SCYL2_MOUSE
ID SCYL2_MOUSE Reviewed; 930 AA.
AC Q8CFE4; Q3UT57; Q3UWU9; Q8K0M4;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=SCY1-like protein 2 {ECO:0000305};
DE AltName: Full=Coated vesicle-associated kinase of 104 kDa {ECO:0000303|PubMed:16914521};
GN Name=Scyl2 {ECO:0000312|MGI:MGI:1289172};
GN Synonyms=Cvak104 {ECO:0000303|PubMed:16914521}, D10Ertd802e;
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] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 664-930 (ISOFORMS 1/2).
RC STRAIN=C57BL/6J; TISSUE=Egg;
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 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 817-930 (ISOFORMS 1/2).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Mammary tumor, and Salivary gland;
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 TISSUE SPECIFICITY.
RX PubMed=16914521; DOI=10.1091/mbc.e06-05-0390;
RA Duewel M., Ungewickell E.J.;
RT "Clathrin-dependent association of CVAK104 with endosomes and the trans-
RT Golgi network.";
RL Mol. Biol. Cell 17:4513-4525(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-658 AND SER-677, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-677, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC 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 [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=26203146; DOI=10.1523/jneurosci.2056-14.2015;
RA Gingras S., Earls L.R., Howell S., Smeyne R.J., Zakharenko S.S.,
RA Pelletier S.;
RT "SCYL2 Protects CA3 Pyramidal Neurons from Excitotoxicity during Functional
RT Maturation of the Mouse Hippocampus.";
RL J. Neurosci. 35:10510-10522(2015).
CC -!- FUNCTION: Component of the AP2-containing clathrin coat that may
CC regulate clathrin-dependent trafficking at plasma membrane, TGN and
CC endosomal system. A possible serine/threonine-protein kinase toward the
CC beta2-subunit of the plasma membrane adapter complex AP2 and other
CC proteins in presence of poly-L-lysine has not been confirmed (By
CC similarity). By regulating the expression of excitatory receptors at
CC synapses, plays an essential role in neuronal function and signaling
CC and in brain development (PubMed:26203146).
CC {ECO:0000250|UniProtKB:Q6P3W7, ECO:0000269|PubMed:26203146}.
CC -!- SUBUNIT: Interacts with clathrin and AP2B1; the interaction mediates
CC the association with the AP-2 complex. {ECO:0000250|UniProtKB:Q6P3W7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000250|UniProtKB:Q6P3W7}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000250|UniProtKB:Q6P3W7}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q6P3W7}. Note=Colocalizes to the trans-Golgi
CC network (TGN) and to endosomal membranes with clathrin, transferrin and
CC plasma membrane adapter AP1 and AP3 complexes.
CC {ECO:0000250|UniProtKB:Q6P3W7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CFE4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CFE4-2; Sequence=VSP_020980, VSP_020981, VSP_020982;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:16914521}.
CC -!- PTM: Could autophosphorylate in presence of poly-L-lysine.
CC {ECO:0000250|UniProtKB:Q6P3W7}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the gene results in perinatal
CC lethality due to impaired neuronal functions. Mutant animals that
CC survive to adulthood show growth retardation and severe sensorimotor
CC deficits. The neurologic deficits in these mice is associated with the
CC degeneration of several neuronal populations, most notably CA3
CC pyramidal neurons of the hippocampus, resulting from excitotoxicity.
CC This is associated with excessive expression and activation of calcium-
CC permeable glutamate receptors at the synapse. A wide variety of
CC clathrin-mediated functions and lysosomal pathways are however
CC preserved in mutant mice. {ECO:0000269|PubMed:26203146}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. {ECO:0000305}.
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DR EMBL; AK136092; BAE22815.1; -; mRNA.
DR EMBL; AK139747; BAE24123.1; -; mRNA.
DR EMBL; BC030932; AAH30932.1; -; mRNA.
DR EMBL; BC042443; AAH42443.1; -; mRNA.
DR CCDS; CCDS36027.1; -. [Q8CFE4-1]
DR RefSeq; NP_932138.1; NM_198021.2. [Q8CFE4-1]
DR AlphaFoldDB; Q8CFE4; -.
DR SMR; Q8CFE4; -.
DR BioGRID; 229417; 15.
DR IntAct; Q8CFE4; 1.
DR STRING; 10090.ENSMUSP00000133992; -.
DR iPTMnet; Q8CFE4; -.
DR PhosphoSitePlus; Q8CFE4; -.
DR EPD; Q8CFE4; -.
DR jPOST; Q8CFE4; -.
DR MaxQB; Q8CFE4; -.
DR PaxDb; Q8CFE4; -.
DR PeptideAtlas; Q8CFE4; -.
DR PRIDE; Q8CFE4; -.
DR ProteomicsDB; 253429; -. [Q8CFE4-1]
DR ProteomicsDB; 253430; -. [Q8CFE4-2]
DR Antibodypedia; 17837; 175 antibodies from 25 providers.
DR DNASU; 213326; -.
DR Ensembl; ENSMUST00000174252; ENSMUSP00000133992; ENSMUSG00000069539. [Q8CFE4-1]
DR GeneID; 213326; -.
DR KEGG; mmu:213326; -.
DR UCSC; uc007gsl.1; mouse. [Q8CFE4-2]
DR UCSC; uc007gsm.1; mouse. [Q8CFE4-1]
DR CTD; 55681; -.
DR MGI; MGI:1289172; Scyl2.
DR VEuPathDB; HostDB:ENSMUSG00000069539; -.
DR eggNOG; KOG2137; Eukaryota.
DR GeneTree; ENSGT00880000138031; -.
DR InParanoid; Q8CFE4; -.
DR OMA; MAHKCIP; -.
DR OrthoDB; 196028at2759; -.
DR PhylomeDB; Q8CFE4; -.
DR TreeFam; TF314178; -.
DR BioGRID-ORCS; 213326; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Scyl2; mouse.
DR PRO; PR:Q8CFE4; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8CFE4; protein.
DR Bgee; ENSMUSG00000069539; Expressed in secondary oocyte and 221 other tissues.
DR ExpressionAtlas; Q8CFE4; baseline and differential.
DR Genevisible; Q8CFE4; MM.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0007420; P:brain development; IDA:UniProtKB.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:2000370; P:positive regulation of clathrin-dependent endocytosis; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0021860; P:pyramidal neuron development; IMP:UniProtKB.
DR GO; GO:2000286; P:receptor internalization involved in canonical Wnt signaling pathway; ISO:MGI.
DR Gene3D; 1.25.10.10; -; 1.
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 Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 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; Cytoplasmic vesicle; Endosome; Golgi apparatus;
KW Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..930
FT /note="SCY1-like protein 2"
FT /id="PRO_0000252447"
FT DOMAIN 32..327
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 443..479
FT /note="HEAT"
FT REGION 658..706
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 895..930
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..692
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 658
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 677
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 708
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6P3W7"
FT VAR_SEQ 1..423
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020980"
FT VAR_SEQ 424
FT /note="Q -> M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020981"
FT VAR_SEQ 643
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020982"
SQ SEQUENCE 930 AA; 103317 MW; 1771D113D098189E CRC64;
MESMLNKLKS TVTKVTADVT SAVMGNPVTR EFDVGRHIAS GGNGLAWKIF NGTKKSTKQE
VAVFVFDKKL IDKYQKFEKD QIIDSLKRGV QQLTRLRHPR LLTVQHPLEE SRDCLAFCTE
PVFASLANVL GNWENLPSSI SPDIKDYKLY DVETKYGLLQ VSEGLSFLHS SVKMVHGNVT
PENVILNKSG AWKIMGFDFC VSSSNPSEQE PKFPCKEWDP NLPSLCLPNP EYLAPEYILS
VSCETASDMY SLGAVMYAVF NQGRPIFEVN KQDIYKSFSR QLDQLSRLGS SSLTSIPEEV
REHVKLLLNV TPTVRPDADQ MTKIPFFDDV GAVTLQYFDT LFQRDNLQKS QFFKGLPKVL
PKLPKRVIVQ RILPCLTSEF VNPDMVPFVL PNVLLIAEEC TKEEYIKLIL PELGPVFKQQ
EPIQILLIFL QKMDLLLTKT PPDEIKNSVL PMVYRALEAP SIQIQELCLN IIPTFANLID
YPSMKNALIP RIKNACLQTS SLAVRVNSLV CLGKILEYLD KWFVLDDILP FLQQIPSKEP
AVLMGILGIY KCTFTHKKLG ITKEQLAGKV LPHLIPLSIE NNLNLNQFSS FIAVIKEMLS
RLESEHRTKL EQLHVMQEQQ RSLDIGNQMS TSEETKVAHS GSQQIDKVFN NIGADLLSGS
ESENREDGMQ GKQKRGSLTL EEKQKLAKEQ EQAQKLKSQQ PLKPQVHTPI APIKQTKDLT
DTLMENMSSL TSLSVSTPKI SASSTFTPVP STGLGMMFST PIDNTKRNLT NGLNANMGFQ
TSGFSMPVNP NQNFFSGTGT AGVTTMSLGA PPTMSNFSPL TIPPASVKQP QQRPTDMSAL
NNLFGPQKPK VSMNQLSQQK PNQWLNQFAP PQGSPVMGSA AMGTQGNVMG QAAFGMQGNP
FFNPQNFAQP PPTTMTSSSS ASNDLKDLFG
