2.A.112.1.11 Xkr4 of 650 aas and 10 TMSs in a 2 + 1 + 2 + 2 + 1 + 2 TMS arrangement, suggestive of a 5 TMS repeat unit. Xrk4 catalyzes phosphatidyl serine flipping from the inner leaflet to the outer leaflet of the cell membrane to signal appoptosis. It has a C-terminal caspase recognition signal that may play an important role. Xkr4, 8 and 9 have this activity and have several essential residues in TMS2 and cytoplasmic loop 2 (Suzuki et al. 2014). Xkr4 is activated by caspase-mediated cleavage and binding of the XRCC4 fragment. Zhang et al. 2023 showed that extracellular calcium is a factor needed to activate Xkr4. A constitutively active mutant of Xkr4 was found to induce phospholipid scrambling in an extracellular, but not intracellular, calcium-dependent manner. Other Xkr family members also require extracellular calcium for activation. D123 and D127 of TMS1 and E310 of TMS3 coordinate calcium binding, and the E310K mutation-mediated salt bridge between TMS1 and TMS3 bypasses the requirement for calcium. Disulfide bond formation between these two TMSs also activates phospholipid scrambling without calcium (Zhang et al. 2023).
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Accession Number: | Q5GH76 |
Protein Name: | XK-related protein 4 |
Length: | 650 |
Molecular Weight: | 71501.00 |
Species: | Homo sapiens (Human) [9606] |
Number of TMSs: | 10 |
Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
Substrate |
phospholipid, phosphatidyl-L-serine |
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1: MAAKSDGRLK MKKSSDVAFT PLQNSDHSGS VQGLAPGLPS GSGAEDEEAA GGGCCPDGGG
61: CSRCCCCCAG SGGSAGSGGS GGVAGPGGGG AGSAALCLRL GREQRRYSLW DCLWILAAVA
121: VYFADVGTDV WLAVDYYLRG QRWWFGLTLF FVVLGSLSVQ VFSFRWFVHD FSTEDSATAA
181: AASSCPQPGA DCKTVVGGGS AAGEGEARPS TPQRQASNAS KSNIAAANSG SNSSGATRAS
241: GKHRSASCSF CIWLLQSLIH ILQLGQIWRY FHTIYLGIRS RQSGENDRWR FYWKMVYEYA
301: DVSMLHLLAT FLESAPQLVL QLCIIVQTHS LQALQGFTAA ASLVSLAWAL ASYQKALRDS
361: RDDKKPISYM AVIIQFCWHF FTIAARVITF ALFASVFQLY FGIFIVLHWC IMTFWIVHCE
421: TEFCITKWEE IVFDMVVGII YIFSWFNVKE GRTRCRLFIY YFVILLENTA LSALWYLYKA
481: PQIADAFAIP ALCVVFSSFL TGVVFMLMYY AFFHPNGPRF GQSPSCACED PAAAFTLPPD
541: VATSTLRSIS NNRSVVSDRD QKFAERDGCV PVFQVRPTAP STPSSRPPRI EESVIKIDLF
601: RNRYPAWERH VLDRSLRKAI LAFECSPSPP RLQYKDDALI QERLEYETTL