LOCUS       NP_005875                591 aa            linear   PRI 18-APR-2025
DEFINITION  serine/threonine-protein kinase PAK 4 isoform 1 [Homo sapiens].
ACCESSION   NP_005875
VERSION     NP_005875.1
DBSOURCE    REFSEQ: accession NM_005884.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 591)
  AUTHORS   Zhang,J., Song,Y., Ahn,A.R., Park,H.S., Park,S.H., Moon,Y.J.,
            Kim,K.M. and Jang,K.Y.
  TITLE     PAK4 Is Involved in the Stabilization of PD-L1 and the Resistance
            to Doxorubicin in Osteosarcoma and Predicts the Survival of
            Diagnosed Patients
  JOURNAL   Cells 13 (17), 1444 (2024)
   PUBMED   39273017
  REMARK    GeneRIF: PAK4 Is Involved in the Stabilization of PD-L1 and the
            Resistance to Doxorubicin in Osteosarcoma and Predicts the Survival
            of Diagnosed Patients.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 591)
  AUTHORS   Wu,D., Yu,H.C., Cha,H.N., Park,S., Lee,Y., Yoon,S.J., Park,S.Y.,
            Park,B.H. and Bae,E.J.
  TITLE     PAK4 phosphorylates and inhibits AMPKalpha to control glucose
            uptake
  JOURNAL   Nat Commun 15 (1), 6858 (2024)
   PUBMED   39127697
  REMARK    GeneRIF: PAK4 phosphorylates and inhibits AMPKalpha to control
            glucose uptake.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 591)
  AUTHORS   Chi,X.J., Song,Y.B., Zhang,H., Wei,L.Q., Gao,Y., Miao,X.J.,
            Yang,S.T., Lin,C.Y., Lan,D. and Zhang,X.
  TITLE     TBC1D10B promotes tumor progression in colon cancer via
            PAK4-mediated promotion of the PI3K/AKT/mTOR pathway
  JOURNAL   Apoptosis 29 (7-8), 1185-1197 (2024)
   PUBMED   38824479
  REMARK    GeneRIF: TBC1D10B promotes tumor progression in colon cancer via
            PAK4-mediated promotion of the PI3K/AKT/mTOR pathway.
REFERENCE   4  (residues 1 to 591)
  AUTHORS   Tang,L., Ye,H., Chen,L., Dong,W., Hu,X. and Yu,L.
  TITLE     Tumorigenic role of Pak4 in ovarian cancer and its correlation with
            immune infiltration
  JOURNAL   BMC Med Genomics 17 (1), 148 (2024)
   PUBMED   38807162
  REMARK    GeneRIF: Tumorigenic role of Pak4 in ovarian cancer and its
            correlation with immune infiltration.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 591)
  AUTHORS   Segal,D., Maier,S., Mastromarco,G.J., Qian,W.W., Nabeel-Shah,S.,
            Lee,H., Moore,G., Lacoste,J., Larsen,B., Lin,Z.Y.,
            Selvabaskaran,A., Liu,K., Smibert,C., Zhang,Z., Greenblatt,J.,
            Peng,J., Lee,H.O., Gingras,A.C. and Taipale,M.
  TITLE     A central chaperone-like role for 14-3-3 proteins in human cells
  JOURNAL   Mol Cell 83 (6), 974-993 (2023)
   PUBMED   36931259
REFERENCE   6  (residues 1 to 591)
  AUTHORS   Lu,Y., Pan,Z.Z., Devaux,Y. and Ray,P.
  TITLE     p21-activated protein kinase 4 (PAK4) interacts with the
            keratinocyte growth factor receptor and participates in
            keratinocyte growth factor-mediated inhibition of oxidant-induced
            cell death
  JOURNAL   J Biol Chem 278 (12), 10374-10380 (2003)
   PUBMED   12529371
  REMARK    GeneRIF: PAK4 interacts with KGF receptor and mediate
            anti-apoptosis effects of KGF on epithelial cells.
REFERENCE   7  (residues 1 to 591)
  AUTHORS   Zhang,H., Li,Z., Viklund,E.K. and Stromblad,S.
  TITLE     P21-activated kinase 4 interacts with integrin alpha v beta 5 and
            regulates alpha v beta 5-mediated cell migration
  JOURNAL   J Cell Biol 158 (7), 1287-1297 (2002)
   PUBMED   12356872
REFERENCE   8  (residues 1 to 591)
  AUTHORS   Dan,C., Kelly,A., Bernard,O. and Minden,A.
  TITLE     Cytoskeletal changes regulated by the PAK4 serine/threonine kinase
            are mediated by LIM kinase 1 and cofilin
  JOURNAL   J Biol Chem 276 (34), 32115-32121 (2001)
   PUBMED   11413130
REFERENCE   9  (residues 1 to 591)
  AUTHORS   Bagrodia,S. and Cerione,R.A.
  TITLE     Pak to the future
  JOURNAL   Trends Cell Biol 9 (9), 350-355 (1999)
   PUBMED   10461188
  REMARK    Review article
REFERENCE   10 (residues 1 to 591)
  AUTHORS   Abo,A., Qu,J., Cammarano,M.S., Dan,C., Fritsch,A., Baud,V.,
            Belisle,B. and Minden,A.
  TITLE     PAK4, a novel effector for Cdc42Hs, is implicated in the
            reorganization of the actin cytoskeleton and in the formation of
            filopodia
  JOURNAL   EMBO J 17 (22), 6527-6540 (1998)
   PUBMED   9822598
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BG773480.1, AF005046.1 and
            AB032968.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: PAK proteins, a family of serine/threonine p21-activating
            kinases, include PAK1, PAK2, PAK3 and PAK4. PAK proteins are
            critical effectors that link Rho GTPases to cytoskeleton
            reorganization and nuclear signaling. They serve as targets for the
            small GTP binding proteins Cdc42 and Rac and have been implicated
            in a wide range of biological activities. PAK4 interacts
            specifically with the GTP-bound form of Cdc42Hs and weakly
            activates the JNK family of MAP kinases. PAK4 is a mediator of
            filopodia formation and may play a role in the reorganization of
            the actin cytoskeleton. Multiple alternatively spliced transcript
            variants encoding distinct isoforms have been found for this gene.
            [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR11853563.16957.1, AF005046.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1966682, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000360442.8/ ENSP00000353625.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..591
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19q13.2"
     Protein         1..591
                     /product="serine/threonine-protein kinase PAK 4 isoform 1"
                     /EC_number="2.7.11.1"
                     /note="protein kinase related to S. cerevisiae STE20,
                     effector for Cdc42Hs; p21(CDKN1A)-activated kinase 4;
                     serine/threonine-protein kinase PAK 4; p21 protein
                     (Cdc42/Rac)-activated kinase 4"
                     /calculated_mol_wt=63941
     Region          10..55
                     /region_name="CRIB_PAK_like"
                     /note="PAK (p21 activated kinase) Binding Domain (PBD),
                     binds Cdc42p- and/or Rho-like small GTPases; also known as
                     the Cdc42/Rac interactive binding (CRIB) motif; has been
                     shown to inhibit transcriptional activation and cell
                     transformation mediated by the...; cd01093"
                     /db_xref="CDD:238526"
     Site            order(11,14,17,19,22,39,43)
                     /site_type="other"
                     /note="GTPase interaction site [polypeptide binding]"
                     /db_xref="CDD:238526"
     Region          25..320
                     /region_name="Linker"
                     /note="propagated from UniProtKB/Swiss-Prot (O96013.1)"
     Site            41
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163;
                     propagated from UniProtKB/Swiss-Prot (O96013.1)"
     Site            78
                     /site_type="methylation"
                     /note="N6-methyllysine.
                     /evidence=ECO:0007744|PubMed:24129315; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Region          95..301
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O96013.1)"
     Site            104
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Site            148
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Site            167
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Site            181
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
                     ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
                     ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569;
                     propagated from UniProtKB/Swiss-Prot (O96013.1)"
     Site            187
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Site            195
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Site            207
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Site            258
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Site            267
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Site            291
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     Region          298..323
                     /region_name="GEF-interaction domain (GID)"
                     /note="propagated from UniProtKB/Swiss-Prot (O96013.1)"
     Region          300..591
                     /region_name="STKc_PAK4"
                     /note="Catalytic domain of the Serine/Threonine Kinase,
                     p21-activated kinase 4; cd06657"
                     /db_xref="CDD:132988"
     Site            order(327..331,335,348,350,379,395..399,401..402,405,440,
                     442..445,447,457..458,461,474..478,480,507,516..518)
                     /site_type="active"
                     /db_xref="CDD:132988"
     Site            order(327..331,335,348,350,379,395..399,401..402,405,
                     444..445,447,457..458)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:132988"
     Site            order(330..331,359,440,442..444,461,474..478,480,507,
                     516..518)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:132988"
     Site            457..480
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:132988"
     Site            474
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by autocatalysis.
                     /evidence=ECO:0000269|Ref.32, ECO:0007744|PubMed:17081983,
                     ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
                     ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (O96013.1)"
     CDS             1..591
                     /gene="PAK4"
                     /coded_by="NM_005884.5:230..2005"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS12528.1"
                     /db_xref="GeneID:10298"
                     /db_xref="HGNC:HGNC:16059"
                     /db_xref="MIM:605451"
ORIGIN      
        1 mfgkrkkrve isapsnfehr vhtgfdqheq kftglprqwq slieesarrp kplvdpacit
       61 siqpgapkti vrgskgakdg altllldefe nmsvtrsnsl rrdsppppar arqengmpee
      121 pattarggpg kagsrgrfag hseagggsgd rrragpekrp kssregsggp qessrdkrpl
      181 sgpdvgtpqp aglasgakla agrpfntypr adtdhpsrga qgephdvapn gpsagglaip
      241 qssssssrpp trargapspg vlgphasepq lappactpaa pavpgppgpr spqrepqrvs
      301 heqfraalql vvdpgdprsy ldnfikigeg stgivciatv rssgklvavk kmdlrkqqrr
      361 ellfnevvim rdyqhenvve mynsylvgde lwvvmefleg galtdivtht rmneeqiaav
      421 clavlqalsv lhaqgvihrd iksdsillth dgrvklsdfg fcaqvskevp rrkslvgtpy
      481 wmapelisrl pygpevdiws lgimviemvd geppyfnepp lkamkmirdn lpprlknlhk
      541 vspslkgfld rllvrdpaqr ataaellkhp flakagppas ivplmrqnrt r
//
