CC50A_MOUSE
ID CC50A_MOUSE Reviewed; 364 AA.
AC Q8VEK0; Q3TCJ5; Q3UDH8; Q8R0X6; Q8VEH1;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Cell cycle control protein 50A {ECO:0000305};
DE AltName: Full=P4-ATPase flippase complex beta subunit TMEM30A;
DE AltName: Full=Transmembrane protein 30A;
GN Name=Tmem30a {ECO:0000312|MGI:MGI:106402}; Synonyms=Cdc50a, D9Wsu20e;
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].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, and Testis;
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 MRNA].
RC STRAIN=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 [3]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
RX PubMed=22641037; DOI=10.1016/j.febslet.2012.05.018;
RA Xu Q., Yang G.Y., Liu N., Xu P., Chen Y.L., Zhou Z., Luo Z.G., Ding X.;
RT "P4-ATPase ATP8A2 acts in synergy with CDC50A to enhance neurite
RT outgrowth.";
RL FEBS Lett. 586:1803-1812(2012).
RN [6]
RP GLYCOSYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22253360; DOI=10.1369/0022155411435705;
RA Folmer D.E., Mok K.S., de Wee S.W., Duijst S., Hiralall J.K., Seppen J.,
RA Oude Elferink R.P., Paulusma C.C.;
RT "Cellular localization and biochemical analysis of mammalian CDC50A, a
RT glycosylated beta-subunit for P4 ATPases.";
RL J. Histochem. Cytochem. 60:205-218(2012).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=22307598; DOI=10.1073/pnas.1108862109;
RA Coleman J.A., Vestergaard A.L., Molday R.S., Vilsen B., Andersen J.P.;
RT "Critical role of a transmembrane lysine in aminophospholipid transport by
RT mammalian photoreceptor P4-ATPase ATP8A2.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:1449-1454(2012).
RN [8]
RP FUNCTION, AND INTERACTION WITH ATP8A1.
RX PubMed=23269685; DOI=10.1074/jbc.m112.402701;
RA Kato U., Inadome H., Yamamoto M., Emoto K., Kobayashi T., Umeda M.;
RT "Role for phospholipid flippase complex of ATP8A1 and CDC50A proteins in
RT cell migration.";
RL J. Biol. Chem. 288:4922-4934(2013).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=24413176; DOI=10.1242/jcs.145052;
RA Coleman J.A., Zhu X., Djajadi H.R., Molday L.L., Smith R.S., Libby R.T.,
RA John S.W., Molday R.S.;
RT "Phospholipid flippase ATP8A2 is required for normal visual and auditory
RT function and photoreceptor and spiral ganglion cell survival.";
RL J. Cell Sci. 127:1138-1149(2014).
RN [10]
RP FUNCTION, AND INTERACTION WITH ATP11A.
RX PubMed=29799007; DOI=10.1038/s41467-018-04436-w;
RA Tsuchiya M., Hara Y., Okuda M., Itoh K., Nishioka R., Shiomi A., Nagao K.,
RA Mori M., Mori Y., Ikenouchi J., Suzuki R., Tanaka M., Ohwada T., Aoki J.,
RA Kanagawa M., Toda T., Nagata Y., Matsuda R., Takayama Y., Tominaga M.,
RA Umeda M.;
RT "Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-
RT mediated myotube formation.";
RL Nat. Commun. 9:2049-2049(2018).
RN [11]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RX PubMed=30018401; DOI=10.1038/s41598-018-29108-z;
RA Wang J., Molday L.L., Hii T., Coleman J.A., Wen T., Andersen J.P.,
RA Molday R.S.;
RT "Proteomic Analysis and Functional Characterization of P4-ATPase
RT Phospholipid Flippases from Murine Tissues.";
RL Sci. Rep. 8:10795-10795(2018).
CC -!- FUNCTION: Accessory component of a P4-ATPase flippase complex which
CC catalyzes the hydrolysis of ATP coupled to the transport of
CC aminophospholipids from the outer to the inner leaflet of various
CC membranes and ensures the maintenance of asymmetric distribution of
CC phospholipids. Phospholipid translocation seems also to be implicated
CC in vesicle formation and in uptake of lipid signaling molecules. The
CC beta subunit may assist in binding of the phospholipid substrate.
CC Required for the proper folding, assembly and ER to Golgi exit of the
CC ATP8A2:TMEM30A flippase complex. ATP8A2:TMEM30A may be involved in
CC regulation of neurite outgrowth, and, reconstituted to liposomes,
CC predomiminantly transports phosphatidylserine (PS) and to a lesser
CC extent phosphatidylethanolamine (PE). The ATP8A1:TMEM30A flippase
CC complex seems to play a role in regulation of cell migration probably
CC involving flippase-mediated translocation of phosphatidylethanolamine
CC (PE) at the plasma membrane. Required for the formation of the ATP8A2,
CC ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes. Involved
CC in uptake of platelet-activating factor (PAF). Can also mediate the
CC export of alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A,
CC ATP10B, ATP10D, ATP11A, ATP11B and ATP11C from the ER to other membrane
CC localizations. {ECO:0000269|PubMed:22641037,
CC ECO:0000269|PubMed:23269685, ECO:0000269|PubMed:29799007,
CC ECO:0000269|PubMed:30018401}.
CC -!- SUBUNIT: Component of various P4-ATPase flippase complexes which
CC consists of a catalytic alpha subunit and an accessory beta subunit.
CC Interacts with ATP8A1 to form a flippase complex; this complex forms an
CC intermediate phosphoenzyme. The ATP8A2:TMEM30A flippase complex has
CC been purified, and ATP8B1:TMEM30A and ATP8B2:TMEM30A flippase complexes
CC have been shown to form intermediate phosphoenzymes in vitro (By
CC similarity). Interacts with alpha subunits ATP8A1, ATP8B1, ATP8B2,
CC ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C
CC (PubMed:23269685, PubMed:30018401, PubMed:29799007).
CC {ECO:0000250|UniProtKB:Q9NV96, ECO:0000269|PubMed:23269685}.
CC -!- INTERACTION:
CC Q8VEK0; P70704: Atp8a1; NbExp=2; IntAct=EBI-8381028, EBI-20828407;
CC Q8VEK0; P05067-4: APP; Xeno; NbExp=6; IntAct=EBI-8381028, EBI-302641;
CC Q8VEK0; PRO_0000000091 [P05067]: APP; Xeno; NbExp=3; IntAct=EBI-8381028, EBI-3894543;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:22253360}; Multi-
CC pass membrane protein {ECO:0000269|PubMed:22253360}. Cell membrane
CC {ECO:0000250}. Golgi apparatus {ECO:0000269|PubMed:22253360}.
CC Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000269|PubMed:22253360}. Apical cell membrane
CC {ECO:0000269|PubMed:22253360}.
CC -!- TISSUE SPECIFICITY: Expressed in photoreceptor cells; detected in
CC retina outer segment (at protein level). Detected in hepatocytes liver
CC sinusoidal endothelial cells and kidney brush border of the proximal
CC tubules (at protein level). Expressed in brain (at protein level).
CC {ECO:0000269|PubMed:22253360, ECO:0000269|PubMed:22307598,
CC ECO:0000269|PubMed:24413176, ECO:0000269|PubMed:30018401}.
CC -!- DOMAIN: The N-terminal domain seems to play a role in the reaction
CC cycle of thr catalytic subunit such as ATP8A2. {ECO:0000250}.
CC -!- PTM: N-glycosylated. Contains high mannose-type oligosaccharides.
CC {ECO:0000269|PubMed:22253360}.
CC -!- SIMILARITY: Belongs to the CDC50/LEM3 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH26136.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAE41961.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK077065; BAC36588.1; -; mRNA.
DR EMBL; AK150071; BAE29283.1; -; mRNA.
DR EMBL; AK159364; BAE35022.1; -; mRNA.
DR EMBL; AK170697; BAE41961.1; ALT_FRAME; mRNA.
DR EMBL; AK170171; BAE41615.1; -; mRNA.
DR EMBL; BC018367; AAH18367.1; -; mRNA.
DR EMBL; BC018491; AAH18491.1; -; mRNA.
DR EMBL; BC026136; AAH26136.1; ALT_INIT; mRNA.
DR CCDS; CCDS23367.1; -.
DR RefSeq; NP_598479.1; NM_133718.4.
DR AlphaFoldDB; Q8VEK0; -.
DR SMR; Q8VEK0; -.
DR BioGRID; 213794; 1.
DR IntAct; Q8VEK0; 2.
DR STRING; 10090.ENSMUSP00000034878; -.
DR GlyConnect; 2201; 10 N-Linked glycans (1 site).
DR GlyGen; Q8VEK0; 2 sites, 10 N-linked glycans (1 site).
DR iPTMnet; Q8VEK0; -.
DR PhosphoSitePlus; Q8VEK0; -.
DR SwissPalm; Q8VEK0; -.
DR EPD; Q8VEK0; -.
DR jPOST; Q8VEK0; -.
DR MaxQB; Q8VEK0; -.
DR PaxDb; Q8VEK0; -.
DR PeptideAtlas; Q8VEK0; -.
DR PRIDE; Q8VEK0; -.
DR ProteomicsDB; 283720; -.
DR Antibodypedia; 31507; 62 antibodies from 24 providers.
DR DNASU; 69981; -.
DR Ensembl; ENSMUST00000034878; ENSMUSP00000034878; ENSMUSG00000032328.
DR GeneID; 69981; -.
DR KEGG; mmu:69981; -.
DR UCSC; uc009quw.2; mouse.
DR CTD; 55754; -.
DR MGI; MGI:106402; Tmem30a.
DR VEuPathDB; HostDB:ENSMUSG00000032328; -.
DR eggNOG; KOG2952; Eukaryota.
DR GeneTree; ENSGT00390000004660; -.
DR InParanoid; Q8VEK0; -.
DR OMA; TWNNDQP; -.
DR OrthoDB; 889671at2759; -.
DR PhylomeDB; Q8VEK0; -.
DR TreeFam; TF300873; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 69981; 10 hits in 72 CRISPR screens.
DR ChiTaRS; Tmem30a; mouse.
DR PRO; PR:Q8VEK0; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8VEK0; protein.
DR Bgee; ENSMUSG00000032328; Expressed in ventromedial nucleus of hypothalamus and 255 other tissues.
DR ExpressionAtlas; Q8VEK0; baseline and differential.
DR Genevisible; Q8VEK0; MM.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015247; F:aminophospholipid flippase activity; ISO:MGI.
DR GO; GO:0015917; P:aminophospholipid transport; ISO:MGI.
DR GO; GO:0045332; P:phospholipid translocation; IMP:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0061092; P:positive regulation of phospholipid translocation; ISO:MGI.
DR GO; GO:0070863; P:positive regulation of protein exit from endoplasmic reticulum; ISO:MGI.
DR GO; GO:0036010; P:protein localization to endosome; ISO:MGI.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; ISO:MGI.
DR InterPro; IPR005045; CDC50/LEM3_fam.
DR InterPro; IPR030351; TMEM30A.
DR PANTHER; PTHR10926; PTHR10926; 1.
DR PANTHER; PTHR10926:SF17; PTHR10926:SF17; 1.
DR Pfam; PF03381; CDC50; 1.
DR PIRSF; PIRSF015840; DUF284_TM_euk; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Lipid transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:17242355"
FT CHAIN 2..364
FT /note="Cell cycle control protein 50A"
FT /id="PRO_0000244470"
FT TOPO_DOM 2..49
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 50..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..328
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 329..349
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 350..364
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 91..104
FT /evidence="ECO:0000250|UniProtKB:Q9NV96"
FT DISULFID 94..102
FT /evidence="ECO:0000250|UniProtKB:Q9NV96"
FT DISULFID 157..171
FT /evidence="ECO:0000250|UniProtKB:Q9NV96"
FT CONFLICT 90
FT /note="P -> H (in Ref. 1; BAE29283)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="P -> L (in Ref. 2; AAH18491)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 364 AA; 41061 MW; F662D38B5B1E7E8F CRC64;
MAMNYSAKDE VDGGPAGPPG GAAKTRRPDN TAFKQQRLPA WQPILTAGTV LPTFFIIGLI
FIPIGIGIFV TSNNIREIEI DYTGTEPSSP CNKCLSPNVT SCACTINFTL KQSFEGNVFM
YYGLSNFYQN HRRYVKSRDD SQLNGDPSAL LNPSKECEPY RRNEDRPIAP CGAIANSMFN
DTLELYLVAN ESDPKPIPIP LKKKGIAWWT DKNVKFRNPP GKESLEEKFK DTIKPVNWHK
AVYELDPEDE SNNGFINEDF IVWMRTAALP TFRKLYRLIE RRDDLHPTLP AGQYFLNITY
NYPVHSFDGR KRMILSTISW MGGKNPFLGI AYITIGSISF LLGVVLLVIN HKYRNSSNTA
DITI
