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Protein

Serine/threonine-protein kinase ULK3

Gene

Ulk3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei44 – 441ATPPROSITE-ProRule annotation
Active sitei137 – 1371Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi20 – 289ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Autophagy

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-5632684. Hedgehog 'on' state.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase ULK3 (EC:2.7.11.1)
Alternative name(s):
Unc-51-like kinase 3
Gene namesi
Name:Ulk3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1918992. Ulk3.

Subcellular locationi

  • Cytoplasm By similarity

  • Note: Localizes to pre-autophagosomal structure during cellular senescence.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL3832.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 472472Serine/threonine-protein kinase ULK3PRO_0000250151Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei176 – 1761PhosphoserineBy similarity
Modified residuei350 – 3501Phosphoserine; by autocatalysisBy similarity
Modified residuei384 – 3841Phosphoserine; by autocatalysisBy similarity
Modified residuei464 – 4641Phosphoserine; by autocatalysisBy similarity

Post-translational modificationi

Autophosphorylated. Autophosphorylation is blocked by interaction with SUFU (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ3U3Q1.
MaxQBiQ3U3Q1.
PaxDbiQ3U3Q1.
PRIDEiQ3U3Q1.

PTM databases

iPTMnetiQ3U3Q1.
PhosphoSiteiQ3U3Q1.

Expressioni

Gene expression databases

BgeeiQ3U3Q1.
CleanExiMM_ULK3.
GenevisibleiQ3U3Q1. MM.

Interactioni

Subunit structurei

Interacts (via protein kinase domain) with SUFU.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000059947.

Chemistry

BindingDBiQ3U3Q1.

Structurei

3D structure databases

ProteinModelPortaliQ3U3Q1.
SMRiQ3U3Q1. Positions 7-446.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 270257Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini280 – 34869MIT 1Add
BLAST
Domaini375 – 44470MIT 2Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi300 – 3034Poly-Ala

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.PROSITE-ProRule annotation
Contains 2 MIT domains.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0595. Eukaryota.
ENOG410XR01. LUCA.
GeneTreeiENSGT00820000126991.
HOGENOMiHOG000233016.
HOVERGENiHBG094133.
InParanoidiQ3U3Q1.
KOiK08269.
OMAiCSALEHF.
OrthoDBiEOG71G9VJ.
PhylomeDBiQ3U3Q1.
TreeFamiTF324551.

Family and domain databases

Gene3Di1.20.58.280. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR007330. MIT.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF04212. MIT. 2 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00745. MIT. 2 hits.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF116846. SSF116846. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3U3Q1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGPSWGLPR LDGFILTERL GSGTYATVYK AYAKKDTREV VAIKCVAKKS
60 70 80 90 100
LNKASVENLL TEIEILKGIR HPHIVQLKDF QWDNDNIYLI MEFCAGGDLS
110 120 130 140 150
RFIHTRRILP EKVARVFMQQ LASALQFLHE RNISHLDLKP QNILLSSLEK
160 170 180 190 200
PHLKLADFGF AQHMSPWDEK HVLRGSPLYM APEMVCRRQY DARVDLWSVG
210 220 230 240 250
VILYEALFGQ PPFASRSFSE LEEKIRSNRV IELPLRPQLS LDCRDLLQRL
260 270 280 290 300
LERDPARRIS FKDFFAHPWV DLEHMPSGES LAQARALVVE AVKKDQEGDA
310 320 330 340 350
AAALSLYCKA LDFFVPALHY EVDAQRKEAI KAKVGQYVSR AEELKAIVSS
360 370 380 390 400
SNQALLRQGT TVQELLREMA RDKPRLLAAL EVASAALAKE EEAGKEQDAL
410 420 430 440 450
DLYQHSLGEL LVLLAAEAPG RRRELLHTEV QNLMARAEYL KEQIKIRESH
460 470
WEAESLDKEG LSESVRSSCT LQ
Length:472
Mass (Da):53,572
Last modified:October 11, 2005 - v1
Checksum:i9FBAA9761CC80292
GO
Isoform 2 (identifier: Q3U3Q1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     431-472: QNLMARAEYL...ESVRSSCTLQ → GVGVEKCSFP...VRSVTQDFCA

Note: No experimental confirmation available.
Show »
Length:471
Mass (Da):53,286
Checksum:i7C7ABD2FFF02C1DB
GO
Isoform 3 (identifier: Q3U3Q1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     205-295: EALFGQPPFA...ALVVEAVKKD → GETSLPLLST...RRKDSQQSGD
     296-472: Missing.

Note: No experimental confirmation available.
Show »
Length:295
Mass (Da):33,580
Checksum:i0A234ABE7369AE6A
GO

Sequence cautioni

The sequence AAH37093.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti151 – 1511P → S in AAH37093 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei205 – 29591EALFG…AVKKD → GETSLPLLSTLRVTLYLGQA FLGLSWVQMRIKGSTLRDFW SPFCGRARPDLTLFPSGPSS AFFHRSPLWAAPLCLQIVLR ARRKDSQQSGD in isoform 3. 1 PublicationVSP_020602Add
BLAST
Alternative sequencei296 – 472177Missing in isoform 3. 1 PublicationVSP_020603Add
BLAST
Alternative sequencei431 – 47242QNLMA…SCTLQ → GVGVEKCSFPSSYSGLWDIN RSHMDFPCLRIVRSVTQDFC A in isoform 2. 1 PublicationVSP_020604Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK004783 mRNA. Translation: BAB23561.1.
AK154642 mRNA. Translation: BAE32734.1.
CH466522 Genomic DNA. Translation: EDL25913.1.
BC037093 mRNA. Translation: AAH37093.1. Different initiation.
BC151153 mRNA. Translation: AAI51154.1.
CCDSiCCDS52809.1. [Q3U3Q1-1]
RefSeqiNP_082171.1. NM_027895.1. [Q3U3Q1-1]
UniGeneiMm.155877.

Genome annotation databases

EnsembliENSMUST00000053230; ENSMUSP00000059947; ENSMUSG00000032308. [Q3U3Q1-1]
GeneIDi71742.
KEGGimmu:71742.
UCSCiuc009pvf.2. mouse. [Q3U3Q1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK004783 mRNA. Translation: BAB23561.1.
AK154642 mRNA. Translation: BAE32734.1.
CH466522 Genomic DNA. Translation: EDL25913.1.
BC037093 mRNA. Translation: AAH37093.1. Different initiation.
BC151153 mRNA. Translation: AAI51154.1.
CCDSiCCDS52809.1. [Q3U3Q1-1]
RefSeqiNP_082171.1. NM_027895.1. [Q3U3Q1-1]
UniGeneiMm.155877.

3D structure databases

ProteinModelPortaliQ3U3Q1.
SMRiQ3U3Q1. Positions 7-446.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000059947.

Chemistry

BindingDBiQ3U3Q1.
ChEMBLiCHEMBL3832.

PTM databases

iPTMnetiQ3U3Q1.
PhosphoSiteiQ3U3Q1.

Proteomic databases

EPDiQ3U3Q1.
MaxQBiQ3U3Q1.
PaxDbiQ3U3Q1.
PRIDEiQ3U3Q1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000053230; ENSMUSP00000059947; ENSMUSG00000032308. [Q3U3Q1-1]
GeneIDi71742.
KEGGimmu:71742.
UCSCiuc009pvf.2. mouse. [Q3U3Q1-1]

Organism-specific databases

CTDi25989.
MGIiMGI:1918992. Ulk3.

Phylogenomic databases

eggNOGiKOG0595. Eukaryota.
ENOG410XR01. LUCA.
GeneTreeiENSGT00820000126991.
HOGENOMiHOG000233016.
HOVERGENiHBG094133.
InParanoidiQ3U3Q1.
KOiK08269.
OMAiCSALEHF.
OrthoDBiEOG71G9VJ.
PhylomeDBiQ3U3Q1.
TreeFamiTF324551.

Enzyme and pathway databases

ReactomeiR-MMU-5632684. Hedgehog 'on' state.

Miscellaneous databases

PROiQ3U3Q1.
SOURCEiSearch...

Gene expression databases

BgeeiQ3U3Q1.
CleanExiMM_ULK3.
GenevisibleiQ3U3Q1. MM.

Family and domain databases

Gene3Di1.20.58.280. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR007330. MIT.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF04212. MIT. 2 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00745. MIT. 2 hits.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF116846. SSF116846. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
    Strain: C57BL/6J and NOD.
    Tissue: Lung.
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: FVB/N.
    Tissue: Brain and Mammary tumor.

Entry informationi

Entry nameiULK3_MOUSE
AccessioniPrimary (citable) accession number: Q3U3Q1
Secondary accession number(s): B2RXB9, Q8K1X6, Q9DBR8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: October 11, 2005
Last modified: June 8, 2016
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.