P51811 (XK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Membrane transport protein XK

Alternative name(s):
Kell complex 37 kDa component
Kx antigen
XK-related protein 1

Gene names

Name:	XK
Synonyms:	XKR1, XRG1

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

General annotation (Comments)

Function	May be involved in sodium-dependent transport of neutral amino acids or oligopeptides.
Subunit structure	Heterodimer with Kell; disulfide-linked. Ref.7
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	High levels in skeletal muscle, heart, brain, and pancreas; low levels in placenta, lung, liver, and kidney.
Post-translational modification	Not glycosylated. Ref.6
Polymorphism	XK is responsible for the Kx blood group system.
Involvement in disease	McLeod syndrome (MLS) [MIM:300842]: A multisystem disorder characterized by the absence of red blood cell Kx antigen, weak espression of Kell red blood cell antigens, acanthocytosis, and compensated hemolysis. Most carriers of this McLeod blood group phenotype have acanthocytosis and elevated serum creatine kinase levels and are prone to develop a severe neurologic disorder resembling Huntington disease. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrythmias, and dilated cardiomyopathy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the XK family.

Ontologies

Keywords
Biological process	Amino-acid transport Transport
Cellular component	Membrane
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Molecular function	Blood group antigen
PTM	Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	amino acid transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Traceable author statement PubMed 9647734. Source: HGNC
Molecular_function	transporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 444	444	Membrane transport protein XK		PRO_0000190767
Regions
	Topological domain	1 – 2	2	Cytoplasmic Potential
	Transmembrane	3 – 23	21	Helical; Potential
	Topological domain	24 – 37	14	Extracellular Potential
	Transmembrane	38 – 58	21	Helical; Potential
	Topological domain	59 – 68	10	Cytoplasmic Potential
	Transmembrane	69 – 89	21	Helical; Potential
	Topological domain	90 – 140	51	Extracellular Potential
	Transmembrane	141 – 161	21	Helical; Potential
	Topological domain	162 – 171	10	Cytoplasmic Potential
	Transmembrane	172 – 192	21	Helical; Potential
	Topological domain	193 – 208	16	Extracellular Potential
	Transmembrane	209 – 229	21	Helical; Potential
	Topological domain	230 – 235	6	Cytoplasmic Potential
	Transmembrane	236 – 256	21	Helical; Potential
	Topological domain	257 – 277	21	Extracellular Potential
	Transmembrane	278 – 298	21	Helical; Potential
	Topological domain	299 – 317	19	Cytoplasmic Potential
	Transmembrane	318 – 338	21	Helical; Potential
	Topological domain	339 – 349	11	Extracellular Potential
	Transmembrane	350 – 370	21	Helical; Potential
	Topological domain	371 – 444	74	Cytoplasmic Potential
Amino acid modifications
	Disulfide bond	347		Interchain (with C-72 in Kell) Ref.7
Natural variations
	Natural variant	222	1	R → G in MLS. Ref.9		VAR_013817
	Natural variant	294	1	C → R in MLS. Ref.8 Corresponds to variant rs28933690 [ dbSNP | Ensembl ].		VAR_013818
	Natural variant	327	1	E → K in MLS; atypical without hematologic, neuromuscular, or cerebral involvement; protein seems functional. Ref.10		VAR_023581
Experimental info
	Mutagenesis	347	1	C → S: Loss of Kell-XK complex. Ref.7
	Sequence conflict	248	1	F → L Ref.3
	Sequence conflict	248	1	F → L Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P51811 [UniParc]. Last modified January 24, 2006. Version 5. Checksum: 6F90B0B45659A1DA	FASTA	444	50,902
	10 20 30 40 50 60 MKFPASVLAS VFLFVAETTA ALSLSSTYRS GGDRMWQALT LLFSLLPCAL VQLTLLFVHR 70 80 90 100 110 120 DLSRDRPLVL LLHLLQLGPL FRCFEVFCIY FQSGNNEEPY VSITKKRQMP KNGLSEEIEK 130 140 150 160 170 180 EVGQAEGKLI THRSAFSRAS VIQAFLGSAP QLTLQLYISV MQQDVTVGRS LLMTISLLSI 190 200 210 220 230 240 VYGALRCNIL AIKIKYDEYE VKVKPLAYVC IFLWRSFEIA TRVVVLVLFT SVLKTWVVVI 250 260 270 280 290 300 ILINFFSFFL YPWILFWCSG SPFPENIEKA LSRVGTTIVL CFLTLLYTGI NMFCWSAVQL 310 320 330 340 350 360 KIDSPDLISK SHNWYQLLVY YMIRFIENAI LLLLWYLFKT DIYMYVCAPL LVLQLLIGYC 370 380 390 400 410 420 TAILFMLVFY QFFHPCKKLF SSSVSEGFQR WLRCFCWACR QQKPCEPIGK EDLQSSRDRD 430 440 ETPSSSKTSP EPGQFLNAED LCSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein." Ho M., Chelly J., Carter N., Danek A., Crocker P., Monaco A.P. Cell 77:869-880(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Ho M. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 204-205.
[3]	"A superfamily of XK-related genes (XRG) widely expressed in vertebrates and invertebrates." Huang C.-H., Chen Y. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	SeattleSNPs variation discovery resource Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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]. Tissue: Testis.
[6]	"Purification and partial characterization of the erythrocyte Kx protein deficient in McLeod patients." Khamlichi S., Bailly P., Blanchard D., Goossens D., Cartron J.-P., Bertrand O. Eur. J. Biochem. 228:931-934(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-22, LACK OF GLYCOSYLATION.
[7]	"Association of XK and Kell blood group proteins." Russo D., Redman C., Lee S. J. Biol. Chem. 273:13950-13956(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, DISULFIDE BOND, MUTAGENESIS OF CYS-347.
[8]	"McLeod neuroacanthocytosis: genotype and phenotype." Danek A., Rubio J.P., Rampoldi L., Ho M., Dobson-Stone C., Tison F., Symmans W.A., Oechsner M., Kalckreuth W., Watt J.M., Corbett A.J., Hamdalla H.H., Marshall A.G., Sutton I., Dotti M.T., Malandrini A., Walker R.H., Daniels G., Monaco A.P. Ann. Neurol. 50:755-764(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MLS ARG-294.
[9]	"Point mutations causing the McLeod phenotype." Russo D.C., Lee S., Reid M.E., Redman C.M. Transfusion 42:287-293(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MLS GLY-222.
[10]	"McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement." Jung H.H., Hergersberg M., Vogt M., Pahnke J., Treyer V., Rothlisberger B., Kollias S.S., Russo D., Frey B.M. Transfusion 43:928-938(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MLS LYS-327.
+	Additional computationally mapped references.

Web resources

GeneReviews

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z32684 mRNA. Translation: CAA83632.2. AY534238 mRNA. Translation: AAT07087.1. DQ062746 Genomic DNA. Translation: AAY43132.1. BC036019 mRNA. Translation: AAH36019.1.
IPI	IPI00020896.
PIR	I39294.
RefSeq	NP_066569.1. NM_021083.2.
UniGene	Hs.78919.
3D structure databases
ProteinModelPortal	P51811.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51811. 1 interaction.
STRING	9606.ENSP00000367879.
Protein family/group databases
TCDB	9.B.5.1.1. KX blood-group antigen (KXA) family.
PTM databases
PhosphoSite	P51811.
Polymorphism databases
DMDM	85700269.
Proteomic databases
PaxDb	P51811.
PRIDE	P51811.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378616; ENSP00000367879; ENSG00000047597. ENST00000601300; ENSP00000469825; ENSG00000269380.
GeneID	7504.
KEGG	hsa:7504.
UCSC	uc004ddq.3. human.
Organism-specific databases
CTD	7504.
GeneCards	GC0XP037545.
HGNC	HGNC:12811. XK.
HPA	HPA019036.
MIM	300842. phenotype. 314850. gene.
neXtProt	NX_P51811.
Orphanet	59306. McLeod neuroacanthocytosis syndrome.
PharmGKB	PA37410.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG149424.
HOGENOM	HOG000118070.
HOVERGEN	HBG055838.
InParanoid	P51811.
OMA	TYRSAGD.
OrthoDB	EOG40ZQXS.
PhylomeDB	P51811.
Gene expression databases
ArrayExpress	P51811.
Bgee	P51811.
CleanEx	HS_XK.
Genevestigator	P51811.
GermOnline	ENSG00000047597. Homo sapiens.
Family and domain databases
InterPro	IPR018629. Transport_prot_XK. [Graphical view]
Pfam	PF09815. XK-related. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7504.
NextBio	29381.
SOURCE	Search...

Entry information

Entry name

XK_HUMAN

Accession

Primary (citable) accession number: P51811
Secondary accession number(s): Q4TTN6, Q8IUK6, Q9UC77

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 24, 2006
Last modified:	May 1, 2013
This is version 106 of the entry and version 5 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.