CNNM2_MOUSE
ID CNNM2_MOUSE Reviewed; 875 AA.
AC Q3TWN3; A0PJF1; E9PUH1; Q7TT07; Q8C8V4; Q9JIM8;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Metal transporter CNNM2;
DE AltName: Full=Ancient conserved domain-containing protein 2;
DE Short=mACDP2;
DE AltName: Full=Cyclin-M2;
GN Name=Cnnm2; Synonyms=Acdp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-875 (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Mammary gland, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 27-36, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 176-875 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=14723793; DOI=10.1186/1471-2164-5-7;
RA Wang C.-Y., Yang P., Shi J.-D., Purohit S., Guo D., An H., Gu J.-G.,
RA Ling J., Dong Z., She J.-X.;
RT "Molecular cloning and characterization of the mouse Acdp gene family.";
RL BMC Genomics 5:7-7(2004).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15899945; DOI=10.1152/physiolgenomics.00058.2005;
RA Goytain A., Quamme G.A.;
RT "Functional characterization of ACDP2 (ancient conserved domain protein), a
RT divalent metal transporter.";
RL Physiol. Genomics 22:382-389(2005).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-112.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [8]
RP DIMERIZATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MEMBRANE TOPOLOGY,
RP MUTAGENESIS OF 62-GLY--ALA-65; ASN-112; ASN-327; ASN-527 AND ASN-591, AND
RP GLYCOSYLATION AT ASN-112.
RX PubMed=22399287; DOI=10.1074/jbc.m112.342204;
RA de Baaij J.H., Stuiver M., Meij I.C., Lainez S., Kopplin K., Venselaar H.,
RA Mueller D., Bindels R.J., Hoenderop J.G.;
RT "Membrane topology and intracellular processing of Cyclin M2 (CNNM2).";
RL J. Biol. Chem. 287:13644-13655(2012).
CC -!- FUNCTION: Divalent metal cation transporter. Mediates transport of
CC divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+)
CC > Ba(2+) > Cu(2+) > Fe(2+). {ECO:0000269|PubMed:15899945}.
CC -!- SUBUNIT: Isoform 1 and isoform 2 may interact with each other.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22399287};
CC Multi-pass membrane protein {ECO:0000269|PubMed:22399287}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=CNNM2a;
CC IsoId=Q3TWN3-1; Sequence=Displayed;
CC Name=2; Synonyms=CNNM2b;
CC IsoId=Q3TWN3-2; Sequence=VSP_027081;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in kidney,
CC lung, spleen and testis. In the kidney, predominantly expressed in the
CC distal convoluted tubule and, at lower levels, in the connecting tubule
CC (at protein level). {ECO:0000269|PubMed:14723793,
CC ECO:0000269|PubMed:15899945, ECO:0000269|PubMed:22399287}.
CC -!- INDUCTION: By low Mg(2+) concentration. {ECO:0000269|PubMed:15899945}.
CC -!- PTM: The N-terminus is cleaved within the endoplasmic reticulum. The
CC signal peptidase complex seems to be involved in the processing, but
CC the exact cleavage site has not been identified (PubMed:22399287).
CC {ECO:0000269|PubMed:22399287}.
CC -!- MISCELLANEOUS: Shares weak sequence similarity with the cyclin family,
CC hence its name. However, it has no cyclin-like function in vivo.
CC -!- SIMILARITY: Belongs to the ACDP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF86373.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH27387.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH52513.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK044400; BAC31904.1; -; mRNA.
DR EMBL; AK159616; BAE35233.1; -; mRNA.
DR EMBL; AC122442; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC161865; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027387; AAH27387.1; ALT_SEQ; mRNA.
DR EMBL; BC052513; AAH52513.1; ALT_INIT; mRNA.
DR EMBL; AF216961; AAF86373.1; ALT_INIT; mRNA.
DR CCDS; CCDS50459.1; -. [Q3TWN3-1]
DR CCDS; CCDS50460.1; -. [Q3TWN3-2]
DR RefSeq; NP_001095941.1; NM_001102471.1. [Q3TWN3-2]
DR RefSeq; NP_291047.2; NM_033569.3. [Q3TWN3-1]
DR PDB; 4P1G; X-ray; 2.60 A; A=430-580.
DR PDB; 4P1O; X-ray; 3.06 A; A/B=430-580.
DR PDB; 5LXQ; X-ray; 3.33 A; A/H=430-584.
DR PDB; 5MMZ; X-ray; 2.40 A; A=430-584.
DR PDB; 6WUS; X-ray; 2.76 A; A=430-580.
DR PDBsum; 4P1G; -.
DR PDBsum; 4P1O; -.
DR PDBsum; 5LXQ; -.
DR PDBsum; 5MMZ; -.
DR PDBsum; 6WUS; -.
DR AlphaFoldDB; Q3TWN3; -.
DR SMR; Q3TWN3; -.
DR STRING; 10090.ENSMUSP00000096972; -.
DR TCDB; 1.A.112.1.1; the cyclin m mg2+ exporter (cnnm) family.
DR GlyGen; Q3TWN3; 1 site.
DR iPTMnet; Q3TWN3; -.
DR PhosphoSitePlus; Q3TWN3; -.
DR SwissPalm; Q3TWN3; -.
DR EPD; Q3TWN3; -.
DR MaxQB; Q3TWN3; -.
DR PaxDb; Q3TWN3; -.
DR PeptideAtlas; Q3TWN3; -.
DR PRIDE; Q3TWN3; -.
DR ProteomicsDB; 283454; -. [Q3TWN3-1]
DR ProteomicsDB; 283455; -. [Q3TWN3-2]
DR Antibodypedia; 46052; 168 antibodies from 22 providers.
DR DNASU; 94219; -.
DR Ensembl; ENSMUST00000077666; ENSMUSP00000076850; ENSMUSG00000064105. [Q3TWN3-2]
DR Ensembl; ENSMUST00000099373; ENSMUSP00000096972; ENSMUSG00000064105. [Q3TWN3-1]
DR GeneID; 94219; -.
DR KEGG; mmu:94219; -.
DR UCSC; uc008hue.1; mouse. [Q3TWN3-1]
DR UCSC; uc008huf.1; mouse. [Q3TWN3-2]
DR CTD; 54805; -.
DR MGI; MGI:2151054; Cnnm2.
DR VEuPathDB; HostDB:ENSMUSG00000064105; -.
DR eggNOG; KOG2118; Eukaryota.
DR GeneTree; ENSGT00940000159034; -.
DR HOGENOM; CLU_011310_1_1_1; -.
DR InParanoid; Q3TWN3; -.
DR OMA; CFMITAE; -.
DR OrthoDB; 1446644at2759; -.
DR PhylomeDB; Q3TWN3; -.
DR TreeFam; TF101012; -.
DR BRENDA; 4.2.1.22; 3474.
DR BioGRID-ORCS; 94219; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Cnnm2; mouse.
DR PRO; PR:Q3TWN3; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q3TWN3; protein.
DR Bgee; ENSMUSG00000064105; Expressed in animal zygote and 191 other tissues.
DR Genevisible; Q3TWN3; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0015095; F:magnesium ion transmembrane transporter activity; IDA:MGI.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0010960; P:magnesium ion homeostasis; ISO:MGI.
DR GO; GO:0015693; P:magnesium ion transport; IDA:MGI.
DR CDD; cd04590; CBS_pair_CorC_HlyC_assoc; 1.
DR Gene3D; 2.60.120.10; -; 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 InterPro; IPR014710; RmlC-like_jellyroll.
DR PANTHER; PTHR12064; PTHR12064; 1.
DR Pfam; PF00571; CBS; 1.
DR Pfam; PF01595; DUF21; 1.
DR SUPFAM; SSF54631; SSF54631; 1.
DR PROSITE; PS51371; CBS; 2.
DR PROSITE; PS51846; CNNM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; CBS domain; Cell membrane;
KW Direct protein sequencing; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..875
FT /note="Metal transporter CNNM2"
FT /id="PRO_0000295761"
FT TOPO_DOM 1..250
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..313
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 314..334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 335..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 360..368
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..875
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 251..431
FT /note="CNNM transmembrane"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01193"
FT DOMAIN 450..511
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 518..584
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 121..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 741..763
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 761
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H8M5"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:22399287"
FT VAR_SEQ 721..742
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027081"
FT MUTAGEN 62..65
FT /note="GCTA->LLLV: Impairs N-terminal cleavage."
FT /evidence="ECO:0000269|PubMed:22399287"
FT MUTAGEN 62..64
FT /note="GCT->LCL: No effect on N-terminal cleavage."
FT MUTAGEN 63..65
FT /note="CTA->LTV: No effect on N-terminal cleavage."
FT MUTAGEN 112
FT /note="N->A: Loss of N-glycosylation; 90% decrease of
FT plasma membrane expression."
FT /evidence="ECO:0000269|PubMed:22399287"
FT MUTAGEN 327
FT /note="N->A: No effect on N-glycosylation."
FT /evidence="ECO:0000269|PubMed:22399287"
FT MUTAGEN 527
FT /note="N->A: No effect on N-glycosylation."
FT /evidence="ECO:0000269|PubMed:22399287"
FT MUTAGEN 591
FT /note="N->A: No effect on N-glycosylation."
FT /evidence="ECO:0000269|PubMed:22399287"
FT CONFLICT 131
FT /note="S -> G (in Ref. 1; BAC31904 and 2; AAH27387)"
FT /evidence="ECO:0000305"
FT CONFLICT 664
FT /note="Y -> C (in Ref. 1; BAE35233)"
FT /evidence="ECO:0000305"
FT HELIX 430..440
FT /evidence="ECO:0007829|PDB:5MMZ"
FT TURN 441..443
FT /evidence="ECO:0007829|PDB:5MMZ"
FT HELIX 446..449
FT /evidence="ECO:0007829|PDB:5MMZ"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:5MMZ"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:5MMZ"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:4P1G"
FT HELIX 467..476
FT /evidence="ECO:0007829|PDB:5MMZ"
FT STRAND 479..487
FT /evidence="ECO:0007829|PDB:5MMZ"
FT STRAND 491..496
FT /evidence="ECO:0007829|PDB:5MMZ"
FT HELIX 497..500
FT /evidence="ECO:0007829|PDB:5MMZ"
FT HELIX 505..507
FT /evidence="ECO:0007829|PDB:5MMZ"
FT HELIX 511..517
FT /evidence="ECO:0007829|PDB:5MMZ"
FT STRAND 523..526
FT /evidence="ECO:0007829|PDB:5MMZ"
FT HELIX 531..540
FT /evidence="ECO:0007829|PDB:5MMZ"
FT STRAND 545..552
FT /evidence="ECO:0007829|PDB:5MMZ"
FT STRAND 555..557
FT /evidence="ECO:0007829|PDB:5MMZ"
FT STRAND 560..568
FT /evidence="ECO:0007829|PDB:5MMZ"
FT HELIX 569..577
FT /evidence="ECO:0007829|PDB:5MMZ"
SQ SEQUENCE 875 AA; 96704 MW; 8074D56C079E0F6C CRC64;
MIGCGACEPE VKMAGGQAAA ALPTWKMAAR RSLSARGRGV LQAAAGRLLP LLLLSCCWGA
GGCTAAGENE ETVIIGLRLE DTNDVSFMEG GALRVSERTR VKLRVYGQNI NNETWSRIAF
TEHERRRHTP SERGLGGPAP PEPDSGPQRC GIRTSDIIIL PHIILNRRTS GIIEIEIKPL
RKMEKSKSYY LCTSLSTPAL GAGGSGSASG TVGGKGGAGV AGLPPPPWAE TTWIYHDGED
TKMIVGEEKK FLLPFWLQVI FISLLLCLSG MFSGLNLGLM ALDPMELRIV QNCGTEKEKN
YAKRIEPVRR QGNYLLCSLL LGNVLVNTTL TILLDDIAGS GLVAVVVSTI GIVIFGEIVP
QAICSRHGLA VGANTIFLTK FFMMMTFPAS YPVSKLLDCV LGQEIGTVYN REKLLEMLRV
TDPYNDLVKE ELNIIQGALE LRTKTVEDVM TPLRDCFMIT GEAILDFNTM SEIMESGYTR
IPVFEGERSN IVDLLFVKDL AFVDPDDCTP LKTITKFYNH PLHFVFNDTK LDAMLEEFKK
GKSHLAIVQR VNNEGEGDPF YEVLGIVTLE DVIEEIIKSE ILDETDLYTD NRTKKKVAHR
ERKQDFSAFK QTDSEMKVKI SPQLLLAMHR FLATEVEAFS PSQMSEKILL RLLKHPNVIQ
ELKYDEKNKK APECYLYQRN KPVDYFVLIL QGKVEVEAGK EGMKFEASAF SYYGVMALTA
SPVPLSLSRT FVVSRTEVLA AGSPGENKSP PRPCGLNHSD SLSRSDRIDA MTPTLGSSNN
QLSSSFLQVY IPDYSVRALS DLQFVKISRQ QYQNALMASR MDKTPQSSDS ENTKIELTLT
ELHDGLPDET ANLLNEQNCV SHNKANHSLH SEGAI
