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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). 

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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FASTA formatted sequence
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