XK_HUMAN
ID XK_HUMAN Reviewed; 444 AA.
AC P51811; Q4TTN6; Q8IUK6; Q9UC77;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 5.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Endoplasmic reticulum membrane adapter protein XK {ECO:0000305};
DE AltName: Full=Kell complex 37 kDa component {ECO:0000303|PubMed:9593744};
DE AltName: Full=Kx antigen {ECO:0000303|PubMed:8004674};
DE AltName: Full=Membrane transport protein XK {ECO:0000305};
DE AltName: Full=XK-related protein 1;
GN Name=XK {ECO:0000303|PubMed:8004674, ECO:0000312|HGNC:HGNC:12811};
GN Synonyms=XKR1, XRG1 {ECO:0000303|Ref.3};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8004674; DOI=10.1016/0092-8674(94)90136-8;
RA Ho M., Chelly J., Carter N., Danek A., Crocker P., Monaco A.P.;
RT "Isolation of the gene for McLeod syndrome that encodes a novel membrane
RT transport protein.";
RL Cell 77:869-880(1994).
RN [2]
RP SEQUENCE REVISION TO 204-205.
RA Ho M.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Huang C.-H., Chen Y.;
RT "A superfamily of XK-related genes (XRG) widely expressed in vertebrates
RT and invertebrates.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 1-22, AND LACK OF GLYCOSYLATION.
RX PubMed=7737196; DOI=10.1111/j.1432-1033.1995.0931m.x;
RA Khamlichi S., Bailly P., Blanchard D., Goossens D., Cartron J.-P.,
RA Bertrand O.;
RT "Purification and partial characterization of the erythrocyte Kx protein
RT deficient in McLeod patients.";
RL Eur. J. Biochem. 228:931-934(1995).
RN [7]
RP SUBUNIT, SUBCELLULAR LOCATION, DISULFIDE BOND, MUTAGENESIS OF CYS-347, AND
RP POLYMORPHISM.
RX PubMed=9593744; DOI=10.1074/jbc.273.22.13950;
RA Russo D., Redman C., Lee S.;
RT "Association of XK and Kell blood group proteins.";
RL J. Biol. Chem. 273:13950-13956(1998).
RN [8]
RP FUNCTION, INTERACTION WITH VPS13A, AND SUBCELLULAR LOCATION.
RX PubMed=32845802; DOI=10.1091/mbc.e19-08-0439-t;
RA Park J.S., Neiman A.M.;
RT "XK is a partner for VPS13A: a molecular link between Chorea-Acanthocytosis
RT and McLeod Syndrome.";
RL Mol. Biol. Cell 31:2425-2436(2020).
RN [9]
RP VARIANT MLS ARG-294.
RX PubMed=11761473; DOI=10.1002/ana.10035;
RA Danek A., Rubio J.P., Rampoldi L., Ho M., Dobson-Stone C., Tison F.,
RA Symmans W.A., Oechsner M., Kalckreuth W., Watt J.M., Corbett A.J.,
RA Hamdalla H.H., Marshall A.G., Sutton I., Dotti M.T., Malandrini A.,
RA Walker R.H., Daniels G., Monaco A.P.;
RT "McLeod neuroacanthocytosis: genotype and phenotype.";
RL Ann. Neurol. 50:755-764(2001).
RN [10]
RP VARIANT MLS GLY-222.
RX PubMed=11961232; DOI=10.1046/j.1537-2995.2002.00049.x;
RA Russo D.C., Lee S., Reid M.E., Redman C.M.;
RT "Point mutations causing the McLeod phenotype.";
RL Transfusion 42:287-293(2002).
RN [11]
RP VARIANT MLS LYS-327.
RX PubMed=12823753; DOI=10.1046/j.1537-2995.2003.t01-1-00434.x;
RA Jung H.H., Hergersberg M., Vogt M., Pahnke J., Treyer V., Rothlisberger B.,
RA Kollias S.S., Russo D., Frey B.M.;
RT "McLeod phenotype associated with a XK missense mutation without
RT hematologic, neuromuscular, or cerebral involvement.";
RL Transfusion 43:928-938(2003).
RN [12]
RP INVOLVEMENT IN MCLEOD SYNDROME, INTERACTION WITH VPS13A, VARIANT MLS
RP 124-GLN--ALA-444 DEL, AND VARIANT MLS 133-ARG--ALA-444 DEL.
RX PubMed=31086825; DOI=10.1212/nxg.0000000000000328;
RA Urata Y., Nakamura M., Sasaki N., Shiokawa N., Nishida Y., Arai K.,
RA Hiwatashi H., Yokoyama I., Narumi S., Terayama Y., Murakami T., Ugawa Y.,
RA Sakamoto H., Kaneko S., Nakazawa Y., Yamasaki R., Sadashima S., Sakai T.,
RA Arai H., Sano A.;
RT "Novel pathogenic XK mutations in McLeod syndrome and interaction between
RT XK protein and chorein.";
RL Neurol. Genet. 5:e328-e328(2019).
CC -!- FUNCTION: Recruits the lipid transfer protein VPS13A from lipid
CC droplets to the endoplasmic reticulum (ER) membrane.
CC {ECO:0000269|PubMed:32845802}.
CC -!- SUBUNIT: Heterodimer with Kell; disulfide-linked (PubMed:9593744).
CC Interacts with VPS13A (PubMed:32845802, PubMed:31086825).
CC {ECO:0000269|PubMed:31086825, ECO:0000269|PubMed:32845802,
CC ECO:0000269|PubMed:9593744}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:32845802, ECO:0000269|PubMed:9593744}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: High levels in skeletal muscle, heart, brain, and
CC pancreas; low levels in placenta, lung, liver, and kidney.
CC {ECO:0000269|PubMed:8004674}.
CC -!- PTM: Not glycosylated. {ECO:0000269|PubMed:7737196}.
CC -!- POLYMORPHISM: XK is responsible for the Kx blood group system.
CC {ECO:0000305|PubMed:9593744}.
CC -!- DISEASE: McLeod syndrome (MLS) [MIM:300842]: A multisystem disorder
CC characterized by the absence of red blood cell Kx antigen, weak
CC expression of Kell red blood cell antigens, acanthocytosis, and
CC compensated hemolysis. Most carriers of this McLeod blood group
CC phenotype have acanthocytosis and elevated serum creatine kinase levels
CC and are prone to develop a severe neurologic disorder resembling
CC Huntington disease. Additional symptoms include generalized seizures,
CC neuromuscular symptoms leading to weakness and atrophy, and
CC cardiomyopathy mainly manifesting with atrial fibrillation, malignant
CC arrhythmias, and dilated cardiomyopathy. {ECO:0000269|PubMed:11761473,
CC ECO:0000269|PubMed:11961232, ECO:0000269|PubMed:12823753,
CC ECO:0000269|PubMed:31086825}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the XK family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/xk/";
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DR EMBL; Z32684; CAA83632.2; -; mRNA.
DR EMBL; AY534238; AAT07087.1; -; mRNA.
DR EMBL; DQ062746; AAY43132.1; -; Genomic_DNA.
DR EMBL; BC036019; AAH36019.1; -; mRNA.
DR CCDS; CCDS14241.1; -.
DR PIR; I39294; I39294.
DR RefSeq; NP_066569.1; NM_021083.3.
DR AlphaFoldDB; P51811; -.
DR SMR; P51811; -.
DR BioGRID; 113341; 8.
DR IntAct; P51811; 1.
DR STRING; 9606.ENSP00000367879; -.
DR TCDB; 2.A.112.1.1; the kx blood-group antigen (kxa) family.
DR iPTMnet; P51811; -.
DR PhosphoSitePlus; P51811; -.
DR SwissPalm; P51811; -.
DR BioMuta; XK; -.
DR DMDM; 85700269; -.
DR EPD; P51811; -.
DR jPOST; P51811; -.
DR MassIVE; P51811; -.
DR MaxQB; P51811; -.
DR PaxDb; P51811; -.
DR PeptideAtlas; P51811; -.
DR PRIDE; P51811; -.
DR ProteomicsDB; 56407; -.
DR Antibodypedia; 10552; 162 antibodies from 26 providers.
DR DNASU; 7504; -.
DR Ensembl; ENST00000378616.5; ENSP00000367879.3; ENSG00000047597.7.
DR GeneID; 7504; -.
DR KEGG; hsa:7504; -.
DR MANE-Select; ENST00000378616.5; ENSP00000367879.3; NM_021083.4; NP_066569.1.
DR UCSC; uc004ddq.4; human.
DR CTD; 7504; -.
DR DisGeNET; 7504; -.
DR GeneCards; XK; -.
DR GeneReviews; XK; -.
DR HGNC; HGNC:12811; XK.
DR HPA; ENSG00000047597; Tissue enhanced (bone marrow, intestine, stomach).
DR MalaCards; XK; -.
DR MIM; 300842; phenotype.
DR MIM; 314850; gene.
DR neXtProt; NX_P51811; -.
DR OpenTargets; ENSG00000047597; -.
DR Orphanet; 59306; McLeod neuroacanthocytosis syndrome.
DR PharmGKB; PA37410; -.
DR VEuPathDB; HostDB:ENSG00000047597; -.
DR eggNOG; ENOG502QTTF; Eukaryota.
DR GeneTree; ENSGT00390000003231; -.
DR HOGENOM; CLU_037429_1_1_1; -.
DR InParanoid; P51811; -.
DR OMA; ICVLQQE; -.
DR OrthoDB; 768086at2759; -.
DR PhylomeDB; P51811; -.
DR TreeFam; TF331465; -.
DR PathwayCommons; P51811; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR SABIO-RK; P51811; -.
DR SignaLink; P51811; -.
DR BioGRID-ORCS; 7504; 6 hits in 700 CRISPR screens.
DR ChiTaRS; XK; human.
DR GenomeRNAi; 7504; -.
DR Pharos; P51811; Tbio.
DR PRO; PR:P51811; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P51811; protein.
DR Bgee; ENSG00000047597; Expressed in trabecular bone tissue and 152 other tissues.
DR Genevisible; P51811; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:HGNC-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IMP:UniProtKB.
DR GO; GO:0006865; P:amino acid transport; IEA:UniProtKB-KW.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0010961; P:cellular magnesium ion homeostasis; IEA:Ensembl.
DR GO; GO:0042552; P:myelination; IEA:Ensembl.
DR GO; GO:0031133; P:regulation of axon diameter; IEA:Ensembl.
DR GO; GO:0008361; P:regulation of cell size; IEA:Ensembl.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:Ensembl.
DR InterPro; IPR018629; XK-rel.
DR Pfam; PF09815; XK-related; 1.
PE 1: Evidence at protein level;
KW Amino-acid transport; Blood group antigen; Direct protein sequencing;
KW Disease variant; Disulfide bond; Endoplasmic reticulum; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..444
FT /note="Endoplasmic reticulum membrane adapter protein XK"
FT /id="PRO_0000190767"
FT TOPO_DOM 1..2
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 24..37
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..140
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..208
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..277
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..317
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 339..349
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 371..444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 408..444
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..425
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5GH61"
FT DISULFID 347
FT /note="Interchain (with C-72 in Kell)"
FT /evidence="ECO:0000269|PubMed:9593744"
FT VARIANT 124..444
FT /note="Missing (in MLS)"
FT /evidence="ECO:0000269|PubMed:31086825"
FT /id="VAR_086162"
FT VARIANT 133..444
FT /note="Missing (in MLS)"
FT /evidence="ECO:0000269|PubMed:31086825"
FT /id="VAR_086163"
FT VARIANT 222
FT /note="R -> G (in MLS)"
FT /evidence="ECO:0000269|PubMed:11961232"
FT /id="VAR_013817"
FT VARIANT 294
FT /note="C -> R (in MLS; dbSNP:rs28933690)"
FT /evidence="ECO:0000269|PubMed:11761473"
FT /id="VAR_013818"
FT VARIANT 327
FT /note="E -> K (in MLS; atypical without hematologic,
FT neuromuscular, or cerebral involvement)"
FT /evidence="ECO:0000269|PubMed:12823753"
FT /id="VAR_023581"
FT MUTAGEN 347
FT /note="C->S: Loss of Kell-XK complex."
FT /evidence="ECO:0000269|PubMed:9593744"
FT CONFLICT 248
FT /note="F -> L (in Ref. 3 and 5)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 444 AA; 50902 MW; 6F90B0B45659A1DA CRC64;
MKFPASVLAS VFLFVAETTA ALSLSSTYRS GGDRMWQALT LLFSLLPCAL VQLTLLFVHR
DLSRDRPLVL LLHLLQLGPL FRCFEVFCIY FQSGNNEEPY VSITKKRQMP KNGLSEEIEK
EVGQAEGKLI THRSAFSRAS VIQAFLGSAP QLTLQLYISV MQQDVTVGRS LLMTISLLSI
VYGALRCNIL AIKIKYDEYE VKVKPLAYVC IFLWRSFEIA TRVVVLVLFT SVLKTWVVVI
ILINFFSFFL YPWILFWCSG SPFPENIEKA LSRVGTTIVL CFLTLLYTGI NMFCWSAVQL
KIDSPDLISK SHNWYQLLVY YMIRFIENAI LLLLWYLFKT DIYMYVCAPL LVLQLLIGYC
TAILFMLVFY QFFHPCKKLF SSSVSEGFQR WLRCFCWACR QQKPCEPIGK EDLQSSRDRD
ETPSSSKTSP EPGQFLNAED LCSA
