XKR4_HUMAN
ID XKR4_HUMAN Reviewed; 650 AA.
AC Q5GH76; Q96PZ8;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=XK-related protein 4 {ECO:0000305};
DE Short=hXKR4 {ECO:0000303|PubMed:25231987};
DE Contains:
DE RecName: Full=XK-related protein 4, processed form {ECO:0000305|PubMed:33725486};
GN Name=XKR4 {ECO:0000303|PubMed:25231987, ECO:0000312|HGNC:HGNC:29394};
GN Synonyms=KIAA1889 {ECO:0000303|PubMed:11572484}, XRG4 {ECO:0000303|Ref.1};
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 146-650.
RC TISSUE=Brain;
RX PubMed=11572484; DOI=10.1093/dnares/8.4.179;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXI. The
RT complete sequences of 60 new cDNA clones from brain which code for large
RT proteins.";
RL DNA Res. 8:179-187(2001).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25231987; DOI=10.1074/jbc.m114.583419;
RA Suzuki J., Imanishi E., Nagata S.;
RT "Exposure of phosphatidylserine by Xk-related protein family members during
RT apoptosis.";
RL J. Biol. Chem. 289:30257-30267(2014).
RN [4]
RP FUNCTION, SUBUNIT, INTERACTION WITH XRCC4, AND ACTIVITY REGULATION.
RX PubMed=33725486; DOI=10.1016/j.molcel.2021.02.025;
RA Maruoka M., Zhang P., Mori H., Imanishi E., Packwood D.M., Harada H.,
RA Kosako H., Suzuki J.;
RT "Caspase cleavage releases a nuclear protein fragment that stimulates
RT phospholipid scrambling at the plasma membrane.";
RL Mol. Cell 81:1397-1410(2021).
CC -!- FUNCTION: [XK-related protein 4, processed form]: Phospholipid
CC scramblase that promotes phosphatidylserine exposure on apoptotic cell
CC surface (PubMed:25231987, PubMed:33725486). Phosphatidylserine is a
CC specific marker only present at the surface of apoptotic cells and acts
CC as a specific signal for engulfment (PubMed:25231987, PubMed:33725486).
CC {ECO:0000269|PubMed:25231987, ECO:0000269|PubMed:33725486}.
CC -!- CATALYTIC ACTIVITY: [XK-related protein 4, processed form]:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-
CC sn-glycero-3-phospho-L-serine(out); Xref=Rhea:RHEA:38663,
CC ChEBI:CHEBI:57262; Evidence={ECO:0000305|PubMed:25231987};
CC -!- ACTIVITY REGULATION: Phospholipid scramblase activity is activated upon
CC caspase cleavage to generate the XK-related protein 4, processed form
CC (By similarity). Does not act prior the onset of apoptosis (By
CC similarity). {ECO:0000250|UniProtKB:Q5GH67}.
CC -!- ACTIVITY REGULATION: [XK-related protein 4, processed form]:
CC Homodimerizes upon caspase cleavage (By similarity). Phospholipid
CC scramblase activity is activated following interaction with the
CC processed C-terminus of XRCC4 (protein XRCC4, C-terminus)
CC (PubMed:33725486). {ECO:0000250|UniProtKB:Q5GH67,
CC ECO:0000269|PubMed:33725486}.
CC -!- SUBUNIT: [XK-related protein 4, processed form]: Homodimer;
CC homodimerization takes place upon caspase cleavage (PubMed:33725486).
CC Interacts with the processed C-terminus of XRCC4 (protein XRCC4, C-
CC terminus); interaction promotes the phospholipid scramblase activity
CC (PubMed:33725486). {ECO:0000269|PubMed:33725486}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q5GH67};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- PTM: [XK-related protein 4, processed form]: Undergoes proteolytic
CC processing by caspase-3 (CASP3), caspase-6 (CASP6) and caspase-7
CC (CASP7) to generate the XK-related protein 4, processed form, leading
CC to its activation. {ECO:0000250|UniProtKB:Q5GH67}.
CC -!- SIMILARITY: Belongs to the XK family. {ECO:0000305}.
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DR EMBL; AY534241; AAT07090.1; -; mRNA.
DR EMBL; AB067476; BAB67782.1; -; mRNA.
DR CCDS; CCDS34893.1; -.
DR RefSeq; NP_443130.1; NM_052898.1.
DR AlphaFoldDB; Q5GH76; -.
DR SMR; Q5GH76; -.
DR BioGRID; 125348; 28.
DR IntAct; Q5GH76; 2.
DR STRING; 9606.ENSP00000328326; -.
DR TCDB; 2.A.112.1.11; the kx blood-group antigen (kxa) family.
DR iPTMnet; Q5GH76; -.
DR PhosphoSitePlus; Q5GH76; -.
DR BioMuta; XKR4; -.
DR DMDM; 74707818; -.
DR jPOST; Q5GH76; -.
DR MassIVE; Q5GH76; -.
DR PaxDb; Q5GH76; -.
DR PeptideAtlas; Q5GH76; -.
DR PRIDE; Q5GH76; -.
DR ProteomicsDB; 62834; -.
DR Antibodypedia; 11703; 85 antibodies from 17 providers.
DR DNASU; 114786; -.
DR Ensembl; ENST00000327381.7; ENSP00000328326.5; ENSG00000206579.9.
DR Ensembl; ENST00000622811.1; ENSP00000480076.1; ENSG00000206579.9.
DR GeneID; 114786; -.
DR KEGG; hsa:114786; -.
DR MANE-Select; ENST00000327381.7; ENSP00000328326.5; NM_052898.2; NP_443130.1.
DR UCSC; uc003xsf.4; human.
DR CTD; 114786; -.
DR DisGeNET; 114786; -.
DR GeneCards; XKR4; -.
DR HGNC; HGNC:29394; XKR4.
DR HPA; ENSG00000206579; Tissue enriched (brain).
DR neXtProt; NX_Q5GH76; -.
DR OpenTargets; ENSG00000206579; -.
DR PharmGKB; PA142670563; -.
DR VEuPathDB; HostDB:ENSG00000206579; -.
DR eggNOG; KOG4790; Eukaryota.
DR GeneTree; ENSGT00990000203579; -.
DR HOGENOM; CLU_028534_1_0_1; -.
DR InParanoid; Q5GH76; -.
DR OMA; SDGRRKM; -.
DR OrthoDB; 1230316at2759; -.
DR PhylomeDB; Q5GH76; -.
DR TreeFam; TF316454; -.
DR PathwayCommons; Q5GH76; -.
DR SignaLink; Q5GH76; -.
DR BioGRID-ORCS; 114786; 8 hits in 1061 CRISPR screens.
DR ChiTaRS; XKR4; human.
DR GenomeRNAi; 114786; -.
DR Pharos; Q5GH76; Tbio.
DR PRO; PR:Q5GH76; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q5GH76; protein.
DR Bgee; ENSG00000206579; Expressed in lateral nuclear group of thalamus and 129 other tissues.
DR Genevisible; Q5GH76; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:UniProtKB.
DR GO; GO:1902742; P:apoptotic process involved in development; IBA:GO_Central.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IBA:GO_Central.
DR GO; GO:0070782; P:phosphatidylserine exposure on apoptotic cell surface; IDA:UniProtKB.
DR InterPro; IPR018629; XK-rel.
DR Pfam; PF09815; XK-related; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell membrane; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..650
FT /note="XK-related protein 4"
FT /id="PRO_0000190777"
FT CHAIN 1..567
FT /note="XK-related protein 4, processed form"
FT /evidence="ECO:0000250|UniProtKB:Q5GH67"
FT /id="PRO_0000453289"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 331..351
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..418
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 457..477
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 487..507
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..238
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..238
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 567..568
FT /note="Cleavage; by caspase-3, caspase-6 and caspase-7"
FT /evidence="ECO:0000250|UniProtKB:Q5GH67"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5GH67"
SQ SEQUENCE 650 AA; 71501 MW; 12FD197BD5F54C19 CRC64;
MAAKSDGRLK MKKSSDVAFT PLQNSDHSGS VQGLAPGLPS GSGAEDEEAA GGGCCPDGGG
CSRCCCCCAG SGGSAGSGGS GGVAGPGGGG AGSAALCLRL GREQRRYSLW DCLWILAAVA
VYFADVGTDV WLAVDYYLRG QRWWFGLTLF FVVLGSLSVQ VFSFRWFVHD FSTEDSATAA
AASSCPQPGA DCKTVVGGGS AAGEGEARPS TPQRQASNAS KSNIAAANSG SNSSGATRAS
GKHRSASCSF CIWLLQSLIH ILQLGQIWRY FHTIYLGIRS RQSGENDRWR FYWKMVYEYA
DVSMLHLLAT FLESAPQLVL QLCIIVQTHS LQALQGFTAA ASLVSLAWAL ASYQKALRDS
RDDKKPISYM AVIIQFCWHF FTIAARVITF ALFASVFQLY FGIFIVLHWC IMTFWIVHCE
TEFCITKWEE IVFDMVVGII YIFSWFNVKE GRTRCRLFIY YFVILLENTA LSALWYLYKA
PQIADAFAIP ALCVVFSSFL TGVVFMLMYY AFFHPNGPRF GQSPSCACED PAAAFTLPPD
VATSTLRSIS NNRSVVSDRD QKFAERDGCV PVFQVRPTAP STPSSRPPRI EESVIKIDLF
RNRYPAWERH VLDRSLRKAI LAFECSPSPP RLQYKDDALI QERLEYETTL
