CNNM3_CAEEL
ID CNNM3_CAEEL Reviewed; 797 AA.
AC A0A131MCZ8; A0A131MBV5; A0A131MD56; Q21469;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Metal transporter cnnm-3 {ECO:0000305};
DE AltName: Full=CNNM family homolog 3 {ECO:0000312|WormBase:C33D12.2a};
DE Flags: Precursor;
GN Name=cnnm-3 {ECO:0000312|WormBase:C33D12.2a};
GN ORFNames=C33D12.2 {ECO:0000312|WormBase:C33D12.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=27564576; DOI=10.1371/journal.pgen.1006276;
RA Ishii T., Funato Y., Hashizume O., Yamazaki D., Hirata Y., Nishiwaki K.,
RA Kono N., Arai H., Miki H.;
RT "Mg2+ extrusion from intestinal epithelia by CNNM proteins is essential for
RT gonadogenesis via AMPK-TORC1 signaling in Caenorhabditis elegans.";
RL PLoS Genet. 12:E1006276-E1006276(2016).
CC -!- FUNCTION: Probable metal transporter. Probably acts redundantly with
CC the other metal transport proteins cnnm-1, cnnm-2, cnnm-4 and cnnm-5 to
CC regulate Mg(2+) homeostasis. Promotes postembryonic gonad development
CC by regulating Mg(2+) levels, probably via AMPK signaling.
CC {ECO:0000269|PubMed:27564576}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:27564576}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=a {ECO:0000312|WormBase:C33D12.2a};
CC IsoId=A0A131MCZ8-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C33D12.2b};
CC IsoId=A0A131MCZ8-2; Sequence=VSP_058662;
CC Name=c {ECO:0000312|WormBase:C33D12.2c};
CC IsoId=A0A131MCZ8-3; Sequence=VSP_058663, VSP_058664;
CC Name=d {ECO:0000312|WormBase:C33D12.2d};
CC IsoId=A0A131MCZ8-4; Sequence=VSP_058662, VSP_058663, VSP_058664;
CC -!- TISSUE SPECIFICITY: Highly expressed in the intestine and in neurons,
CC but it is also expressed in a variety of tissues including the pharynx,
CC hypodermis, rectum and in muscles. {ECO:0000269|PubMed:27564576}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Double knockout with cnnm-1
CC results in increased levels of intestinal Mg(2+) and reduced levels in
CC other tissues. This Mg(2+) deficiency in tissues leads to a reduced
CC lifespan, 100% sterility, and smaller animals that exhibit a
CC developmental delay with defective gonad development and which
CC therefore do not produce oocytes or form vulva. In addition, the gonad
CC development defect in the cnnm-1 and cnnm-3 double knockout is rescued
CC when the AMPK alpha subunit aak-2 is also knocked out. Double knockout
CC with cnnm-2 results in 22% sterility. Quintuple knockout with cnnm-1,
CC cnnm-2, cnnm-4 and cnnm-5 results in a reduced lifespan and 100%
CC sterility. {ECO:0000269|PubMed:27564576}.
CC -!- SIMILARITY: Belongs to the ACDP family. {ECO:0000305}.
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DR EMBL; BX284606; CCD66487.1; -; Genomic_DNA.
DR EMBL; BX284606; CZR14596.1; -; Genomic_DNA.
DR EMBL; BX284606; CZR14597.1; -; Genomic_DNA.
DR EMBL; BX284606; CZR14608.1; -; Genomic_DNA.
DR PIR; T16631; T16631.
DR RefSeq; NP_001309670.1; NM_001322613.1. [A0A131MCZ8-1]
DR RefSeq; NP_001309671.1; NM_001322614.1.
DR RefSeq; NP_001309682.1; NM_001322615.1.
DR RefSeq; NP_508520.1; NM_076119.3.
DR AlphaFoldDB; A0A131MCZ8; -.
DR SMR; A0A131MCZ8; -.
DR IntAct; A0A131MCZ8; 1.
DR STRING; 6239.C33D12.2; -.
DR PaxDb; A0A131MCZ8; -.
DR EnsemblMetazoa; C33D12.2a.1; C33D12.2a.1; WBGene00016343. [A0A131MCZ8-1]
DR EnsemblMetazoa; C33D12.2b.1; C33D12.2b.1; WBGene00016343. [A0A131MCZ8-2]
DR EnsemblMetazoa; C33D12.2b.2; C33D12.2b.2; WBGene00016343. [A0A131MCZ8-2]
DR EnsemblMetazoa; C33D12.2b.3; C33D12.2b.3; WBGene00016343. [A0A131MCZ8-2]
DR EnsemblMetazoa; C33D12.2b.4; C33D12.2b.4; WBGene00016343. [A0A131MCZ8-2]
DR EnsemblMetazoa; C33D12.2b.5; C33D12.2b.5; WBGene00016343. [A0A131MCZ8-2]
DR EnsemblMetazoa; C33D12.2b.6; C33D12.2b.6; WBGene00016343. [A0A131MCZ8-2]
DR EnsemblMetazoa; C33D12.2c.1; C33D12.2c.1; WBGene00016343. [A0A131MCZ8-3]
DR EnsemblMetazoa; C33D12.2d.1; C33D12.2d.1; WBGene00016343. [A0A131MCZ8-4]
DR GeneID; 180591; -.
DR KEGG; cel:CELE_C33D12.2; -.
DR UCSC; M02F4.3; c. elegans.
DR CTD; 180591; -.
DR WormBase; C33D12.2a; CE51453; WBGene00016343; cnnm-3. [A0A131MCZ8-1]
DR WormBase; C33D12.2b; CE04764; WBGene00016343; cnnm-3. [A0A131MCZ8-2]
DR WormBase; C33D12.2c; CE51420; WBGene00016343; cnnm-3. [A0A131MCZ8-3]
DR WormBase; C33D12.2d; CE51314; WBGene00016343; cnnm-3. [A0A131MCZ8-4]
DR eggNOG; KOG2118; Eukaryota.
DR GeneTree; ENSGT00940000169533; -.
DR OMA; MSTCHKI; -.
DR OrthoDB; 1446644at2759; -.
DR PRO; PR:A0A131MCZ8; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00016343; Expressed in larva and 3 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; HEP:WormBase.
DR GO; GO:0010960; P:magnesium ion homeostasis; IGI:UniProtKB.
DR GO; GO:0015693; P:magnesium ion transport; IGI:UniProtKB.
DR GO; GO:1905941; P:positive regulation of gonad development; IGI:UniProtKB.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IGI:UniProtKB.
DR GO; GO:0040026; P:positive regulation of vulval development; IGI:UniProtKB.
DR GO; GO:0032026; P:response to magnesium ion; IGI:UniProtKB.
DR CDD; cd04590; CBS_pair_CorC_HlyC_assoc; 1.
DR Gene3D; 3.10.580.10; -; 1.
DR InterPro; IPR045095; ACDP.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR002550; CNNM.
DR InterPro; IPR044751; Ion_transp-like_CBS.
DR PANTHER; PTHR12064; PTHR12064; 1.
DR Pfam; PF01595; DUF21; 1.
DR SUPFAM; SSF54631; SSF54631; 1.
DR PROSITE; PS51371; CBS; 2.
DR PROSITE; PS51846; CNNM; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; CBS domain; Cell membrane; Glycoprotein;
KW Ion transport; Membrane; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..797
FT /note="Metal transporter cnnm-3"
FT /evidence="ECO:0000305"
FT /id="PRO_5007283697"
FT TOPO_DOM 24..200
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 256..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..280
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 281..301
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 302..322
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 323..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 344..797
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT DOMAIN 193..373
FT /note="CNNM transmembrane"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01193"
FT DOMAIN 393..454
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 461..527
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 676
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 692
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 724
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 731
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 761
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 1..547
FT /note="Missing (in isoform b and isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_058662"
FT VAR_SEQ 753..766
FT /note="DAVSTPIRNGSVKL -> KYLIGRWKRRGTYV (in isoform c and
FT isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_058663"
FT VAR_SEQ 767..797
FT /note="Missing (in isoform c and isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_058664"
SQ SEQUENCE 797 AA; 89288 MW; 25AD3EA350EB4E85 CRC64;
MSKTPWALGL LIFLLTFTSP LSSSPVRSTD NSTSSKGLLN VNSSVILEPS ILPSSASKPE
SLHLSKVRVS GLRLEAHASS TENIVLGHNK KHNVVVVPNK NVRVVLFGQN FQDIGALTFT
ADGSCKDLAH FFEADFSSMT PIRVVVEMSF PKTTESKDSF KLCVSEKFYA NPQFVIVEDP
FTMVTTEIPP VDEYMPKWLS WICLLILLCF SGLFSGLNLG LMTLSPYELQ LYIASGTEQE
KRDAGRILPI RKKGNQLLCT LLIGNVVVNV GVSLLMDQLV GSGFAVLVAA TSCIVVFGEI
IPQALCVKLG LPIGARTIPI TQVLLFLMYP LTWPISKVLD IFLKEELTRS LERNKLVEML
KLSEKSIIGG QSDEFKMVLG ALELYDKTVA HAMTRYEDIF MLPHTLTLGA GMVTQILDMG
YTRIPIYEND RKNIVALLFV KDLALLDPDD NHNVMKIASI YNHEVRRVLV DMPLRNMLEE
FKRGEYHMAL VERLVEQEDK DPIYELCGLI TLEDIIEEII QCEIIDETDA VCDNVHRKKR
QRKRNHDMSQ IVNTAHAKCA INIQMLAVTI QVMSTCHKIF SSNYILPTIL EKLIRKNCKK
VETTQFSCLK EVGVVQPKPA VLFTKGEFSN KFIMILSGRA VVTIGKEEMR LEAGAWHSFG
TEVLDAMAEA IERSLNQSTS RSTVSLNTEI TNNSIGFIPD FDTVILYECV FCEITAADLL
LAYNSSQIMQ NNTKMQVVRS NSRISLIEEI PKDAVSTPIR NGSVKLRTVS EGETVHLLPK
NMECHFNKQE KYEEEEE
