CNKR3_MOUSE
ID CNKR3_MOUSE Reviewed; 555 AA.
AC Q8BMA3; Q3UDS2; Q8K2K0;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Connector enhancer of kinase suppressor of ras 3;
DE Short=Connector enhancer of KSR 3;
DE AltName: Full=CNK homolog protein 3;
DE Short=CNK3;
DE AltName: Full=CNKSR family member 3;
DE AltName: Full=Maguin-like protein;
GN Name=Cnksr3;
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 [MRNA] (ISOFORM 1).
RC STRAIN=FVB/N;
RA Tzolovsky G., McGurk L., Pathirana S., Slee R., Hillier S., Clinton M.,
RA Bownes M.;
RT "Cloning, expression and comparison of human and mouse ML (maguin-like)
RT genes, and expression in mouse oogenesis.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Muellerian duct;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N-3; TISSUE=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 IDENTIFICATION BY MASS SPECTROMETRY [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 [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19567370; DOI=10.1096/fj.09-134759;
RA Ziera T., Irlbacher H., Fromm A., Latouche C., Krug S.M., Fromm M.,
RA Jaisser F., Borden S.A.;
RT "Cnksr3 is a direct mineralocorticoid receptor target gene and plays a key
RT role in the regulation of the epithelial sodium channel.";
RL FASEB J. 23:3936-3946(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-381 AND SER-383, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and 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 [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22851176; DOI=10.1074/jbc.m112.389148;
RA Soundararajan R., Ziera T., Koo E., Ling K., Wang J., Borden S.A.,
RA Pearce D.;
RT "Scaffold protein connector enhancer of kinase suppressor of Ras isoform 3
RT (CNK3) coordinates assembly of a multiprotein epithelial sodium channel
RT (ENaC)-regulatory complex.";
RL J. Biol. Chem. 287:33014-33025(2012).
CC -!- FUNCTION: Involved in transepithelial sodium transport. Regulates
CC aldosterone-induced and epithelial sodium channel (ENaC)-mediated
CC sodium transport through regulation of ENaC cell surface expression.
CC Acts as a scaffold protein coordinating the assembly of an ENaC-
CC regulatory complex (ERC). {ECO:0000269|PubMed:19567370,
CC ECO:0000269|PubMed:22851176}.
CC -!- SUBUNIT: Interacts with epithelial sodium channel ENaC. Interacts
CC directly with SCNN1A (ENaC subunit alpha) and SCNN1B (ENaC subunit
CC beta) C-terminal tails. Interacts with ENaC regulatory proteins NEDD4L,
CC RAF1 and SGK1. {ECO:0000250|UniProtKB:Q6P9H4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22851176}. Apical
CC cell membrane {ECO:0000269|PubMed:22851176}; Peripheral membrane
CC protein {ECO:0000269|PubMed:22851176}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BMA3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BMA3-2; Sequence=VSP_029391, VSP_029615;
CC -!- TISSUE SPECIFICITY: Expressed in kidney. {ECO:0000269|PubMed:19567370}.
CC -!- DOMAIN: The PDZ domain is required for interaction with ENaC and SGK1,
CC but not for interaction with NEDDL4 and RAF1.
CC {ECO:0000250|UniProtKB:Q6P9H4}.
CC -!- SIMILARITY: Belongs to the CNKSR family. {ECO:0000305}.
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DR EMBL; AY151137; AAN72835.1; -; mRNA.
DR EMBL; AK033015; BAC28127.1; -; mRNA.
DR EMBL; AK149951; BAE29189.1; -; mRNA.
DR EMBL; BC031194; AAH31194.1; -; mRNA.
DR CCDS; CCDS56690.1; -. [Q8BMA3-1]
DR RefSeq; NP_766134.1; NM_172546.2. [Q8BMA3-1]
DR AlphaFoldDB; Q8BMA3; -.
DR SMR; Q8BMA3; -.
DR BioGRID; 229657; 3.
DR IntAct; Q8BMA3; 3.
DR STRING; 10090.ENSMUSP00000015346; -.
DR iPTMnet; Q8BMA3; -.
DR PhosphoSitePlus; Q8BMA3; -.
DR MaxQB; Q8BMA3; -.
DR PaxDb; Q8BMA3; -.
DR PeptideAtlas; Q8BMA3; -.
DR PRIDE; Q8BMA3; -.
DR ProteomicsDB; 285509; -. [Q8BMA3-1]
DR ProteomicsDB; 285510; -. [Q8BMA3-2]
DR DNASU; 215748; -.
DR Ensembl; ENSMUST00000015346; ENSMUSP00000015346; ENSMUSG00000015202. [Q8BMA3-1]
DR Ensembl; ENSMUST00000150282; ENSMUSP00000115863; ENSMUSG00000015202. [Q8BMA3-2]
DR GeneID; 215748; -.
DR KEGG; mmu:215748; -.
DR UCSC; uc007efb.1; mouse. [Q8BMA3-1]
DR UCSC; uc007efc.1; mouse. [Q8BMA3-2]
DR CTD; 154043; -.
DR MGI; MGI:2674130; Cnksr3.
DR VEuPathDB; HostDB:ENSMUSG00000015202; -.
DR eggNOG; KOG1738; Eukaryota.
DR GeneTree; ENSGT00940000154428; -.
DR HOGENOM; CLU_037920_0_0_1; -.
DR InParanoid; Q8BMA3; -.
DR OMA; PNSFLDH; -.
DR OrthoDB; 1121556at2759; -.
DR PhylomeDB; Q8BMA3; -.
DR TreeFam; TF326495; -.
DR BioGRID-ORCS; 215748; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Cnksr3; mouse.
DR PRO; PR:Q8BMA3; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8BMA3; protein.
DR Bgee; ENSMUSG00000015202; Expressed in renal corpuscle and 219 other tissues.
DR Genevisible; Q8BMA3; MM.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IMP:UniProtKB.
DR GO; GO:2000651; P:positive regulation of sodium ion transmembrane transporter activity; IMP:MGI.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IMP:UniProtKB.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR010599; CNK2/3_dom.
DR InterPro; IPR017874; CRIC_domain.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF10534; CRIC_ras_sig; 1.
DR Pfam; PF06663; DUF1170; 1.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF00536; SAM_1; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS51290; CRIC; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..555
FT /note="Connector enhancer of kinase suppressor of ras 3"
FT /id="PRO_0000311106"
FT DOMAIN 7..72
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 80..174
FT /note="CRIC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00621"
FT DOMAIN 211..293
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 325..546
FT /note="DUF1170"
FT REGION 308..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 359..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 518..538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 381
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..241
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029391"
FT VAR_SEQ 242..243
FT /note="EN -> MQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029615"
FT CONFLICT 243
FT /note="N -> Q (in Ref. 3; AAH31194)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="L -> Q (in Ref. 2; BAE29189)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 555 AA; 61870 MW; 341AF9A4425904F2 CRC64;
MEPVTKWSPK QVVDWTRGLD DCLQPYVHKF EREKIDGEQL LKISHQDLEE LGVTRIGHQE
LVLEAVDLLC ALNYGLETDT MKNLVLKLRA SSHNLQNYIS SRRKSPAYDG NTSRKPPNEF
LTSVVELIGA AKALLAWLDR APFTGITDLS VTKNKIIQLC LDLTTAVQKD CLIAEMEDKV
LNVVKVLNGI CDKTMRSTTD PVMSQCACLE EVHLPNVRPG EGLGMYIKST YDGLHVITGT
TENSPADRSQ KIHAGDEVIQ VNRQTVVGWQ LKNLVRKLRE NPTGVVLLLK KRPTGSFSFT
PAPLKNLRWK PPLVQTSPPP TTTQSPESTM DASLKKEKPA ILDLYIPPPP AVPYSPRDEN
VSFGYRGHSK SKQPLPVRKG SESPNSFLDQ ESQRRRFTIA DSDQLPGYSV ETNVLPTKMR
GKTPSYGKPR PLSMPADGNW MGIVDPFAKP RGNGRKGEDA LCRYFSNERI TPITEESASP
MYRFSRPLTE RHLVRGADYI RGSRCYINSD LHSSATIPFQ EEGSKKKSAS SSAKASSGEP
SLLVSWLTRL KLLTH
