PKDCC_MOUSE
ID PKDCC_MOUSE Reviewed; 492 AA.
AC Q5RJI4; B6F136; Q3UZD3; Q8VBZ6;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Extracellular tyrosine-protein kinase PKDCC {ECO:0000305};
DE EC=2.7.10.2 {ECO:0000269|PubMed:25171405};
DE AltName: Full=Protein kinase domain-containing protein, cytoplasmic {ECO:0000312|MGI:MGI:2147077};
DE AltName: Full=Protein kinase-like protein SgK493;
DE AltName: Full=Sugen kinase 493;
DE AltName: Full=Vertebrate lonesome kinase {ECO:0000303|PubMed:19465597};
DE Flags: Precursor;
GN Name=Pkdcc {ECO:0000312|MGI:MGI:2147077};
GN Synonyms=Sgk493, Vlk {ECO:0000303|PubMed:19465597};
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 [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND ALTERNATIVE SPLICING.
RC TISSUE=Embryo;
RX PubMed=19097194; DOI=10.1002/dvdy.21822;
RA Imuta Y., Nishioka N., Kiyonari H., Sasaki H.;
RT "Short limbs, cleft palate, and delayed formation of flat proliferative
RT chondrocytes in mice with targeted disruption of a putative protein kinase
RT gene, Pkdcc (AW548124).";
RL Dev. Dyn. 238:210-222(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP PHOSPHORYLATION AT TYR-148 AND SER-177, AND MUTAGENESIS OF LYS-166.
RX PubMed=19465597; DOI=10.1242/dev.026435;
RA Kinoshita M., Era T., Jakt L.M., Nishikawa S.;
RT "The novel protein kinase Vlk is essential for stromal function of
RT mesenchymal cells.";
RL Development 136:2069-2079(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Liver;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 381-492 (ISOFORMS 1/2).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [5]
RP FUNCTION.
RX PubMed=23792766; DOI=10.1016/j.diff.2013.03.002;
RA Probst S., Zeller R., Zuniga A.;
RT "The hedgehog target Vlk genetically interacts with Gli3 to regulate
RT chondrocyte differentiation during mouse long bone development.";
RL Differentiation 85:121-130(2013).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION,
RP PHOSPHORYLATION, AND MUTAGENESIS OF TYR-148; LYS-166; GLU-199 AND ASP-295.
RX PubMed=25171405; DOI=10.1016/j.cell.2014.06.048;
RA Bordoli M.R., Yum J., Breitkopf S.B., Thon J.N., Italiano J.E. Jr.,
RA Xiao J., Worby C., Wong S.K., Lin G., Edenius M., Keller T.L., Asara J.M.,
RA Dixon J.E., Yeo C.Y., Whitman M.;
RT "A secreted tyrosine kinase acts in the extracellular environment.";
RL Cell 158:1033-1044(2014).
CC -!- FUNCTION: Secreted tyrosine-protein kinase that mediates
CC phosphorylation of extracellular proteins and endogenous proteins in
CC the secretory pathway, which is essential for patterning at
CC organogenesis stages. Mediates phosphorylation of MMP1, MMP13, MMP14,
CC MMP19 and ERP29 (PubMed:25171405). May also have serine/threonine
CC protein kinase activity (PubMed:25171405). Required for longitudinal
CC bone growth through regulation of chondrocyte differentiation
CC (PubMed:19097194, PubMed:23792766). May be indirectly involved in
CC protein transport from the Golgi apparatus to the plasma membrane
CC (PubMed:19465597). Probably plays a role in platelets: rapidly and
CC quantitatively secreted from platelets in response to stimulation of
CC platelet degranulation (PubMed:25171405). {ECO:0000269|PubMed:19097194,
CC ECO:0000269|PubMed:19465597, ECO:0000269|PubMed:23792766,
CC ECO:0000269|PubMed:25171405}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000269|PubMed:25171405};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10597;
CC Evidence={ECO:0000269|PubMed:25171405};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25171405}. Golgi
CC apparatus {ECO:0000269|PubMed:19465597}. Note=Both secreted and present
CC in the Golgi apparatus. {ECO:0000269|PubMed:19465597,
CC ECO:0000269|PubMed:25171405}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5RJI4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5RJI4-2; Sequence=VSP_038822;
CC -!- TISSUE SPECIFICITY: Strongly expressed in adult heart, liver and testis
CC with weak expression in brain, spleen, lung and thymus. In the humerus,
CC strongly expressed in early flat proliferative chondrocytes. In the
CC embryo, expressed in the anterior visceral endoderm and anterior
CC primitive streak at 6.5 dpc. At 7.5 dpc, expressed in the anterior
CC definitive endoderm (ADE) and anterior mesoderm but not in the
CC notochord. At 8.0 dpc, expressed in the ADE and anterior embryonic
CC mesoderm. At 8.5 dpc, expressed more broadly in anterior tissues and at
CC the midline of the neural plate in the midbrain region as well as the
CC lateral margins of the neural plate posterior to the metencephalic
CC region. Also weakly expressed in the anterior mesenchyme. At 9.5 dpc,
CC strongest expression in branchial arches and limb buds. During mid-
CC gestation, expression continues in mesenchymal cells, particularly in
CC areas where these cells condense. {ECO:0000269|PubMed:19097194,
CC ECO:0000269|PubMed:19465597}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryogenesis and in
CC adulthood. During embryogenesis, expression is high at transition
CC phases of mesenchymal cell differentiation such as from mesenchymal
CC cells to chondrocytes and from mesenchymal to mesothelial cells.
CC Expressed throughout all stages of humerus bone formation. During lung
CC development, expressed in all mesenchymal cells at the early
CC pseudoglandular stage. Expression is rapidly lost from the mesenchyme
CC of the lung interstitium during the mid-to-late pseudoglandular stage
CC but continues throughout life in the mesothelial pleural cells.
CC {ECO:0000269|PubMed:19097194, ECO:0000269|PubMed:19465597}.
CC -!- INDUCTION: Down-regulated by hedgehog (Hh) signaling.
CC {ECO:0000269|PubMed:23792766}.
CC -!- PTM: Phosphorylated on tyrosines; probably via autophosphorylation.
CC {ECO:0000269|PubMed:25171405}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:25171405}.
CC -!- DISRUPTION PHENOTYPE: Morphological defects at birth including growth
CC retardation, short limbs, cleft palate, sternal dysraphia, shortened
CC intestine and cyanosis. Long bones display reduced mineralization due
CC to delayed chondrocyte differentiation. Neonates breathe abnormally, do
CC not suckle and die within a day after birth, probably due to
CC insufficient respiration as a result of the cleft palate.
CC {ECO:0000269|PubMed:19097194, ECO:0000269|PubMed:19465597}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH86639.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB436780; BAG82823.1; -; mRNA.
DR EMBL; AB381893; BAH66379.1; -; mRNA.
DR EMBL; BC022157; AAH22157.1; -; mRNA.
DR EMBL; BC086639; AAH86639.1; ALT_FRAME; mRNA.
DR EMBL; AK133913; BAE21924.1; -; mRNA.
DR CCDS; CCDS28994.2; -. [Q5RJI4-1]
DR RefSeq; NP_598878.2; NM_134117.2. [Q5RJI4-1]
DR RefSeq; XP_011244536.1; XM_011246234.1.
DR AlphaFoldDB; Q5RJI4; -.
DR SMR; Q5RJI4; -.
DR STRING; 10090.ENSMUSP00000129238; -.
DR GlyGen; Q5RJI4; 5 sites.
DR iPTMnet; Q5RJI4; -.
DR PhosphoSitePlus; Q5RJI4; -.
DR PaxDb; Q5RJI4; -.
DR PRIDE; Q5RJI4; -.
DR ProteomicsDB; 289602; -. [Q5RJI4-1]
DR ProteomicsDB; 289603; -. [Q5RJI4-2]
DR Antibodypedia; 29709; 66 antibodies from 21 providers.
DR Ensembl; ENSMUST00000170794; ENSMUSP00000129238; ENSMUSG00000024247. [Q5RJI4-1]
DR GeneID; 106522; -.
DR KEGG; mmu:106522; -.
DR UCSC; uc012axu.1; mouse. [Q5RJI4-1]
DR CTD; 91461; -.
DR MGI; MGI:2147077; Pkdcc.
DR VEuPathDB; HostDB:ENSMUSG00000024247; -.
DR eggNOG; KOG1187; Eukaryota.
DR GeneTree; ENSGT00390000001205; -.
DR HOGENOM; CLU_044025_1_0_1; -.
DR InParanoid; Q5RJI4; -.
DR OMA; CESHVQC; -.
DR OrthoDB; 490155at2759; -.
DR PhylomeDB; Q5RJI4; -.
DR TreeFam; TF329248; -.
DR BioGRID-ORCS; 106522; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Pkdcc; mouse.
DR PRO; PR:Q5RJI4; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q5RJI4; protein.
DR Bgee; ENSMUSG00000024247; Expressed in internal carotid artery and 244 other tissues.
DR ExpressionAtlas; Q5RJI4; baseline and differential.
DR Genevisible; Q5RJI4; MM.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048566; P:embryonic digestive tract development; IMP:UniProtKB.
DR GO; GO:0035108; P:limb morphogenesis; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0042997; P:negative regulation of Golgi to plasma membrane protein transport; IDA:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:UniProtKB.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0060021; P:roof of mouth development; IMP:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR InterPro; IPR022049; FAM69_kinase_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR042983; PKDCC.
DR InterPro; IPR000719; Prot_kinase_dom.
DR PANTHER; PTHR46448; PTHR46448; 1.
DR Pfam; PF12260; PIP49_C; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Developmental protein; Differentiation;
KW Glycoprotein; Golgi apparatus; Kinase; Nucleotide-binding; Osteogenesis;
KW Phosphoprotein; Protein transport; Reference proteome; Secreted; Signal;
KW Transferase; Transport; Tyrosine-protein kinase.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..492
FT /note="Extracellular tyrosine-protein kinase PKDCC"
FT /id="PRO_0000263011"
FT DOMAIN 138..422
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 29..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..69
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..126
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 278
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 144..152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 166
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 148
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:19465597"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19465597"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 72..118
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038822"
FT MUTAGEN 148
FT /note="Y->F: Does not affect kinase activity nor secretion
FT to the extracellular medium."
FT /evidence="ECO:0000269|PubMed:25171405"
FT MUTAGEN 166
FT /note="K->M: Complete loss of kinase activity.
FT Phosphorylation is restored by co-transfection with wild-
FT type protein."
FT /evidence="ECO:0000269|PubMed:19465597,
FT ECO:0000269|PubMed:25171405"
FT MUTAGEN 199
FT /note="E->A: Complete loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:25171405"
FT MUTAGEN 295
FT /note="D->A: Complete loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:25171405"
SQ SEQUENCE 492 AA; 53841 MW; AD95CAF730625FF9 CRC64;
MRRRRAAVAA GFCASFLLGS VLNVLFAPGS EPPRPGQSPG SSAAPGPGRR GGRGELARQI
RERYEEVQRY SRGGPGPGAG RPERRRLMDL APGGPGLQRP RPPRVRSPPD GAPGWPPAPG
PGSPGPGPRL GCAALRNVSG AQYVGSGYTK AVYRVRLPGG AAVALKAVDF SGHDLGSCVR
EFGARRGCYR LAAHKLLKEM VLLERLRHPN VLQLYGYCYQ DSEGIPDTLT TITELGAPVE
MIQLLQTSWE DRFRICLSLG RLLHHLAHSP LGSVTLLDFR PRQFVLVNGE LKVTDLDDAR
VEETPCTSSA DCTLEFPARN FSLPCSAQGW CEGMNEKRNL YNAYRFFFTY LLPHSAPPSL
RPLLDSIVNA TGELAWGVDE TLAQLETALH LFRSGQYLQN STSSRAEYQR IPDSAITQED
YRCWPSYHHG GCLLSVFNLA EAIDVCESHA QCRAFVVTNQ TTWTGRKLVF FKTGWNQVVP
DAGKTTYVKA PG
