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Conserved domains on  [gi|2504391378|ref|XP_055952397|]
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calcium uptake protein 1 homolog, mitochondrial-like isoform X1 [Argiope bruennichi]

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

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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, ...
 272-491 9.73e-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.


:

Pssm-ID: 320080 [Multi-domain]  Cd Length: 152  Bit Score: 232.89  E-value: 9.73e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 272 HFEIAFRMFDLNGDGNVDYEEFEKVQTIIRSQTSVGMRHRDHSNTGSIYKFMGSALSTYFFGPNLDKKLTIEKFLEFQHQ 351
Cdd:cd15900     1 HFEIAFKMFDLDGDGELDKEEFNKVQSIIRSQTSVGQRHRDHTNGESTKLGMNSTLARYFFGKDGKQKLSIEKFLEFQEN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 352 LQTEiltlefqrkrpnadgyirevdfadllltyaglsekkhvkmlkrvkkifknsrgislddyllffhflndINDVDTAL 431
Cdd:cd15900    81 LQEE--------------------------------------------------------------------IDDVDTAL 92

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 432 TFYHIAGASIDQATLKHVAKTVTHLDLSDHVIDVVFTLFDENSDGQLSNREFVAVMKDRL 491
Cdd:cd15900    93 TFYHLAGASIDRKTFKRAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMKDRL 152
 
Name Accession Description Interval E-value
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
 272-491 9.73e-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.


Pssm-ID: 320080 [Multi-domain]  Cd Length: 152  Bit Score: 232.89  E-value: 9.73e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 272 HFEIAFRMFDLNGDGNVDYEEFEKVQTIIRSQTSVGMRHRDHSNTGSIYKFMGSALSTYFFGPNLDKKLTIEKFLEFQHQ 351
Cdd:cd15900     1 HFEIAFKMFDLDGDGELDKEEFNKVQSIIRSQTSVGQRHRDHTNGESTKLGMNSTLARYFFGKDGKQKLSIEKFLEFQEN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 352 LQTEiltlefqrkrpnadgyirevdfadllltyaglsekkhvkmlkrvkkifknsrgislddyllffhflndINDVDTAL 431
Cdd:cd15900    81 LQEE--------------------------------------------------------------------IDDVDTAL 92

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 432 TFYHIAGASIDQATLKHVAKTVTHLDLSDHVIDVVFTLFDENSDGQLSNREFVAVMKDRL 491
Cdd:cd15900    93 TFYHLAGASIDRKTFKRAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMKDRL 152
EF-hand_8 pfam13833
EF-hand domain pair;
438-490 3.04e-05

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 41.53  E-value: 3.04e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2504391378 438 GASIDQATLKHVAKTVTHLDLSDHVIDVVFTLFDENSDGQLSNREFVAVMKDR 490
Cdd:pfam13833   2 KGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
253-293 1.58e-03

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 39.00  E-value: 1.58e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2504391378 253 LIGFSEYMFLITILSASKRHFEIAFRMFDLNGDGNVDYEEF 293
Cdd:COG5126    85 KISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEF 125
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 276-296 2.18e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.43  E-value: 2.18e-03
                           10        20
                   ....*....|....*....|.
gi 2504391378  276 AFRMFDLNGDGNVDYEEFEKV 296
Cdd:smart00054   5 AFRLFDKDGDGKIDFEEFKDL 25
 
Name Accession Description Interval E-value
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
 272-491 9.73e-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.


Pssm-ID: 320080 [Multi-domain]  Cd Length: 152  Bit Score: 232.89  E-value: 9.73e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 272 HFEIAFRMFDLNGDGNVDYEEFEKVQTIIRSQTSVGMRHRDHSNTGSIYKFMGSALSTYFFGPNLDKKLTIEKFLEFQHQ 351
Cdd:cd15900     1 HFEIAFKMFDLDGDGELDKEEFNKVQSIIRSQTSVGQRHRDHTNGESTKLGMNSTLARYFFGKDGKQKLSIEKFLEFQEN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 352 LQTEiltlefqrkrpnadgyirevdfadllltyaglsekkhvkmlkrvkkifknsrgislddyllffhflndINDVDTAL 431
Cdd:cd15900    81 LQEE--------------------------------------------------------------------IDDVDTAL 92

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 432 TFYHIAGASIDQATLKHVAKTVTHLDLSDHVIDVVFTLFDENSDGQLSNREFVAVMKDRL 491
Cdd:cd15900    93 TFYHLAGASIDRKTFKRAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMKDRL 152
EFh_MICU1 cd16173
EF-hand, calcium binding motif, found in calcium uptake protein 1, mitochondrial (MICU1) and ...
 272-491 7.45e-51

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: 170.97  E-value: 7.45e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 272 HFEIAFRMFDLNGDGNVDYEEFEKVQTIIRSQTSVGMRHRDHSNTGSIYKF-MGSALSTYFFGPNLDKKLTIEKFLEFQH 350
Cdd:cd16173     1 NFEIAFKMFDLNGDGEVDMEEFEQVQSIIRSQTSMGMRHRDRSTTGNTLKTgFSSALTTYFFGADLKGKLTIKNFLEFQR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 351 QLQteiltlefqrkrpnadgyirevdfadllltyaglsekkhvkmlkrvkkifknsrgislddyllffhflNDINDVDTA 430
Cdd:cd16173    81 KLQ--------------------------------------------------------------------HDVNDVDTA 92

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2504391378 431 LTFYHIAGASIDQATLKHVAKTVTHLDLSDHVIDVVFTLFDENSDGQLSNREFVAVMKDRL 491
Cdd:cd16173    93 LSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVAIMKQRL 153
EFh_MICU3 cd16175
EF-hand, calcium binding motif, found in calcium uptake protein 3, mitochondrial (MICU3) and ...
 273-491 6.96e-14

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: 68.31  E-value: 6.96e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 273 FEIAFRMFDLNGDGNVDYEEFEKVQTIIRSqtsvgmrhrdhsntgsiykfmgsaLSTYFFGPNLDKKLTIEKFLEFQHQL 352
Cdd:cd16175     2 FRIAFNMFDTDGNEMVDKKEFLVLQEIFRT------------------------LLVHFFGKKGKAELNFEDFYRFMDNL 57

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 353 QTEIltlefqrkrpnadgyirevdfadllltyaglsekkhvkmlkrvkkifknsrgislddyllffhflndiNDVDTALT 432
Cdd:cd16175    58 QTEV--------------------------------------------------------------------EDFTIAMR 69

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2504391378 433 FYHIAGASIDQATLKHVAKTVTHLDLSDHVIDVVFTLFDENSDGQLSNREFVAVMKDRL 491
Cdd:cd16175    70 MYTFADRSISQDEFARAVKVCTGLKLSPHLVNTVFKIFDVDGDGQLSYKEFIGIMKDRL 128
EFh_MICU2 cd16174
EF-hand, calcium binding motif, found in calcium uptake protein 2, mitochondrial (MICU2) and ...
 273-491 2.59e-11

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: 61.81  E-value: 2.59e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 273 FEIAFRMFDLNGDGNVDYEEFEKVQTIIRSQTSVGMRHRDHSNTGSIYKFMG--SALSTYFFGPNLDKKLTIEKFLEFQH 350
Cdd:cd16174     2 FHIAFKMLDTDGNEQVEKREFFKLQKIIGKKDDLMTQGGTETYQEASDNSDEvnTTLQVHFFGKDGNEKLQYKEFCRFME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2504391378 351 QLQTEIltlefqrkrpnadgyirevdfadllltyaglsekkhvkmlkrvkkifknsrgislddyllffhflndiNDVDTA 430
Cdd:cd16174    82 NLQTEV--------------------------------------------------------------------EDFAIA 93

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2504391378 431 LTFYHIAGASIDQATLKHVAKTVTHLDLSDHVIDVVFTLFDENSDGQLSNREFVAVMKDRL 491
Cdd:cd16174    94 MKMFSEANRPIKLAEFKRAVKVATGQELSDNVLDTVFKIFDLDGDDCLSHGEFLGVLKNRV 154
EF-hand_8 pfam13833
EF-hand domain pair;
438-490 3.04e-05

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 41.53  E-value: 3.04e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2504391378 438 GASIDQATLKHVAKTVTHLDLSDHVIDVVFTLFDENSDGQLSNREFVAVMKDR 490
Cdd:pfam13833   2 KGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
253-293 1.58e-03

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 39.00  E-value: 1.58e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2504391378 253 LIGFSEYMFLITILSASKRHFEIAFRMFDLNGDGNVDYEEF 293
Cdd:COG5126    85 KISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEF 125
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 276-296 2.18e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.43  E-value: 2.18e-03
                           10        20
                   ....*....|....*....|.
gi 2504391378  276 AFRMFDLNGDGNVDYEEFEKV 296
Cdd:smart00054   5 AFRLFDKDGDGKIDFEEFKDL 25
EF-hand_5 pfam13202
EF hand;
273-296 3.69e-03

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 34.99  E-value: 3.69e-03
                          10        20
                  ....*....|....*....|....
gi 2504391378 273 FEIAFRMFDLNGDGNVDYEEFEKV 296
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRRL 24
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 272-296 3.91e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 35.07  E-value: 3.91e-03
                          10        20
                  ....*....|....*....|....*
gi 2504391378 272 HFEIAFRMFDLNGDGNVDYEEFEKV 296
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKEL 25
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 262-319 4.05e-03

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 38.35  E-value: 4.05e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2504391378 262 LITILSASKRHFEIA-----FRMFDLNGDGNVDYEEFEKVQTIIrSQTSVGMRHRDHSNTGSI 319
Cdd:cd16185    22 LQKALAGGGLLFSLAtaeklIRMFDRDGNGTIDFEEFAALHQFL-SNMQNGFEQRDTSRSGRL 83
 
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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