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Protein

Extracellular tyrosine-protein kinase PKDCC

Gene

Pkdcc

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Secreted tyrosine-protein kinase that mediates phosphorylation of extracellular proteins and endogenous proteins in the secretory pathway, which is essential for patterning at organogenesis stages. Mediates phosphorylation of MMP1, MMP13, MMP14, MMP19 and ERP29 (PubMed:25171405). May also have serine/threonine protein kinase activity (PubMed:25171405). Required for longitudinal bone growth through regulation of chondrocyte differentiation (PubMed:19097194, PubMed:23792766). May be indirectly involved in protein transport from the Golgi apparatus to the plasma membrane (PubMed:19465597). Probably plays a role in platelets: rapidly and quantitatively secreted from platelets in response to stimulation of platelet degranulation (PubMed:25171405).4 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei166ATPPROSITE-ProRule annotation1
Active sitei278Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi144 – 152ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  • protein kinase activity Source: UniProtKB

GO - Biological processi

  • bone mineralization Source: MGI
  • cell differentiation Source: UniProtKB-KW
  • embryonic digestive tract development Source: UniProtKB
  • limb morphogenesis Source: MGI
  • lung alveolus development Source: UniProtKB
  • multicellular organism growth Source: MGI
  • negative regulation of Golgi to plasma membrane protein transport Source: UniProtKB
  • palate development Source: UniProtKB
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of bone mineralization Source: UniProtKB
  • positive regulation of chondrocyte differentiation Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • skeletal system development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Differentiation, Osteogenesis, Protein transport, Transport

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Extracellular tyrosine-protein kinase PKDCCCurated (EC:2.7.10.21 Publication)
Alternative name(s):
Protein kinase domain-containing protein, cytoplasmicImported
Protein kinase-like protein SgK493
Sugen kinase 493
Vertebrate lonesome kinase1 Publication
Gene namesi
Name:PkdccImported
Synonyms:Sgk493, Vlk1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:2147077. Pkdcc.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Secreted

Pathology & Biotechi

Disruption phenotypei

Morphological defects at birth including growth retardation, short limbs, cleft palate, sternal dysraphia, shortened intestine and cyanosis. Long bones display reduced mineralization due to delayed chondrocyte differentiation. Neonates breathe abnormally, do not suckle and die within a day after birth, probably due to insufficient respiration as a result of the cleft palate.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi148Y → F: Does not affect kinase activity nor secretion to the extracellular medium. 1 Publication1
Mutagenesisi166K → M: Complete loss of kinase activity. Phosphorylation is restored by co-transfection with wild-type protein. 2 Publications1
Mutagenesisi199E → A: Complete loss of kinase activity. 1 Publication1
Mutagenesisi295D → A: Complete loss of kinase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000026301133 – 492Extracellular tyrosine-protein kinase PKDCCAdd BLAST460

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi137N-linked (GlcNAc...)PROSITE-ProRule annotation1
Modified residuei148Phosphotyrosine1 Publication1
Modified residuei177Phosphoserine1 Publication1
Glycosylationi320N-linked (GlcNAc...)PROSITE-ProRule annotation1
Glycosylationi369N-linked (GlcNAc...)PROSITE-ProRule annotation1
Glycosylationi400N-linked (GlcNAc...)PROSITE-ProRule annotation1
Glycosylationi459N-linked (GlcNAc...)PROSITE-ProRule annotation1

Post-translational modificationi

Phosphorylated on tyrosines; probably via autophosphorylation.1 Publication
N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ5RJI4.
PRIDEiQ5RJI4.

PTM databases

iPTMnetiQ5RJI4.
PhosphoSitePlusiQ5RJI4.

Expressioni

Tissue specificityi

Strongly expressed in adult heart, liver and testis with weak expression in brain, spleen, lung and thymus. In the humerus, strongly expressed in early flat proliferative chondrocytes. In the embryo, expressed in the anterior visceral endoderm and anterior primitive streak at E6.5. At E7.5, expressed in the anterior definitive endoderm (ADE) and anterior mesoderm but not in the notochord. At E8.0, expressed in the ADE and anterior embryonic mesoderm. At E8.5, expressed more broadly in anterior tissues and at the midline of the neural plate in the midbrain region as well as the lateral margins of the neural plate posterior to the metencephalic region. Also weakly expressed in the anterior mesenchyme. At E9.5, strongest expression in branchial arches and limb buds. During mid-gestation, expression continues in mesenchymal cells, particularly in areas where these cells condense.2 Publications

Developmental stagei

Expressed throughout embryogenesis and in adulthood. During embryogenesis, expression is high at transition phases of mesenchymal cell differentiation such as from mesenchymal cells to chondrocytes and from mesenchymal to mesothelial cells. Expressed throughout all stages of humerus bone formation. During lung development, expressed in all mesenchymal cells at the early pseudoglandular stage. Expression is rapidly lost from the mesenchyme of the lung interstitium during the mid-to-late pseudoglandular stage but continues throughout life in the mesothelial pleural cells.2 Publications

Inductioni

Down-regulated by hedgehog (Hh) signaling.1 Publication

Gene expression databases

BgeeiENSMUSG00000024247.
ExpressionAtlasiQ5RJI4. baseline and differential.
GenevisibleiQ5RJI4. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000129238.

Structurei

3D structure databases

ProteinModelPortaliQ5RJI4.
SMRiQ5RJI4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini138 – 422Protein kinasePROSITE-ProRule annotationAdd BLAST285

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi75 – 128Pro-richAdd BLAST54

Sequence similaritiesi

Belongs to the protein kinase superfamily.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1187. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00390000001205.
HOGENOMiHOG000054185.
HOVERGENiHBG079871.
InParanoidiQ5RJI4.
KOiK17548.
OMAiGYTKAVY.
OrthoDBiEOG091G0JWN.
PhylomeDBiQ5RJI4.
TreeFamiTF329248.

Family and domain databases

InterProiIPR022049. FAM69_kinase_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PfamiPF12260. PIP49_C. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5RJI4-1) [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
MRRRRAAVAA GFCASFLLGS VLNVLFAPGS EPPRPGQSPG SSAAPGPGRR
60 70 80 90 100
GGRGELARQI RERYEEVQRY SRGGPGPGAG RPERRRLMDL APGGPGLQRP
110 120 130 140 150
RPPRVRSPPD GAPGWPPAPG PGSPGPGPRL GCAALRNVSG AQYVGSGYTK
160 170 180 190 200
AVYRVRLPGG AAVALKAVDF SGHDLGSCVR EFGARRGCYR LAAHKLLKEM
210 220 230 240 250
VLLERLRHPN VLQLYGYCYQ DSEGIPDTLT TITELGAPVE MIQLLQTSWE
260 270 280 290 300
DRFRICLSLG RLLHHLAHSP LGSVTLLDFR PRQFVLVNGE LKVTDLDDAR
310 320 330 340 350
VEETPCTSSA DCTLEFPARN FSLPCSAQGW CEGMNEKRNL YNAYRFFFTY
360 370 380 390 400
LLPHSAPPSL RPLLDSIVNA TGELAWGVDE TLAQLETALH LFRSGQYLQN
410 420 430 440 450
STSSRAEYQR IPDSAITQED YRCWPSYHHG GCLLSVFNLA EAIDVCESHA
460 470 480 490
QCRAFVVTNQ TTWTGRKLVF FKTGWNQVVP DAGKTTYVKA PG
Length:492
Mass (Da):53,841
Last modified:March 23, 2010 - v2
Checksum:iAD95CAF730625FF9
GO
Isoform 2 (identifier: Q5RJI4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     72-118: Missing.

Note: No experimental confirmation available.
Show »
Length:445
Mass (Da):48,988
Checksum:i5329234F964F15E9
GO

Sequence cautioni

The sequence AAH86639 differs from that shown. Reason: Frameshift at position 72.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03882272 – 118Missing in isoform 2. 1 PublicationAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB436780 mRNA. Translation: BAG82823.1.
AB381893 mRNA. Translation: BAH66379.1.
BC022157 mRNA. Translation: AAH22157.1.
BC086639 mRNA. Translation: AAH86639.1. Frameshift.
AK133913 mRNA. Translation: BAE21924.1.
CCDSiCCDS28994.2. [Q5RJI4-1]
RefSeqiNP_598878.2. NM_134117.2. [Q5RJI4-1]
XP_011244536.1. XM_011246234.1.
UniGeneiMm.311974.

Genome annotation databases

EnsembliENSMUST00000170794; ENSMUSP00000129238; ENSMUSG00000024247. [Q5RJI4-1]
GeneIDi106522.
KEGGimmu:106522.
UCSCiuc012axu.1. mouse. [Q5RJI4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB436780 mRNA. Translation: BAG82823.1.
AB381893 mRNA. Translation: BAH66379.1.
BC022157 mRNA. Translation: AAH22157.1.
BC086639 mRNA. Translation: AAH86639.1. Frameshift.
AK133913 mRNA. Translation: BAE21924.1.
CCDSiCCDS28994.2. [Q5RJI4-1]
RefSeqiNP_598878.2. NM_134117.2. [Q5RJI4-1]
XP_011244536.1. XM_011246234.1.
UniGeneiMm.311974.

3D structure databases

ProteinModelPortaliQ5RJI4.
SMRiQ5RJI4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000129238.

PTM databases

iPTMnetiQ5RJI4.
PhosphoSitePlusiQ5RJI4.

Proteomic databases

PaxDbiQ5RJI4.
PRIDEiQ5RJI4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000170794; ENSMUSP00000129238; ENSMUSG00000024247. [Q5RJI4-1]
GeneIDi106522.
KEGGimmu:106522.
UCSCiuc012axu.1. mouse. [Q5RJI4-1]

Organism-specific databases

CTDi91461.
MGIiMGI:2147077. Pkdcc.

Phylogenomic databases

eggNOGiKOG1187. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00390000001205.
HOGENOMiHOG000054185.
HOVERGENiHBG079871.
InParanoidiQ5RJI4.
KOiK17548.
OMAiGYTKAVY.
OrthoDBiEOG091G0JWN.
PhylomeDBiQ5RJI4.
TreeFamiTF329248.

Miscellaneous databases

ChiTaRSiPkdcc. mouse.
PROiQ5RJI4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024247.
ExpressionAtlasiQ5RJI4. baseline and differential.
GenevisibleiQ5RJI4. MM.

Family and domain databases

InterProiIPR022049. FAM69_kinase_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PfamiPF12260. PIP49_C. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPKDCC_MOUSE
AccessioniPrimary (citable) accession number: Q5RJI4
Secondary accession number(s): B6F136, Q3UZD3, Q8VBZ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: March 23, 2010
Last modified: November 2, 2016
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.