SitesBLAST
Comparing BWI76_RS27595 FitnessBrowser__Koxy:BWI76_RS27595 to proteins with known functional sites using BLASTp with E ≤ 0.001.
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Found 11 hits to proteins with known functional sites (download)
P30878 Melibiose permease; Melibiose carrier; Melibiose transporter; Melibiose/cation symporter; Na+ (Li+)/melibiose symporter; Thiomethylgalactoside permease II from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) (see 2 papers)
30% identity, 99% coverage: 6:463/464 of query aligns to 3:467/476 of P30878
- K18 (≠ S21) mutation to C: Loss of transporter activity.
- KD 18:19 (≠ SH 21:22) binding
- D19 (≠ H22) mutation to C: Loss of transporter activity.
- R52 (= R55) mutation to C: Retains weak activity with Na(+), Li(+) or H(+).
- D55 (= D58) mutation to C: Alters cation selectivity. Retains a low level of H(+)-coupled melibiose transport, but retains only a weak activity with Na(+) or Li(+).
- N58 (≠ S61) mutation to C: Alters cation selectivity. Decreases H(+)- and Na(+)-coupled activity, with little effect on Li(+)-coupled melibiose transport.
- D59 (= D62) mutation to C: Alters cation selectivity. Retains only a low level of H(+)-coupled melibiose binding and active transport, but Na(+) or Li(+) does not stimulate either binding or transport.
- Y120 (= Y123) mutation to C: Loss of transporter activity.
- T121 (= T124) mutation to C: Alters cation selectivity. Inhibits H(+)- and Na(+)-coupled activity, with little effect on Li(+)-coupled melibiose transport.
- M123 (≠ V126) mutation to C: Does not affect transporter activity.
- D124 (≠ N127) binding ; mutation to C: Alters cation selectivity. Loss of transporter activity.
- W128 (≠ C131) binding ; mutation to C: Loss of transporter activity.
- R149 (≠ F152) binding ; mutation to C: Retains weak activity with Na(+), Li(+) or H(+).
- K377 (= K371) mutation to C: Inhibits Na(+)- and Li(+)-coupled activity, with little effect on H(+)-coupled melibiose transport.
7l17A Crystal structure of sugar-bound melibiose permease melb (see paper)
30% identity, 96% coverage: 6:449/464 of query aligns to 2:453/453 of 7l17A
7l16A Crystal structure of sugar-bound melibiose permease melb (see paper)
30% identity, 96% coverage: 6:449/464 of query aligns to 2:453/453 of 7l16A
P02921 Melibiose permease; Melibiose carrier; Melibiose transporter; Melibiose/cation symporter; Na+ (Li+)/melibiose symporter; Thiomethylgalactoside permease II from Escherichia coli (strain K12) (see 5 papers)
29% identity, 97% coverage: 6:456/464 of query aligns to 3:461/473 of P02921
- K18 (≠ S21) mutation to C: Abolishes transporter activity.
- D19 (≠ H22) mutation to C: Abolishes transporter activity. Can bind Na(+). Large decrease in the affinity for melibiose in the presence of H(+).
- D35 (= D38) mutation to C: Abolishes transporter activity.
- R52 (= R55) mutation to C: Abolishes transporter activity.
- D55 (= D58) mutation to C: Abolishes transporter activity. Chemical restoration of the charge via the oxidation of the thiol to the sulfinic and/or sulfonic acid results in partial recovery of transporter activity. Does not bind Na(+). Binds melibiose in the presence of H(+).
- D59 (= D62) mutation to C: Loses ability to catalyze Na(+) or H(+)-coupled melibiose transport against a concentration gradient. Does not bind Na(+). Binds melibiose in the presence of H(+).
- D124 (≠ N127) mutation to C: Abolishes transporter activity. Chemical restoration of the charge via the oxidation of the thiol to the sulfinic and/or sulfonic acid results in partial recovery of transporter activity. Can bind Na(+), but structural changes induced by Na(+) are less complete and of smaller amplitude. Large decrease in the affinity for melibiose in the presence of H(+).
- K138 (≠ P141) mutation to C: Can transport melibiose.
- R139 (≠ T142) mutation to C: Can transport melibiose.
- R141 (= R144) mutation R->C,Q: Abolishes melibiose transport. Decreases affinity for melibiose.; mutation to K: Retains ion-coupled melibiose transport.
- R149 (≠ F152) mutation to C: Abolishes melibiose transport.; mutation R->K,Q: Retains ion-coupled melibiose transport.
- R199 (vs. gap) mutation to C: Does not affect transporter activity.
- E203 (vs. gap) mutation to C: Does not affect transporter activity.
Sites not aligning to the query:
- 1 modified: Initiator methionine, Removed
8d2sA Zebrafish mfsd2a isoform b in inward open ligand bound conformation (see paper)
28% identity, 36% coverage: 6:170/464 of query aligns to 3:167/475 of 8d2sA
- binding [(2~{R})-2-oxidanyl-3-[oxidanyl-[2-(trimethyl-$l^{4}-azanyl)ethoxy]phosphoryl]oxy-propyl] (9~{Z},12~{Z},15~{Z})-octadeca-9,12,15-trienoate: R52 (= R55), D55 (= D58), D142 (≠ I145), R148 (= R151), M149 (≠ F152), T150 (≠ V153), E152 (≠ A155), V153 (≠ T156), T156 (≠ G159), L157 (≠ M160)
Sites not aligning to the query:
- binding [(2~{R})-2-oxidanyl-3-[oxidanyl-[2-(trimethyl-$l^{4}-azanyl)ethoxy]phosphoryl]oxy-propyl] (9~{Z},12~{Z},15~{Z})-octadeca-9,12,15-trienoate: 280, 302, 305, 306, 306, 307, 309, 356, 364, 368, 368, 389, 389, 393, 393, 400, 401
7mjsX Single-particle cryo-em structure of major facilitator superfamily domain containing 2a in complex with lpc-18:3 (see paper)
28% identity, 36% coverage: 6:170/464 of query aligns to 1:165/458 of 7mjsX
Sites not aligning to the query:
F1NCD6 Sodium-dependent lysophosphatidylcholine symporter 1; NLS1; Sodium-dependent LPC symporter 1; Major facilitator superfamily domain-containing protein 2A; GgMFSD2A from Gallus gallus (Chicken) (see paper)
28% identity, 36% coverage: 6:170/464 of query aligns to 36:200/528 of F1NCD6
Sites not aligning to the query:
- 207 modified: Disulfide link with 460
- 218 modified: carbohydrate, N-linked (GlcNAc...) asparagine
- 227 modified: carbohydrate, N-linked (GlcNAc...) asparagine
- 460 modified: Disulfide link with 207
A6NFX1 Sphingosine-1-phosphate transporter MFSD2B; Major facilitator superfamily domain-containing protein 2B; hMfsd2b from Homo sapiens (Human) (see paper)
23% identity, 92% coverage: 6:433/464 of query aligns to 39:485/504 of A6NFX1
- D95 (= D62) mutation to A: Abolishes export of sphingosine-1-phosphate.
- T157 (= T124) mutation to A: Abolishes export of sphingosine-1-phosphate.
- K423 (= K371) mutation to A: Does not affect export of sphingosine-1-phosphate.
Q3T9M1 Sphingosine-1-phosphate transporter MFSD2B; Major facilitator superfamily domain-containing protein 2B; mMfsd2b from Mus musculus (Mouse) (see 2 papers)
26% identity, 38% coverage: 2:178/464 of query aligns to 25:201/494 of Q3T9M1
- D85 (= D62) mutation to A: Decreased sphingosine-1-phosphate transport.
- T147 (= T124) mutation to A: Decreased export of sphingosine-1-phosphate.
Sites not aligning to the query:
- 413 K→A: Decreased sphingosine-1-phosphate transport.
Q9DA75 Sodium-dependent lysophosphatidylcholine symporter 1; NLS1; Sodium-dependent LPC symporter 1; Major facilitator superfamily domain-containing protein 2A; Mfsd2a from Mus musculus (Mouse) (see 2 papers)
26% identity, 41% coverage: 2:193/464 of query aligns to 36:230/534 of Q9DA75
- Y55 (≠ S21) mutation to A: Significant reduction in LPC transport.
- Q56 (≠ H22) mutation to A: Slightly reduced LPC transport.
- F64 (≠ L30) mutation to A: Slightly increased LPC transport.
- Q67 (≠ M33) mutation to H: Abolishes LPC transport.
- S82 (≠ G48) mutation to A: No effect on LPC transport.
- F86 (≠ L52) mutation to A: Slightly reduced LPC transport.
- R89 (= R55) mutation to A: No effect on LPC transport.
- D92 (= D58) mutation to A: Significant reduction in LPC transport. Abolishes LPC transport; when associated with A-96.
- T95 (≠ S61) mutation to A: Significant reduction in LPC transport.
- D96 (= D62) mutation to A: Abolishes LPC transport. Abolishes LPC transport; when associated with A-92.
- E159 (≠ T120) mutation to A: Slightly reduced LPC transport.
- T163 (= T124) mutation to A: Slightly reduced LPC transport.; mutation to M: Abolishes LPC transport.
- H166 (≠ N127) mutation to A: Abolishes LPC transport.
- P168 (= P129) mutation to T: Significant reduction in LPC transport.
- S170 (≠ C131) mutation to L: Significant reduction in LPC transport.
- R190 (= R151) mutation to A: Abolishes LPC transport.
- E194 (≠ A155) mutation to A: Significant reduction in LPC transport.
- T202 (= T163) mutation to A: Slightly increased LPC transport.; mutation to F: Significant reduction in LPC transport.; mutation to M: Significant reduction in LPC transport.
- Q207 (≠ P168) mutation to A: Slightly reduced LPC transport.
- C216 (vs. gap) modified: Disulfide link with 464; mutation to A: Significant reduction in LPC transport.
Sites not aligning to the query:
- 254 A→F: Abolishes LPC transport.
- 305 F→A: Significant reduction in LPC transport.
- 309 S→A: Significant reduction in LPC transport.
- 330 R→H: No effect on LPC transport.
- 334 Q→A: Slightly reduced LPC transport.
- 335 N→A: Significant reduction in LPC transport.
- 343 S→L: Significant reduction in LPC transport.
- 403 F→A: Significant reduction in LPC transport.
- 406 P→H: Significant reduction in LPC transport.
- 407 W→A: Significant reduction in LPC transport.
- 439 T→A: No effect on LPC transport.
- 440 K→A: Abolishes LPC transport.
- 451 T→A: Slightly reduced LPC transport.
- 455 D→A: Slightly reduced LPC transport.
- 461 R→A: Slightly reduced LPC transport.
- 464 modified: Disulfide link with 216; C→A: Significant reduction in LPC transport.
- 497 P→L: Abolishes LPC transport.
Q8NA29 Sodium-dependent lysophosphatidylcholine symporter 1; NLS1; Sodium-dependent LPC symporter 1; Major facilitator superfamily domain-containing protein 2A; HsMFSD2A; MFSD2a from Homo sapiens (Human) (see 6 papers)
26% identity, 36% coverage: 6:170/464 of query aligns to 41:218/543 of Q8NA29
- Q57 (≠ H22) mutation to E: Does not affect lysophosphatidylcholine (LPC) transport.; mutation to L: Abolished lysophosphatidylcholine (LPC) transport.
- F65 (≠ L30) mutation to A: Abolished lysophosphatidylcholine (LPC) transport.
- F66 (≠ Y31) mutation to A: Abolished lysophosphatidylcholine (LPC) transport.
- D73 (= D38) mutation to A: Abolished lysophosphatidylcholine (LPC) transport.
- V81 (vs. gap) natural variant: Missing (in NEDMISBA; uncertain significance; dbSNP:rs1570238098)
- R103 (= R55) mutation R->A,K,E: Reduced lysophosphatidylcholine (LPC) transport.; mutation to A: No effect on cell sensitivity toward tunicamycin.
- D106 (= D58) mutation to A: No effect on cell sensitivity toward tunicamycin.
- D110 (= D62) mutation to A: Drastic loss of cell sensitivity toward tunicamycin. Abolished lysophosphatidylcholine (LPC) transport.
- T172 (= T124) to M: in NEDMISBA; no effect on cell membrane localization; loss of LPC transport activity; dbSNP:rs1057517688
- P177 (= P129) mutation to T: Reduced expression; no effect on cell membrane localization; decreased LPC transport activity.
- S179 (≠ C131) to L: in NEDMISBA; no effect on cell membrane localization; decreased LPC transport activity; dbSNP:rs1057517689
- M200 (≠ F152) mutation to F: Reduced lysophosphatidylcholine (LPC) transport.
- T211 (= T163) to M: in NEDMISBA; reduced expression; no effect on cell membrane localization; decreased LPC transport activity; dbSNP:rs756467073
Sites not aligning to the query:
- 225 C→A: Reduced lysophosphatidylcholine (LPC) transport.
- 230 N→Q: Loss of glycosylation; when associated with Q-240.
- 240 N→Q: Loss of glycosylation; when associated with Q-230.
- 263 V → F: in NEDMISBA; reduced expression; no effect on cell membrane localization; decreased LPC transport activity
- 325 mutation E->A,D,Q,R: Abolished lysophosphatidylcholine (LPC) transport.
- 328 mutation F->A,Y: Reduced lysophosphatidylcholine (LPC) transport.
- 334 Y→A: Does not affect lysophosphatidylcholine (LPC) transport.
- 339 R → H: in NEDMISBA; reduced expression; no effect on cell membrane localization; no effect on LPC transport activity; dbSNP:rs776741331; R→A: Reduced lysophosphatidylcholine (LPC) transport.
- 342 F→A: Abolished lysophosphatidylcholine (LPC) transport.
- 346 L→A: Abolished lysophosphatidylcholine (LPC) transport.
- 349 I→A: Reduced lysophosphatidylcholine (LPC) transport.
- 350 M→A: Reduced lysophosphatidylcholine (LPC) transport.
- 352 S → L: in NEDMISBA; no effect on cell membrane localization; decreased LPC transport activity; dbSNP:rs1057519087
- 357 I→A: Does not affect lysophosphatidylcholine (LPC) transport.; I→W: Abolished lysophosphatidylcholine (LPC) transport.
- 361 Q→W: Reduced lysophosphatidylcholine (LPC) transport.
- 404 A→W: Abolished lysophosphatidylcholine (LPC) transport.
- 412 mutation F->I,W: Reduced lysophosphatidylcholine (LPC) transport.
- 416 mutation W->A,F: Reduced lysophosphatidylcholine (LPC) transport.
- 449 mutation K->A,R,Q: Reduced lysophosphatidylcholine (LPC) transport.; K→A: Loss of plasma membrane localization. Loss of cell sensitivity toward tunicamycin.
- 468 Y→A: Abolished lysophosphatidylcholine (LPC) transport.
- 473 C→A: Reduced lysophosphatidylcholine (LPC) transport.
- 506 P → L: in NEDMISBA; reduced expression; no effect on cell membrane localization; loss of LPC transport activity
Query Sequence
>BWI76_RS27595 FitnessBrowser__Koxy:BWI76_RS27595
MKDHILSVKEKIGYGMGDAASHIIFDNVMLYMMFFYTDIFGIPAGYVGTMFLLARALDAI
SDPCMGLLADRTRSRWGKFRPWILFGAIPFGLVCVLAYSSPDLSHNGKLIYAAVTYTLLT
LLYTVVNIPYCALGGVITDNPTQRISLQSWRFVLATAGGMLSTVLMMPLVNFIGGEDKAF
GFQGGIAVLSVIAFLMLAFCFFTTKERVEAPPSSTSMREDLRDIWRNDQWRVVGLLTILN
ILAVCVRGGAMMYYTSWIMGSAGLFTAFLTTYCVGNLIGSALAKPLTDWKCKVSVFWWTN
AILAVLSVAMFFVPMDAEITMFAFIFVIGVLHQLVTPIQWVMMSDTVDYGEWCNGKRLTG
ISFAGTLFVLKLGLALGGALIGWMLAGGGYDAAAKTQNSATITIIISLFTLAPAVCYLLS
AVIAKRYYTLKTPFLKKMMAELAQGARRNEQEFIAAPNGKELQN
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SitesBLAST's Database
SitesBLAST's database includes
(1) SwissProt
entries with experimentally-supported functional features;
and (2) protein structures with bound ligands, from the
BioLip database.
by Morgan Price,
Arkin group
Lawrence Berkeley National Laboratory