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Conserved domains on  [gi|1034583969|ref|XP_016875922|]
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calcium uptake protein 2, mitochondrial isoform X4 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EFh_MICU super family cl28896
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
 1-213 3.10e-75

EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, MICU3, and similar proteins; This family includes mitochondrial calcium uptake protein MICU1 and its two additional paralogs, MICU2 and MICU3. MICU1 localizes to the inner mitochondrial membrane (IMM). It functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) and regulates MCU-mediated mitochondrial Ca2+ uptake, which is essential for maintaining mitochondrial homoeostasis. MICU1 and MICU2 are physically associated within the uniporter complex and are co-expressed across all tissues. They may play non-redundant roles in the regulation of the mitochondrial calcium uniporter. At present, the precise molecular function of MICU2 and MICU3 remain unclear. MICU2 may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU3 likely has a role in mitochondrial calcium handling. All members in this family contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


The actual alignment was detected with superfamily member cd16174:

Pssm-ID: 333716 [Multi-domain]  Cd Length: 154  Bit Score: 225.13  E-value: 3.10e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969   1 MLDTDGNEMIEKREFFKLQKIISKQDDLMTVKTNETgYQEAIVKEPEINTTLQMRFFGKRGQRKLHYKEFRRFMENLQTE 80
Cdd:cd16174     8 MLDTDGNEQVEKREFFKLQKIIGKKDDLMTQGGTET-YQEASDNSDEVNTTLQVHFFGKDGNEKLQYKEFCRFMENLQTE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969  81 IqemeflqfskglsfmrkedfaewllfftntenkdiywknvreklsagesisldefksfchftthlEDFAIAMQMFSLAH 160
Cdd:cd16174    87 V-----------------------------------------------------------------EDFAIAMKMFSEAN 101

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034583969 161 RPVRLAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRM 213
Cdd:cd16174   102 RPIKLAEFKRAVKVATGQELSDNVLDTVFKIFDLDGDDCLSHGEFLGVLKNRV 154
 
Name Accession Description Interval E-value
EFh_MICU2 cd16174
EF-hand, calcium binding motif, found in calcium uptake protein 2, mitochondrial (MICU2) and ...
 1-213 3.10e-75

EF-hand, calcium binding motif, found in calcium uptake protein 2, mitochondrial (MICU2) and similar proteins; MICU2, also termed EF-hand domain-containing family member A1 (EFHA1), is a mitochondrial-localized paralog of MICU1. MICU2 and its paralog, MICU1, are physically associated within the mitochondrial calcium uniporter (MCU) complex and are co-expressed across all tissues. They may operate together with MCU to regulate the channel. At present, the precise molecular function of MICU2 remains unclear. It may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU2 contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320082 [Multi-domain]  Cd Length: 154  Bit Score: 225.13  E-value: 3.10e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969   1 MLDTDGNEMIEKREFFKLQKIISKQDDLMTVKTNETgYQEAIVKEPEINTTLQMRFFGKRGQRKLHYKEFRRFMENLQTE 80
Cdd:cd16174     8 MLDTDGNEQVEKREFFKLQKIIGKKDDLMTQGGTET-YQEASDNSDEVNTTLQVHFFGKDGNEKLQYKEFCRFMENLQTE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969  81 IqemeflqfskglsfmrkedfaewllfftntenkdiywknvreklsagesisldefksfchftthlEDFAIAMQMFSLAH 160
Cdd:cd16174    87 V-----------------------------------------------------------------EDFAIAMKMFSEAN 101

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034583969 161 RPVRLAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRM 213
Cdd:cd16174   102 RPIKLAEFKRAVKVATGQELSDNVLDTVFKIFDLDGDDCLSHGEFLGVLKNRV 154
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
129-206 1.93e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 40.55  E-value: 1.93e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969 129 ESISLDEFKSFCHFTTHLEDFAIAMQMFSLAHRP----VRLAEFKRAVKVAtgqELSNNILDTVFKIFDLDGDECLSHEE 204
Cdd:COG5126    48 GRISREEFVAGMESLFEATVEPFARAAFDLLDTDgdgkISADEFRRLLTAL---GVSEEEADELFARLDTDGDGKISFEE 124


                  ..
gi 1034583969 205 FL 206
Cdd:COG5126   125 FV 126
EF-hand_8 pfam13833
EF-hand domain pair;
166-212 8.17e-04

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 36.52  E-value: 8.17e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034583969 166 AEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNR 212
Cdd:pfam13833   8 EELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
 
Name Accession Description Interval E-value
EFh_MICU2 cd16174
EF-hand, calcium binding motif, found in calcium uptake protein 2, mitochondrial (MICU2) and ...
 1-213 3.10e-75

EF-hand, calcium binding motif, found in calcium uptake protein 2, mitochondrial (MICU2) and similar proteins; MICU2, also termed EF-hand domain-containing family member A1 (EFHA1), is a mitochondrial-localized paralog of MICU1. MICU2 and its paralog, MICU1, are physically associated within the mitochondrial calcium uniporter (MCU) complex and are co-expressed across all tissues. They may operate together with MCU to regulate the channel. At present, the precise molecular function of MICU2 remains unclear. It may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU2 contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320082 [Multi-domain]  Cd Length: 154  Bit Score: 225.13  E-value: 3.10e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969   1 MLDTDGNEMIEKREFFKLQKIISKQDDLMTVKTNETgYQEAIVKEPEINTTLQMRFFGKRGQRKLHYKEFRRFMENLQTE 80
Cdd:cd16174     8 MLDTDGNEQVEKREFFKLQKIIGKKDDLMTQGGTET-YQEASDNSDEVNTTLQVHFFGKDGNEKLQYKEFCRFMENLQTE 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969  81 IqemeflqfskglsfmrkedfaewllfftntenkdiywknvreklsagesisldefksfchftthlEDFAIAMQMFSLAH 160
Cdd:cd16174    87 V-----------------------------------------------------------------EDFAIAMKMFSEAN 101

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034583969 161 RPVRLAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRM 213
Cdd:cd16174   102 RPIKLAEFKRAVKVATGQELSDNVLDTVFKIFDLDGDDCLSHGEFLGVLKNRV 154
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
 1-213 8.41e-51

EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, MICU3, and similar proteins; This family includes mitochondrial calcium uptake protein MICU1 and its two additional paralogs, MICU2 and MICU3. MICU1 localizes to the inner mitochondrial membrane (IMM). It functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) and regulates MCU-mediated mitochondrial Ca2+ uptake, which is essential for maintaining mitochondrial homoeostasis. MICU1 and MICU2 are physically associated within the uniporter complex and are co-expressed across all tissues. They may play non-redundant roles in the regulation of the mitochondrial calcium uniporter. At present, the precise molecular function of MICU2 and MICU3 remain unclear. MICU2 may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU3 likely has a role in mitochondrial calcium handling. All members in this family contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320080 [Multi-domain]  Cd Length: 152  Bit Score: 163.17  E-value: 8.41e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969   1 MLDTDGNEMIEKREFFKLQKIISKQDDLMTVKTNETGyqeAIVKEPEINTTLQMRFFGKRGQRKLHYKEFRRFMENLQTE 80
Cdd:cd15900     8 MFDLDGDGELDKEEFNKVQSIIRSQTSVGQRHRDHTN---GESTKLGMNSTLARYFFGKDGKQKLSIEKFLEFQENLQEE 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969  81 IqemeflqfskglsfmrkedfaewllfftntenkdiywknvreklsagesisldefksfchftthlEDFAIAMQMFSLAH 160
Cdd:cd15900    85 I-----------------------------------------------------------------DDVDTALTFYHLAG 99

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034583969 161 RPVRLAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRM 213
Cdd:cd15900   100 ASIDRKTFKRAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMKDRL 152
EFh_MICU3 cd16175
EF-hand, calcium binding motif, found in calcium uptake protein 3, mitochondrial (MICU3) and ...
 1-213 4.69e-32

EF-hand, calcium binding motif, found in calcium uptake protein 3, mitochondrial (MICU3) and similar proteins; MICU3, also termed EF-hand domain-containing family member A2 (EFHA2), is a paralog of MICU1 and notably found in the central nervous system (CNS) and skeletal muscle. At present, the precise molecular function of MICU3 remains unclear. It likely has a role in mitochondrial calcium handling. MICU3 contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320083 [Multi-domain]  Cd Length: 128  Bit Score: 114.15  E-value: 4.69e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969   1 MLDTDGNEMIEKREFFKLQKIISkqddlmtvktnetgyqeaivkepeintTLQMRFFGKRGQRKLHYKEFRRFMENLQTE 80
Cdd:cd16175     8 MFDTDGNEMVDKKEFLVLQEIFR---------------------------TLLVHFFGKKGKAELNFEDFYRFMDNLQTE 60

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969  81 IqemeflqfskglsfmrkedfaewllfftntenkdiywknvreklsagesisldefksfchftthlEDFAIAMQMFSLAH 160
Cdd:cd16175    61 V-----------------------------------------------------------------EDFTIAMRMYTFAD 75

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034583969 161 RPVRLAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRM 213
Cdd:cd16175    76 RSISQDEFARAVKVCTGLKLSPHLVNTVFKIFDVDGDGQLSYKEFIGIMKDRL 128
EFh_MICU1 cd16173
EF-hand, calcium binding motif, found in calcium uptake protein 1, mitochondrial (MICU1) and ...
 137-213 5.73e-05

EF-hand, calcium binding motif, found in calcium uptake protein 1, mitochondrial (MICU1) and similar proteins; MICU1, also termed atopy-related autoantigen CALC (ara CALC), or calcium-binding atopy-related autoantigen 1 (CBARA1), or Hom s 4, or EFHA3, localizes to the inner mitochondrial membrane (IMM). It functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) and regulates MCU-mediated mitochondrial Ca2+ uptake, which is essential for maintaining mitochondrial homoeostasis. MICU1 and its paralog, MICU2, are physically associated within the uniporter complex and are co-expressed across all tissues. They may operate together with MCU to regulate the channel. The mutations in MICU1 are associated with neuromuscular abnormalities in children. MICU1 contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320081 [Multi-domain]  Cd Length: 153  Bit Score: 42.32  E-value: 5.73e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969 137 KSFCHFTTHLE----DFAIAMQMFSLAHRPVRLAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNR 212
Cdd:cd16173    73 KNFLEFQRKLQhdvnDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVAIMKQR 152


                  .
gi 1034583969 213 M 213
Cdd:cd16173   153 L 153
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
129-206 1.93e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 40.55  E-value: 1.93e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034583969 129 ESISLDEFKSFCHFTTHLEDFAIAMQMFSLAHRP----VRLAEFKRAVKVAtgqELSNNILDTVFKIFDLDGDECLSHEE 204
Cdd:COG5126    48 GRISREEFVAGMESLFEATVEPFARAAFDLLDTDgdgkISADEFRRLLTAL---GVSEEEADELFARLDTDGDGKISFEE 124


                  ..
gi 1034583969 205 FL 206
Cdd:COG5126   125 FV 126
EF-hand_8 pfam13833
EF-hand domain pair;
166-212 8.17e-04

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 36.52  E-value: 8.17e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1034583969 166 AEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNR 212
Cdd:pfam13833   8 EELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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