N4BP2_HUMAN
ID N4BP2_HUMAN Reviewed; 1770 AA.
AC Q86UW6; A0AVR3; Q9NVK2; Q9P2D4;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=NEDD4-binding protein 2;
DE Short=N4BP2;
DE EC=3.-.-.-;
DE AltName: Full=BCL-3-binding protein;
GN Name=N4BP2; Synonyms=B3BP, KIAA1413;
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), FUNCTION, INTERACTION WITH BCL3 AND
RP CREBBP, AND VARIANT ASN-611.
RC TISSUE=T-cell;
RX PubMed=12730195; DOI=10.1074/jbc.m303518200;
RA Watanabe N., Wachi S., Fujita T.;
RT "Identification and characterization of BCL-3-binding protein: implications
RT for transcription and DNA repair or recombination.";
RL J. Biol. Chem. 278:26102-26110(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-611.
RC TISSUE=Lung;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-659.
RC TISSUE=Teratocarcinoma;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 355-1770 (ISOFORM 2), AND VARIANT
RP ASN-611.
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [5]
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).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-906 AND THR-1210, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP STRUCTURE BY NMR OF 1688-1770.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SMR domain of NEDD4-binding protein 2.";
RL Submitted (JUN-2006) to the PDB data bank.
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] ALA-283.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Has 5'-polynucleotide kinase and nicking endonuclease
CC activity. May play a role in DNA repair or recombination.
CC {ECO:0000269|PubMed:12730195}.
CC -!- SUBUNIT: Binds NEDD4 (By similarity). Binds BCL3 and CREBBP.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86UW6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86UW6-2; Sequence=VSP_009721;
CC -!- DOMAIN: The Smr domain has nicking endonuclease activity, but no
CC significant double strand cleavage or exonuclease activity.
CC -!- PTM: Ubiquitinated; this targets the protein for degradation by the
CC proteasome. {ECO:0000250}.
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DR EMBL; AY267013; AAP22172.1; -; mRNA.
DR EMBL; BC126466; AAI26467.1; -; mRNA.
DR EMBL; AK001542; BAA91748.1; -; mRNA.
DR EMBL; AB037834; BAA92651.1; -; mRNA.
DR CCDS; CCDS3457.1; -. [Q86UW6-1]
DR RefSeq; NP_001305288.1; NM_001318359.1.
DR RefSeq; NP_060647.2; NM_018177.5. [Q86UW6-1]
DR RefSeq; XP_011512020.1; XM_011513718.2. [Q86UW6-1]
DR RefSeq; XP_016863887.1; XM_017008398.1. [Q86UW6-1]
DR PDB; 2D9I; NMR; -; A=1688-1770.
DR PDB; 2VKC; NMR; -; A=1657-1770.
DR PDB; 3BHB; X-ray; 2.20 A; C=129-138.
DR PDB; 3FAU; X-ray; 1.90 A; A/B/C/D=1691-1770.
DR PDBsum; 2D9I; -.
DR PDBsum; 2VKC; -.
DR PDBsum; 3BHB; -.
DR PDBsum; 3FAU; -.
DR AlphaFoldDB; Q86UW6; -.
DR SMR; Q86UW6; -.
DR BioGRID; 120848; 75.
DR CORUM; Q86UW6; -.
DR IntAct; Q86UW6; 12.
DR STRING; 9606.ENSP00000261435; -.
DR iPTMnet; Q86UW6; -.
DR PhosphoSitePlus; Q86UW6; -.
DR BioMuta; N4BP2; -.
DR DMDM; 145559498; -.
DR EPD; Q86UW6; -.
DR jPOST; Q86UW6; -.
DR MassIVE; Q86UW6; -.
DR MaxQB; Q86UW6; -.
DR PaxDb; Q86UW6; -.
DR PeptideAtlas; Q86UW6; -.
DR PRIDE; Q86UW6; -.
DR ProteomicsDB; 69917; -. [Q86UW6-1]
DR ProteomicsDB; 69918; -. [Q86UW6-2]
DR Antibodypedia; 23545; 27 antibodies from 12 providers.
DR DNASU; 55728; -.
DR Ensembl; ENST00000261435.11; ENSP00000261435.6; ENSG00000078177.14. [Q86UW6-1]
DR GeneID; 55728; -.
DR KEGG; hsa:55728; -.
DR MANE-Select; ENST00000261435.11; ENSP00000261435.6; NM_018177.6; NP_060647.2.
DR UCSC; uc003guy.5; human. [Q86UW6-1]
DR CTD; 55728; -.
DR DisGeNET; 55728; -.
DR GeneCards; N4BP2; -.
DR HGNC; HGNC:29851; N4BP2.
DR HPA; ENSG00000078177; Tissue enhanced (lymphoid).
DR MIM; 619139; gene.
DR neXtProt; NX_Q86UW6; -.
DR OpenTargets; ENSG00000078177; -.
DR PharmGKB; PA162396580; -.
DR VEuPathDB; HostDB:ENSG00000078177; -.
DR eggNOG; KOG2401; Eukaryota.
DR GeneTree; ENSGT00940000160604; -.
DR InParanoid; Q86UW6; -.
DR OMA; SICYGEN; -.
DR OrthoDB; 76267at2759; -.
DR PhylomeDB; Q86UW6; -.
DR TreeFam; TF327016; -.
DR PathwayCommons; Q86UW6; -.
DR SignaLink; Q86UW6; -.
DR BioGRID-ORCS; 55728; 31 hits in 1075 CRISPR screens.
DR ChiTaRS; N4BP2; human.
DR EvolutionaryTrace; Q86UW6; -.
DR GenomeRNAi; 55728; -.
DR Pharos; Q86UW6; Tbio.
DR PRO; PR:Q86UW6; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q86UW6; protein.
DR Bgee; ENSG00000078177; Expressed in tibia and 164 other tissues.
DR ExpressionAtlas; Q86UW6; baseline and differential.
DR Genevisible; Q86UW6; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0004519; F:endonuclease activity; IDA:MGI.
DR GO; GO:0046404; F:polydeoxyribonucleotide 5'-hydroxyl-kinase activity; IDA:MGI.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR CDD; cd14365; CUE_N4BP2; 1.
DR Gene3D; 3.30.1370.110; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003892; CUE.
DR InterPro; IPR013899; DUF1771.
DR InterPro; IPR041801; N4BP2_CUE.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR002625; Smr_dom.
DR InterPro; IPR036063; Smr_dom_sf.
DR InterPro; IPR009060; UBA-like_sf.
DR Pfam; PF08590; DUF1771; 1.
DR Pfam; PF01713; Smr; 1.
DR SMART; SM01162; DUF1771; 1.
DR SMART; SM00463; SMR; 1.
DR SUPFAM; SSF160443; SSF160443; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51140; CUE; 1.
DR PROSITE; PS50828; SMR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Coiled coil; Cytoplasm;
KW Hydrolase; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..1770
FT /note="NEDD4-binding protein 2"
FT /id="PRO_0000096681"
FT DOMAIN 46..89
FT /note="CUE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468"
FT DOMAIN 1691..1770
FT /note="Smr"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00321"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 712..756
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 795..822
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 836..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 890..913
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1580..1606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 90..177
FT /evidence="ECO:0000255"
FT COILED 218..259
FT /evidence="ECO:0000255"
FT COMPBIAS 113..129
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 712..749
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 796..813
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 843..857
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1587..1606
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 447..454
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 906
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1210
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1596..1612
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10718198"
FT /id="VSP_009721"
FT VARIANT 101
FT /note="S -> I (in dbSNP:rs17511668)"
FT /id="VAR_051215"
FT VARIANT 196
FT /note="M -> V (in dbSNP:rs10014170)"
FT /id="VAR_051216"
FT VARIANT 283
FT /note="P -> A (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035474"
FT VARIANT 611
FT /note="D -> N (in dbSNP:rs794001)"
FT /evidence="ECO:0000269|PubMed:10718198,
FT ECO:0000269|PubMed:12730195, ECO:0000269|PubMed:15489334"
FT /id="VAR_051217"
FT VARIANT 1587
FT /note="T -> A (in dbSNP:rs2271395)"
FT /id="VAR_051218"
FT CONFLICT 118
FT /note="E -> K (in Ref. 2; AAI26467)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="S -> F (in Ref. 3; BAA91748)"
FT /evidence="ECO:0000305"
FT CONFLICT 660
FT /note="K -> Q (in Ref. 1; AAP22172)"
FT /evidence="ECO:0000305"
FT CONFLICT 778
FT /note="K -> E (in Ref. 4; BAA92651)"
FT /evidence="ECO:0000305"
FT CONFLICT 1353
FT /note="S -> R (in Ref. 2; AAI26467 and 4; BAA92651)"
FT /evidence="ECO:0000305"
FT CONFLICT 1524
FT /note="L -> V (in Ref. 1; AAP22172)"
FT /evidence="ECO:0000305"
FT CONFLICT 1591
FT /note="S -> F (in Ref. 1; AAP22172)"
FT /evidence="ECO:0000305"
FT HELIX 1669..1685
FT /evidence="ECO:0007829|PDB:2VKC"
FT HELIX 1686..1688
FT /evidence="ECO:0007829|PDB:2VKC"
FT STRAND 1690..1692
FT /evidence="ECO:0007829|PDB:2D9I"
FT HELIX 1698..1719
FT /evidence="ECO:0007829|PDB:3FAU"
FT STRAND 1724..1728
FT /evidence="ECO:0007829|PDB:3FAU"
FT STRAND 1734..1736
FT /evidence="ECO:0007829|PDB:3FAU"
FT HELIX 1742..1752
FT /evidence="ECO:0007829|PDB:3FAU"
FT STRAND 1757..1761
FT /evidence="ECO:0007829|PDB:3FAU"
FT STRAND 1764..1768
FT /evidence="ECO:0007829|PDB:3FAU"
SQ SEQUENCE 1770 AA; 198801 MW; 9A49FAB19C1BD56D CRC64;
MPRRRKNLGG NPFRKTANPK EVVVSSVASR EEPTTTLPSM GETKVDQEEL FTSISEIFSD
LDPDVVYLML SECDFKVENA MDCLLELSAT DTKIEESSSQ SFVASENQVG AAESKIMEKR
PEEESEDSKM DSFLDMQLTE DLDSLIQNAF EKLNSSPDDQ VYSFLPSQDV NSFNDSSEFI
NPDSSNMTPI FSTQNMNLNG ENLENSGSTL SLNPLPSHSV LNESKCFIKD NTLALESNYP
EDSLLSSSLN VASDSIAGCS SLNQKQKELL ESECVEAQFS EAPVDLDASE PQACLNLPGL
DLPGTGGDQK STRVSDVFLP SEGFNFKPHK HPELPTKGKD VSYCPVLAPL PLLLPPPPPP
PMWNPMIPAF DLFQGNHGFV APVVTTAAHW RSVNYTFPPS VISHTSPTKV WRNKDGTSAY
QVQETPVSQV VRKKTSYVGL VLVLLRGLPG SGKSFLARTL QEDNPSGVIL STDDYFYING
QYQFDVKYLG EAHEWNQNRA KEAFEKKISP IIIDNTNLQA WEMKPYVALS QKHKYKVLFR
EPDTWWKFKP KELARRNIHG VSKEKITRML EHYQRFVSVP IIMSSSVPEK IERIELCAYS
CEDRSTSPRD DEDIISEKEE NILSLSLKHL EFTEEKNLDV TKETMLPENV AYLSNADLNK
RRKEISDMNP SIQSALILET PHMYFSDSES KLQATDKSEN EQIEMVAVKG YSKTDTDSSM
ERVSPSTCCS ENNQEDCDLA NSGPLQNEKS SPGEIVEERA TVTKKAFGKQ KSKSTLEKFP
RHELSNFVGD WPVDKTIGQR TKRNRKTEKT SSVQSDKKYN YPQSHKLVNS VSVNTDCVQQ
RGSPHESVED GRKSQCDDAS EPLNSYKYDA YKNIDKNSFN IMGDWPSSDS LAQREHRSRM
PKTGLSEPNL EIGTNDKMNE ISLSTAHEAC WGTSSQKLKT LGSSNLGSSE MLLSEMTCES
QTCLSKKSHG QHTSLPLTFT NSAPTVSGVV EPQTLAECQE QMPKRDPGKE VGMCTQTEPQ
DFALLWKIEK NKISISDSIK VLTGRLDGFK PKVFNINTKS DVQEAIPYRV MYDKSTFVEE
SELTSADESE NLNILCKLFG SFSLEALKDL YERCNKDIIW ATSLLLDSET KLCEDTEFEN
FQKSCDGSQI GPFSLGLNLK EIISQRGTLE NSNSPVPEFS HGIGISNADS QSTCDAERGN
SEQAEMRAVT PENHESMTSI FPSAAVGLKN NNDILPNSQE ELLYSSKQSF PGILKATTPK
DMSETEKNLV VTETGDNIHS PSHFSDIFNF VSSTSNLELN EEIYFTDSLE IKRNENFPKD
YVKFSDEEEF MNEDEKEMKE ILMAGSSLSA GVSGEDKTEI LNPTPAMAKS LTIDCLELAL
PPELAFQLNE LFGPVGIDSG SLTVEDCVVH IDLNLAKVIH EKWKESVMER QRQEEVSCGK
FMQDPSLVGH TGLDNPEQKS SQRTGKKLLK TLTASEMLPL LDHWNTQTKK VSLREIMSEE
IALQEKHNLK RETLMFEKDC ATKLKEKQLF KIFPAINQNF LVDIFKDHNY SLEHTVQFLN
CVLEGDPVKT VVAQEFVHQN ENVTSHTGQK SKEKKPKKLK ETEETPSELS FQDFEYPDYD
DYRAEAFLHQ QKRMECYSKA KEAYRIGKKN VATFYAQQGT LHEQKMKEAN HLAAIEIFEK
VNASLLPQNV LDLHGLHVDE ALEHLMRVLE KKTEEFKQNG GKPYLSVITG RGNHSQGGVA
RIKPAVIKYL ISHSFRFSEI KPGCLKVMLK