Q9JHL1 (NHRF2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Na(+)/H(+) exchange regulatory cofactor NHE-RF2
Short name=NHERF-2

Alternative name(s):
NHE3 kinase A regulatory protein E3KARP
Octs2
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 names

Name:	Slc9a3r2
Synonyms:	Nherf2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	337 AA.
Sequence status	Complete.
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 By similarity.
Subunit structure	Homodimer, and heterodimer with SLC9A3R1. Binds PDZK1. Interacts with SRY. Binds ADRB2, SLC9A3, P2RY1, P2YR2, RDX and LPAR2 By similarity. Interacts with MCC By similarity. 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. Interacts with SGK1 and KCNJ1/ROMK1 By similarity. Ref.4 Ref.5
Subcellular location	Endomembrane system; Peripheral membrane protein By similarity. Nucleus By similarity. Apical cell membrane By similarity. Note: Localizes with EZR and PODXL at the apical cell membrane of glomerular epithelium cells and the sides of the food processes. Nuclear, in a punctate pattern By similarity.
Sequence similarities	Contains 2 PDZ (DHR) domains.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of phosphatidylinositol 3-kinase cascade Inferred from genetic interaction PubMed 16456542. Source: MGI
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 12169661. Source: MGI cytoplasm Inferred from direct assay PubMed 10410901. Source: MGI endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay PubMed 10410901. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9JHL1-1)

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: Q9JHL1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-111: Missing.
     112-138: LPPAHNPWEPKPDWACSGSLGSDTGQK → MARSRTSMLPASAPGAPPVNSQLGLTQ

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_0000096806
Regions
	Domain	11 – 91	81	PDZ 1
	Domain	151 – 231	81	PDZ 2
Amino acid modifications
	Modified residue	183	1	Phosphoserine By similarity
	Modified residue	254	1	Phosphoserine By similarity
	Modified residue	272	1	Phosphoserine Ref.6
Natural variations
	Alternative sequence	1 – 111	111	Missing in isoform 2.		VSP_009379
	Alternative sequence	112 – 138	27	LPPAH…DTGQK → MARSRTSMLPASAPGAPPVN SQLGLTQ in isoform 2.		VSP_009380
Experimental info
	Sequence conflict	4	1	P → L in BAC30366. Ref.2
	Sequence conflict	4	1	P → L in BAC35980. Ref.2
	Sequence conflict	4	1	P → L in BAC39282. Ref.2
	Sequence conflict	143	1	P → S in BAA97568. Ref.1
	Sequence conflict	143	1	P → S in BAA97569. Ref.1
	Sequence conflict	143	1	P → S in BAE41537. Ref.2
	Sequence conflict	242	1	V → I in BAC30366. Ref.2
	Sequence conflict	242	1	V → I in BAC35980. Ref.2
	Sequence conflict	242	1	V → I in BAC39282. Ref.2
	Sequence conflict	242	1	V → I in AAH65778. Ref.3
	Sequence conflict	326	1	D → A in BAB22185. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 29, 2007. Version 2. Checksum: A28ED245DE453A5F	FASTA	337	37,403
	10 20 30 40 50 60 MAAPESLRPR LCRLVRGEQG YGFHLHGEKG RRGQFIRRVE PGSPAEAAAL RAGDRLVEVN 70 80 90 100 110 120 GVNVEGETHH QVVQRIKAVE GQTQLLVVDK ETDEELCRRQ LTCTEEMAHR GLPPAHNPWE 130 140 150 160 170 180 PKPDWACSGS LGSDTGQKDV NGPPRELRPR LCHLRRGPQG YGFNLHSDKS RPGQYIRSVD 190 200 210 220 230 240 PGSPASHSGL RAQDRLIEVN GQNVEGLRHA EVVARIKAQE DEARLLVVDP ETDEHFKRLR 250 260 270 280 290 300 VVPTEEHVEG PLPSPVTNGT SPAQLNGGSV CSSRSDLPGS EKDNEDGSTW KRDPFQESGL 310 320 330 HLSPTAAEAK EKARATRVNK RAPQMDWNRK REIFSNF
	Isoform 2 [UniParc]. Checksum: 09162261FE6ABCD9	FASTA	226	24,861
	10 20 30 40 50 60 MARSRTSMLP ASAPGAPPVN SQLGLTQDVN GPPRELRPRL CHLRRGPQGY GFNLHSDKSR 70 80 90 100 110 120 PGQYIRSVDP GSPASHSGLR AQDRLIEVNG QNVEGLRHAE VVARIKAQED EARLLVVDPE 130 140 150 160 170 180 TDEHFKRLRV VPTEEHVEGP LPSPVTNGTS PAQLNGGSVC SSRSDLPGSE KDNEDGSTWK 190 200 210 220 RDPFQESGLH LSPTAAEAKE KARATRVNKR APQMDWNRKR EIFSNF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning, genomic structure and sequence analysis of the mouse mSlc9a3r2/E3karp/Sip-1/Tka-1/Octs2 gene." Sarker A.H., Akiyama K., Tsutsui K., Seki S. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). Strain: BALB/c. Tissue: Blood and Embryo.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J and NOD. Tissue: Embryonic heart, Kidney, Small intestine and Spinal cord.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Mammary gland.
[4]	"PDZK1: I. a major scaffolder in brush borders of proximal tubular cells." Gisler S.M., Pribanic S., Bacic D., Forrer P., Gantenbein A., Sabourin L.A., Tsuji A., Zhao Z.-S., Manser E., Biber J., Murer H. Kidney Int. 64:1733-1745(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDZK1.
[5]	"NHERF2/SIP-1 interacts with mouse SRY via a different mechanism than human SRY." Thevenet L., Albrecht K.H., Malki S., Berta P., Boizet-Bonhoure B., Poulat F. J. Biol. Chem. 280:38625-38630(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SRY.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB026489 mRNA. Translation: BAA97568.1. AB026490 Genomic DNA. Translation: BAA97569.1. AK002557 mRNA. Translation: BAB22185.1. AK039491 mRNA. Translation: BAC30366.1. AK075813 mRNA. Translation: BAC35980.1. AK084801 mRNA. Translation: BAC39282.1. AK170057 mRNA. Translation: BAE41537.1. BC065778 mRNA. Translation: AAH65778.1.
IPI	IPI00308063. IPI00399912.
RefSeq	NP_075542.2. NM_023055.2. NP_075938.2. NM_023449.3.
UniGene	Mm.21587.
3D structure databases
ProteinModelPortal	Q9JHL1.
SMR	Q9JHL1. Positions 9-91, 143-337.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9JHL1. 1 interaction.
MINT	MINT-152409.
PTM databases
PhosphoSite	Q9JHL1.
Proteomic databases
PaxDb	Q9JHL1.
PRIDE	Q9JHL1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000002572; ENSMUSP00000002572; ENSMUSG00000002504. ENSMUST00000019684; ENSMUSP00000019684; ENSMUSG00000002504.
GeneID	65962.
KEGG	mmu:65962.
UCSC	uc008axj.2. mouse. uc008axk.2. mouse.
Organism-specific databases
CTD	9351.
MGI	MGI:1890662. Slc9a3r2.
Phylogenomic databases
eggNOG	NOG319972.
GeneTree	ENSGT00530000062999.
HOGENOM	HOG000089940.
HOVERGEN	HBG052616.
InParanoid	Q9JHL1.
KO	K13358.
Gene expression databases
ArrayExpress	Q9JHL1.
Bgee	Q9JHL1.
Genevestigator	Q9JHL1.
GermOnline	ENSMUSG00000002504. Mus musculus.
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.
ProDom	PD283022. EBP50_C-term. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00228. PDZ. 2 hits. [Graphical view]
SUPFAM	SSF50156. PDZ. 2 hits.
PROSITE	PS50106. PDZ. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	320388.
SOURCE	Search...

Entry information

Entry name

NHRF2_MOUSE

Accession

Primary (citable) accession number: Q9JHL1
Secondary accession number(s): Q3TDR3 , Q6P074, Q8BGL9, Q8BW05, Q9DCR6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 16, 2004
Last sequence update:	May 29, 2007
Last modified:	April 3, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program