LOCUS       NP_001182447             476 aa            linear   PRI 12-JUN-2025
DEFINITION  calcium uptake protein 1, mitochondrial isoform 2 [Homo sapiens].
ACCESSION   NP_001182447
VERSION     NP_001182447.1
DBSOURCE    REFSEQ: accession NM_001195518.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 476)
  AUTHORS   Hasan,P., Berezhnaya,E., Rodriguez-Prados,M., Weaver,D.,
            Bekeova,C., Cartes-Saavedra,B., Birch,E., Beyer,A.M., Santos,J.H.,
            Seifert,E.L., Elrod,J.W. and Hajnoczky,G.
  TITLE     MICU1 and MICU2 control mitochondrial calcium signaling in the
            mammalian heart
  JOURNAL   Proc Natl Acad Sci U S A 121 (35), e2402491121 (2024)
   PUBMED   39163336
  REMARK    GeneRIF: MICU1 and MICU2 control mitochondrial calcium signaling in
            the mammalian heart.
REFERENCE   2  (residues 1 to 476)
  AUTHORS   Rodriguez-Prados,M., Berezhnaya,E., Castromonte,M.T.,
            Menezes-Filho,S.L., Paillard,M. and Hajnoczky,G.
  TITLE     MICU1 occludes the mitochondrial calcium uniporter in divalent-free
            conditions
  JOURNAL   Proc Natl Acad Sci U S A 120 (19), e2218999120 (2023)
   PUBMED   37126688
REFERENCE   3  (residues 1 to 476)
  AUTHORS   Tomar,D., Thomas,M., Garbincius,J.F., Kolmetzky,D.W., Salik,O.,
            Jadiya,P., Joseph,S.K., Carpenter,A.C., Hajnoczky,G. and Elrod,J.W.
  TITLE     MICU1 regulates mitochondrial cristae structure and function
            independently of the mitochondrial Ca2+ uniporter channel
  JOURNAL   Sci Signal 16 (782), eabi8948 (2023)
   PUBMED   37098122
REFERENCE   4  (residues 1 to 476)
  AUTHORS   Tsai,C.W., Liu,T.Y., Chao,F.Y., Tu,Y.C., Rodriguez,M.X., Van
            Keuren,A.M., Ma,Z., Bankston,J. and Tsai,M.F.
  TITLE     Evidence supporting the MICU1 occlusion mechanism and against the
            potentiation model in the mitochondrial calcium uniporter complex
  JOURNAL   Proc Natl Acad Sci U S A 120 (16), e2217665120 (2023)
   PUBMED   37036971
REFERENCE   5  (residues 1 to 476)
  AUTHORS   Mallilankaraman,K., Doonan,P., Cardenas,C., Chandramoorthy,H.C.,
            Muller,M., Miller,R., Hoffman,N.E., Gandhirajan,R.K., Molgo,J.,
            Birnbaum,M.J., Rothberg,B.S., Mak,D.O., Foskett,J.K. and Madesh,M.
  TITLE     MICU1 is an essential gatekeeper for MCU-mediated mitochondrial
            Ca(2+) uptake that regulates cell survival
  JOURNAL   Cell 151 (3), 630-644 (2012)
   PUBMED   23101630
  REMARK    GeneRIF: MICU1 is a gatekeeper of mitochondrial calcium
            uniporter-mediated Ca(2 )uptake that is essential to prevent [Ca(2
            )]overload and associated stress.
REFERENCE   6  (residues 1 to 476)
  AUTHORS   Baughman,J.M., Perocchi,F., Girgis,H.S., Plovanich,M.,
            Belcher-Timme,C.A., Sancak,Y., Bao,X.R., Strittmatter,L.,
            Goldberger,O., Bogorad,R.L., Koteliansky,V. and Mootha,V.K.
  TITLE     Integrative genomics identifies MCU as an essential component of
            the mitochondrial calcium uniporter
  JOURNAL   Nature 476 (7360), 341-345 (2011)
   PUBMED   21685886
  REMARK    GeneRIF: MICU1 physically interacts with MCU, a principal component
            of the mitochondrial calcium uniporter.
            Publication Status: Online-Only
REFERENCE   7  (residues 1 to 476)
  AUTHORS   Hendrickson,S.L., Lautenberger,J.A., Chinn,L.W., Malasky,M.,
            Sezgin,E., Kingsley,L.A., Goedert,J.J., Kirk,G.D., Gomperts,E.D.,
            Buchbinder,S.P., Troyer,J.L. and O'Brien,S.J.
  TITLE     Genetic variants in nuclear-encoded mitochondrial genes influence
            AIDS progression
  JOURNAL   PLoS One 5 (9), e12862 (2010)
   PUBMED   20877624
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
            Publication Status: Online-Only
REFERENCE   8  (residues 1 to 476)
  AUTHORS   Perocchi,F., Gohil,V.M., Girgis,H.S., Bao,X.R., McCombs,J.E.,
            Palmer,A.E. and Mootha,V.K.
  TITLE     MICU1 encodes a mitochondrial EF hand protein required for Ca(2+)
            uptake
  JOURNAL   Nature 467 (7313), 291-296 (2010)
   PUBMED   20693986
  REMARK    GeneRIF: MICU1 represents the founding member of a set of proteins
            required for high-capacity mitochondrial calcium uptake
            GeneRIF: MICU1 (CBARA1) is an EF-hand containing protein associated
            with the mitochondrial inner membrane.  It is required for
            mitochondrial calcium uptake in HeLa cells.
REFERENCE   9  (residues 1 to 476)
  AUTHORS   Bordicchia,M., Battistoni,I., Mancinelli,L., Giannini,E., Refi,G.,
            Minardi,D., Muzzonigro,G., Mazzucchelli,R., Montironi,R.,
            Piscitelli,F., Petrosino,S., Dessi-Fulgheri,P., Rappelli,A., Di
            Marzo,V. and Sarzani,R.
  TITLE     Cannabinoid CB1 receptor expression in relation to visceral adipose
            depots, endocannabinoid levels, microvascular damage, and the
            presence of the Cnr1 A3813G variant in humans
  JOURNAL   Metabolism 59 (5), 734-741 (2010)
   PUBMED   19919870
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   10 (residues 1 to 476)
  AUTHORS   Natter,S., Seiberler,S., Hufnagl,P., Binder,B.R., Hirschl,A.M.,
            Ring,J., Abeck,D., Schmidt,T., Valent,P. and Valenta,R.
  TITLE     Isolation of cDNA clones coding for IgE autoantigens with serum IgE
            from atopic dermatitis patients
  JOURNAL   FASEB J 12 (14), 1559-1569 (1998)
   PUBMED   9806765
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK023318.1, AL513185.12 and
            AC091769.6.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: This gene encodes an essential regulator of mitochondrial
            Ca2+ uptake under basal conditions. The encoded protein interacts
            with the mitochondrial calcium uniporter, a mitochondrial inner
            membrane Ca2+ channel, and is essential in preventing mitochondrial
            Ca2+ overload, which can cause excessive production of reactive
            oxygen species and cell stress. Alternatively spliced transcript
            variants encoding different isoforms have been described. [provided
            by RefSeq, Mar 2013].
            
            Transcript Variant: This variant (2) lacks an alternate in-frame
            exon in the 5' coding region compared to variant 1. The encoded
            protein (isoform 2) is shorter compared to isoform 1.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC004216.2, AK225298.1 [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000350]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000361114.10/
                                                  ENSP00000354415.5
            RefSeq Select criteria             :: based on expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..476
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q22.1"
     Protein         1..476
                     /product="calcium uptake protein 1, mitochondrial isoform
                     2"
                     /note="calcium uptake protein 1, mitochondrial;
                     calcium-binding atopy-related autoantigen 1; atopy-related
                     autoantigen CALC"
                     /calculated_mol_wt=50585
     transit_peptide 1..33
                     /note="Mitochondrion. /evidence=ECO:0000255,
                     ECO:0000305|PubMed:26387864; propagated from
                     UniProtKB/Swiss-Prot (Q9BPX6.1)"
                     /calculated_mol_wt=3784
     mat_peptide     34..476
                     /product="Calcium uptake protein 1, mitochondrial.
                     /id=PRO_0000322990"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9BPX6.1)"
                     /calculated_mol_wt=50585
     Region          68..106
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9BPX6.1)"
     Region          99..110
                     /region_name="Polybasic region.
                     /evidence=ECO:0000269|PubMed:27099988"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9BPX6.1)"
     Site            122
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q8VCX5; propagated from
                     UniProtKB/Swiss-Prot (Q9BPX6.1)"
     Region          126..129
                     /region_name="K/R-ring.
                     /evidence=ECO:0000269|PubMed:32494073"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9BPX6.1)"
     Region          222..441
                     /region_name="EFh_MICU1"
                     /note="EF-hand, calcium binding motif, found in calcium
                     uptake protein 1, mitochondrial (MICU1) and similar
                     proteins; cd16173"
                     /db_xref="CDD:320081"
     Region          222..251
                     /region_name="EF-hand motif"
                     /note="EF-hand motif [structural motif]"
                     /db_xref="CDD:320081"
     Site            order(224,376,379,382..383,385,403)
                     /site_type="other"
                     /note="homodimer interface [polypeptide binding]"
                     /db_xref="CDD:320081"
     Site            order(231,233,235,242,421,423,425,432)
                     /site_type="other"
                     /note="Ca binding site [ion binding]"
                     /db_xref="CDD:320081"
     Region          259..263
                     /region_name="K/R-ring.
                     /evidence=ECO:0000269|PubMed:32494073"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9BPX6.1)"
     Region          277..307
                     /region_name="EF-hand motif"
                     /note="EF-hand motif [structural motif]"
                     /db_xref="CDD:320081"
     Region          375..404
                     /region_name="EF-hand motif"
                     /note="EF-hand motif [structural motif]"
                     /db_xref="CDD:320081"
     Region          412..441
                     /region_name="EF-hand motif"
                     /note="EF-hand motif [structural motif]"
                     /db_xref="CDD:320081"
     Region          455..465
                     /region_name="C-helix region.
                     /evidence=ECO:0000269|PubMed:24514027"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9BPX6.1)"
     Site            455
                     /site_type="methylation"
                     /note="Asymmetric dimethylarginine.
                     /evidence=ECO:0000269|PubMed:27642082; propagated from
                     UniProtKB/Swiss-Prot (Q9BPX6.1)"
     CDS             1..476
                     /gene="MICU1"
                     /gene_synonym="ara CALC; CALC; CBARA1; EFHA3; MPXPS"
                     /coded_by="NM_001195518.2:72..1502"
                     /note="isoform 2 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS55715.1"
                     /db_xref="GeneID:10367"
                     /db_xref="HGNC:HGNC:1530"
                     /db_xref="MIM:605084"
ORIGIN      
        1 mfrlnslsal aelavgsrwy hggsqpiqir rrlmmvaflg asavtastgl lwkrahaesp
       61 pcvdnlksdi gdkgknkdeg dvcnhekkta dlaphpeekk kkrsgfrdrk vmeyenrira
      121 ystpdkifry fatlkvisep geaevfmtpe dfvrsitpne kqpehlgldq yiikrfdgkk
      181 isqerekfad egsifytlge cglisfsdyi flttvlstpq rnfeiafkmf dlngdgevdm
      241 eefeqvqsii rsqtsmgmrh rdrpttgntl ksglcsaltt yffgadlkgk ltiknflefq
      301 rklqhdvlkl eferhdpvdg riterqfggm llaysgvqsk kltamqrqlk khfkegkglt
      361 fqevenfftf lknindvdta lsfyhmagas ldkvtmqqva rtvakvelsd hvcdvvfalf
      421 dcdgngelsn kefvsimkqr lmrglekpkd mgftrlmqam wkcaqetawd falpkq
//
