PKH2_CANAL
ID PKH2_CANAL Reviewed; 947 AA.
AC Q5A3P6; A0A1D8PFF1; Q5A3V9;
DT 27-MAY-2015, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Serine/threonine-protein kinase PKH2 {ECO:0000250|UniProtKB:Q12236};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q12236};
DE AltName: Full=PKB-activating kinase homolog 2 {ECO:0000250|UniProtKB:Q12236};
GN Name=PKH2 {ECO:0000303|PubMed:23911092};
GN Synonyms=PKH1 {ECO:0000303|PubMed:24281718};
GN OrderedLocusNames=CAALFM_C112410CA;
GN ORFNames=CaO19.12690, CaO19.5224, orf19.5224;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=24281718; DOI=10.1128/mbio.00723-13;
RA Douglas L.M., Wang H.X., Konopka J.B.;
RT "The MARVEL domain protein Nce102 regulates actin organization and invasive
RT growth of Candida albicans.";
RL MBio 4:E00723-E00723(2013).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.16 ANGSTROMS), AND DOMAIN.
RC STRAIN=SC5314 / CAI4 / ATCC MYA-682;
RX PubMed=23911092; DOI=10.1021/cb400452z;
RA Pastor-Flores D., Schulze J.O., Bahi A., Giacometti R., Ferrer-Dalmau J.,
RA Passeron S., Engel M., Suss E., Casamayor A., Biondi R.M.;
RT "PIF-pocket as a target for C. albicans Pkh selective inhibitors.";
RL ACS Chem. Biol. 8:2283-2292(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase which is part sphingolipid-
CC mediated signaling pathway that is required for the internalization
CC step of endocytosis by regulating eisosome assembly and organization,
CC and modulating the organization of the plasma membrane. Phosphorylates
CC and activates PKC1. Activates YPK1 and YPK2, 2 components of signaling
CC cascade required for maintenance of cell wall integrity. Required for
CC stress-induced P-body assembly and regulates global mRNA decay at the
CC deadenylation step. {ECO:0000250|UniProtKB:Q12236}.
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: Nucleus {ECO:0000250|UniProtKB:Q12236}.
CC Cytoplasm, cell cortex {ECO:0000250|UniProtKB:Q12236}. Note=Localizes
CC at eisosomes, large, immobile complexes that mark sites of endocytosis
CC near the plasma membrane. {ECO:0000250|UniProtKB:Q12236}.
CC -!- DOMAIN: The PIF-pocket is a small lobe in the catalytic domain required
CC by the enzyme for the binding to the hydrophobic motif of its
CC substrates. It is an allosteric regulatory site that can accommodate
CC small compounds acting as allosteric inhibitors.
CC {ECO:0000305|PubMed:23911092}.
CC -!- DISRUPTION PHENOTYPE: Sensitive to cell wall-damaging agents SDS and
CC Congo red.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PDPK1 subfamily. {ECO:0000305}.
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DR EMBL; CP017623; AOW26859.1; -; Genomic_DNA.
DR RefSeq; XP_716293.2; XM_711200.2.
DR PDB; 4C0T; X-ray; 3.16 A; A=1-944.
DR PDBsum; 4C0T; -.
DR AlphaFoldDB; Q5A3P6; -.
DR SMR; Q5A3P6; -.
DR STRING; 237561.Q5A3P6; -.
DR PRIDE; Q5A3P6; -.
DR GeneID; 3642058; -.
DR KEGG; cal:CAALFM_C112410CA; -.
DR CGD; CAL0000187991; PKH2.
DR eggNOG; KOG0592; Eukaryota.
DR HOGENOM; CLU_005768_0_0_1; -.
DR OrthoDB; 398317at2759; -.
DR PRO; PR:Q5A3P6; -.
DR Proteomes; UP000000559; Chromosome 1.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IDA:CGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR CDD; cd05581; STKc_PDK1; 1.
DR DisProt; DP02500; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR039046; PDPK1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 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.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Endocytosis; Kinase;
KW Nucleotide-binding; Nucleus; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..947
FT /note="Serine/threonine-protein kinase PKH2"
FT /id="PRO_0000433083"
FT DOMAIN 240..502
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 108..132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 162..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..316
FT /note="PIF-pocket"
FT /evidence="ECO:0000305|PubMed:23911092"
FT REGION 550..598
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 611..644
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 794..816
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..43
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..130
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 162..178
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 364
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 250..252
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 269
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 319..321
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 325
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT BINDING 382
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O15530"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 240..248
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 250..259
FT /evidence="ECO:0007829|PDB:4C0T"
FT TURN 260..262
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 265..272
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 273..278
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 282..294
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 311..319
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 326..330
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 338..357
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 369..372
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 383..385
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 405..407
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 417..422
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 427..443
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 454..462
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 473..482
FT /evidence="ECO:0007829|PDB:4C0T"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 493..497
FT /evidence="ECO:0007829|PDB:4C0T"
FT STRAND 499..502
FT /evidence="ECO:0007829|PDB:4C0T"
FT HELIX 510..514
FT /evidence="ECO:0007829|PDB:4C0T"
SQ SEQUENCE 947 AA; 106555 MW; C8E682E4517872EA CRC64;
MHKFRYSLHQ HYSKRNSSDK SKDSPISQNS NEENDSTKLS SSSLQDLHDD LDDIYNNYTL
AQGTNNNSVD TLDSENNQAI NKFIDKPPAI HGMEPQLPVM HVSSRLSSLG NTTNETGESI
AKSAPGTPLS SHSFDFRPHH PRAVTNSSLN VLLDTPNVSS EFNHLVDQTP PNESVERFDD
SNNTVDNTEE EENNDDTDEI PKSETLKQNE ENWEKKGAAV KTIKTMDGEM KTIRRNVTDF
KFGKELGEGS YSTVILATDK ITGKQYAVKV LDKRHIIKEK KVKYVNIEKH ALNRLSNRLG
VISLYFTFQD KDSLYFVLDY ASNGELLTLI KRYNTLNEEC TRHFGAQILD AIKYMHDNGV
IHRDLKPENI LLDDKMRIQI TDFGTARLLE KKNDESEEYP VDVRAKSFVG TAEYVSPELL
ENKYCGKPGD VWAFGCIIYQ MIAGKPPFKA TNEYLTFQKI TKLQFAFSAG FPTIIRDLIK
KILVLQPSRR ATIPEIQKHY FFQSVDFKDF DSIWLSDPPE IGPYKMTAKS MMKVPELNKA
PITTVIKKNV KKSTNSNSNT NNVATAVGGS SSNGHKGSSP TPEKEPSPAT INNKSTEKVS
AASVAAYVLN KPATNQNSST SEDSSKRSSN SNETRKLSYS QQDYIPGTNI LRPQISTRPS
VGSYVKTTPS KDRKTLTKVP SNIHQQQEKV KPKVMEVKPA TTLEAAWEPY LTHPDERILR
IGPVIAHKEP TEPFEKKNKA SLHISPLDIN KEQRSRSNTS LLTQIVNEVN NNTSELKKVE
NADESLAIIE PQYNMKRSPT SDSKKSMDIE RSASTSGSRI SKKAIFKKLG FSHLEKNDSE
ESNGPSLTEK PQTCTLVVTT HGRALLFIRN DIESNYLLIA EIKLKYPFIH FQELVISQTK
FSKLVPSVGV FVISSIDNSL IFEVEKFEVN QWTEALAKSK YNEIGKR
