Details of the Target

General Information of Target

Target ID LDTP08498
Target Name Methylmalonic aciduria type A protein, mitochondrial (MMAA)
Gene Name MMAA
Gene ID 166785
Synonyms
Methylmalonic aciduria type A protein, mitochondrial; EC 3.6.-.-
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MPMLLPHPHQHFLKGLLRAPFRCYHFIFHSSTHLGSGIPCAQPFNSLGLHCTKWMLLSDG
LKRKLCVQTTLKDHTEGLSDKEQRFVDKLYTGLIQGQRACLAEAITLVESTHSRKKELAQ
VLLQKVLLYHREQEQSNKGKPLAFRVGLSGPPGAGKSTFIEYFGKMLTERGHKLSVLAVD
PSSCTSGGSLLGDKTRMTELSRDMNAYIRPSPTRGTLGGVTRTTNEAILLCEGAGYDIIL
IETVGVGQSEFAVADMVDMFVLLLPPAGGDELQGIKRGIIEMADLVAVTKSDGDLIVPAR
RIQAEYVSALKLLRKRSQVWKPKVIRISARSGEGISEMWDKMKDFQDLMLASGELTAKRR
KQQKVWMWNLIQESVLEHFRTHPTVREQIPLLEQKVLIGALSPGLAADFLLKAFKSRD
Target Bioclass
Enzyme
Family
SIMIBI class G3E GTPase family, ArgK/MeaB subfamily
Subcellular location
Mitochondrion
Function
GTPase, binds and hydrolyzes GTP. Involved in intracellular vitamin B12 metabolism, mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis. Functions as a G-protein chaperone that assists AdoCbl cofactor delivery from MMAB to the methylmalonyl-CoA mutase (MMUT). Plays a dual role as both a protectase and a reactivase for MMUT. Protects MMUT from progressive inactivation by oxidation by decreasing the rate of the formation of the oxidized inactive cofactor hydroxocobalamin (OH2Cbl). Additionally acts a reactivase by promoting the replacement of OH2Cbl by the active cofactor AdoCbl, restoring the activity of MMUT in the presence and hydrolysis of GTP.
Uniprot ID
Q8IVH4
Ensemble ID
ENST00000541599.5
HGNC ID
HGNC:18871

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 9 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		15.00  LDD0402  [1]
STPyne
 Probe Info  		K116(2.04)  LDD0277  [2]
DBIA
 Probe Info  		C184(2.74)  LDD3312  [3]
4-Iodoacetamidophenylacetylene
 Probe Info  		C100(0.00); C184(0.00)  LDD0038  [4]
IA-alkyne
 Probe Info  		C100(0.00); C184(0.00)  LDD0036  [4]
Lodoacetamide azide
 Probe Info  		C100(0.00); C184(0.00)  LDD0037  [4]
IPM
 Probe Info  		N.A.  LDD0147  [5]
TFBX
 Probe Info  		N.A.  LDD0148  [5]
NAIA_5
 Probe Info  		N.A.  LDD2223  [6]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HEK-293T C100(0.92)  LDD1507  [7]
 LDCM0215  AC10 HEK-293T C100(1.10)  LDD1508  [7]
 LDCM0226  AC11 HEK-293T C100(0.90)  LDD1509  [7]
 LDCM0259  AC14 HEK-293T C100(1.09)  LDD1512  [7]
 LDCM0270  AC15 HEK-293T C100(0.94); C184(1.16)  LDD1513  [7]
 LDCM0276  AC17 HEK-293T C100(1.04)  LDD1515  [7]
 LDCM0277  AC18 HEK-293T C100(0.89)  LDD1516  [7]
 LDCM0278  AC19 HEK-293T C100(0.84)  LDD1517  [7]
 LDCM0279  AC2 HEK-293T C100(1.07)  LDD1518  [7]
 LDCM0282  AC22 HEK-293T C100(0.91)  LDD1521  [7]
 LDCM0283  AC23 HEK-293T C100(0.94); C184(0.99)  LDD1522  [7]
 LDCM0284  AC24 HEK-293T C100(0.98)  LDD1523  [7]
 LDCM0285  AC25 HEK-293T C100(0.93)  LDD1524  [7]
 LDCM0286  AC26 HEK-293T C100(1.12)  LDD1525  [7]
 LDCM0287  AC27 HEK-293T C100(0.93)  LDD1526  [7]
 LDCM0290  AC3 HEK-293T C100(1.09)  LDD1529  [7]
 LDCM0291  AC30 HEK-293T C100(1.11)  LDD1530  [7]
 LDCM0292  AC31 HEK-293T C100(0.98); C184(0.90)  LDD1531  [7]
 LDCM0293  AC32 HEK-293T C100(1.05)  LDD1532  [7]
 LDCM0294  AC33 HEK-293T C100(1.10)  LDD1533  [7]
 LDCM0295  AC34 HEK-293T C100(0.96)  LDD1534  [7]
 LDCM0296  AC35 HEK-293T C100(0.89)  LDD1535  [7]
 LDCM0299  AC38 HEK-293T C100(0.97)  LDD1538  [7]
 LDCM0300  AC39 HEK-293T C100(1.11); C184(1.06)  LDD1539  [7]
 LDCM0302  AC40 HEK-293T C100(1.10)  LDD1541  [7]
 LDCM0303  AC41 HEK-293T C100(1.09)  LDD1542  [7]
 LDCM0304  AC42 HEK-293T C100(1.06)  LDD1543  [7]
 LDCM0305  AC43 HEK-293T C100(1.00)  LDD1544  [7]
 LDCM0308  AC46 HEK-293T C100(1.02)  LDD1547  [7]
 LDCM0309  AC47 HEK-293T C100(1.17); C184(1.09)  LDD1548  [7]
 LDCM0310  AC48 HEK-293T C100(0.99)  LDD1549  [7]
 LDCM0311  AC49 HEK-293T C100(0.95)  LDD1550  [7]
 LDCM0313  AC50 HEK-293T C100(0.86)  LDD1552  [7]
 LDCM0314  AC51 HEK-293T C100(1.00)  LDD1553  [7]
 LDCM0317  AC54 HEK-293T C100(1.06)  LDD1556  [7]
 LDCM0318  AC55 HEK-293T C100(1.12); C184(0.98)  LDD1557  [7]
 LDCM0319  AC56 HEK-293T C100(1.06)  LDD1558  [7]
 LDCM0320  AC57 HEK-293T C100(1.04)  LDD1559  [7]
 LDCM0321  AC58 HEK-293T C100(0.79)  LDD1560  [7]
 LDCM0322  AC59 HEK-293T C100(1.12)  LDD1561  [7]
 LDCM0323  AC6 HEK-293T C100(0.88)  LDD1562  [7]
 LDCM0326  AC62 HEK-293T C100(0.88)  LDD1565  [7]
 LDCM0327  AC63 HEK-293T C100(1.00); C184(1.09)  LDD1566  [7]
 LDCM0328  AC64 HEK-293T C100(0.95)  LDD1567  [7]
 LDCM0334  AC7 HEK-293T C100(1.21); C184(1.07)  LDD1568  [7]
 LDCM0345  AC8 HEK-293T C100(0.91)  LDD1569  [7]
 LDCM0356  AKOS034007680 HEK-293T C100(1.16)  LDD1570  [7]
 LDCM0275  AKOS034007705 HEK-293T C100(0.94)  LDD1514  [7]
 LDCM0156  Aniline NCI-H1299 12.02  LDD0403  [1]
 LDCM0632  CL-Sc Hep-G2 C100(0.82)  LDD2227  [6]
 LDCM0367  CL1 HEK-293T C100(0.80); C184(0.94)  LDD1571  [7]
 LDCM0368  CL10 HEK-293T C100(1.07)  LDD1572  [7]
 LDCM0369  CL100 HEK-293T C100(1.18)  LDD1573  [7]
 LDCM0370  CL101 HEK-293T C100(0.92); C184(1.03)  LDD1574  [7]
 LDCM0371  CL102 HEK-293T C100(0.98)  LDD1575  [7]
 LDCM0372  CL103 HEK-293T C100(1.18)  LDD1576  [7]
 LDCM0373  CL104 HEK-293T C100(0.96)  LDD1577  [7]
 LDCM0374  CL105 HEK-293T C100(0.90); C184(0.99)  LDD1578  [7]
 LDCM0375  CL106 HEK-293T C100(1.02)  LDD1579  [7]
 LDCM0376  CL107 HEK-293T C100(1.03)  LDD1580  [7]
 LDCM0377  CL108 HEK-293T C100(1.15)  LDD1581  [7]
 LDCM0378  CL109 HEK-293T C100(1.03); C184(1.01)  LDD1582  [7]
 LDCM0379  CL11 HEK-293T C100(1.21); C184(1.29)  LDD1583  [7]
 LDCM0380  CL110 HEK-293T C100(0.93)  LDD1584  [7]
 LDCM0381  CL111 HEK-293T C100(0.89)  LDD1585  [7]
 LDCM0382  CL112 HEK-293T C100(1.11)  LDD1586  [7]
 LDCM0383  CL113 HEK-293T C100(1.06); C184(1.07)  LDD1587  [7]
 LDCM0384  CL114 HEK-293T C100(1.13)  LDD1588  [7]
 LDCM0385  CL115 HEK-293T C100(1.16)  LDD1589  [7]
 LDCM0386  CL116 HEK-293T C100(1.02)  LDD1590  [7]
 LDCM0387  CL117 HEK-293T C100(0.90); C184(1.07)  LDD1591  [7]
 LDCM0388  CL118 HEK-293T C100(1.00)  LDD1592  [7]
 LDCM0389  CL119 HEK-293T C100(1.19)  LDD1593  [7]
 LDCM0390  CL12 HEK-293T C100(1.10)  LDD1594  [7]
 LDCM0391  CL120 HEK-293T C100(0.99)  LDD1595  [7]
 LDCM0392  CL121 HEK-293T C100(0.95); C184(1.21)  LDD1596  [7]
 LDCM0393  CL122 HEK-293T C100(0.83)  LDD1597  [7]
 LDCM0394  CL123 HEK-293T C100(1.26)  LDD1598  [7]
 LDCM0395  CL124 HEK-293T C100(0.85)  LDD1599  [7]
 LDCM0396  CL125 HEK-293T C100(0.79); C184(1.07)  LDD1600  [7]
 LDCM0397  CL126 HEK-293T C100(1.15)  LDD1601  [7]
 LDCM0398  CL127 HEK-293T C100(1.14)  LDD1602  [7]
 LDCM0399  CL128 HEK-293T C100(1.01)  LDD1603  [7]
 LDCM0400  CL13 HEK-293T C100(0.92); C184(1.13)  LDD1604  [7]
 LDCM0401  CL14 HEK-293T C100(1.25)  LDD1605  [7]
 LDCM0402  CL15 HEK-293T C100(1.01)  LDD1606  [7]
 LDCM0403  CL16 HEK-293T C100(1.14)  LDD1607  [7]
 LDCM0404  CL17 HEK-293T C100(1.22)  LDD1608  [7]
 LDCM0405  CL18 HEK-293T C100(0.81)  LDD1609  [7]
 LDCM0406  CL19 HEK-293T C100(0.93)  LDD1610  [7]
 LDCM0407  CL2 HEK-293T C100(1.23)  LDD1611  [7]
 LDCM0410  CL22 HEK-293T C100(0.98)  LDD1614  [7]
 LDCM0411  CL23 HEK-293T C100(1.04); C184(1.16)  LDD1615  [7]
 LDCM0412  CL24 HEK-293T C100(1.04)  LDD1616  [7]
 LDCM0413  CL25 HEK-293T C100(0.93); C184(0.95)  LDD1617  [7]
 LDCM0414  CL26 HEK-293T C100(1.15)  LDD1618  [7]
 LDCM0415  CL27 HEK-293T C100(1.04)  LDD1619  [7]
 LDCM0416  CL28 HEK-293T C100(1.18)  LDD1620  [7]
 LDCM0417  CL29 HEK-293T C100(0.98)  LDD1621  [7]
 LDCM0418  CL3 HEK-293T C100(1.07)  LDD1622  [7]
 LDCM0419  CL30 HEK-293T C100(0.73)  LDD1623  [7]
 LDCM0420  CL31 HEK-293T C100(0.97)  LDD1624  [7]
 LDCM0423  CL34 HEK-293T C100(1.09)  LDD1627  [7]
 LDCM0424  CL35 HEK-293T C100(0.99); C184(1.15)  LDD1628  [7]
 LDCM0425  CL36 HEK-293T C100(0.97)  LDD1629  [7]
 LDCM0426  CL37 HEK-293T C100(0.83); C184(1.13)  LDD1630  [7]
 LDCM0428  CL39 HEK-293T C100(1.95)  LDD1632  [7]
 LDCM0429  CL4 HEK-293T C100(1.08)  LDD1633  [7]
 LDCM0430  CL40 HEK-293T C100(1.02)  LDD1634  [7]
 LDCM0431  CL41 HEK-293T C100(1.04)  LDD1635  [7]
 LDCM0432  CL42 HEK-293T C100(0.86)  LDD1636  [7]
 LDCM0433  CL43 HEK-293T C100(0.91)  LDD1637  [7]
 LDCM0436  CL46 HEK-293T C100(0.84)  LDD1640  [7]
 LDCM0437  CL47 HEK-293T C100(0.99); C184(1.15)  LDD1641  [7]
 LDCM0438  CL48 HEK-293T C100(1.17)  LDD1642  [7]
 LDCM0439  CL49 HEK-293T C100(0.81); C184(1.17)  LDD1643  [7]
 LDCM0440  CL5 HEK-293T C100(1.13)  LDD1644  [7]
 LDCM0441  CL50 HEK-293T C100(0.98)  LDD1645  [7]
 LDCM0443  CL52 HEK-293T C100(1.01)  LDD1646  [7]
 LDCM0444  CL53 HEK-293T C100(0.89)  LDD1647  [7]
 LDCM0445  CL54 HEK-293T C100(0.92)  LDD1648  [7]
 LDCM0446  CL55 HEK-293T C100(1.00)  LDD1649  [7]
 LDCM0449  CL58 HEK-293T C100(0.96)  LDD1652  [7]
 LDCM0450  CL59 HEK-293T C100(1.09); C184(1.22)  LDD1653  [7]
 LDCM0451  CL6 HEK-293T C100(0.89)  LDD1654  [7]
 LDCM0452  CL60 HEK-293T C100(1.15)  LDD1655  [7]
 LDCM0453  CL61 HEK-293T C100(0.89); C184(1.01)  LDD1656  [7]
 LDCM0454  CL62 HEK-293T C100(0.97)  LDD1657  [7]
 LDCM0455  CL63 HEK-293T C100(1.16)  LDD1658  [7]
 LDCM0456  CL64 HEK-293T C100(0.87)  LDD1659  [7]
 LDCM0457  CL65 HEK-293T C100(1.03)  LDD1660  [7]
 LDCM0458  CL66 HEK-293T C100(0.88)  LDD1661  [7]
 LDCM0459  CL67 HEK-293T C100(1.05)  LDD1662  [7]
 LDCM0462  CL7 HEK-293T C100(0.92)  LDD1665  [7]
 LDCM0463  CL70 HEK-293T C100(1.00)  LDD1666  [7]
 LDCM0464  CL71 HEK-293T C100(1.26); C184(1.18)  LDD1667  [7]
 LDCM0465  CL72 HEK-293T C100(1.06)  LDD1668  [7]
 LDCM0466  CL73 HEK-293T C100(0.92); C184(1.05)  LDD1669  [7]
 LDCM0467  CL74 HEK-293T C100(1.14)  LDD1670  [7]
 LDCM0469  CL76 HEK-293T C100(0.88)  LDD1672  [7]
 LDCM0470  CL77 HEK-293T C100(1.24)  LDD1673  [7]
 LDCM0471  CL78 HEK-293T C100(0.94)  LDD1674  [7]
 LDCM0472  CL79 HEK-293T C100(0.97)  LDD1675  [7]
 LDCM0476  CL82 HEK-293T C100(1.06)  LDD1679  [7]
 LDCM0477  CL83 HEK-293T C100(1.09); C184(1.03)  LDD1680  [7]
 LDCM0478  CL84 HEK-293T C100(1.01)  LDD1681  [7]
 LDCM0479  CL85 HEK-293T C100(0.89); C184(1.07)  LDD1682  [7]
 LDCM0480  CL86 HEK-293T C100(0.97)  LDD1683  [7]
 LDCM0481  CL87 HEK-293T C100(1.31)  LDD1684  [7]
 LDCM0482  CL88 HEK-293T C100(0.97)  LDD1685  [7]
 LDCM0483  CL89 HEK-293T C100(0.78)  LDD1686  [7]
 LDCM0485  CL90 HEK-293T C100(0.93)  LDD1688  [7]
 LDCM0486  CL91 HEK-293T C100(0.78)  LDD1689  [7]
 LDCM0489  CL94 HEK-293T C100(1.12)  LDD1692  [7]
 LDCM0490  CL95 HEK-293T C100(0.88); C184(1.06)  LDD1693  [7]
 LDCM0491  CL96 HEK-293T C100(0.98)  LDD1694  [7]
 LDCM0492  CL97 HEK-293T C100(0.91); C184(1.04)  LDD1695  [7]
 LDCM0493  CL98 HEK-293T C100(1.23)  LDD1696  [7]
 LDCM0494  CL99 HEK-293T C100(1.40)  LDD1697  [7]
 LDCM0495  E2913 HEK-293T C100(1.77)  LDD1698  [7]
 LDCM0625  F8 Ramos C184(1.51)  LDD2187  [8]
 LDCM0572  Fragment10 Ramos C184(1.61)  LDD2189  [8]
 LDCM0574  Fragment12 Ramos C184(0.68)  LDD2191  [8]
 LDCM0575  Fragment13 Ramos C184(0.98)  LDD2192  [8]
 LDCM0576  Fragment14 Ramos C184(0.73)  LDD2193  [8]
 LDCM0579  Fragment20 Ramos C184(0.75)  LDD2194  [8]
 LDCM0580  Fragment21 Ramos C184(0.69)  LDD2195  [8]
 LDCM0582  Fragment23 Ramos C184(0.82)  LDD2196  [8]
 LDCM0578  Fragment27 Ramos C184(0.74)  LDD2197  [8]
 LDCM0586  Fragment28 Ramos C184(0.55)  LDD2198  [8]
 LDCM0588  Fragment30 Ramos C184(0.46)  LDD2199  [8]
 LDCM0589  Fragment31 Ramos C184(0.79)  LDD2200  [8]
 LDCM0590  Fragment32 Ramos C184(1.91)  LDD2201  [8]
 LDCM0468  Fragment33 HEK-293T C100(1.30)  LDD1671  [7]
 LDCM0596  Fragment38 Ramos C184(0.73)  LDD2203  [8]
 LDCM0566  Fragment4 Ramos C184(0.97)  LDD2184  [8]
 LDCM0427  Fragment51 HEK-293T C100(1.15)  LDD1631  [7]
 LDCM0610  Fragment52 Ramos C184(1.01)  LDD2204  [8]
 LDCM0614  Fragment56 Ramos C184(0.99)  LDD2205  [8]
 LDCM0569  Fragment7 Ramos C184(1.41)  LDD2186  [8]
 LDCM0022  KB02 22RV1 C184(1.96)  LDD2243  [3]
 LDCM0023  KB03 Ramos C184(0.79)  LDD2183  [8]
 LDCM0024  KB05 HMCB C184(2.74)  LDD3312  [3]
 LDCM0131  RA190 MM1.R C184(1.06)  LDD0304  [9]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Methylmalonyl-CoA mutase, mitochondrial (MMUT) Methylmalonyl-CoA mutase family P22033
Methylmalonic aciduria type A protein, mitochondrial (MMAA) SIMIBI class G3E GTPase family Q8IVH4

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cyanocobalamin Small molecular drug DB00115
Hydroxocobalamin Small molecular drug DB00200

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
3 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
4 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
5 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
6 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
7 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
8 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
9 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell Chem Biol. 2020 Nov 19;27(11):1371-1382.e6. doi: 10.1016/j.chembiol.2020.08.007. Epub 2020 Aug 27.