Full text data of ULK3
ULK3
[Confidence: low (only semi-automatic identification from reviews)]
Serine/threonine-protein kinase ULK3; 2.7.11.1 (Unc-51-like kinase 3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serine/threonine-protein kinase ULK3; 2.7.11.1 (Unc-51-like kinase 3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q6PHR2
ID ULK3_HUMAN Reviewed; 472 AA.
AC Q6PHR2; B2RXK3; B4DRQ7; D3DW68; Q9NPN5; Q9UFS4;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 22-SEP-2009, sequence version 2.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=Serine/threonine-protein kinase ULK3;
DE EC=2.7.11.1;
DE AltName: Full=Unc-51-like kinase 3;
GN Name=ULK3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Tongue;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Blood, and Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 162-472 (ISOFORM 2).
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=19279323; DOI=10.1101/gad.519709;
RA Young A.R., Narita M., Ferreira M., Kirschner K., Sadaie M.,
RA Darot J.F., Tavare S., Arakawa S., Shimizu S., Watt F.M., Narita M.;
RT "Autophagy mediates the mitotic senescence transition.";
RL Genes Dev. 23:798-803(2009).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-44 AND LYS-139.
RX PubMed=19878745; DOI=10.1016/j.yexcr.2009.10.018;
RA Maloverjan A., Piirsoo M., Michelson P., Kogerman P., Osterlund T.;
RT "Identification of a novel serine/threonine kinase ULK3 as a positive
RT regulator of Hedgehog pathway.";
RL Exp. Cell Res. 316:627-637(2010).
RN [10]
RP FUNCTION, AUTOPHOSPHORYLATION, INTERACTION WITH SUFU, MUTAGENESIS OF
RP LYS-139, AND PHOSPHORYLATION AT SER-300; SER-350; SER-384 AND SER-464.
RX PubMed=20643644; DOI=10.1074/jbc.M110.133991;
RA Maloverjan A., Piirsoo M., Kasak L., Peil L., Osterlund T.,
RA Kogerman P.;
RT "Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog
RT signaling pathway.";
RL J. Biol. Chem. 285:30079-30090(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Serine/threonine protein kinase that acts as a regulator
CC of Sonic hedgehog (SHH) signaling and autophagy. Acts as a
CC negative regulator of SHH signaling in the absence of SHH ligand:
CC interacts with SUFU, thereby inactivating the protein kinase
CC activity and preventing phosphorylation of GLI proteins (GLI1,
CC GLI2 and/or GLI3). Positively regulates SHH signaling in the
CC presence of SHH: dissociates from SUFU, autophosphorylates and
CC mediates phosphorylation of GLI2, activating it and promoting its
CC nuclear translocation. Phosphorylates in vitro GLI2, as well as
CC GLI1 and GLI3, although less efficiently. Also acts as a regulator
CC of autophagy: following cellular senescence, able to induce
CC autophagy.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- SUBUNIT: Interacts (via protein kinase domain) with SUFU.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Localizes to pre-
CC autophagosomal structure during cellular senescence.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6PHR2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PHR2-2; Sequence=VSP_038147, VSP_038148;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3;
CC IsoId=Q6PHR2-3; Sequence=VSP_039925;
CC Note=May be due to competing donor splice site. No experimental
CC confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels observed in
CC fetal brain. In adult tissues, high levels in brain, liver and
CC kidney, moderate levels in testis and adrenal gland and low levels
CC in heart, lung, stomach, thymus, prostate and placenta. In the
CC brain, highest expression in the hippocampus, high levels also
CC detected in the cerebellum, olfactory bulb and optic nerve. In the
CC central nervous system, lowest levels in the spinal cord.
CC -!- INDUCTION: Up-regulated during senescence.
CC -!- PTM: Autophosphorylated. Autophosphorylation is blocked by
CC interaction with SUFU.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
CC protein kinase family. APG1/unc-51/ULK1 subfamily.
CC -!- SIMILARITY: Contains 2 MIT domains.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB55955.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AK299380; BAG61369.1; -; mRNA.
DR EMBL; AL117482; CAB55955.2; ALT_INIT; mRNA.
DR EMBL; AC091230; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036117; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC056423; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471136; EAW99301.1; -; Genomic_DNA.
DR EMBL; CH471136; EAW99303.1; -; Genomic_DNA.
DR EMBL; BC157884; AAI57885.1; -; mRNA.
DR EMBL; AL360256; CAB96176.1; -; mRNA.
DR PIR; T17265; T17265.
DR RefSeq; NP_001092906.2; NM_001099436.2.
DR RefSeq; NP_001271293.1; NM_001284364.1.
DR RefSeq; NP_001271294.1; NM_001284365.1.
DR UniGene; Hs.513034; -.
DR ProteinModelPortal; Q6PHR2; -.
DR SMR; Q6PHR2; 7-345.
DR STRING; 9606.ENSP00000400312; -.
DR BindingDB; Q6PHR2; -.
DR ChEMBL; CHEMBL5047; -.
DR GuidetoPHARMACOLOGY; 2273; -.
DR PhosphoSite; Q6PHR2; -.
DR DMDM; 259016166; -.
DR PaxDb; Q6PHR2; -.
DR PRIDE; Q6PHR2; -.
DR DNASU; 25989; -.
DR Ensembl; ENST00000440863; ENSP00000400312; ENSG00000140474.
DR Ensembl; ENST00000569437; ENSP00000456051; ENSG00000140474.
DR GeneID; 25989; -.
DR KEGG; hsa:25989; -.
DR UCSC; uc010bkf.1; human.
DR CTD; 25989; -.
DR GeneCards; GC15M075128; -.
DR H-InvDB; HIX0012431; -.
DR HGNC; HGNC:19703; ULK3.
DR HPA; HPA040474; -.
DR MIM; 613472; gene.
DR neXtProt; NX_Q6PHR2; -.
DR PharmGKB; PA134908392; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233016; -.
DR HOVERGEN; HBG094133; -.
DR InParanoid; Q6PHR2; -.
DR KO; K08269; -.
DR OrthoDB; EOG71G9VJ; -.
DR SignaLink; Q6PHR2; -.
DR GenomeRNAi; 25989; -.
DR NextBio; 47686; -.
DR PRO; PR:Q6PHR2; -.
DR ArrayExpress; Q6PHR2; -.
DR Bgee; Q6PHR2; -.
DR CleanEx; HS_ULK3; -.
DR Genevestigator; Q6PHR2; -.
DR GO; GO:0000407; C:pre-autophagosomal structure; TAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; TAS:UniProtKB.
DR GO; GO:0090398; P:cellular senescence; TAS:UniProtKB.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR007330; MIT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF04212; MIT; 2.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00745; MIT; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Autophagy; Complete proteome;
KW Cytoplasm; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1 472 Serine/threonine-protein kinase ULK3.
FT /FTId=PRO_0000250150.
FT DOMAIN 14 270 Protein kinase.
FT DOMAIN 280 348 MIT 1.
FT DOMAIN 375 444 MIT 2.
FT NP_BIND 20 28 ATP (By similarity).
FT ACT_SITE 137 137 Proton acceptor (By similarity).
FT BINDING 44 44 ATP (By similarity).
FT MOD_RES 176 176 Phosphoserine.
FT MOD_RES 300 300 Phosphoserine; by autocatalysis.
FT MOD_RES 350 350 Phosphoserine; by autocatalysis.
FT MOD_RES 384 384 Phosphoserine; by autocatalysis.
FT MOD_RES 464 464 Phosphoserine; by autocatalysis.
FT VAR_SEQ 205 214 EALFGQPPFA -> GETSFPCFSP (in isoform 2).
FT /FTId=VSP_038147.
FT VAR_SEQ 215 472 Missing (in isoform 2).
FT /FTId=VSP_038148.
FT VAR_SEQ 444 445 Missing (in isoform 3).
FT /FTId=VSP_039925.
FT VARIANT 101 101 R -> H (in dbSNP:rs34945944).
FT /FTId=VAR_057113.
FT VARIANT 445 445 K -> R (in dbSNP:rs12898397).
FT /FTId=VAR_059771.
FT MUTAGEN 44 44 K->R: Decreased kinase activity.
FT MUTAGEN 139 139 K->R: Loss of kinase activity. Does not
FT promote GLI1 nuclear localization.
FT CONFLICT 47 47 A -> S (in Ref. 1; BAG61369).
SQ SEQUENCE 472 AA; 53444 MW; 11D03E311AF36162 CRC64;
MAGPGWGPPR LDGFILTERL GSGTYATVYK AYAKKDTREV VAIKCVAKKS LNKASVENLL
TEIEILKGIR HPHIVQLKDF QWDSDNIYLI MEFCAGGDLS RFIHTRRILP EKVARVFMQQ
LASALQFLHE RNISHLDLKP QNILLSSLEK PHLKLADFGF AQHMSPWDEK HVLRGSPLYM
APEMVCQRQY DARVDLWSMG VILYEALFGQ PPFASRSFSE LEEKIRSNRV IELPLRPLLS
RDCRDLLQRL LERDPSRRIS FQDFFAHPWV DLEHMPSGES LGRATALVVQ AVKKDQEGDS
AAALSLYCKA LDFFVPALHY EVDAQRKEAI KAKVGQYVSR AEELKAIVSS SNQALLRQGT
SARDLLREMA RDKPRLLAAL EVASAAMAKE EAAGGEQDAL DLYQHSLGEL LLLLAAEPPG
RRRELLHTEV QNLMARAEYL KEQVKMRESR WEADTLDKEG LSESVRSSCT LQ
//
ID ULK3_HUMAN Reviewed; 472 AA.
AC Q6PHR2; B2RXK3; B4DRQ7; D3DW68; Q9NPN5; Q9UFS4;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 22-SEP-2009, sequence version 2.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=Serine/threonine-protein kinase ULK3;
DE EC=2.7.11.1;
DE AltName: Full=Unc-51-like kinase 3;
GN Name=ULK3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Tongue;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Blood, and Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 162-472 (ISOFORM 2).
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=19279323; DOI=10.1101/gad.519709;
RA Young A.R., Narita M., Ferreira M., Kirschner K., Sadaie M.,
RA Darot J.F., Tavare S., Arakawa S., Shimizu S., Watt F.M., Narita M.;
RT "Autophagy mediates the mitotic senescence transition.";
RL Genes Dev. 23:798-803(2009).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-44 AND LYS-139.
RX PubMed=19878745; DOI=10.1016/j.yexcr.2009.10.018;
RA Maloverjan A., Piirsoo M., Michelson P., Kogerman P., Osterlund T.;
RT "Identification of a novel serine/threonine kinase ULK3 as a positive
RT regulator of Hedgehog pathway.";
RL Exp. Cell Res. 316:627-637(2010).
RN [10]
RP FUNCTION, AUTOPHOSPHORYLATION, INTERACTION WITH SUFU, MUTAGENESIS OF
RP LYS-139, AND PHOSPHORYLATION AT SER-300; SER-350; SER-384 AND SER-464.
RX PubMed=20643644; DOI=10.1074/jbc.M110.133991;
RA Maloverjan A., Piirsoo M., Kasak L., Peil L., Osterlund T.,
RA Kogerman P.;
RT "Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog
RT signaling pathway.";
RL J. Biol. Chem. 285:30079-30090(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Serine/threonine protein kinase that acts as a regulator
CC of Sonic hedgehog (SHH) signaling and autophagy. Acts as a
CC negative regulator of SHH signaling in the absence of SHH ligand:
CC interacts with SUFU, thereby inactivating the protein kinase
CC activity and preventing phosphorylation of GLI proteins (GLI1,
CC GLI2 and/or GLI3). Positively regulates SHH signaling in the
CC presence of SHH: dissociates from SUFU, autophosphorylates and
CC mediates phosphorylation of GLI2, activating it and promoting its
CC nuclear translocation. Phosphorylates in vitro GLI2, as well as
CC GLI1 and GLI3, although less efficiently. Also acts as a regulator
CC of autophagy: following cellular senescence, able to induce
CC autophagy.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- SUBUNIT: Interacts (via protein kinase domain) with SUFU.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Localizes to pre-
CC autophagosomal structure during cellular senescence.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6PHR2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PHR2-2; Sequence=VSP_038147, VSP_038148;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3;
CC IsoId=Q6PHR2-3; Sequence=VSP_039925;
CC Note=May be due to competing donor splice site. No experimental
CC confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels observed in
CC fetal brain. In adult tissues, high levels in brain, liver and
CC kidney, moderate levels in testis and adrenal gland and low levels
CC in heart, lung, stomach, thymus, prostate and placenta. In the
CC brain, highest expression in the hippocampus, high levels also
CC detected in the cerebellum, olfactory bulb and optic nerve. In the
CC central nervous system, lowest levels in the spinal cord.
CC -!- INDUCTION: Up-regulated during senescence.
CC -!- PTM: Autophosphorylated. Autophosphorylation is blocked by
CC interaction with SUFU.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
CC protein kinase family. APG1/unc-51/ULK1 subfamily.
CC -!- SIMILARITY: Contains 2 MIT domains.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB55955.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AK299380; BAG61369.1; -; mRNA.
DR EMBL; AL117482; CAB55955.2; ALT_INIT; mRNA.
DR EMBL; AC091230; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036117; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC056423; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471136; EAW99301.1; -; Genomic_DNA.
DR EMBL; CH471136; EAW99303.1; -; Genomic_DNA.
DR EMBL; BC157884; AAI57885.1; -; mRNA.
DR EMBL; AL360256; CAB96176.1; -; mRNA.
DR PIR; T17265; T17265.
DR RefSeq; NP_001092906.2; NM_001099436.2.
DR RefSeq; NP_001271293.1; NM_001284364.1.
DR RefSeq; NP_001271294.1; NM_001284365.1.
DR UniGene; Hs.513034; -.
DR ProteinModelPortal; Q6PHR2; -.
DR SMR; Q6PHR2; 7-345.
DR STRING; 9606.ENSP00000400312; -.
DR BindingDB; Q6PHR2; -.
DR ChEMBL; CHEMBL5047; -.
DR GuidetoPHARMACOLOGY; 2273; -.
DR PhosphoSite; Q6PHR2; -.
DR DMDM; 259016166; -.
DR PaxDb; Q6PHR2; -.
DR PRIDE; Q6PHR2; -.
DR DNASU; 25989; -.
DR Ensembl; ENST00000440863; ENSP00000400312; ENSG00000140474.
DR Ensembl; ENST00000569437; ENSP00000456051; ENSG00000140474.
DR GeneID; 25989; -.
DR KEGG; hsa:25989; -.
DR UCSC; uc010bkf.1; human.
DR CTD; 25989; -.
DR GeneCards; GC15M075128; -.
DR H-InvDB; HIX0012431; -.
DR HGNC; HGNC:19703; ULK3.
DR HPA; HPA040474; -.
DR MIM; 613472; gene.
DR neXtProt; NX_Q6PHR2; -.
DR PharmGKB; PA134908392; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233016; -.
DR HOVERGEN; HBG094133; -.
DR InParanoid; Q6PHR2; -.
DR KO; K08269; -.
DR OrthoDB; EOG71G9VJ; -.
DR SignaLink; Q6PHR2; -.
DR GenomeRNAi; 25989; -.
DR NextBio; 47686; -.
DR PRO; PR:Q6PHR2; -.
DR ArrayExpress; Q6PHR2; -.
DR Bgee; Q6PHR2; -.
DR CleanEx; HS_ULK3; -.
DR Genevestigator; Q6PHR2; -.
DR GO; GO:0000407; C:pre-autophagosomal structure; TAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; TAS:UniProtKB.
DR GO; GO:0090398; P:cellular senescence; TAS:UniProtKB.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR007330; MIT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF04212; MIT; 2.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00745; MIT; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Autophagy; Complete proteome;
KW Cytoplasm; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1 472 Serine/threonine-protein kinase ULK3.
FT /FTId=PRO_0000250150.
FT DOMAIN 14 270 Protein kinase.
FT DOMAIN 280 348 MIT 1.
FT DOMAIN 375 444 MIT 2.
FT NP_BIND 20 28 ATP (By similarity).
FT ACT_SITE 137 137 Proton acceptor (By similarity).
FT BINDING 44 44 ATP (By similarity).
FT MOD_RES 176 176 Phosphoserine.
FT MOD_RES 300 300 Phosphoserine; by autocatalysis.
FT MOD_RES 350 350 Phosphoserine; by autocatalysis.
FT MOD_RES 384 384 Phosphoserine; by autocatalysis.
FT MOD_RES 464 464 Phosphoserine; by autocatalysis.
FT VAR_SEQ 205 214 EALFGQPPFA -> GETSFPCFSP (in isoform 2).
FT /FTId=VSP_038147.
FT VAR_SEQ 215 472 Missing (in isoform 2).
FT /FTId=VSP_038148.
FT VAR_SEQ 444 445 Missing (in isoform 3).
FT /FTId=VSP_039925.
FT VARIANT 101 101 R -> H (in dbSNP:rs34945944).
FT /FTId=VAR_057113.
FT VARIANT 445 445 K -> R (in dbSNP:rs12898397).
FT /FTId=VAR_059771.
FT MUTAGEN 44 44 K->R: Decreased kinase activity.
FT MUTAGEN 139 139 K->R: Loss of kinase activity. Does not
FT promote GLI1 nuclear localization.
FT CONFLICT 47 47 A -> S (in Ref. 1; BAG61369).
SQ SEQUENCE 472 AA; 53444 MW; 11D03E311AF36162 CRC64;
MAGPGWGPPR LDGFILTERL GSGTYATVYK AYAKKDTREV VAIKCVAKKS LNKASVENLL
TEIEILKGIR HPHIVQLKDF QWDSDNIYLI MEFCAGGDLS RFIHTRRILP EKVARVFMQQ
LASALQFLHE RNISHLDLKP QNILLSSLEK PHLKLADFGF AQHMSPWDEK HVLRGSPLYM
APEMVCQRQY DARVDLWSMG VILYEALFGQ PPFASRSFSE LEEKIRSNRV IELPLRPLLS
RDCRDLLQRL LERDPSRRIS FQDFFAHPWV DLEHMPSGES LGRATALVVQ AVKKDQEGDS
AAALSLYCKA LDFFVPALHY EVDAQRKEAI KAKVGQYVSR AEELKAIVSS SNQALLRQGT
SARDLLREMA RDKPRLLAAL EVASAAMAKE EAAGGEQDAL DLYQHSLGEL LLLLAAEPPG
RRRELLHTEV QNLMARAEYL KEQVKMRESR WEADTLDKEG LSESVRSSCT LQ
//
MIM
613472
*RECORD*
*FIELD* NO
613472
*FIELD* TI
*613472 UNC51-LIKE KINASE 3; ULK3
*FIELD* TX
CLONING
By searching a human protein database for sequences similar to STK36
read more(607652), followed by PCR of a testis cDNA library, Maloverjan et al.
(2010) cloned ULK3. The deduced 472-amino acid protein has a calculated
molecular mass of 53 kD. ULK3 has an N-terminal 270-amino acid kinase
domain followed by a microtubule-interacting domain. The kinase domain
of ULK3 shares 38% identity with that of STK36 and 37% identity with
that of Drosophila Fu, a kinase involved in hedgehog signaling (see SHH;
600725). Quantitative RT-PCR detected ULK3 expression in all tissues
analyzed, with highest expression in fetal brain. In adult tissues,
expression was highest in brain, liver, and kidney, with moderate
expression in testis and adrenal gland, and low expression in heart,
lung, stomach, thymus, prostate, and placenta. Within adult human brain
regions, highest ULK3 expression was detected in hippocampus.
GENE FUNCTION
Using a reporter gene assay, Maloverjan et al. (2010) showed that ULK3
enhanced GLI (see GLI1; 165220)-dependent hedgehog signaling in
Shh-expressing L2 rat yolk sac cells. Mutation analysis showed that the
kinase domain of ULK3 was required for reporter activation. ULK3 showed
autophosphorylation activity, and it showed serine/threonine kinase
activity toward GLI2 (165230), with lower kinase activity toward GLI1
and GLI3 (165240). Phosphorylation of GLI1 by ULK3 resulted in GLI1
nuclear accumulation.
GENE STRUCTURE
Maloverjan et al. (2010) determined that the ULK3 gene has 16 exons.
MAPPING
By genomic sequence analysis, Maloverjan et al. (2010) mapped the ULK3
gene to chromosome 15.
*FIELD* RF
1. Maloverjan, A.; Piirsoo, M.; Michelson, P.; Kogerman, P.; Osterlund,
T.: Identification of a novel serine/threonine kinase ULK3 as a positive
regulator of Hedgehog pathway. Exp. Cell Res. 316: 627-637, 2010.
*FIELD* CD
Patricia A. Hartz: 7/9/2010
*FIELD* ED
mgross: 07/09/2010
*RECORD*
*FIELD* NO
613472
*FIELD* TI
*613472 UNC51-LIKE KINASE 3; ULK3
*FIELD* TX
CLONING
By searching a human protein database for sequences similar to STK36
read more(607652), followed by PCR of a testis cDNA library, Maloverjan et al.
(2010) cloned ULK3. The deduced 472-amino acid protein has a calculated
molecular mass of 53 kD. ULK3 has an N-terminal 270-amino acid kinase
domain followed by a microtubule-interacting domain. The kinase domain
of ULK3 shares 38% identity with that of STK36 and 37% identity with
that of Drosophila Fu, a kinase involved in hedgehog signaling (see SHH;
600725). Quantitative RT-PCR detected ULK3 expression in all tissues
analyzed, with highest expression in fetal brain. In adult tissues,
expression was highest in brain, liver, and kidney, with moderate
expression in testis and adrenal gland, and low expression in heart,
lung, stomach, thymus, prostate, and placenta. Within adult human brain
regions, highest ULK3 expression was detected in hippocampus.
GENE FUNCTION
Using a reporter gene assay, Maloverjan et al. (2010) showed that ULK3
enhanced GLI (see GLI1; 165220)-dependent hedgehog signaling in
Shh-expressing L2 rat yolk sac cells. Mutation analysis showed that the
kinase domain of ULK3 was required for reporter activation. ULK3 showed
autophosphorylation activity, and it showed serine/threonine kinase
activity toward GLI2 (165230), with lower kinase activity toward GLI1
and GLI3 (165240). Phosphorylation of GLI1 by ULK3 resulted in GLI1
nuclear accumulation.
GENE STRUCTURE
Maloverjan et al. (2010) determined that the ULK3 gene has 16 exons.
MAPPING
By genomic sequence analysis, Maloverjan et al. (2010) mapped the ULK3
gene to chromosome 15.
*FIELD* RF
1. Maloverjan, A.; Piirsoo, M.; Michelson, P.; Kogerman, P.; Osterlund,
T.: Identification of a novel serine/threonine kinase ULK3 as a positive
regulator of Hedgehog pathway. Exp. Cell Res. 316: 627-637, 2010.
*FIELD* CD
Patricia A. Hartz: 7/9/2010
*FIELD* ED
mgross: 07/09/2010