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Protein

Serine/threonine-protein kinase ULK3

Gene

ULK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei44ATPPROSITE-ProRule annotation1
Active sitei137Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi20 – 28ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processAutophagy
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-5632684 Hedgehog 'on' state
SignaLinkiQ6PHR2

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000140474.12
HGNCiHGNC:19703 ULK3
MIMi613472 gene
neXtProtiNX_Q6PHR2

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44K → R: Decreased kinase activity. 1 Publication1
Mutagenesisi139K → R: Loss of kinase activity. Does not promote GLI1 nuclear localization. 2 Publications1

Organism-specific databases

DisGeNETi25989
OpenTargetsiENSG00000140474
PharmGKBiPA134908392

Chemistry databases

ChEMBLiCHEMBL5047

Polymorphism and mutation databases

DMDMi259016166

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002501501 – 472Serine/threonine-protein kinase ULK3Add BLAST472

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei176PhosphoserineCombined sources1
Modified residuei300Phosphoserine; by autocatalysis1 Publication1
Modified residuei350Phosphoserine; by autocatalysis1 Publication1
Modified residuei384Phosphoserine; by autocatalysis1 Publication1
Modified residuei464Phosphoserine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated. Autophosphorylation is blocked by interaction with SUFU.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6PHR2
MaxQBiQ6PHR2
PaxDbiQ6PHR2
PeptideAtlasiQ6PHR2
PRIDEiQ6PHR2
ProteomicsDBi67125
67126 [Q6PHR2-2]
67127 [Q6PHR2-3]

PTM databases

iPTMnetiQ6PHR2
PhosphoSitePlusiQ6PHR2

Expressioni

Tissue specificityi

Widely expressed. Highest levels observed in fetal brain. In adult tissues, high levels in brain, liver and kidney, moderate levels in testis and adrenal gland and low levels in heart, lung, stomach, thymus, prostate and placenta. In the brain, highest expression in the hippocampus, high levels also detected in the cerebellum, olfactory bulb and optic nerve. In the central nervous system, lowest levels in the spinal cord.1 Publication

Inductioni

Up-regulated during senescence.1 Publication

Gene expression databases

BgeeiENSG00000140474 Expressed in 189 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_ULK3
ExpressionAtlasiQ6PHR2 baseline and differential
GenevisibleiQ6PHR2 HS

Organism-specific databases

HPAiHPA040474

Interactioni

Subunit structurei

Interacts (via protein kinase domain) with SUFU.1 Publication

Protein-protein interaction databases

BioGridi117470, 7 interactors
IntActiQ6PHR2, 1 interactor
STRINGi9606.ENSP00000400312

Chemistry databases

BindingDBiQ6PHR2

Structurei

Secondary structure

1472
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6PHR2
SMRiQ6PHR2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 270Protein kinasePROSITE-ProRule annotationAdd BLAST257
Domaini280 – 348MIT 1Add BLAST69
Domaini375 – 444MIT 2Add BLAST70

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0595 Eukaryota
ENOG410XR01 LUCA
GeneTreeiENSGT00910000144033
HOGENOMiHOG000233016
HOVERGENiHBG094133
InParanoidiQ6PHR2
KOiK21358
OMAiYEVDAQR
OrthoDBiEOG091G0JGC
PhylomeDBiQ6PHR2
TreeFamiTF324551

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR007330 MIT
IPR036181 MIT_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF04212 MIT, 2 hits
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00745 MIT, 2 hits
SM00220 S_TKc, 1 hit
SUPFAMiSSF116846 SSF116846, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q6PHR2-1) [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
MAGPGWGPPR LDGFILTERL GSGTYATVYK AYAKKDTREV VAIKCVAKKS
60 70 80 90 100
LNKASVENLL TEIEILKGIR HPHIVQLKDF QWDSDNIYLI MEFCAGGDLS
110 120 130 140 150
RFIHTRRILP EKVARVFMQQ LASALQFLHE RNISHLDLKP QNILLSSLEK
160 170 180 190 200
PHLKLADFGF AQHMSPWDEK HVLRGSPLYM APEMVCQRQY DARVDLWSMG
210 220 230 240 250
VILYEALFGQ PPFASRSFSE LEEKIRSNRV IELPLRPLLS RDCRDLLQRL
260 270 280 290 300
LERDPSRRIS FQDFFAHPWV DLEHMPSGES LGRATALVVQ AVKKDQEGDS
310 320 330 340 350
AAALSLYCKA LDFFVPALHY EVDAQRKEAI KAKVGQYVSR AEELKAIVSS
360 370 380 390 400
SNQALLRQGT SARDLLREMA RDKPRLLAAL EVASAAMAKE EAAGGEQDAL
410 420 430 440 450
DLYQHSLGEL LLLLAAEPPG RRRELLHTEV QNLMARAEYL KEQVKMRESR
460 470
WEADTLDKEG LSESVRSSCT LQ
Length:472
Mass (Da):53,444
Last modified:September 22, 2009 - v2
Checksum:i11D03E311AF36162
GO
Isoform 2 (identifier: Q6PHR2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     205-214: EALFGQPPFA → GETSFPCFSP
     215-472: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:214
Mass (Da):24,402
Checksum:iB51B24CC2A2A0D0E
GO
Isoform 3 (identifier: Q6PHR2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     444-445: Missing.

Note: May be due to competing donor splice site. No experimental confirmation available.
Show »
Length:470
Mass (Da):53,217
Checksum:iB00A71FDAD785B64
GO
Isoform 4 (identifier: Q6PHR2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MAGPGWGPPRLDGFILTERLGSGTYATVYKAYAK → MQRNGSASRG...ESWEARCWCA

Note: No experimental confirmation available.
Show »
Length:483
Mass (Da):54,997
Checksum:i6987C57ACDD4B6CC
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BT78H3BT78_HUMAN
Serine/threonine-protein kinase ULK...
ULK3
136Annotation score:
H3BPN6H3BPN6_HUMAN
Serine/threonine-protein kinase ULK...
ULK3
84Annotation score:
H3BP85H3BP85_HUMAN
Serine/threonine-protein kinase ULK...
ULK3
41Annotation score:
H3BTS3H3BTS3_HUMAN
Serine/threonine-protein kinase ULK...
ULK3
42Annotation score:
H3BS27H3BS27_HUMAN
Serine/threonine-protein kinase ULK...
ULK3
61Annotation score:
H3BMW8H3BMW8_HUMAN
Serine/threonine-protein kinase ULK...
ULK3
50Annotation score:
H3BV76H3BV76_HUMAN
Serine/threonine-protein kinase ULK...
ULK3
49Annotation score:

Sequence cautioni

The sequence CAB55955 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti47A → S in BAG61369 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_057113101R → H. Corresponds to variant dbSNP:rs34945944Ensembl.1
Natural variantiVAR_059771445K → R. Corresponds to variant dbSNP:rs12898397Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0574111 – 34MAGPG…KAYAK → MQRNGSASRGLEKTRLRLCR EARIPESAFLTGLTRESWEA RCWCA in isoform 4. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_038147205 – 214EALFGQPPFA → GETSFPCFSP in isoform 2. 3 Publications10
Alternative sequenceiVSP_038148215 – 472Missing in isoform 2. 3 PublicationsAdd BLAST258
Alternative sequenceiVSP_039925444 – 445Missing in isoform 3. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK294245 mRNA Translation: BAG57541.1
AK299380 mRNA Translation: BAG61369.1
AL117482 mRNA Translation: CAB55955.2 Different initiation.
AC091230 Genomic DNA No translation available.
BC036117 mRNA No translation available.
BC056423 mRNA No translation available.
CH471136 Genomic DNA Translation: EAW99301.1
CH471136 Genomic DNA Translation: EAW99303.1
BC157884 mRNA Translation: AAI57885.1
AL360256 mRNA Translation: CAB96176.1
CCDSiCCDS45305.1 [Q6PHR2-1]
CCDS76779.1 [Q6PHR2-3]
PIRiT17265
RefSeqiNP_001092906.3, NM_001099436.3 [Q6PHR2-1]
NP_001271293.2, NM_001284364.2 [Q6PHR2-3]
NP_001271294.1, NM_001284365.2
XP_005254346.1, XM_005254289.2 [Q6PHR2-4]
UniGeneiHs.513034

Genome annotation databases

EnsembliENST00000440863; ENSP00000400312; ENSG00000140474 [Q6PHR2-1]
ENST00000568667; ENSP00000457853; ENSG00000140474 [Q6PHR2-4]
ENST00000569437; ENSP00000456051; ENSG00000140474 [Q6PHR2-3]
GeneIDi25989
KEGGihsa:25989
UCSCiuc010ulq.3 human
uc059llp.1 human [Q6PHR2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK294245 mRNA Translation: BAG57541.1
AK299380 mRNA Translation: BAG61369.1
AL117482 mRNA Translation: CAB55955.2 Different initiation.
AC091230 Genomic DNA No translation available.
BC036117 mRNA No translation available.
BC056423 mRNA No translation available.
CH471136 Genomic DNA Translation: EAW99301.1
CH471136 Genomic DNA Translation: EAW99303.1
BC157884 mRNA Translation: AAI57885.1
AL360256 mRNA Translation: CAB96176.1
CCDSiCCDS45305.1 [Q6PHR2-1]
CCDS76779.1 [Q6PHR2-3]
PIRiT17265
RefSeqiNP_001092906.3, NM_001099436.3 [Q6PHR2-1]
NP_001271293.2, NM_001284364.2 [Q6PHR2-3]
NP_001271294.1, NM_001284365.2
XP_005254346.1, XM_005254289.2 [Q6PHR2-4]
UniGeneiHs.513034

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WZXX-ray1.39A359-449[»]
6FDYX-ray1.70U2-277[»]
6FDZX-ray2.55U2-277[»]
ProteinModelPortaliQ6PHR2
SMRiQ6PHR2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117470, 7 interactors
IntActiQ6PHR2, 1 interactor
STRINGi9606.ENSP00000400312

Chemistry databases

BindingDBiQ6PHR2
ChEMBLiCHEMBL5047

PTM databases

iPTMnetiQ6PHR2
PhosphoSitePlusiQ6PHR2

Polymorphism and mutation databases

DMDMi259016166

Proteomic databases

EPDiQ6PHR2
MaxQBiQ6PHR2
PaxDbiQ6PHR2
PeptideAtlasiQ6PHR2
PRIDEiQ6PHR2
ProteomicsDBi67125
67126 [Q6PHR2-2]
67127 [Q6PHR2-3]

Protocols and materials databases

DNASUi25989
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000440863; ENSP00000400312; ENSG00000140474 [Q6PHR2-1]
ENST00000568667; ENSP00000457853; ENSG00000140474 [Q6PHR2-4]
ENST00000569437; ENSP00000456051; ENSG00000140474 [Q6PHR2-3]
GeneIDi25989
KEGGihsa:25989
UCSCiuc010ulq.3 human
uc059llp.1 human [Q6PHR2-1]

Organism-specific databases

CTDi25989
DisGeNETi25989
EuPathDBiHostDB:ENSG00000140474.12
GeneCardsiULK3
H-InvDBiHIX0012431
HGNCiHGNC:19703 ULK3
HPAiHPA040474
MIMi613472 gene
neXtProtiNX_Q6PHR2
OpenTargetsiENSG00000140474
PharmGKBiPA134908392
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0595 Eukaryota
ENOG410XR01 LUCA
GeneTreeiENSGT00910000144033
HOGENOMiHOG000233016
HOVERGENiHBG094133
InParanoidiQ6PHR2
KOiK21358
OMAiYEVDAQR
OrthoDBiEOG091G0JGC
PhylomeDBiQ6PHR2
TreeFamiTF324551

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-5632684 Hedgehog 'on' state
SignaLinkiQ6PHR2

Miscellaneous databases

ChiTaRSiULK3 human
GenomeRNAii25989
PROiPR:Q6PHR2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140474 Expressed in 189 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_ULK3
ExpressionAtlasiQ6PHR2 baseline and differential
GenevisibleiQ6PHR2 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR007330 MIT
IPR036181 MIT_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF04212 MIT, 2 hits
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00745 MIT, 2 hits
SM00220 S_TKc, 1 hit
SUPFAMiSSF116846 SSF116846, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiULK3_HUMAN
AccessioniPrimary (citable) accession number: Q6PHR2
Secondary accession number(s): B2RXK3
, B4DFT0, B4DRQ7, D3DW68, Q9NPN5, Q9UFS4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: September 22, 2009
Last modified: October 10, 2018
This is version 141 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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