ID   PKDCC_HUMAN             Reviewed;         493 AA.
AC   Q504Y2; D6W5A0; Q96I09;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-MAR-2010, sequence version 2.
DT   27-MAR-2024, entry version 143.
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|HGNC:HGNC:25123};
DE   AltName: Full=Protein kinase-like protein SgK493;
DE   AltName: Full=Sugen kinase 493;
DE   AltName: Full=Vertebrate lonesome kinase {ECO:0000250|UniProtKB:Q5RJI4};
DE   Flags: Precursor;
GN   Name=PKDCC {ECO:0000312|HGNC:HGNC:25123};
GN   Synonyms=SGK493, VLK {ECO:0000250|UniProtKB:Q5RJI4};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 129-493.
RC   TISSUE=Muscle;
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   IDENTIFICATION.
RX   PubMed=12471243; DOI=10.1126/science.1075762;
RA   Manning G., Whyte D.B., Martinez R., Hunter T., Sudarsanam S.;
RT   "The protein kinase complement of the human genome.";
RL   Science 298:1912-1934(2002).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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).
RN   [6]
RP   INVOLVEMENT IN RLSDF, AND VARIANT RLSDF 217-TYR--GLY-493 DEL.
RX   PubMed=30478137; DOI=10.1136/jmedgenet-2018-105639;
RA   Sajan S.A., Ganesh J., Shinde D.N., Powis Z., Scarano M.I., Stone J.,
RA   Winter S., Tang S.;
RT   "Biallelic disruption of PKDCC is associated with a skeletal disorder
RT   characterised by rhizomelic shortening of extremities and dysmorphic
RT   features.";
RL   J. Med. Genet. 56:850-854(2019).
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). Probably plays a role in platelets:
CC       rapidly and quantitatively secreted from platelets in response to
CC       stimulation of platelet degranulation (PubMed:25171405). May also have
CC       serine/threonine protein kinase activity. Required for longitudinal
CC       bone growth through regulation of chondrocyte differentiation. May be
CC       indirectly involved in protein transport from the Golgi apparatus to
CC       the plasma membrane (By similarity). {ECO:0000250|UniProtKB:Q5RJI4,
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:0000250|UniProtKB:Q5RJI4}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in platelets.
CC       {ECO:0000269|PubMed:25171405}.
CC   -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q5RJI4}.
CC   -!- PTM: Phosphorylated on tyrosines; probably via autophosphorylation.
CC       {ECO:0000250|UniProtKB:Q5RJI4}.
CC   -!- DISEASE: Rhizomelic limb shortening with dysmorphic features (RLSDF)
CC       [MIM:618821]: An autosomal recessive skeletal dysplasia characterized
CC       by rhizomelic shortening of limbs as well as variable dysmorphic
CC       features, including macrocephaly, short neck, micrognathia, mild
CC       proptosis, downslanting palpebral fissures, depressed or broad nasal
CC       bridge and long philtrum. {ECO:0000269|PubMed:30478137}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH94697.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAI10514.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAI10515.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AC013480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471053; EAX00325.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAX00326.1; -; Genomic_DNA.
DR   EMBL; BC007901; AAH07901.2; -; mRNA.
DR   EMBL; BC062988; AAH62988.1; -; mRNA.
DR   EMBL; BC094697; AAH94697.1; ALT_INIT; mRNA.
DR   EMBL; BC110513; AAI10514.1; ALT_INIT; mRNA.
DR   EMBL; BC110514; AAI10515.1; ALT_INIT; mRNA.
DR   CCDS; CCDS33186.2; -.
DR   RefSeq; NP_612379.2; NM_138370.2.
DR   AlphaFoldDB; Q504Y2; -.
DR   SMR; Q504Y2; -.
DR   BioGRID; 124837; 17.
DR   IntAct; Q504Y2; 14.
DR   STRING; 9606.ENSP00000294964; -.
DR   GlyCosmos; Q504Y2; 6 sites, No reported glycans.
DR   GlyGen; Q504Y2; 7 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q504Y2; -.
DR   PhosphoSitePlus; Q504Y2; -.
DR   BioMuta; PKDCC; -.
DR   DMDM; 292495024; -.
DR   jPOST; Q504Y2; -.
DR   MassIVE; Q504Y2; -.
DR   PaxDb; 9606-ENSP00000294964; -.
DR   PeptideAtlas; Q504Y2; -.
DR   ProteomicsDB; 62416; -.
DR   Antibodypedia; 29709; 70 antibodies from 21 providers.
DR   DNASU; 91461; -.
DR   Ensembl; ENST00000294964.6; ENSP00000294964.5; ENSG00000162878.13.
DR   GeneID; 91461; -.
DR   KEGG; hsa:91461; -.
DR   MANE-Select; ENST00000294964.6; ENSP00000294964.5; NM_138370.3; NP_612379.2.
DR   UCSC; uc002rsg.4; human.
DR   AGR; HGNC:25123; -.
DR   CTD; 91461; -.
DR   DisGeNET; 91461; -.
DR   GeneCards; PKDCC; -.
DR   HGNC; HGNC:25123; PKDCC.
DR   HPA; ENSG00000162878; Tissue enhanced (skeletal).
DR   MalaCards; PKDCC; -.
DR   MIM; 614150; gene.
DR   MIM; 618821; phenotype.
DR   neXtProt; NX_Q504Y2; -.
DR   OpenTargets; ENSG00000162878; -.
DR   PharmGKB; PA165697259; -.
DR   VEuPathDB; HostDB:ENSG00000162878; -.
DR   eggNOG; KOG1187; Eukaryota.
DR   GeneTree; ENSGT00390000001205; -.
DR   HOGENOM; CLU_044025_1_0_1; -.
DR   InParanoid; Q504Y2; -.
DR   OMA; HEGCLLS; -.
DR   OrthoDB; 5392475at2759; -.
DR   PhylomeDB; Q504Y2; -.
DR   TreeFam; TF329248; -.
DR   PathwayCommons; Q504Y2; -.
DR   SignaLink; Q504Y2; -.
DR   BioGRID-ORCS; 91461; 13 hits in 1152 CRISPR screens.
DR   ChiTaRS; PKDCC; human.
DR   GenomeRNAi; 91461; -.
DR   Pharos; Q504Y2; Tbio.
DR   PRO; PR:Q504Y2; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q504Y2; Protein.
DR   Bgee; ENSG00000162878; Expressed in right ovary and 167 other cell types or tissues.
DR   ExpressionAtlas; Q504Y2; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; ISS: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; ISS:UniProtKB.
DR   GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0048566; P:embryonic digestive tract development; ISS:UniProtKB.
DR   GO; GO:0035108; P:limb morphogenesis; IEA:Ensembl.
DR   GO; GO:0048286; P:lung alveolus development; ISS:UniProtKB.
DR   GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR   GO; GO:0042997; P:negative regulation of Golgi to plasma membrane protein transport; ISS:UniProtKB.
DR   GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR   GO; GO:0032332; P:positive regulation of chondrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   GO; GO:0060021; P:roof of mouth development; ISS:UniProtKB.
DR   GO; GO:0001501; P:skeletal system development; IMP:UniProtKB.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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:SF3; EXTRACELLULAR TYROSINE-PROTEIN KINASE PKDCC; 1.
DR   PANTHER; PTHR46448; PROTEIN KINASE DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF12260; PIP49_C; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   Genevisible; Q504Y2; HS.
PE   1: Evidence at protein level;
KW   ATP-binding; Developmental protein; Differentiation; Disease variant;
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..493
FT                   /note="Extracellular tyrosine-protein kinase PKDCC"
FT                   /id="PRO_0000263010"
FT   DOMAIN          138..493
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          28..128
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        32..46
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        54..68
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        95..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:0000250|UniProtKB:Q5RJI4"
FT   MOD_RES         177
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5RJI4"
FT   CARBOHYD        137
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        320
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        369
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        460
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        484
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         217..493
FT                   /note="Missing (in RLSDF)"
FT                   /evidence="ECO:0000269|PubMed:30478137"
FT                   /id="VAR_083938"
SQ   SEQUENCE   493 AA;  54132 MW;  9E6F2AF7BECDA26C CRC64;
     MRRRRAAVAA GFCASFLLGS VLNVLFAPGS EPPRPGQSPE PSPAPGPGRR GGRGELARQI
     RARYEEVQRY SRGGPGPGAG RPERRRLMDL APGGPGLPRP RPPWARPLSD GAPGWPPAPG
     PGSPGPGPRL GCAALRNVSG AQYMGSGYTK AVYRVRLPGG AAVALKAVDF SGHDLGSCVR
     EFGVRRGCYR LAAHKLLKEM VLLERLRHPN VLQLYGYCYQ DSEDIPDTLT TITELGAPVE
     MIQLLQTSWE DRFRICLSLG RLLHHLAHSP LGSVTLLDFR PRQFVLVDGE LKVTDLDDAR
     VEETPCAGST DCILEFPARN FTLPCSAQGW CEGMNEKRNL YNAYRFFFTY LLPHSAPPSL
     RPLLDSIVNA TGELAWGVDE TLAQLEKVLH LYRSGQYLQN STASSSTEYQ CIPDSTIPQE
     DYRCWPSYHH GSCLLSVFNL AEAVDVCESH AQCRAFVVTN QTTWTGRQLV FFKTGWSQVV
     PDPNKTTYVK ASG
//