Q02094 (RHAG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ammonium transporter Rh type A

Alternative name(s):
Erythrocyte membrane glycoprotein Rh50
Erythrocyte plasma membrane 50 kDa glycoprotein
Short name=Rh50A
Rhesus blood group family type A glycoprotein
Short name=Rh family type A glycoprotein
Short name=Rh type A glycoprotein
Rhesus blood group-associated ammonia channel
Rhesus blood group-associated glycoprotein
CD_antigen=CD241

Gene names

Name:	RHAG
Synonyms:	RH50

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	409 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Associated with rhesus blood group antigen expression. May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane. Ref.8 Ref.9
Subunit structure	Heterotetramer.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Erythrocytes. Ref.6
Involvement in disease	Regulator type Rh-null hemolytic anemia (RHN) [MIM:268150]: Form of chronic hemolytic anemia in which the red blood cells have a stomatocytosis and spherocytosis morphology, an increased osmotic fragility, an altered ion transport system, and abnormal membrane phospholipid organization. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily. [View classification]

Ontologies

Keywords
Biological process	Ammonia transport Transport
Cellular component	Membrane
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	bicarbonate transport Traceable author statement. Source: Reactome carbon dioxide transport Inferred from direct assay PubMed 16574458PubMed 17712059PubMed 19273840. Source: UniProtKB cellular ion homeostasis Inferred from direct assay PubMed 15856280. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ammonia transmembrane transporter activity Inferred from direct assay PubMed 19273840. Source: UniProtKB ammonium transmembrane transporter activity Inferred from direct assay PubMed 15856280PubMed 15929723PubMed 16866382PubMed 17712059. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 409	409	Ammonium transporter Rh type A		PRO_0000168199
Regions
	Topological domain	1 – 2	2	Cytoplasmic Potential
	Transmembrane	3 – 23	21	Helical; Potential
	Topological domain	24 – 51	28	Extracellular Potential
	Transmembrane	52 – 72	21	Helical; Potential
	Topological domain	73 – 79	7	Cytoplasmic Potential
	Transmembrane	80 – 100	21	Helical; Potential
	Topological domain	101 – 113	13	Extracellular Potential
	Transmembrane	114 – 134	21	Helical; Potential
	Topological domain	135 – 142	8	Cytoplasmic Potential
	Transmembrane	143 – 163	21	Helical; Potential
	Topological domain	164 – 167	4	Extracellular Potential
	Transmembrane	168 – 188	21	Helical; Potential
	Topological domain	189 – 208	20	Cytoplasmic Potential
	Transmembrane	209 – 229	21	Helical; Potential
	Topological domain	230 – 239	10	Extracellular Potential
	Transmembrane	240 – 260	21	Helical; Potential
	Topological domain	261 – 268	8	Cytoplasmic Potential
	Transmembrane	269 – 291	23	Helical; Potential
	Topological domain	292 – 295	4	Extracellular Potential
	Transmembrane	296 – 318	23	Helical; Potential
	Topological domain	319 – 332	14	Cytoplasmic Potential
	Transmembrane	333 – 353	21	Helical; Potential
	Topological domain	354 – 362	9	Extracellular Potential
	Transmembrane	363 – 383	21	Helical; Potential
	Topological domain	384 – 409	26	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	37	1	N-linked (GlcNAc...) Potential
	Glycosylation	355	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	79	1	S → N in RHN. Ref.11		VAR_006921
	Natural variant	242	1	N → D. Ref.1 Corresponds to variant rs1058063 [ dbSNP | Ensembl ].		VAR_047999
	Natural variant	270	1	V → I in RHN. Ref.3 Ref.14 Corresponds to variant rs16879498 [ dbSNP | Ensembl ].		VAR_015855
	Natural variant	279	1	G → E in RHN. Ref.12 Ref.13 Corresponds to variant rs28933991 [ dbSNP | Ensembl ].		VAR_015856
	Natural variant	280	1	G → R in RHN. Ref.14		VAR_015857
	Natural variant	380	1	G → V in RHN. Ref.14		VAR_015858
Experimental info
	Sequence conflict	2	1	R → C AA sequence Ref.7
	Sequence conflict	37	1	N → P AA sequence Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q02094 [UniParc]. Last modified December 16, 2008. Version 2. Checksum: F6F024399CC0C88D	FASTA	409	44,198
	10 20 30 40 50 60 MRFTFPLMAI VLEIAMIVLF GLFVEYETDQ TVLEQLNITK PTDMGIFFEL YPLFQDVHVM 70 80 90 100 110 120 IFVGFGFLMT FLKKYGFSSV GINLLVAALG LQWGTIVQGI LQSQGQKFNI GIKNMINADF 130 140 150 160 170 180 SAATVLISFG AVLGKTSPTQ MLIMTILEIV FFAHNEYLVS EIFKASDIGA SMTIHAFGAY 190 200 210 220 230 240 FGLAVAGILY RSGLRKGHEN EESAYYSDLF AMIGTLFLWM FWPSFNSAIA EPGDKQCRAI 250 260 270 280 290 300 VNTYFSLAAC VLTAFAFSSL VEHRGKLNMV HIQNATLAGG VAVGTCADMA IHPFGSMIIG 310 320 330 340 350 360 SIAGMVSVLG YKFLTPLFTT KLRIHDTCGV HNLHGLPGVV GGLAGIVAVA MGASNTSMAM 370 380 390 400 QAAALGSSIG TAVVGGLMTG LILKLPLWGQ PSDQNCYDDS VYWKVPKTR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of cDNA clones for a 50 kDa glycoprotein of the human erythrocyte membrane associated with Rh (rhesus) blood-group antigen expression." Ridgwell K., Spurr N.K., Laguda B., Macgeoch C., Avent N.D., Tanner M.J.A. Biochem. J. 287:223-228(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-242. Tissue: Bone marrow and Liver.
[2]	"The human Rh50 glycoprotein gene. Structural organization and associated splicing defect resulting in Rh(null) disease." Huang C.-H. J. Biol. Chem. 273:2207-2213(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-270. Tissue: Heart.
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Identification of 5' flanking sequence of RH50 gene and the core region for erythroid-specific expression." Iwamoto S., Omi T., Yamasaki M., Okuda H., Kawano M., Kajii E. Biochem. Biophys. Res. Commun. 243:233-240(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-52, TISSUE SPECIFICITY.
[7]	"Protein-sequence studies on Rh-related polypeptides suggest the presence of at least two groups of proteins which associate in the human red-cell membrane." Avent N.D., Ridgwell K., Mawby W.J., Tanner M.J.A., Anstee D.J., Kumpel B. Biochem. J. 256:1043-1046(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-39.
[8]	"The human Rhesus-associated RhAG protein and a kidney homologue promote ammonium transport in yeast." Marini A.-M., Matassi G., Raynal V., Andre B., Cartron J.-P., Cherif-Zahar B. Nat. Genet. 26:341-344(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Identification of the erythrocyte Rh blood group glycoprotein as a mammalian ammonium transporter." Westhoff C.M., Ferreri-Jacobia M., Mak D.-O.D., Foskett J.K. J. Biol. Chem. 277:12499-12502(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Mechanism of genetic complementation of ammonium transport in yeast by human erythrocyte Rh-associated glycoprotein." Westhoff C.M., Siegel D.L., Burd C.G., Foskett J.K. J. Biol. Chem. 279:17443-17448(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[11]	"Candidate gene acting as a suppressor of the RH locus in most cases of Rh-deficiency." Cherif-Zahar B., Raynal V., Gane P., Mattei M.-G., Bailly P., Gibbs B., Colin Y., Cartron J.-P. Nat. Genet. 12:168-173(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RHN ASN-79.
[12]	"A novel single missense mutation identified along the RH50 gene in a composite heterozygous Rhnull blood donor of the regulator type." Hyland C.A., Cherif-Zahar B., Cowley N., Raynal V., Parkes J., Saul A., Cartron J.-P. Blood 91:1458-1463(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RHN GLU-279.
[13]	"Rh50 glycoprotein gene and rhnull disease: a silent splice donor is trans to a Gly279-->Glu missense mutation in the conserved transmembrane segment." Huang C.-H., Liu Z., Cheng G., Chen Y. Blood 92:1776-1784(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT RHN GLU-279.
[14]	"Molecular basis for Rh(null) syndrome: identification of three new missense mutations in the Rh50 glycoprotein gene." Huang C.-H., Cheng G., Liu Z., Chen Y., Reid M.E., Halverson G., Okubo Y. Am. J. Hematol. 62:25-32(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RHN ILE-270; ARG-280 AND VAL-380.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X64594 mRNA. Translation: CAA45883.1. AF031548 mRNA. Translation: AAC04247.1. AF237387 , AF237382, AF237383, AF237384, AF237385, AF237386 Genomic DNA. Translation: AAF78209.1. AK313505 mRNA. Translation: BAG36285.1. AL121950, AL590244 Genomic DNA. Translation: CAC10519.2. AL590244, AL121950 Genomic DNA. Translation: CAI13085.1. CH471081 Genomic DNA. Translation: EAX04338.1.
IPI	IPI00024094.
PIR	S29124.
RefSeq	NP_000315.2. NM_000324.2.
UniGene	Hs.120950.
3D structure databases
ProteinModelPortal	Q02094.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000360217.
Protein family/group databases
TCDB	1.A.11.4.3. ammonia transporter channel (Amt) family.
PTM databases
PhosphoSite	Q02094.
Polymorphism databases
DMDM	218511807.
Proteomic databases
PaxDb	Q02094.
PRIDE	Q02094.
Protocols and materials databases
DNASU	6005.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371175; ENSP00000360217; ENSG00000112077.
GeneID	6005.
KEGG	hsa:6005.
UCSC	uc003ozk.4. human.
Organism-specific databases
CTD	6005.
GeneCards	GC06M049619.
H-InvDB	HIX0005947.
HGNC	HGNC:10006. RHAG.
HPA	HPA055331.
MIM	180297. gene. 268150. phenotype.
neXtProt	NX_Q02094.
Orphanet	3203. Overhydrated hereditary stomatocytosis. 71275. Rh deficiency syndrome.
PharmGKB	PA34381.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG276393.
HOGENOM	HOG000007656.
HOVERGEN	HBG004374.
InParanoid	Q02094.
KO	K06580.
OMA	NEESAYY.
OrthoDB	EOG4J9N05.
PhylomeDB	Q02094.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules. REACT_20679. Amine compound SLC transporters.
Gene expression databases
ArrayExpress	Q02094.
Bgee	Q02094.
CleanEx	HS_RHAG.
Genevestigator	Q02094.
GermOnline	ENSG00000112077. Homo sapiens.
Family and domain databases
InterPro	IPR024041. NH4_transpt_AmtB-like_dom. IPR002229. RhesusRHD. [Graphical view]
Pfam	PF00909. Ammonium_transp. 1 hit. [Graphical view]
PRINTS	PR00342. RHESUSRHD.
SUPFAM	SSF111352. RH_like_transpt. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	6005.
NextBio	23423.
SOURCE	Search...

Entry information

Entry name

RHAG_HUMAN

Accession

Primary (citable) accession number: Q02094
Secondary accession number(s): B2R8T8 , O43514, Q7L8L3, Q9H454

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	December 16, 2008
Last modified:	May 1, 2013
This is version 111 of the entry and version 2 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.