General Structure Information
| PDB ID | 3b1u |
| HGNC Gene Label(s) | PADI4 |
| Structure Name | crystal structure of human peptidylarginine deiminase 4 in complex with o-f-amidine |
| Resolution | 2.1Å |
| Reference | AUTH C.P.CAUSEY,J.E.JONES,J.L.SLACK,D.KAMEI,L.E.JONES JR,AUTH 2 V.SUBRAMANIAN,B.KNUCKLEY,P.EBRAHIMI,A.A.CHUMANEVICH,Y.LUO,AUTH 3 H.HASHIMOTO,M.SATO,L.J.HOFSETH,P.R.THOMPSONTITL THE DEVELOPMENT OFTITL 2 N-ALPHA-(2-CARBOXYL)BENZOYL-N(5)-(2-FLUORO-1-IMINOETHYL)-L-TITL 3 ORNITHINE AMIDE (O-F-AMIDINE) ANDTITL 4 N-ALPHA-(2-CARBOXYL)BENZOYL-N(5)-(2-CHLORO-1-IMINOETHYL)-L-TITL 5 ORNITHINE AMIDE (O-CL-AMIDINE) AS SECOND GENERATION PROTEINTITL 6 ARGININE DEIMINASE (PAD) INHIBITORSREF J.MED.CHEM. V. 54 6919 2011REFN ISSN 0022-2623PMID 21882827DOI 10.1021/JM2008985 |
Variant Set Distributions
ExAC Variants
| Number Of Residues | 628 |
| Number Of SNVs | 198 |
| Number Of Permutations | 90583 |
| Optimal Distance Threshold | 7.0 |
| K Statistic | 0.011 |
| p-value | 0.824 |
COSMIC
| Number Of Residues | 628 |
| Number Of SNVs | 10 |
| Number Of Permutations | 9984 |
| Optimal Distance Threshold | 15.0 |
| K Statistic | 0.022 |
| p-value | 0.914 |
Ripley’s K Analysis Plots
ExACCOSMIC
Variant Set Comparisons
Cosmic vs. ExAC
| Number Of ExAC SNVs | 198 |
| Number Of COSMIC SNVs | 9 |
| Optimal Distance Threshold | 55.0 |
| K Statistic | 0.149 |
| p-value | 0.622 |
Pathogenic Proximity Analysis
COSMIC PathProx Analysis
Mapped Variants
[+] ExAC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:17634727 | rs377643304 | G>R | A:4 | (5.95, -11.13, 28.04) |
| 1:17634730 | T>P | A:5 | (7.08, -10.99, 31.64) | |
| 1:17634740 | rs35381732 | R>H | A:8 | (15.22, -10.10, 36.64) |
| 1:17634746 | rs201885629 | T>N | A:10 | (15.74, -11.56, 45.02) |
| 1:17634764 | rs370820749 | H>R | A:16 | (6.15, -6.93, 45.48) |
| 1:17634769 | rs371193672 COSM4025372 |
V>M | A:18 | (1.16, -7.49, 38.11) |
| 1:17634772 | C>G | A:19 | (0.02, -11.16, 36.60) | |
| 1:17634779 | rs547720396 | L>P | A:21 | (-4.90, -13.49, 33.40) |
| 1:17634781 | rs367980085 | G>S | A:22 | (-2.86, -14.69, 29.20) |
| 1:17634784 | rs567560287 | T>P | A:23 | (0.26, -13.25, 29.82) |
| 1:17634797 | L>P | A:27 | (10.65, -16.92, 37.24) | |
| 1:17634803 | I>N | A:29 | (15.72, -18.51, 39.79) | |
| 1:17634808 | S>G | A:31 | (20.88, -14.07, 38.09) | |
| 1:17657484 | T>M | A:38 | (23.57, -25.35, 43.49) | |
| 1:17657501 | COSM1336546 | A>T | A:44 | (3.03, -22.23, 45.29) |
| 1:17657511 | G>E | A:47 | (-3.34, -20.30, 42.06) | |
| 1:17657519 | V>M | A:50 | (4.65, -23.68, 38.68) | |
| 1:17657570 | T>S | A:67 | (13.70, -31.27, 42.83) | |
| 1:17657576 | P>S | A:69 | (18.97, -27.74, 38.66) | |
| 1:17657583 | D>G | A:71 | (20.72, -24.34, 34.52) | |
| 1:17657588 | G>R | A:73 | (17.77, -23.15, 31.16) | |
| 1:17657591 | V>L | A:74 | (15.55, -23.90, 34.09) | |
| 1:17657592 | rs57969340 | V>A | A:74 | (15.55, -23.90, 34.09) |
| 1:17657594 | E>K | A:75 | (12.01, -22.71, 30.68) | |
| 1:17657596 | E>D | A:75 | (12.01, -22.71, 30.68) | |
| 1:17657601 | T>N | A:77 | (6.19, -20.97, 33.71) | |
| 1:17657610 | M>T | A:80 | (-2.23, -17.02, 37.70) | |
| 1:17657616 | rs11203367 | V>A | A:82 | (-7.78, -16.18, 38.91) |
| 1:17657637 | D>G | A:89 | (-3.53, -12.98, 46.72) | |
| 1:17657640 | Q>P | A:90 | (-1.48, -15.74, 44.98) | |
| 1:17660463 | rs141113951 | K>R | A:100 | (27.57, -28.86, 53.41) |
| 1:17660468 | rs34309058 | P>T | A:102 | (21.01, -24.08, 55.08) |
| 1:17660474 | rs138247576 | V>I | A:104 | (17.88, -19.43, 51.17) |
| 1:17660486 | L>V | A:108 | (7.01, -13.46, 44.12) | |
| 1:17660490 | rs144397490 | Y>C | A:109 | (4.53, -11.20, 48.09) |
| 1:17660495 | rs575630557 | T>S | A:111 | (-1.47, -9.23, 41.79) |
| 1:17660502 | V>A | A:113 | (-5.32, -8.76, 36.75) | |
| 1:17662663 | L>W | A:117 | (-9.61, -4.57, 24.44) | |
| 1:17662678 | T>S | A:122 | (-15.86, -13.17, 14.89) | |
| 1:17662680 | rs375277347 | R>C | A:123 | (-15.51, -10.87, 10.82) |
| 1:17662684 | rs571787244 COSM1626642 |
T>N | A:124 | (-20.96, -12.28, 14.56) |
| 1:17662686 | G>S | A:125 | (-22.25, -9.00, 16.25) | |
| 1:17662720 | Q>R | A:136 | (-3.64, -14.03, 14.99) | |
| 1:17664534 | R>K | A:137 | (-0.62, -9.73, 18.63) | |
| 1:17664551 | rs373293662 | P>S | A:143 | (-13.88, -17.22, 5.93) |
| 1:17664558 | G>V | A:145 | (-10.76, -14.88, 9.87) | |
| 1:17664563 | rs371334403 | G>S | A:147 | (-11.46, -8.82, 12.46) |
| 1:17664564 | rs374085936 | G>D | A:147 | (-11.46, -8.82, 12.46) |
| 1:17664566 | A>T | A:148 | (-12.91, -5.75, 13.20) | |
| 1:17664569 | I>V | A:149 | (-15.52, -4.29, 10.59) | |
| 1:17664597 | N>S | A:158 | (-28.58, 15.38, 13.01) | |
| 1:17664615 | rs11588132 | M>T | A:164 | (-20.57, 14.12, 7.49) |
| 1:17664616 | rs200898889 | M>I | A:164 | (-20.57, 14.12, 7.49) |
| 1:17664621 | C>Y | A:166 | (-17.74, 12.46, 11.26) | |
| 1:17664623 | rs377675051 | E>K | A:167 | (-17.82, 16.78, 9.92) |
| 1:17664626 | D>N | A:168 | (-18.82, 16.30, 15.30) | |
| 1:17664635 | V>L | A:171 | (-22.97, 11.35, 19.98) | |
| 1:17664638 | L>F | A:172 | (-25.74, 14.84, 18.24) | |
| 1:17664647 | rs370710302 | E>K | A:175 | (-30.61, 6.98, 16.22) |
| 1:17666191 | rs373664151 | D>N | A:179 | (-23.60, 3.77, 12.22) |
| 1:17666194 | M>V | A:180 | (-20.70, 3.81, 16.00) | |
| 1:17666222 | rs142590988 | T>N | A:189 | (-9.21, -5.89, 39.80) |
| 1:17666225 | P>L | A:190 | (-8.01, -5.84, 43.11) | |
| 1:17666234 | F>S | A:193 | (-4.97, -2.70, 40.60) | |
| 1:17666263 | rs147414271 | V>M | A:203 | (-4.39, 5.96, 18.67) |
| 1:17666270 | R>K | A:205 | (0.44, 11.28, 17.64) | |
| 1:17666279 | M>T | A:208 | (-5.05, 10.88, 15.46) | |
| 1:17666293 | V>M | A:213 | (-13.28, 6.79, 20.56) | |
| 1:17666302 | A>P | A:216 | (-20.34, 4.75, 27.39) | |
| 1:17668464 | rs140720020 | V>I | A:227 | (-14.46, 12.28, 23.18) |
| 1:17668476 | P>T | A:231 | (-8.51, 13.98, 15.72) | |
| 1:17668480 | K>R | A:232 | (-7.35, 17.40, 19.36) | |
| 1:17668488 | S>T | A:235 | (-4.21, 9.72, 24.74) | |
| 1:17668501 | M>T | A:239 | (-11.23, 7.18, 35.27) | |
| 1:17668506 | P>A | A:241 | (-13.53, 0.90, 38.92) | |
| 1:17668512 | rs141838236 | G>R | A:243 | (-12.97, -5.00, 40.33) |
| 1:17668516 | K>R | A:244 | (-16.31, -7.77, 38.90) | |
| 1:17668525 | rs371809837 | M>R | A:247 | (-15.46, 0.76, 30.05) |
| 1:17668543 | A>V | A:253 | (-14.60, 6.23, 10.86) | |
| 1:17668551 | F>I | A:256 | (-13.95, 5.77, 3.01) | |
| 1:17668553 | F>L | A:256 | (-13.95, 5.77, 3.01) | |
| 1:17668555 | rs373057735 | P>L | A:257 | (-10.00, 3.22, 2.30) |
| 1:17668557 | D>N | A:258 | (-7.07, 6.35, -0.12) | |
| 1:17668563 | rs35903413 | D>N | A:260 | (-2.68, 8.02, 2.58) |
| 1:17668569 | P>S | A:262 | (-4.10, 1.08, 4.28) | |
| 1:17668570 | rs34743635 | P>L | A:262 | (-4.10, 1.08, 4.28) |
| 1:17668575 | L>I | A:264 | (-5.77, -1.17, 9.19) | |
| 1:17668588 | T>I | A:268 | (-3.93, 0.18, 22.48) | |
| 1:17668606 | rs41265997 | T>M | A:274 | (1.36, 4.56, 39.20) |
| 1:17668609 | rs1748020 | S>F | A:275 | (3.62, 2.79, 42.61) |
| 1:17668804 | E>V | A:281 | (4.01, 6.44, 33.49) | |
| 1:17668805 | E>D | A:281 | (4.01, 6.44, 33.49) | |
| 1:17668821 | D>N | A:287 | (-4.13, -5.79, 24.34) | |
| 1:17668827 | rs143220365 | V>M | A:289 | (-8.21, -3.84, 18.89) |
| 1:17668836 | rs375905749 COSM1260820 COSM4143061 |
R>C | A:292 | (-9.61, -3.36, 7.31) |
| 1:17668837 | R>H | A:292 | (-9.61, -3.36, 7.31) | |
| 1:17668839 | rs199545354 | V>M | A:293 | (-12.14, 0.87, 7.26) |
| 1:17668849 | W>S | A:296 | (-18.01, 3.03, -2.81) | |
| 1:17668851 | I>F | A:297 | (-19.11, -1.64, -2.21) | |
| 1:17668852 | I>T | A:297 | (-19.11, -1.64, -2.21) | |
| 1:17668860 | P>S | A:300 | (-24.15, -4.61, -10.18) | |
| 1:17668876 | P>L | A:305 | (-33.94, -2.77, -8.25) | |
| 1:17668883 | E>D | A:307 | (-34.27, 4.65, -5.14) | |
| 1:17668888 | rs33981382 | Y>C | A:309 | (-32.27, 8.17, -8.08) |
| 1:17668890 | COSM530722 | A>T | A:310 | (-34.59, 11.58, -12.36) |
| 1:17668891 | A>V | A:310 | (-34.59, 11.58, -12.36) | |
| 1:17672524 | rs201509687 | I>F | A:313 | (-36.16, 19.11, -18.33) |
| 1:17672558 | T>N | A:324 | (-42.77, 6.23, -13.49) | |
| 1:17672566 | rs145819522 | A>P | A:327 | (-40.52, 1.79, -11.39) |
| 1:17672597 | C>Y | A:337 | (-34.63, 16.57, -9.65) | |
| 1:17672612 | N>S | A:342 | (-31.95, 20.24, -12.10) | |
| 1:17672616 | M>I | A:343 | (-30.06, 24.59, -12.55) | |
| 1:17674448 | I>V | A:354 | (-25.62, 4.90, -5.45) | |
| 1:17674454 | Y>D | A:356 | (-22.44, -1.62, -0.42) | |
| 1:17674458 | I>T | A:357 | (-20.92, 1.05, 3.82) | |
| 1:17674467 | P>L | A:360 | (-21.37, -6.99, 10.95) | |
| 1:17674469 | H>Y | A:361 | (-22.62, -3.22, 12.93) | |
| 1:17674476 | rs370574008 | T>M | A:363 | (-25.66, -2.10, 5.90) |
| 1:17674484 | rs139880564 | V>M | A:366 | (-22.72, 5.40, 0.21) |
| 1:17674485 | rs574906391 | V>A | A:366 | (-22.72, 5.40, 0.21) |
| 1:17674527 | P>R | A:380 | (-25.70, 14.68, -3.89) | |
| 1:17674533 | K>R | A:382 | (-29.88, 19.60, -0.39) | |
| 1:17674535 | rs375767707 | R>C | A:383 | (-33.23, 16.65, -0.42) |
| 1:17674541 | M>V | A:385 | (-26.43, 13.21, 2.70) | |
| 1:17681029 | rs577972490 | G>V | A:386 | (-28.70, 10.98, 5.19) |
| 1:17681053 | rs200925491 | R>Q | A:394 | (-12.41, 11.52, -2.98) |
| 1:17681062 | Q>R | A:397 | (-14.68, 19.84, -6.13) | |
| 1:17681067 | G>R | A:399 | (-11.43, 21.88, -11.36) | |
| 1:17681075 | I>M | A:401 | (-12.48, 17.86, -14.27) | |
| 1:17681080 | G>E | A:403 | (-15.83, 13.54, -18.70) | |
| 1:17681085 | D>H | A:405 | (-14.39, 12.50, -14.00) | |
| 1:17681103 | COSM1687086 | E>K | A:411 | (-20.39, 1.16, -14.50) |
| 1:17681116 | P>Q | A:415 | (-20.58, -11.66, -9.85) | |
| 1:17681122 | T>R | A:417 | (-14.44, -16.62, -11.55) | |
| 1:17681128 | R>K | A:419 | (-7.51, -17.53, -16.18) | |
| 1:17681143 | rs150896296 | P>L | A:424 | (-17.42, -11.95, -5.10) |
| 1:17681163 | G>R | A:431 | (-12.55, 4.76, -18.76) | |
| 1:17681182 | S>I | A:437 | (-1.98, 11.95, -25.27) | |
| 1:17682479 | rs368065925 | N>D | A:438 | (-1.06, 16.10, -25.64) |
| 1:17682485 | S>C | A:440 | (-5.77, 12.13, -23.86) | |
| 1:17682491 | Q>K | A:442 | (-7.32, 10.63, -17.06) | |
| 1:17682501 | Q>R | A:445 | (-5.19, 9.02, -10.46) | |
| 1:17682503 | A>S | A:446 | (-8.15, 10.57, -7.16) | |
| 1:17682519 | rs139459202 | L>R | A:451 | (-12.05, 3.15, -7.19) |
| 1:17682551 | rs139847062 | L>F | A:462 | (-12.30, -0.25, -20.19) |
| 1:17682567 | L>P | A:467 | (-16.77, 7.66, -27.17) | |
| 1:17682572 | rs200193047 | V>M | A:469 | (-19.02, 11.62, -23.96) |
| 1:17682573 | V>A | A:469 | (-19.02, 11.62, -23.96) | |
| 1:17682581 | V>M | A:472 | (-18.22, 2.63, -20.25) | |
| 1:17682587 | COSM1295531 | E>K | A:474 | (-21.43, 5.59, -24.72) |
| 1:17682597 | S>N | A:477 | (-24.73, -3.32, -20.35) | |
| 1:17682608 | A>T | A:481 | (-29.81, -14.32, -16.59) | |
| 1:17682611 | P>S | A:482 | (-31.77, -17.45, -16.52) | |
| 1:17682614 | rs142426054 | D>N | A:483 | (-28.67, -18.95, -18.17) |
| 1:17682621 | K>R | A:485 | (-21.66, -16.75, -15.67) | |
| 1:17682856 | F>S | A:487 | (-23.82, -12.40, -16.65) | |
| 1:17682858 | R>W | A:488 | (-26.13, -13.15, -20.92) | |
| 1:17682859 | R>Q | A:488 | (-26.13, -13.15, -20.92) | |
| 1:17682871 | A>V | A:492 | (-22.37, -2.25, -29.15) | |
| 1:17682875 | S>R | A:493 | (-22.84, -4.00, -32.88) | |
| 1:17682892 | K>R | A:499 | (-26.36, -9.38, -39.95) | |
| 1:17682900 | Q>K | A:502 | (-27.76, -6.65, -46.33) | |
| 1:17682916 | E>G | A:507 | (-36.74, -10.10, -47.04) | |
| 1:17682924 | G>R | A:510 | (-34.49, -0.78, -49.06) | |
| 1:17682946 | COSM3478941 | G>A | A:517 | (-41.65, 9.30, -36.97) |
| 1:17685340 | K>N | A:522 | (-33.64, 14.89, -43.93) | |
| 1:17685363 | rs372338820 | L>P | A:530 | (-25.94, -0.51, -46.64) |
| 1:17685372 | K>R | A:533 | (-17.99, 3.68, -49.44) | |
| 1:17685387 | rs566872956 | H>L | A:538 | (-16.59, 6.64, -39.78) |
| 1:17685392 | S>A | A:540 | (-14.97, -0.25, -39.06) | |
| 1:17685401 | rs535922742 COSM1260821 |
E>K | A:543 | (-16.04, -3.20, -35.30) |
| 1:17685786 | D>E | A:547 | (-13.72, -5.64, -31.00) | |
| 1:17685793 | rs531113425 | R>C | A:550 | (-16.05, -8.63, -27.39) |
| 1:17685796 | COSM3478963 | E>K | A:551 | (-11.10, -9.71, -26.42) |
| 1:17685806 | K>M | A:554 | (-13.29, -12.13, -23.46) | |
| 1:17685808 | R>W | A:555 | (-7.71, -10.20, -20.18) | |
| 1:17685809 | rs145342708 | R>Q | A:555 | (-7.71, -10.20, -20.18) |
| 1:17685815 | rs200041623 | L>P | A:557 | (-14.64, -10.17, -16.46) |
| 1:17685826 | rs199904250 | E>K | A:561 | (-18.39, -14.97, -27.35) |
| 1:17685828 | rs564794141 | E>D | A:561 | (-18.39, -14.97, -27.35) |
| 1:17685830 | S>T | A:562 | (-21.72, -17.49, -24.14) | |
| 1:17685832 | D>N | A:563 | (-21.16, -14.77, -21.38) | |
| 1:17685838 | I>V | A:565 | (-25.75, -10.33, -26.35) | |
| 1:17685839 | I>T | A:565 | (-25.75, -10.33, -26.35) | |
| 1:17685842 | D>V | A:566 | (-23.73, -8.33, -30.11) | |
| 1:17685848 | P>L | A:568 | (-28.09, -3.63, -32.90) | |
| 1:17685854 | L>P | A:570 | (-25.01, 2.38, -36.59) | |
| 1:17685881 | A>V | A:579 | (-17.98, 8.77, -31.34) | |
| 1:17685892 | F>L | A:583 | (-29.31, 4.27, -34.15) | |
| 1:17685893 | F>Y | A:583 | (-29.31, 4.27, -34.15) | |
| 1:17685898 | N>D | A:585 | (-26.99, 4.00, -27.61) | |
| 1:17685901 | M>L | A:586 | (-30.42, 0.33, -28.23) | |
| 1:17690026 | L>M | A:590 | (-33.09, 1.64, -17.03) | |
| 1:17690029 | V>M | A:591 | (-31.39, -2.46, -15.89) | |
| 1:17690035 | G>R | A:593 | (-34.32, -6.29, -13.89) | |
| 1:17690047 | G>S | A:597 | (-35.06, 0.75, -20.73) | |
| 1:17690050 | I>L | A:598 | (-34.48, 0.14, -24.46) | |
| 1:17690059 | P>S | A:601 | (-34.54, 3.16, -32.29) | |
| 1:17690060 | COSM1626645 | P>H | A:601 | (-34.54, 3.16, -32.29) |
| 1:17690065 | G>R | A:603 | (-36.39, 2.34, -37.35) | |
| 1:17690066 | G>E | A:603 | (-36.39, 2.34, -37.35) | |
| 1:17690071 | V>I | A:605 | (-41.06, 0.03, -40.27) | |
| 1:17690083 | rs142092052 | R>C | A:609 | (-41.92, -4.71, -34.64) |
| 1:17690084 | rs201235053 | R>H | A:609 | (-41.92, -4.71, -34.64) |
| 1:17690087 | C>Y | A:610 | (-38.70, -1.53, -35.56) | |
| 1:17690090 | rs550253663 | C>Y | A:611 | (-35.99, -3.81, -37.36) |
| 1:17690119 | E>Q | A:621 | (-38.15, -11.51, -25.50) | |
| 1:17690135 | Q>L | A:626 | (-39.93, -7.77, -20.21) | |
| 1:17690140 | T>S | A:628 | (-39.76, -0.65, -22.60) | |
| 1:17690152 | rs192286295 | D>N | A:632 | (-34.60, 9.57, -25.96) |
| 1:17690170 | I>L | A:638 | (-30.55, 15.97, -29.49) | |
| 1:17690180 | G>E | A:641 | (-27.88, 10.85, -24.67) | |
| 1:17690189 | H>R | A:644 | (-27.72, 4.58, -17.94) | |
| 1:17690194 | G>S | A:646 | (-30.94, 10.18, -17.16) | |
| 1:17690195 | rs371018366 | G>D | A:646 | (-30.94, 10.18, -17.16) |
| 1:17690207 | rs200090088 | R>H | A:650 | (-31.18, 2.50, -3.82) |
| 1:17690210 | rs368700849 COSM254884 |
R>K | A:651 | (-28.89, -1.22, -8.24) |
| 1:17690219 | COSM4143063 | F>C | A:654 | (-23.37, -7.90, -3.54) |
| 1:17690242 | V>M | A:662 | (-8.93, -13.33, -0.51) |
[+] COSMIC Missense Variants
| Position | Variant | AA Change | PDB Chain Position | Structure Coordinates |
|---|---|---|---|---|
| 1:17657616 | COSM3746671 | V>A | A:82 | (-7.78, -16.18, 38.91) |
| 1:17660499 | COSM3746672 | G>A | A:112 | (-4.14, -11.22, 39.48) |
| 1:17662684 | COSM1626642 | T>I | A:124 | (-20.96, -12.28, 14.56) |
| 1:17668563 | COSM3750635 | D>N | A:260 | (-2.68, 8.02, 2.58) |
| 1:17668594 | COSM1667184 | S>F | A:270 | (-1.89, 0.56, 28.44) |
| 1:17668843 | COSM424663 | A>V | A:294 | (-15.25, -0.18, 5.21) |
| 1:17674510 | COSM254885 | R>S | A:374 | (-22.50, 19.81, -15.28) |
| 1:17681136 | COSM3478939 | E>K | A:422 | (-13.61, -16.09, -6.11) |
| 1:17690098 | COSM3478970 | E>K | A:614 | (-38.25, -7.78, -34.29) |
| 1:17690210 | COSM254884 | R>T | A:651 | (-28.89, -1.22, -8.24) |