ULK4_MOUSE
ID ULK4_MOUSE Reviewed; 1303 AA.
AC Q3V129; Q2VP87; Q32LZ6; Q8BLS0; Q8C8Z5; Q9D4H6;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Serine/threonine-protein kinase ULK4;
DE EC=2.7.11.1;
DE AltName: Full=Unc-51-like kinase 4;
GN Name=Ulk4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 5 AND 6).
RC STRAIN=C57BL/6J; TISSUE=Brain cortex, Cerebellum, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 303-1303 (ISOFORM 3).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=21746835; DOI=10.1177/0300985811415708;
RA Vogel P., Read R.W., Hansen G.M., Payne B.J., Small D., Sands A.T.,
RA Zambrowicz B.P.;
RT "Congenital hydrocephalus in genetically engineered mice.";
RL Vet. Pathol. 49:166-181(2012).
RN [5]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=24284070; DOI=10.1242/jcs.137604;
RA Lang B., Pu J., Hunter I., Liu M., Martin-Granados C., Reilly T.J.,
RA Gao G.D., Guan Z.L., Li W.D., Shi Y.Y., He G., He L., Stefansson H.,
RA St Clair D., Blackwood D.H., McCaig C.D., Shen S.;
RT "Recurrent deletions of ULK4 in schizophrenia: a gene crucial for
RT neuritogenesis and neuronal motility.";
RL J. Cell Sci. 127:630-640(2014).
CC -!- FUNCTION: May be involved in the remodeling of cytoskeletal components,
CC such as alpha-tubulin, and in this way regulates neurite branching and
CC elongation, as well as cell motility. {ECO:0000250|UniProtKB:Q96C45}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q3V129-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3V129-2; Sequence=VSP_020607, VSP_020608;
CC Name=3;
CC IsoId=Q3V129-3; Sequence=VSP_020611, VSP_020612;
CC Name=4;
CC IsoId=Q3V129-4; Sequence=VSP_020606, VSP_020609, VSP_020610;
CC Name=5;
CC IsoId=Q3V129-5; Sequence=VSP_020605;
CC Name=6;
CC IsoId=Q3V129-6; Sequence=VSP_020613;
CC -!- TISSUE SPECIFICITY: Expressed in embryonic and adult brain. In the
CC brain, widely expressed, with highest levels in layers II/III and V of
CC the cortex, piriform cortex, CA1-3 of hippocampus, dentate gyrus,
CC ependymal cells lining the ventricles and choroid plexus, and in the
CC thalamic reticular nucleus (at protein level).
CC {ECO:0000269|PubMed:24284070}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are smaller than sex-matched
CC littermates, and all exhibit domed heads typical of hydrocephalus. The
CC majority die before reaching 4 months of age. Brain lateral and third
CC ventricles are severaly dilated with frequent hemorrhage, sometimes
CC accompanied by fibrosis and neovascularization of the meninges and
CC choroid. Nasal passages and maxillary sinuses are partially filled with
CC varying combinations of proteinaceous fluid or suppurative exudates.
CC Suppurative otitis media is frequently observed. On the respiratory
CC epithelium and ependymal cells lining the dilated ventricles, cilia are
CC shorter than those in wild-type littermate control mice
CC (PubMed:21746835). Partial agenesis of the corpus callosum has also
CC been reported (PubMed:24284070). {ECO:0000269|PubMed:21746835,
CC ECO:0000269|PubMed:24284070}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. APG1/unc-51/ULK1 subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AK016524; BAB30285.1; -; mRNA.
DR EMBL; AK043477; BAC31554.1; -; mRNA.
DR EMBL; AK043628; BAC31600.1; -; mRNA.
DR EMBL; AK132731; BAE21324.1; -; mRNA.
DR EMBL; BC109364; AAI09365.1; -; mRNA.
DR EMBL; BC109365; AAI09366.1; -; mRNA.
DR RefSeq; NP_808257.2; NM_177589.3.
DR AlphaFoldDB; Q3V129; -.
DR SMR; Q3V129; -.
DR STRING; 10090.ENSMUSP00000131342; -.
DR PhosphoSitePlus; Q3V129; -.
DR MaxQB; Q3V129; -.
DR PaxDb; Q3V129; -.
DR PRIDE; Q3V129; -.
DR ProteomicsDB; 298433; -. [Q3V129-1]
DR ProteomicsDB; 298434; -. [Q3V129-2]
DR ProteomicsDB; 298435; -. [Q3V129-3]
DR ProteomicsDB; 298436; -. [Q3V129-4]
DR ProteomicsDB; 298437; -. [Q3V129-5]
DR ProteomicsDB; 298438; -. [Q3V129-6]
DR Antibodypedia; 6576; 112 antibodies from 28 providers.
DR Ensembl; ENSMUST00000171061; ENSMUSP00000129214; ENSMUSG00000040936. [Q3V129-3]
DR GeneID; 209012; -.
DR KEGG; mmu:209012; -.
DR UCSC; uc009scz.2; mouse. [Q3V129-3]
DR UCSC; uc012hcp.1; mouse. [Q3V129-4]
DR CTD; 54986; -.
DR MGI; MGI:1921622; Ulk4.
DR VEuPathDB; HostDB:ENSMUSG00000040936; -.
DR eggNOG; KOG0597; Eukaryota.
DR GeneTree; ENSGT00940000156541; -.
DR HOGENOM; CLU_002110_0_0_1; -.
DR InParanoid; Q3V129; -.
DR OrthoDB; 219167at2759; -.
DR PhylomeDB; Q3V129; -.
DR BioGRID-ORCS; 209012; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Ulk4; mouse.
DR PRO; PR:Q3V129; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q3V129; protein.
DR Bgee; ENSMUSG00000040936; Expressed in spermatid and 93 other tissues.
DR ExpressionAtlas; Q3V129; baseline and differential.
DR Genevisible; Q3V129; MM.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0030534; P:adult behavior; IMP:MGI.
DR GO; GO:0035082; P:axoneme assembly; IMP:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0022010; P:central nervous system myelination; IMP:MGI.
DR GO; GO:0090660; P:cerebrospinal fluid circulation; IMP:MGI.
DR GO; GO:0032053; P:ciliary basal body organization; IMP:MGI.
DR GO; GO:0022038; P:corpus callosum development; IMP:MGI.
DR GO; GO:0003351; P:epithelial cilium movement involved in extracellular fluid movement; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0097154; P:GABAergic neuron differentiation; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISO:MGI.
DR GO; GO:0044458; P:motile cilium assembly; IMP:MGI.
DR GO; GO:0022008; P:neurogenesis; IMP:MGI.
DR GO; GO:0150076; P:neuroinflammatory response; IMP:MGI.
DR GO; GO:0036445; P:neuronal stem cell division; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0046328; P:regulation of JNK cascade; ISO:MGI.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:MGI.
DR GO; GO:2001222; P:regulation of neuron migration; ISO:MGI.
DR GO; GO:0010975; P:regulation of neuron projection development; ISO:MGI.
DR GO; GO:1900744; P:regulation of p38MAPK cascade; ISO:MGI.
DR GO; GO:0090036; P:regulation of protein kinase C signaling; ISO:MGI.
DR GO; GO:0035176; P:social behavior; IMP:MGI.
DR GO; GO:0021591; P:ventricular system development; IMP:MGI.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR045906; ULK4.
DR PANTHER; PTHR46240; PTHR46240; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Kinase; Nucleotide-binding;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1303
FT /note="Serine/threonine-protein kinase ULK4"
FT /id="PRO_0000250154"
FT DOMAIN 4..280
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 504..543
FT /note="HEAT 1"
FT REPEAT 727..765
FT /note="HEAT 2"
FT REPEAT 796..834
FT /note="HEAT 3"
FT REPEAT 926..964
FT /note="HEAT 4"
FT REPEAT 1025..1063
FT /note="HEAT 5"
FT REPEAT 1105..1143
FT /note="HEAT 6"
FT REPEAT 1151..1189
FT /note="HEAT 7"
FT REGION 304..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..401
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..332
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 382..401
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 121
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..1050
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020605"
FT VAR_SEQ 1..430
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020606"
FT VAR_SEQ 527..530
FT /note="RSKV -> LLYV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020607"
FT VAR_SEQ 531..1303
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020608"
FT VAR_SEQ 775..835
FT /note="LVMYIERDSRKTSPGKEQQSGNEYLARCLDLLIQHMVQEPPRILGDILNALA
FT NVSGRKHPS -> RHSQRPGKRVRPEAPIHGPGEAAEDVSPHDACGASSGDVAGISTSS
FT CDRRVSLQLRNYSCE (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020609"
FT VAR_SEQ 836..1303
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020610"
FT VAR_SEQ 879..910
FT /note="SHIKSIDLGETNIDGAIGIVASEEFIKVTLSA -> VSSRSHVWPAPLPWLQ
FT HGCEKGGIERLSGICL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_020611"
FT VAR_SEQ 911..1303
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_020612"
FT VAR_SEQ 1165..1185
FT /note="LPSEDPEISEVSSKCLSILVQ -> VRAHLCASAEVQRLKQFYLNF (in
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020613"
SQ SEQUENCE 1303 AA; 145342 MW; D875519D87A21672 CRC64;
MENFVLYEEI GRGSRTVVYK GRRKGTINFV AILCTEKCKR PEITNWVRLT HEIKHKNIVT
FHEWYETSNH LWLVVELCTG GSLETVIAQD ENLPEDVVRE FGVDLVTGLH HLHRLGILFC
DLSPGKILLE GPGTLKFSNF CLAKVAGESL EEFFALVAAE EGGGDSGENA LKKSMKTRVR
GSLIYAAPEI VKGTEFSVTS DLWSLGCLLY EMFSGKPPFF SETVSELVEK ILYEDPLPPI
PKDSSFPKAS SDFLNLLDGL LQKDPQKRFS WEGVLQHPFW KDALRGEDSG WASEDSPFSR
NVMECSGPHD SRELLQSPKN GQAKGQKAAH RLSQSFRLEN PTELRPKSIM GGQLNESIFL
LSSRPTPRTS AMVELNPGEG EDPSSPQKTS PLSKMTSGHL SQGALESQMR ELIYTDSDLV
ITPIIDNPKI MKQPAIKFDP KILHLPAYSV EKLLVLKDQD WNDFLQQVCS QIDSSEKSTG
ALRAKLNLLC YLCVVATHKE VATRLLHSPL FQLLIQHLRI APNWDIRSKV ARVVGMLALH
TTELQENVPV IEAITLLTEL IRENFRSGKL KQCLLPTLGQ LLYLVATQEE KNQHSRDCWA
VPLAAYTVLM RCLREGEERV VNHMAAKIIE NVCTTFSAQA QGFTTGEIGP VLWHLFRHST
VDALRITAIS ALCRITRQSP TAFQNVIEKV GLNAVISSLA SAICKVQQYM LTLFTAMLSC
GIHLQRLIQE KDFVSTVIRL LDSPSTPIRA KAFLVLLYIL IHNRDMLLLS CQARLVMYIE
RDSRKTSPGK EQQSGNEYLA RCLDLLIQHM VQEPPRILGD ILNALANVSG RKHPSTVQGK
QLKMCLPMMP VVLHLVMSQV FRPQVVTEEF LFSYGTILSH IKSIDLGETN IDGAIGIVAS
EEFIKVTLSA FEAVIQYPVL LADYRSTVMD YILPPLVSLV QSQNVEWRLF SLRLLSETTT
LLVSQEPEDG DEEASCDSDS SLLALIRDEL LPQYEHILME PDPVPAYALK LLVAMTEHNP
AFTRLVEESK LVPLIFEVIL EHQESILGNT MQSVIALLNN LVAYKDSNMQ LLYEQGLVGH
VCNMFTETAT LCLDRDNKTN TEPASTLLAS LLDILLGMLT YTSRIVRQAL QVQKSGSRGD
TQAAEDLLLL SKPLTDLISL LIPLLPSEDP EISEVSSKCL SILVQLYGGE NPESLSPENM
VTFANLLMTK EDPKDQKLLL RILKRMVTSN ERLLESLKNT GSLLQALERL APAHRLRGPW
AGISCALFQQ RAAAQGIPEL PPYGIPCCGP SHKRVTGVKL YPC
