMART | SM00228. PDZ. 2 hits. [Graphical view] | ||||||||||||||||||||||||
| PROSITE | PS50106. PDZ. 2 hits. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||
| NextBio | 35017. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | NHRF2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q15599 Secondary accession number(s): O00272, O00556, Q3KQY7 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 16 Human chromosome 16: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |
| SIMILARITY comments Index of protein domains and families |

Clusters with


