ZAK1_DICDI
ID ZAK1_DICDI Reviewed; 781 AA.
AC Q75JK0; Q552C7; Q9U478;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Dual specificity protein kinase zakA;
DE EC=2.7.12.1;
DE AltName: Full=Zaphod K Kinase 1;
DE Short=Zaphod kinase 1;
DE AltName: Full=Zaphod kinase A;
GN Name=zakA; Synonyms=zak1; ORFNames=DDB_G0276025;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
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).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-759, FUNCTION, DEVELOPMENTAL STAGE, AND
RP AUTOPHOSPHORYLATION.
RX PubMed=10571182; DOI=10.1016/s0092-8674(00)81526-3;
RA Kim L., Liu J., Kimmel A.R.;
RT "The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate
RT specification.";
RL Cell 99:399-408(1999).
RN [4]
RP FUNCTION.
RX PubMed=17085634; DOI=10.1128/ec.00204-06;
RA Strmecki L., Bloomfield G., Araki T., Dalton E., Skelton J., Schilde C.,
RA Harwood A., Williams J.G., Ivens A., Pears C.;
RT "Proteomic and microarray analyses of the Dictyostelium Zak1-GSK-3
RT signaling pathway reveal a role in early development.";
RL Eukaryot. Cell 6:245-252(2007).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21205787; DOI=10.1242/dev.055335;
RA Kim L., Brzostowski J., Majithia A., Lee N.S., McMains V., Kimmel A.R.;
RT "Combinatorial cell-specific regulation of GSK3 directs cell
RT differentiation and polarity in Dictyostelium.";
RL Development 138:421-430(2011).
CC -!- FUNCTION: Positive regulator of gsk3/gskA activity required for cell
CC pattern formation and a downstream effector of carC. The kinases,
CC gsk3/gskA, zakA and zak2, form part of a signaling pathway that
CC responds to extracellular cyclic AMP. The pathway has a role in
CC transcriptional regulation; required to direct prespore/spore fates
CC during development. ZakA negatively regulates prestalk differentiation
CC by regulating expression of ecmB. Phosphorylates Y-214 of gsk3/gskA, in
CC vitro. {ECO:0000269|PubMed:10571182, ECO:0000269|PubMed:17085634,
CC ECO:0000269|PubMed:21205787}.
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=2.7.12.1;
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=2.7.12.1;
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=2.7.12.1;
CC -!- TISSUE SPECIFICITY: ZakA and zak2 are coexpressed in prestalk cell
CC population, zakA is enriched in pstB populations and zak1 in pstA
CC populations. ZakA and zak2 are coexpressed in prespore cells, zakA
CC expression levels are 10 fold higher than zak2.
CC {ECO:0000269|PubMed:21205787}.
CC -!- DEVELOPMENTAL STAGE: Expression is first seen at 5 hours of development
CC during aggregation, reaching peak expression at slug stage (15 hours).
CC {ECO:0000269|PubMed:10571182}.
CC -!- PTM: N-terminal serine/threonine domain is capable of
CC autophosphorylation, in vitro, but to a lower extent than the tyrosine
CC kinase domain. May function as a negative regulator of the tyrosine
CC kinase domain.
CC -!- PTM: C-terminal tyrosine kinase domain is capable of
CC autophosphorylation, in vitro.
CC -!- MISCELLANEOUS: 'Zaphod' is a fictional ex-president of the galaxy with
CC 2 heads.
CC -!- SIMILARITY: In the N-terminal section; belongs to the protein kinase
CC superfamily. Ser/Thr protein kinase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the protein kinase
CC superfamily. TKL Tyr protein kinase family. {ECO:0000305}.
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DR EMBL; AAFI02000014; EAL69312.1; -; Genomic_DNA.
DR EMBL; AF200688; AAF14631.1; -; mRNA.
DR RefSeq; XP_643301.1; XM_638209.1.
DR AlphaFoldDB; Q75JK0; -.
DR SMR; Q75JK0; -.
DR STRING; 44689.DDB0185184; -.
DR PaxDb; Q75JK0; -.
DR PRIDE; Q75JK0; -.
DR EnsemblProtists; EAL69312; EAL69312; DDB_G0276025.
DR GeneID; 8620347; -.
DR KEGG; ddi:DDB_G0276025; -.
DR dictyBase; DDB_G0276025; zakA.
DR eggNOG; KOG0192; Eukaryota.
DR eggNOG; KOG4645; Eukaryota.
DR HOGENOM; CLU_431134_0_0_1; -.
DR InParanoid; Q75JK0; -.
DR OMA; TIKICKI; -.
DR PhylomeDB; Q75JK0; -.
DR Reactome; R-DDI-5673000; RAF activation.
DR Reactome; R-DDI-5674135; MAP2K and MAPK activation.
DR Reactome; R-DDI-5675221; Negative regulation of MAPK pathway.
DR PRO; PR:Q75JK0; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; IMP:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:dictyBase.
DR GO; GO:0140582; P:adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0001708; P:cell fate specification; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:dictyBase.
DR GO; GO:0060176; P:regulation of aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0042659; P:regulation of cell fate specification; IMP:dictyBase.
DR GO; GO:0061118; P:regulation of positive chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0007165; P:signal transduction; IDA:dictyBase.
DR GO; GO:0031288; P:sorocarp morphogenesis; IMP:dictyBase.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IMP:dictyBase.
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; IPR008266; Tyr_kinase_AS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00069; Pkinase; 2.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 2.
DR SUPFAM; SSF56112; SSF56112; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Developmental protein; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..781
FT /note="Dual specificity protein kinase zakA"
FT /id="PRO_0000328187"
FT DOMAIN 9..317
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 379..654
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 168..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 132
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 507
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 15..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 385..393
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 406
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CONFLICT 261
FT /note="G -> S (in Ref. 3; AAF14631)"
FT /evidence="ECO:0000305"
FT CONFLICT 759
FT /note="D -> G (in Ref. 3; AAF14631)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 781 AA; 89690 MW; F7AC84F07398782C CRC64;
MHYHNKDDWE EISFIGEGQY GRVIKCRKKN GFILNEQVDY VAIKIISKDK FKRNETDILE
KIRLFNIPRY YSHAEDDNFI YIYMEYIEGE NLANILKTKK QGRFKESRII SMIADLVETL
SFLHKHHVIH RDIKTANLVL DKNKNLKLID FGASTIQNKK QFEQYLNETT NNNNNPNNNN
NNNNNNNNNN NNNNNNNNNN NNINNINNNN DLNGSGSGIS TYLNEQYKQS SFAIIGTFNY
MAPEVKRNYR ATRKSDVWSL GCTIIEMAGG DLSQKLNGIP IIPDHLSDTL KDFLNHCLVI
DPKKRSYMEE LLSHKLIVHI IGPNKSKNYG VEPKFKDDDD FEEIENEKDN YLSSRFPAKF
APQYEKPKWE IEFEELEFDK DDSEGGAGNF GDVKKGLLNE TEVAIKFVKK AHCEAITVCD
TFYHEVLILS NLRHPNIVQF MAACIKYGEK ETNHCIVSEW MSGGNLTQFL MNNHKVLENN
PHLRVKLLTD IAKGILYLHK QHIIHRDLTS NNVLLDFKRE ILPNQLYGSN EFTAKVCDFG
LSSNQSESKK LRGGSIHYMA PENLNGSPIN EKSDIYSFGL LVWQMFSYAP PNTIYSPKEM
ASMVSDPKQN YRPQIPFNVP LKFKELITQC WDRNPLNRPK DFSIIIEKLK EIGLTYNRSS
SNVSPINSPL INNNNNNYNN NHLNSLSSSL NSSPTYYAKT FGDSNSNIDV YHSADSITPI
VSSPPIIKID LTQDDWDSKL KQLDLEHENK SLISISINDN NNNNINNNNT NNNNVNDLGY
C
