ID GAK_RAT Reviewed; 1305 AA. AC P97874; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 02-SEP-2026, entry version 179. DE RecName: Full=Cyclin-G-associated kinase {ECO:0000250|UniProtKB:O14976}; DE EC=2.7.11.1 {ECO:0000250|UniProtKB:O14976}; GN Name=Gak {ECO:0000312|RGD:621589}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RX PubMed=9013862; DOI=10.1016/s0014-5793(96)01484-6; RA Kanaoka Y., Kimura S.H., Okazaki I., Ikeda M., Nojima H.; RT "GAK: a cyclin G associated kinase contains a tensin/auxilin-like domain."; RL FEBS Lett. 402:73-80(1997). RN [2] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-16; SER-809; SER-824 RP AND SER-827, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Associates with cyclin G and CDK5. Seems to act as an auxilin CC homolog that is involved in the uncoating of clathrin-coated vesicles CC by Hsc70 in non-neuronal cells. Expression oscillates slightly during CC the cell cycle, peaking at G1. May play a role in clathrin-mediated CC endocytosis and intracellular trafficking, and in the dynamics of CC clathrin assembly/disassembly. {ECO:0000250|UniProtKB:O14976}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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 Evidence={ECO:0000250|UniProtKB:O14976}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000250|UniProtKB:O14976}; CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:O14976}. Golgi apparatus, trans-Golgi network CC {ECO:0000250|UniProtKB:O14976}. Cell junction, focal adhesion CC {ECO:0000250|UniProtKB:O14976}. Cytoplasmic vesicle, clathrin-coated CC vesicle {ECO:0000250|UniProtKB:O14976}. Note=Localizes to the CC perinuclear area and to the trans-Golgi network. Also seen on the CC plasma membrane, probably at focal adhesions. Recruitment to clathrin- CC coated vesicles depends on temporal variations in phosphoinositide CC composition of clathrin-coated vesicles. CC {ECO:0000250|UniProtKB:O14976}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. 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; D38560; BAA18911.1; -; mRNA. DR PIR; T31096; T31096. DR RefSeq; NP_112292.1; NM_031030.2. DR AlphaFoldDB; P97874; -. DR SMR; P97874; -. DR BioGRID; 249559; 1. DR FunCoup; P97874; 2899. DR IntAct; P97874; 3. DR MINT; P97874; -. DR STRING; 10116.ENSRNOP00000000064; -. DR iPTMnet; P97874; -. DR PhosphoSitePlus; P97874; -. DR jPOST; P97874; -. DR PaxDb; 10116-ENSRNOP00000000064; -. DR GeneID; 81659; -. DR KEGG; rno:81659; -. DR UCSC; RGD:621589; rat. DR AGR; RGD:621589; -. DR CTD; 2580; -. DR RGD; 621589; Gak. DR eggNOG; KOG0431; Eukaryota. DR eggNOG; KOG1989; Eukaryota. DR eggNOG; KOG2283; Eukaryota. DR InParanoid; P97874; -. DR OrthoDB; 1717591at2759; -. DR PhylomeDB; P97874; -. DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis. DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis. DR PRO; PR:P97874; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:GOC. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0031982; C:vesicle; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central. DR GO; GO:0030332; F:cyclin binding; IDA:RGD. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0048468; P:cell development; ISO:RGD. DR GO; GO:0048268; P:clathrin coat assembly; ISO:RGD. DR GO; GO:0072318; P:clathrin coat disassembly; ISO:RGD. DR GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:UniProtKB. DR GO; GO:0007029; P:endoplasmic reticulum organization; ISO:RGD. DR GO; GO:0009913; P:epidermal cell differentiation; ISO:RGD. DR GO; GO:0061436; P:establishment of skin barrier; ISO:RGD. DR GO; GO:0048853; P:forebrain morphogenesis; ISO:RGD. DR GO; GO:0007030; P:Golgi organization; ISO:RGD. DR GO; GO:0090160; P:Golgi to lysosome transport; ISO:RGD. DR GO; GO:0035622; P:intrahepatic bile duct development; ISO:RGD. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:RGD. DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; ISO:RGD. DR GO; GO:0034067; P:protein localization to Golgi apparatus; ISO:RGD. DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:RGD. DR GO; GO:0006898; P:receptor-mediated endocytosis; ISO:RGD. DR GO; GO:1905443; P:regulation of clathrin coat assembly; ISS:UniProtKB. DR CDD; cd06257; DnaJ; 1. DR CDD; cd14564; PTP_GAK; 1. DR CDD; cd14036; STKc_GAK; 1. DR FunFam; 1.10.510.10:FF:000228; cyclin-G-associated kinase isoform X1; 1. DR FunFam; 2.60.40.1110:FF:000001; cyclin-G-associated kinase isoform X2; 1. DR FunFam; 1.10.287.110:FF:000002; putative tyrosine-protein phosphatase auxilin isoform X2; 1. DR FunFam; 3.90.190.10:FF:000008; putative tyrosine-protein phosphatase auxilin isoform X2; 1. DR Gene3D; 2.60.40.1110; -; 1. DR Gene3D; 1.10.287.110; DnaJ domain; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR001623; DnaJ_domain. DR InterPro; IPR036869; J_dom_sf. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR014020; Tensin_C2-dom. DR InterPro; IPR029023; Tensin_phosphatase. DR PANTHER; PTHR23172; AUXILIN/CYCLIN G-ASSOCIATED KINASE-RELATED; 1. DR PANTHER; PTHR23172:SF34; CYCLIN-G-ASSOCIATED KINASE; 1. DR Pfam; PF00226; DnaJ; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF10409; PTEN_C2; 1. DR SMART; SM00271; DnaJ; 1. DR SMART; SM01326; PTEN_C2; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF46565; Chaperone J-domain; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51182; C2_TENSIN; 1. DR PROSITE; PS50076; DNAJ_2; 1. DR PROSITE; PS51181; PPASE_TENSIN; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Cell cycle; Cell junction; Cytoplasm; KW Cytoplasmic vesicle; Golgi apparatus; Kinase; Methylation; KW Nucleotide-binding; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:O14976" FT CHAIN 2..1305 FT /note="Cyclin-G-associated kinase" FT /id="PRO_0000085960" FT DOMAIN 40..315 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 397..564 FT /note="Phosphatase tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590" FT DOMAIN 570..708 FT /note="C2 tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00589" FT DOMAIN 1241..1305 FT /note="J" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286" FT REGION 332..354 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 747..856 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1044..1141 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 776..789 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 805..817 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 822..832 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 836..848 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1105..1131 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 173 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:O14976" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 16 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 454 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O14976" FT MOD_RES 768 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O14976" FT MOD_RES 774 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O14976" FT MOD_RES 781 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O14976" FT MOD_RES 792 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O14976" FT MOD_RES 809 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 824 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 827 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 938 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O14976" FT MOD_RES 1122 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q99KY4" FT MOD_RES 1171 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O14976" SQ SEQUENCE 1305 AA; 143703 MW; 6D36BD38011C44EE CRC64; MSLLQSALDF LAGPGSLGGA AGRDQSDFVG QTVELGELRL RVRRVLAEGG FAFVYEAQDL GSGREYALKR LLSNEEEKNR AIIQEVCFLK KLSGHPNIVQ FCSAASIGKE ESDTGQAEFL LLTELCKGQL VEFLRRVECK GPLSCDSILK IFYQTCRAVQ HMHRQKPPII HRDLKVENLL LSNQGTIKLC DFGSATTISH YPDYSWSAQK RAMVEEEITR NTTPMYRTPE IVDLYSNFPI GEKQDIWALG CILYLLCFRQ HPFEDGAKLR IVNGKYSIPV NDTRYTVFHD LIRGMLKVNP EERLSIAEVV RQLQEIAAAR NVNPKAPITE LLEQNGGYGN SGPSRAQPPS GGPVNSSGVL ALAEYDQPYG GFLDILRGGT ERLFTNLKDT SSKVIQSVAN YAKGDLDISY ITSRIAVMSF PAEGVESAIK NNIEDVRLFL DAKHPGHYAV YNLSPRIYRA SKFHNRVTEC GWAVRRAPHL HSLYTLCRSM HAWLREDHRN VCVVHCMDGR AASAVAVCAF LCFCRLFSTA EAAVYMFSMK RCPPGIWPSH KRYIEYVCDM VAEEPITPHS KPMLVKSVVM TPVPLFSKQR NGCRPFCEVY VGEERVTTTS QEYDRMKEFK IEDGKAVIPL GITVQGDVLT IIYHARSTLG GRLQAKMASM KMFQIQFHTG FVPRNATTVK FAKYDLDACD IQEKYPDLFQ VNLEVEVEPR DRPSRDVPPW ENTSLRGLNP KILFSNREEQ QDILSKFGKP ELPRQPGSTA QYDAEAGSPE AEITESDSPQ SSSTDTNHFL HTLDWQEEKD PETGVDNTSP KESQSNLIAD GDGSEVSDEE EASCPSEERK PGAGEDTPRL AAGTRQQDLI FDVGMLAAPQ EPVQPEEGVD LLGLHSEGDL RPAAPLQASG VQSSNTDLLS SLLEPSDASQ VGPPGDLLGG ETPLLLASPV SLLGVQSNLQ GKVPDTVDPF DQFLLPSSSD TQPCSKPDLF GEFLNSDSVA SSTAFPSTHS APPPSCSTAF LHLGDLPAEP NKVIASSSHP DLLGGWDTWA ETALPGPASM PVPEGTLFSS AGHPAPPGPN PSQTKSQNPD PFADLSDLSS SLQGLPAGLP AGSFVGTSAT THKSNSSWQT TRPTAPGTSW PPQAKPAPRA SEQLRSHFSV IGAREERGVR APSFAQKPKV SENDFEDLLP NQGFSKSDKK GPKTMAEMRK QELARDTDPF KLKLLDWIEG KERNIRALLS TLHTVLWDGE SRWTPVSMAD LVTPEQVKKQ YRRAVLVVHP DKATGQPYEQ SAKMIFMELN DAWSEFENQG SRPLF //