Q9UBY0 (SL9A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium/hydrogen exchanger 2

Alternative name(s):
Na(+)/H(+) exchanger 2
Short name=NHE-2
Solute carrier family 9 member 2

Gene names

Name:	SLC9A2
Synonyms:	NHE2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	812 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Seems to play an important role in colonic sodium absorption.
Subunit structure	Interacts with CHP1 and CHP2 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in skeletal muscle, colon and kidney. Lower levels in the testis, prostate, ovary, and small intestine.
Post-translational modification	Phosphorylated (Possible).
Sequence similarities	Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]
Caution	The number, localization and denomination of hydrophobic domains in the Na+/H+ exchangers vary among authors.

Ontologies

Keywords
Biological process	Antiport Ion transport Sodium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein localization Inferred from electronic annotation. Source: Compara regulation of pH Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Traceable author statement PubMed 7683411. Source: ProtInc plasma membrane Traceable author statement. Source: Reactome
Molecular_function	sodium:hydrogen antiporter activity Traceable author statement PubMed 7683411. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 812	812	Sodium/hydrogen exchanger 2		PRO_0000052352
Regions
	Topological domain	1 – 13	13	Cytoplasmic Potential
	Intramembrane	14 – 33	20	Name=A/M1; By similarity
	Topological domain	34 – 79	46	Cytoplasmic Potential
	Intramembrane	80 – 100	21	Name=B/M2; By similarity
	Topological domain	101 – 106	6	Cytoplasmic Potential
	Transmembrane	107 – 127	21	Helical; Name=C/M3; Potential
	Topological domain	128 – 138	11	Extracellular Potential
	Transmembrane	139 – 159	21	Helical; Name=D/M4; Potential
	Topological domain	160 – 168	9	Cytoplasmic Potential
	Transmembrane	169 – 189	21	Helical; Name=E/M5; Potential
	Topological domain	190 – 208	19	Extracellular Potential
	Transmembrane	209 – 229	21	Helical; Name=F/M5A; Potential
	Topological domain	230 – 236	7	Cytoplasmic Potential
	Transmembrane	237 – 257	21	Helical; Name=G/M5B; Potential
	Topological domain	258 – 277	20	Extracellular Potential
	Transmembrane	278 – 298	21	Helical; Name=H/M6; Potential
	Topological domain	299 – 307	9	Cytoplasmic Potential
	Transmembrane	308 – 328	21	Helical; Name=I/M7; Potential
	Topological domain	329 – 360	32	Extracellular Potential
	Transmembrane	361 – 381	21	Helical; Name=J/M8; Potential
	Topological domain	382 – 391	10	Cytoplasmic Potential
	Transmembrane	392 – 412	21	Helical; Name=K/M9; Potential
	Topological domain	413 – 429	17	Extracellular Potential
	Intramembrane	430 – 450	21	Name=L; By similarity
	Topological domain	451 – 458	8	Extracellular Potential
	Transmembrane	459 – 479	21	Helical; Name=M13; Potential
	Topological domain	480 – 812	333	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	350	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	299	1	T → S in a breast cancer sample; somatic mutation. Ref.5		VAR_035964
	Natural variant	806	1	R → Q in a breast cancer sample; somatic mutation. Ref.5		VAR_035965

Sequences

	Sequence		Length	Mass (Da)
	Q9UBY0 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 17EE177DC3830D0A	FASTA	812	91,520
	10 20 30 40 50 60 MEPLGNWRSL RAPLPPMLLL LLLQVAGPVG ALAETLLNAP RAMGTSSSPP SPASVVAPGT 70 80 90 100 110 120 TLFEESRLPV FTLDYPHVQI PFEITLWILL ASLAKIGFHL YHKLPTIVPE SCLLIMVGLL 130 140 150 160 170 180 LGGIIFGVDE KSPPAMKTDV FFLYLLPPIV LDAGYFMPTR PFFENIGTIF WYAVVGTLWN 190 200 210 220 230 240 SIGIGVSLFG ICQIEAFGLS DITLLQNLLF GSLISAVDPV AVLAVFENIH VNEQLYILVF 250 260 270 280 290 300 GESLLNDAVT VVLYNLFKSF CQMKTIETID VFAGIANFFV VGIGGVLIGI FLGFIAAFTT 310 320 330 340 350 360 RFTHNIRVIE PLFVFLYSYL SYITAEMFHL SGIMAITACA MTMNKYVEEN VSQKSYTTIK 370 380 390 400 410 420 YFMKMLSSVS ETLIFIFMGV STVGKNHEWN WAFVCFTLAF CLMWRALGVF VLTQVINRFR 430 440 450 460 470 480 TIPLTFKDQF IIAYGGLRGA ICFALVFLLP AAVFPRKKLF ITAAIVVIFF TVFILGITIR 490 500 510 520 530 540 PLVEFLDVKR SNKKQQAVSE EIYCRLFDHV KTGIEDVCGH WGHNFWRDKF KKFDDKYLRK 550 560 570 580 590 600 LLIRENQPKS SIVSLYKKLE IKHAIEMAET GMISTVPTFA SLNDCREEKI RKVTSSETDE 610 620 630 640 650 660 IRELLSRNLY QIRQRTLSYN RHSLTADTSE RQAKEILIRR RHSLRESIRK DSSLNREHRA 670 680 690 700 710 720 STSTSRYLSL PKNTKLPEKL QKRRTISIAD GNSSDSDADA GTTVLNLQPR ARRFLPEQFS 730 740 750 760 770 780 KKSPQSYKME WKNEVDVDSG RDMPSTPPTP HSREKGTQTS GLLQQPLLSK DQSGSEREDS 790 800 810 LTEGIPPKPP PRLVWRASEP GSRKARFGSE KP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, tissue distribution, and functional expression of the human Na(+)/H(+) exchanger NHE2." Malakooti J., Dahdal R.Y., Schmidt L., Layden T.J., Dudeja P.K., Ramaswamy K. Am. J. Physiol. 277:G383-G390(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Colon.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[5]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-299 AND GLN-806.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF073299 mRNA. Translation: AAD41635.1. AC007239 Genomic DNA. Translation: AAF19248.1. CH471127 Genomic DNA. Translation: EAX01789.1. BC136377 mRNA. Translation: AAI36378.1. BC136378 mRNA. Translation: AAI36379.1.
IPI	IPI00002841.
RefSeq	NP_003039.2. NM_003048.3.
UniGene	Hs.250083.
3D structure databases
ProteinModelPortal	Q9UBY0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBY0. 1 interaction.
STRING	9606.ENSP00000233969.
PTM databases
PhosphoSite	Q9UBY0.
Polymorphism databases
DMDM	19924293.
Proteomic databases
PaxDb	Q9UBY0.
PRIDE	Q9UBY0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000233969; ENSP00000233969; ENSG00000115616.
GeneID	6549.
KEGG	hsa:6549.
UCSC	uc002tca.3. human.
Organism-specific databases
CTD	6549.
GeneCards	GC02P103236.
HGNC	HGNC:11072. SLC9A2.
HPA	HPA035121.
MIM	600530. gene.
neXtProt	NX_Q9UBY0.
PharmGKB	PA35929.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0025.
HOGENOM	HOG000247044.
HOVERGEN	HBG052615.
InParanoid	Q9UBY0.
KO	K14722.
OMA	FTHNIRV.
OrthoDB	EOG4Z36DC.
PhylomeDB	Q9UBY0.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
Bgee	Q9UBY0.
CleanEx	HS_SLC9A2.
Genevestigator	Q9UBY0.
GermOnline	ENSG00000115616. Homo sapiens.
Family and domain databases
InterPro	IPR006153. Cation/H_exchanger. IPR018422. Cation/H_exchanger_CPA1. IPR001953. Na/H_exchanger_2. IPR004709. NaH_exchanger. [Graphical view]
PANTHER	PTHR10110. PTHR10110. 1 hit.
Pfam	PF00999. Na_H_Exchanger. 1 hit. [Graphical view]
PRINTS	PR01084. NAHEXCHNGR. PR01086. NAHEXCHNGR2.
TIGRFAMs	TIGR00840. b_cpa1. 1 hit.
ProtoNet	Search...
Other
BindingDB	Q9UBY0.
ChEMBL	CHEMBL3133.
GenomeRNAi	6549.
NextBio	25489.
SOURCE	Search...

Entry information

Entry name

SL9A2_HUMAN

Accession

Primary (citable) accession number: Q9UBY0
Secondary accession number(s): B2RMS2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.