SHKA_DICDI
ID SHKA_DICDI Reviewed; 527 AA.
AC Q54RB7; Q9BI25;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Dual specificity protein kinase shkA;
DE EC=2.7.11.1;
DE AltName: Full=SH2 domain-containing protein 1;
DE AltName: Full=SH2 domain-containing protein A;
GN Name=shkA; Synonyms=shk1; ORFNames=DDB_G0283267;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=11274054; DOI=10.1101/gad.871001;
RA Moniakis J.;
RT "An SH2-domain containing kinase is a negative regulator of the
RT phosphatidylinositol-3 kinase pathway.";
RL Genes Dev. 15:687-698(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Required for proper chemotaxis and phagocytosis; proper
CC spatiotemporal control of F-actin levels in chemotaxing cells. Negative
CC regulator of the PI3K (phosphatidylinositol 3 kinase) pathway.
CC Predominantly phosphorylates serines and threonines and tyrosines at a
CC lower level. {ECO:0000269|PubMed:11274054}.
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 -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:11274054}.
CC -!- DISRUPTION PHENOTYPE: Cells lack polarity, move very slowly, and
CC exhibit an elevated and temporally extended chemoattractant-mediated
CC activation of the kinase Akt/PKB. {ECO:0000269|PubMed:11274054}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. SH2 domain-containing protein kinase subfamily.
CC {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; AJ297966; CAC35360.1; -; mRNA.
DR EMBL; AAFI02000052; EAL65774.1; -; Genomic_DNA.
DR RefSeq; XP_639130.1; XM_634038.1.
DR AlphaFoldDB; Q54RB7; -.
DR SMR; Q54RB7; -.
DR STRING; 44689.DDB0191149; -.
DR PaxDb; Q54RB7; -.
DR EnsemblProtists; EAL65774; EAL65774; DDB_G0283267.
DR GeneID; 8624001; -.
DR KEGG; ddi:DDB_G0283267; -.
DR dictyBase; DDB_G0283267; shkA.
DR eggNOG; KOG0192; Eukaryota.
DR HOGENOM; CLU_024030_0_0_1; -.
DR InParanoid; Q54RB7; -.
DR OMA; MICTELM; -.
DR PhylomeDB; Q54RB7; -.
DR Reactome; R-DDI-3295583; TRP channels.
DR Reactome; R-DDI-5213460; RIPK1-mediated regulated necrosis.
DR Reactome; R-DDI-5675482; Regulation of necroptotic cell death.
DR PRO; PR:Q54RB7; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005938; C:cell cortex; IDA:dictyBase.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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; IDA:dictyBase.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:dictyBase.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:dictyBase.
DR GO; GO:0006935; P:chemotaxis; IMP:dictyBase.
DR GO; GO:0009968; P:negative regulation of signal transduction; IMP:dictyBase.
DR GO; GO:0006909; P:phagocytosis; IMP:dictyBase.
DR CDD; cd10356; SH2_ShkA_ShkC; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035844; ShkA/ShkC_SH2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50001; SH2; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Kinase; Membrane; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..527
FT /note="Dual specificity protein kinase shkA"
FT /id="PRO_0000327808"
FT DOMAIN 45..304
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 424..513
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT ACT_SITE 167
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 51..59
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 72
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CONFLICT 65
FT /note="R -> K (in Ref. 1; CAC35360)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="A -> P (in Ref. 1; CAC35360)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="S -> F (in Ref. 1; CAC35360)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 527 AA; 59447 MW; A6640DA19D4A066F CRC64;
MATQQQQQQQ QQQQQQIKAR KDIQIQQAQS ASDILGPPEI SETEITTESI LGDGSFGTVY
KGRCRLKDVA VKVMLKQVDQ KTLTDFRKEV AIMSKIFHPN IVLFLGACTS TPGKLMICTE
LMKGNLESLL LDPMVKLPLI TRMRMAKDAA LGVLWLHSSN PVFIHRDLKT SNLLVDANLT
VKVCDFGLSQ IKQRGENLKD GQDGAKGTPL WMAPEVLQGR LFNEKADVYS FGLVLWQIFT
RQELFPEFDN FFKFVAAICE KQLRPSIPDD CPKSLKELIQ KCWDPNPEVR PSFEGIVSEL
EEIIIDCCIP DEYGAILWKN HFKHENEANW KDFINVFSNF VGLTNANTPS MSDLLQFSPN
LNGSTIELNF KCLKSIIVSS PKGPHEEEVV LMEQFGKVLA WFGNLKEDGS QILDKIRQLM
ECAWFHGDIS TSESENRLRQ KPEGTFLVRF STSEYGAYTI SKVSKNGGIS HQRIHRPQGK
FQVNNSKYLS VKELITGEAQ ALGINTPCLG SRFLSLIYKA QLSGYIN
