Calcium uptake protein 1, mitochondrial (Atopy-related autoantigen CALC) (ara CALC) (Calcium-binding atopy-related autoantigen 1) (allergen Hom s 4)
1_MFRLN 6_ SLSAL 11_ AELAV 16_ GSRWY 21_ HGGSQ 26_ PIQIR 31_ RRLMM 36_ VAFLG 41_ ASAVT 46_ ASTGL 51_ LWKRA 56_ HAESP 61_ PCVDN 66_ LKSDI 71_ GDKGK 76_ NKDEG 81_ DVCNH 86_ EKKTA 91_ DLAPH 96_ PEEKK 101_ KKRSG 106_ FRDRK 111_ VMEYE 116_ NRIRA 121_ YSTPD 126_ KIFRY 131_ FATLK 136_ VISEP 141_ GEAEV 146_ FMTPE 151_ DFVRS 156_ ITPNE 161_ KQPEH 166_ LGLDQ 171_ YIIKR 176_ FDGKK 181_ ISQER 186_ EKFAD 191_ EGSIF 196_ YTLGE 201_ CGLIS 206_ FSDYI 211_ FLTTV 216_ LSTPQ 221_ RNFEI 226_ AFKMF 231_ DLNGD 236_ GEVDM 241_ EEFEQ 246_ VQSII 251_ RSQTS 256_ MGMRH 261_ RDRPT 266_ TGNTL 271_ KSGLC 276_ SALTT 281_ YFFGA 286_ DLKGK 291_ LTIKN 296_ FLEFQ 301_ RKLQH 306_ DVLKL 311_ EFERH 316_ DPVDG 321_ RITER 326_ QFGGM 331_ LLAYS 336_ GVQSK 341_ KLTAM 346_ QRQLK 351_ KHFKE 356_ GKGLT 361_ FQEVE 366_ NFFTF 371_ LKNIN 376_ DVDTA 381_ LSFYH 386_ MAGAS 391_ LDKVT 396_ MQQVA 401_ RTVAK 406_ VELSD 411_ HVCDV 416_ VFALF 421_ DCDGN 426_ GELSN 431_ KEFVS 436_ IMKQR 441_ LMRGL 446_ EKPKD 451_ MGFTR 456_ LMQAM 461_ WKCAQ 466_ ETAWD 471_FALPK
1: Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains (PubMed:20693986, PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854, PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221, PubMed:27099988, PubMed:28615291, PubMed:30454562, PubMed:30638448, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:34463251, PubMed:36206740, PubMed:37036971, PubMed:37126688). MICU1 and MICU2 (or MICU3) form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (PubMed:24560927, PubMed:26903221, PubMed:28615291, PubMed:32148862, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:36206740, PubMed:37036971, PubMed:37126688). At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake (PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:37036971, PubMed:37126688). At higher calcium levels, calcium-binding to MICU1 and MICU2 (or MICU3) induces a conformational change that weakens MCU-MICU1 interactions and moves the MICU1-MICU2 heterodimer away from the pore, allowing calcium permeation through the MCU channel (PubMed:32494073, PubMed:32667285, PubMed:32762847). Also required to protect against manganese toxicity by preventing manganese uptake by MCU: mechanistically, manganese-binding to its EF-hand domains does not induce any conformational change, maintaining MCU pore occlusion (PubMed:30082385, PubMed:30403999). Also acts as a barrier for inhibitors of the MCU channel, such as ruthenium red or its derivative Ru360 (PubMed:37244260). Acts as a regulator of mitochondrial cristae structure independently of its ability to regulate the mitochondrial calcium uniporter channel (PubMed:31427612, PubMed:37098122). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (PubMed:16002733)
2: Isoform that regulates mitochondrial calcium uniporter (MCU) in the skeletal muscle (By similarity). Compared to other isoforms, this isoform has higher affinity for calcium, promoting mitochondrial calcium uptake at lower calcium concentrations (By similarity). This allows a rapid response of mitochondrial metabolism and ensures sustained ATP production needed for resistance and strenuous exercise (By similarity)