NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|125660124|gb|ABN49290|]
View 

IP17639p [Drosophila melanogaster]

Protein Classification

calcium uptake protein( domain architecture ID 11610295)

mitochondrial calcium uptake protein (MICU) may act as a key regulator of mitochondrial calcium uniporter (MCU)

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
 272-492 8.11e-72

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: 225.57  E-value: 8.11e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 272 HFEIAFRMFDLNGDGDVDCEEFEMVATLVRQQTSMGTRHRDHANTGNTFKGVNSALITYFFGPNMDEKLTIEKFLDFQEQ 351
Cdd:cd15900    1 HFEIAFKMFDLDGDGELDKEEFNKVQSIIRSQTSVGQRHRDHTNGESTKLGMNSTLARYFFGKDGKQKLSIEKFLEFQEN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 352 LQREilsleferkepndegniteadfaelllayagyplkkkqkklkrvkrrfrdhgkgiskqdyldffhflnnINDVDTA 431
Cdd:cd15900   81 LQEE---------------------------------------------------------------------IDDVDTA 91

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 125660124 432 LTFYHIAGASIDQQTLQHVAKTVAMVNLSDHVVDVVFTIFDENNDNQLSNKEFISVMKNRV 492
Cdd:cd15900   92 LTFYHLAGASIDRKTFKRAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMKDRL 152
 
Name Accession Description Interval E-value
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
 272-492 8.11e-72

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: 225.57  E-value: 8.11e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 272 HFEIAFRMFDLNGDGDVDCEEFEMVATLVRQQTSMGTRHRDHANTGNTFKGVNSALITYFFGPNMDEKLTIEKFLDFQEQ 351
Cdd:cd15900    1 HFEIAFKMFDLDGDGELDKEEFNKVQSIIRSQTSVGQRHRDHTNGESTKLGMNSTLARYFFGKDGKQKLSIEKFLEFQEN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 352 LQREilsleferkepndegniteadfaelllayagyplkkkqkklkrvkrrfrdhgkgiskqdyldffhflnnINDVDTA 431
Cdd:cd15900   81 LQEE---------------------------------------------------------------------IDDVDTA 91

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 125660124 432 LTFYHIAGASIDQQTLQHVAKTVAMVNLSDHVVDVVFTIFDENNDNQLSNKEFISVMKNRV 492
Cdd:cd15900   92 LTFYHLAGASIDRKTFKRAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMKDRL 152
EF-hand_8 pfam13833
EF-hand domain pair;
439-491 1.35e-06

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 45.38  E-value: 1.35e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 125660124  439 GASIDQQTLQHVAKTVAMVNLSDHVVDVVFTIFDENNDNQLSNKEFISVMKNR 491
Cdd:pfam13833   2 KGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
252-293 3.10e-04

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 40.93  E-value: 3.10e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 125660124 252 GLITFSDYIFLLTVLSISRRHFEIAFRMFDLNGDGDVDCEEF 293
Cdd:COG5126   84 GKISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEF 125
 
Name Accession Description Interval E-value
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
 272-492 8.11e-72

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: 225.57  E-value: 8.11e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 272 HFEIAFRMFDLNGDGDVDCEEFEMVATLVRQQTSMGTRHRDHANTGNTFKGVNSALITYFFGPNMDEKLTIEKFLDFQEQ 351
Cdd:cd15900    1 HFEIAFKMFDLDGDGELDKEEFNKVQSIIRSQTSVGQRHRDHTNGESTKLGMNSTLARYFFGKDGKQKLSIEKFLEFQEN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 352 LQREilsleferkepndegniteadfaelllayagyplkkkqkklkrvkrrfrdhgkgiskqdyldffhflnnINDVDTA 431
Cdd:cd15900   81 LQEE---------------------------------------------------------------------IDDVDTA 91

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 125660124 432 LTFYHIAGASIDQQTLQHVAKTVAMVNLSDHVVDVVFTIFDENNDNQLSNKEFISVMKNRV 492
Cdd:cd15900   92 LTFYHLAGASIDRKTFKRAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMKDRL 152
EFh_MICU1 cd16173
EF-hand, calcium binding motif, found in calcium uptake protein 1, mitochondrial (MICU1) and ...
 272-492 1.30e-46

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: 159.80  E-value: 1.30e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 272 HFEIAFRMFDLNGDGDVDCEEFEMVATLVRQQTSMGTRHRDHANTGNTFK-GVNSALITYFFGPNMDEKLTIEKFLDFQE 350
Cdd:cd16173    1 NFEIAFKMFDLNGDGEVDMEEFEQVQSIIRSQTSMGMRHRDRSTTGNTLKtGFSSALTTYFFGADLKGKLTIKNFLEFQR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 351 QLQreilsleferkepndegniteadfaelllayagyplkkkqkklkrvkrrfrdhgkgiskqdyldffhflNNINDVDT 430
Cdd:cd16173   81 KLQ---------------------------------------------------------------------HDVNDVDT 91

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 125660124 431 ALTFYHIAGASIDQQTLQHVAKTVAMVNLSDHVVDVVFTIFDENNDNQLSNKEFISVMKNRV 492
Cdd:cd16173   92 ALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVAIMKQRL 153
EFh_MICU3 cd16175
EF-hand, calcium binding motif, found in calcium uptake protein 3, mitochondrial (MICU3) and ...
 408-492 3.22e-11

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: 60.99  E-value: 3.22e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 408 KGISKQDYLDFFHFLNN----INDVDTALTFYHIAGASIDQQTLQHVAKTVAMVNLSDHVVDVVFTIFDENNDNQLSNKE 483
Cdd:cd16175   40 KGKAELNFEDFYRFMDNlqteVEDFTIAMRMYTFADRSISQDEFARAVKVCTGLKLSPHLVNTVFKIFDVDGDGQLSYKE 119


                 ....*....
gi 125660124 484 FISVMKNRV 492
Cdd:cd16175  120 FIGIMKDRL 128
EFh_MICU2 cd16174
EF-hand, calcium binding motif, found in calcium uptake protein 2, mitochondrial (MICU2) and ...
 273-492 1.71e-09

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: 56.42  E-value: 1.71e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 273 FEIAFRMFDLNGDGDVDCEEFEMVATLVRQQTSMGTRHRDHANTGNTFK--GVNSALITYFFGPNMDEKLTIEKFLDFQE 350
Cdd:cd16174    2 FHIAFKMLDTDGNEQVEKREFFKLQKIIGKKDDLMTQGGTETYQEASDNsdEVNTTLQVHFFGKDGNEKLQYKEFCRFME 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125660124 351 QLQREIlsleferkepndegniteADFAelllayagyplkkkqkklkrvkrrfrdhgkgiskqdyldffhflnnindvdT 430
Cdd:cd16174   82 NLQTEV------------------EDFA---------------------------------------------------I 92

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 125660124 431 ALTFYHIAGASIDQQTLQHVAKTVAMVNLSDHVVDVVFTIFDENNDNQLSNKEFISVMKNRV 492
Cdd:cd16174   93 AMKMFSEANRPIKLAEFKRAVKVATGQELSDNVLDTVFKIFDLDGDDCLSHGEFLGVLKNRV 154
EF-hand_8 pfam13833
EF-hand domain pair;
439-491 1.35e-06

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 45.38  E-value: 1.35e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 125660124  439 GASIDQQTLQHVAKTVAMVNLSDHVVDVVFTIFDENNDNQLSNKEFISVMKNR 491
Cdd:pfam13833   2 KGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
252-293 3.10e-04

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 40.93  E-value: 3.10e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 125660124 252 GLITFSDYIFLLTVLSISRRHFEIAFRMFDLNGDGDVDCEEF 293
Cdd:COG5126   84 GKISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEF 125
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 252-293 6.26e-03

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 35.22  E-value: 6.26e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 125660124 252 GLITFSDYIFLLTVLSI--SRRHFEIAFRMFDLNGDGDVDCEEF 293
Cdd:cd00051   15 GTISADELKAALKSLGEglSEEEIDEMIREVDKDGDGKIDFEEF 58
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH