ENC1_HUMAN
ID ENC1_HUMAN Reviewed; 589 AA.
AC O14682; B4DHJ1; E9PFU0; O75464; Q9UPG9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Ectoderm-neural cortex protein 1;
DE Short=ENC-1;
DE AltName: Full=Kelch-like protein 37;
DE AltName: Full=Nuclear matrix protein NRP/B;
DE AltName: Full=p53-induced gene 10 protein;
GN Name=ENC1; Synonyms=KLHL37, NRPB, PIG10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION BY TP53.
RC TISSUE=Colon cancer;
RX PubMed=9305847; DOI=10.1038/38525;
RA Polyak K., Xia Y., Zweier J.L., Kinzler K.W., Vogelstein B.;
RT "A model for p53-induced apoptosis.";
RL Nature 389:300-306(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9683534; DOI=10.1006/excr.1998.4109;
RA Hernandez M.-C., Andres-Barquin P.J., Holt I., Israel M.A.;
RT "Cloning of human ENC-1 and evaluation of its expression and regulation in
RT nervous system tumors.";
RL Exp. Cell Res. 242:470-477(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain, and Hippocampus;
RX PubMed=9566959; DOI=10.1083/jcb.141.3.553;
RA Kim T.-A., Lim J., Ota S., Raja S., Rogers R., Rivnay B., Avraham H.,
RA Avraham S.;
RT "NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is
RT involved in neuronal differentiation.";
RL J. Cell Biol. 141:553-566(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [7]
RP IDENTIFICATION IN A COMPLEX WITH CUL3 AND RBX1, AND UBIQUITINATION.
RX PubMed=15983046; DOI=10.1074/jbc.m501279200;
RA Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M.;
RT "Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3,
RT targets Keap1 for degradation by a proteasome-independent pathway.";
RL J. Biol. Chem. 280:30091-30099(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KEAP1.
RX PubMed=19424503; DOI=10.1371/journal.pone.0005492;
RA Wang X.J., Zhang D.D.;
RT "Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational
RT level.";
RL PLoS ONE 4:E5492-E5492(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
CC -!- FUNCTION: Actin-binding protein involved in the regulation of neuronal
CC process formation and in differentiation of neural crest cells. Down-
CC regulates transcription factor NF2L2/NRF2 by decreasing the rate of
CC protein synthesis and not via a ubiquitin-mediated proteasomal
CC degradation mechanism. {ECO:0000269|PubMed:19424503}.
CC -!- SUBUNIT: Binds to RB1. Hypophosphorylated RB1 associates with ENC1
CC during neuronal differentiation, while hyperphosphorylated RB1
CC associates with ENC1 in undifferentiating cells. Part of a complex that
CC contains CUL3, RBX1 and ENC1. Interacts indirectly with KEAP1.
CC {ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:19424503}.
CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000269|PubMed:19424503}.
CC Cytoplasm {ECO:0000269|PubMed:19424503}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:19424503}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14682-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14682-2; Sequence=VSP_045074;
CC -!- TISSUE SPECIFICITY: Detected in fetal brain tissue, moderate expression
CC in fetal heart, lung and kidney. Highly expressed in adult brain,
CC particularly high in the hippocampus and amygdala, and spinal chord.
CC Detectable in adult pancreas. May be down-regulated in neuroblastoma
CC tumors.
CC -!- DEVELOPMENTAL STAGE: Dramatically up-regulated upon neuronal
CC differentiation.
CC -!- INDUCTION: By p53/TP53. {ECO:0000269|PubMed:9305847}.
CC -!- PTM: Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and
CC RBX1 and probably targeted for proteasome-independent degradation.
CC Quinone-induced oxidative stress increases its ubiquitination.
CC {ECO:0000269|PubMed:15983046}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NRPBID40451ch5q12.html";
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DR EMBL; AF010314; AAC39532.1; -; mRNA.
DR EMBL; AF005381; AAC64498.1; -; mRNA.
DR EMBL; AF059611; AAC26109.1; -; mRNA.
DR EMBL; AK295128; BAG58153.1; -; mRNA.
DR EMBL; AC026405; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000418; AAH00418.1; -; mRNA.
DR CCDS; CCDS4021.1; -. [O14682-1]
DR CCDS; CCDS58958.1; -. [O14682-2]
DR RefSeq; NP_001243503.1; NM_001256574.1. [O14682-1]
DR RefSeq; NP_001243504.1; NM_001256575.1. [O14682-1]
DR RefSeq; NP_001243505.1; NM_001256576.1. [O14682-2]
DR RefSeq; NP_003624.1; NM_003633.3. [O14682-1]
DR RefSeq; XP_011541998.1; XM_011543696.2. [O14682-1]
DR RefSeq; XP_011541999.1; XM_011543697.2. [O14682-1]
DR AlphaFoldDB; O14682; -.
DR SMR; O14682; -.
DR BioGRID; 114079; 22.
DR CORUM; O14682; -.
DR IntAct; O14682; 6.
DR STRING; 9606.ENSP00000479101; -.
DR iPTMnet; O14682; -.
DR PhosphoSitePlus; O14682; -.
DR BioMuta; ENC1; -.
DR EPD; O14682; -.
DR jPOST; O14682; -.
DR MassIVE; O14682; -.
DR PaxDb; O14682; -.
DR PeptideAtlas; O14682; -.
DR PRIDE; O14682; -.
DR ProteomicsDB; 20177; -.
DR ProteomicsDB; 48165; -. [O14682-1]
DR Antibodypedia; 24333; 274 antibodies from 36 providers.
DR DNASU; 8507; -.
DR Ensembl; ENST00000302351.9; ENSP00000306356.4; ENSG00000171617.15. [O14682-1]
DR Ensembl; ENST00000510316.5; ENSP00000423804.1; ENSG00000171617.15. [O14682-2]
DR Ensembl; ENST00000537006.1; ENSP00000446289.1; ENSG00000171617.15. [O14682-1]
DR Ensembl; ENST00000618628.4; ENSP00000479101.1; ENSG00000171617.15. [O14682-1]
DR Ensembl; ENST00000651128.1; ENSP00000499185.1; ENSG00000171617.15. [O14682-1]
DR GeneID; 8507; -.
DR KEGG; hsa:8507; -.
DR MANE-Select; ENST00000302351.9; ENSP00000306356.4; NM_003633.4; NP_003624.1.
DR UCSC; uc011css.4; human. [O14682-1]
DR CTD; 8507; -.
DR DisGeNET; 8507; -.
DR GeneCards; ENC1; -.
DR HGNC; HGNC:3345; ENC1.
DR HPA; ENSG00000171617; Tissue enriched (brain).
DR MIM; 605173; gene.
DR neXtProt; NX_O14682; -.
DR OpenTargets; ENSG00000171617; -.
DR PharmGKB; PA27782; -.
DR VEuPathDB; HostDB:ENSG00000171617; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00950000182983; -.
DR HOGENOM; CLU_004253_14_6_1; -.
DR InParanoid; O14682; -.
DR OMA; DSMKMSV; -.
DR PhylomeDB; O14682; -.
DR TreeFam; TF329218; -.
DR PathwayCommons; O14682; -.
DR SignaLink; O14682; -.
DR BioGRID-ORCS; 8507; 9 hits in 1115 CRISPR screens.
DR ChiTaRS; ENC1; human.
DR GeneWiki; ENC1; -.
DR GenomeRNAi; 8507; -.
DR Pharos; O14682; Tbio.
DR PRO; PR:O14682; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O14682; protein.
DR Bgee; ENSG00000171617; Expressed in Brodmann (1909) area 10 and 196 other tissues.
DR ExpressionAtlas; O14682; baseline and differential.
DR Genevisible; O14682; HS.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0010499; P:proteasomal ubiquitin-independent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR011705; BACK.
DR InterPro; IPR017096; BTB-kelch_protein.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR030562; ENC1.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24410:SF5; PTHR24410:SF5; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 4.
DR PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 6.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Developmental protein; Kelch repeat; Nucleus; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1..589
FT /note="Ectoderm-neural cortex protein 1"
FT /id="PRO_0000119068"
FT DOMAIN 46..114
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REPEAT 296..340
FT /note="Kelch 1"
FT REPEAT 341..388
FT /note="Kelch 2"
FT REPEAT 389..444
FT /note="Kelch 3"
FT REPEAT 446..492
FT /note="Kelch 4"
FT REPEAT 494..538
FT /note="Kelch 5"
FT REPEAT 539..585
FT /note="Kelch 6"
FT VAR_SEQ 1..73
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045074"
FT VARIANT 256
FT /note="I -> S (in dbSNP:rs16872126)"
FT /id="VAR_050040"
FT CONFLICT 108
FT /note="S -> F (in Ref. 4; BAG58153)"
FT /evidence="ECO:0000305"
FT CONFLICT 112..130
FT /note="INEENAESLLEAGDMLEFQ -> HQLEGKCRNSLLGSLVTCWSFK (in
FT Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 237..238
FT /note="RL -> TR (in Ref. 1; AAC39532)"
FT /evidence="ECO:0000305"
FT CONFLICT 378
FT /note="R -> M (in Ref. 4; BAG58153)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="C -> S (in Ref. 2; AAC64498)"
FT /evidence="ECO:0000305"
FT CONFLICT 427
FT /note="V -> A (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 430..438
FT /note="LREGVSNAA -> RPRRRYNCAQ (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 484..589
FT /note="YTAAAVLGNQIFIMGGDTEFSACSAYKFNSETYQWTKVGDVTAKRMSCHAVA
FT SGNKLYVVGGYFGIQRCKTLDCYDPTLDVWNSITTVPYSLIPTAFVSTWKHLPS -> I
FT HSQASCPGGTQDFLLWGVIQNFSACFCL (in Ref. 1; AAC39532)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 589 AA; 66130 MW; DB003A1DFA65BAA0 CRC64;
MSVSVHENRK SRASSGSINI YLFHKSSYAD SVLTHLNLLR QQRLFTDVLL HAGNRTFPCH
RAVLAACSRY FEAMFSGGLK ESQDSEVNFD NSIHPEVLEL LLDYAYSSRV IINEENAESL
LEAGDMLEFQ DIRDACAEFL EKNLHPTNCL GMLLLSDAHQ CTKLYELSWR MCLSNFQTIR
KNEDFLQLPQ DMVVQLLSSE ELETEDERLV YESAINWISY DLKKRYCYLP ELLQTVRLAL
LPAIYLMENV AMEELITKQR KSKEIVEEAI RCKLKILQND GVVTSLCARP RKTGHALFLL
GGQTFMCDKL YLVDQKAKEI IPKADIPSPR KEFSACAIGC KVYITGGRGS ENGVSKDVWV
YDTLHEEWSK AAPMLVARFG HGSAELKHCL YVVGGHTAAT GCLPASPSVS LKQVEHYDPT
INKWTMVAPL REGVSNAAVV SAKLKLFAFG GTSVSHDKLP KVQCYDQCEN RWTVPATCPQ
PWRYTAAAVL GNQIFIMGGD TEFSACSAYK FNSETYQWTK VGDVTAKRMS CHAVASGNKL
YVVGGYFGIQ RCKTLDCYDP TLDVWNSITT VPYSLIPTAF VSTWKHLPS
