CLIP3_HUMAN
ID CLIP3_HUMAN Reviewed; 547 AA.
AC Q96DZ5; A8K0E4; Q8WWL1; Q96C99; Q9UFT7;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=CAP-Gly domain-containing linker protein 3;
DE AltName: Full=Cytoplasmic linker protein 170-related 59 kDa protein;
DE Short=CLIP-170-related 59 kDa protein;
DE Short=CLIPR-59;
GN Name=CLIP3; Synonyms=CLIPR59;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11854307; DOI=10.1083/jcb.200111003;
RA Perez F., Pernet-Gallay K., Nizak C., Goodson H.V., Kreis T.E., Goud B.;
RT "CLIPR-59, a new trans-Golgi/TGN cytoplasmic linker protein belonging to
RT the CLIP-170 family.";
RL J. Cell Biol. 156:631-642(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-175.
RC TISSUE=Brain, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 387-547.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP FUNCTION, AND INTERACTION WITH AKT1 AND AKT2.
RX PubMed=19139280; DOI=10.1128/mcb.00754-08;
RA Ding J., Du K.;
RT "ClipR-59 interacts with Akt and regulates Akt cellular
RT compartmentalization.";
RL Mol. Cell. Biol. 29:1459-1471(2009).
RN [6]
RP PALMITOYLATION AT CYS-534 AND CYS-535, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 534-CYS--CYS-535.
RX PubMed=24001771; DOI=10.1128/mcb.00527-13;
RA Ren W., Sun Y., Du K.;
RT "DHHC17 palmitoylates ClipR-59 and modulates ClipR-59 association with the
RT plasma membrane.";
RL Mol. Cell. Biol. 33:4255-4265(2013).
RN [7]
RP INTERACTION WITH ZDHHC17 AND ZDHHC13, AND MUTAGENESIS OF PRO-509.
RX PubMed=26198635; DOI=10.1074/jbc.m115.657668;
RA Lemonidis K., Sanchez-Perez M.C., Chamberlain L.H.;
RT "Identification of a novel sequence motif recognized by the ankyrin repeat
RT domain of zDHHC17/13 S-acyltransferases.";
RL J. Biol. Chem. 290:21939-21950(2015).
RN [8]
RP INTERACTION WITH ZDHHC17.
RX PubMed=28882895; DOI=10.1074/jbc.m117.799650;
RA Lemonidis K., MacLeod R., Baillie G.S., Chamberlain L.H.;
RT "Peptide array based screening reveals a large number of proteins
RT interacting with the ankyrin repeat domain of the zDHHC17 S-
RT acyltransferase.";
RL J. Biol. Chem. 292:17190-17202(2017).
RN [9]
RP STRUCTURE BY NMR OF 285-366.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the 1st CAP-GLY domain in human clip-170-related
RT protein CLIPR59.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Functions as a cytoplasmic linker protein. Involved in TGN-
CC endosome dynamics. May modulate the cellular compartmentalization of
CC AKT kinase family and promote its cell membrane localization, thereby
CC playing a role in glucose transport in adipocytes.
CC {ECO:0000269|PubMed:19139280}.
CC -!- SUBUNIT: Homodimer. Interacts with AKT1 and AKT2; when AKT1 and AKT2
CC are phosphorylated and activated, affinity is higher for AKT2
CC (PubMed:19139280). Interacts with ZDHHC13 (via ANK repeats)
CC (PubMed:26198635). Interacts with ZDHHC17 (via ANK repeats)
CC (PubMed:26198635, PubMed:28882895). {ECO:0000269|PubMed:19139280,
CC ECO:0000269|PubMed:26198635, ECO:0000269|PubMed:28882895}.
CC -!- INTERACTION:
CC Q96DZ5; Q9Y592-2: CEP83; NbExp=3; IntAct=EBI-12823145, EBI-11123098;
CC Q96DZ5; Q08379: GOLGA2; NbExp=3; IntAct=EBI-12823145, EBI-618309;
CC Q96DZ5; P28799: GRN; NbExp=3; IntAct=EBI-12823145, EBI-747754;
CC Q96DZ5; P04792: HSPB1; NbExp=3; IntAct=EBI-12823145, EBI-352682;
CC Q96DZ5; O60333-2: KIF1B; NbExp=3; IntAct=EBI-12823145, EBI-10975473;
CC Q96DZ5; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-12823145, EBI-396669;
CC Q96DZ5; Q08117-2: TLE5; NbExp=3; IntAct=EBI-12823145, EBI-11741437;
CC Q96DZ5; O76024: WFS1; NbExp=3; IntAct=EBI-12823145, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24001771};
CC Lipid-anchor {ECO:0000269|PubMed:24001771}. Cytoplasm
CC {ECO:0000269|PubMed:24001771}. Golgi apparatus, Golgi stack
CC {ECO:0000269|PubMed:24001771}. Note=Localized to Golgi stacks as well
CC as on tubulovesicular elements juxtaposed to Golgi cisternae.
CC -!- DOMAIN: Microtubule association is inhibited by the ANK repeats and the
CC Golgi localization region (GoLD).
CC -!- PTM: Palmitoylation by ZDHHC17 regulates association with the plasma
CC membrane. {ECO:0000269|PubMed:24001771}.
CC -!- MISCELLANEOUS: The N-terminal half is dispensable for proper Golgi
CC targeting, whereas the GoLD region is required.
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DR EMBL; AJ427922; CAD20873.1; -; mRNA.
DR EMBL; AK094738; BAG52921.1; -; mRNA.
DR EMBL; AK289509; BAF82198.1; -; mRNA.
DR EMBL; BC013116; AAH13116.2; -; mRNA.
DR EMBL; BC014486; AAH14486.2; -; mRNA.
DR EMBL; AL117468; CAB55943.1; -; mRNA.
DR CCDS; CCDS12486.1; -.
DR PIR; T17253; T17253.
DR RefSeq; NP_001186499.1; NM_001199570.1.
DR RefSeq; NP_056341.1; NM_015526.2.
DR PDB; 2CP0; NMR; -; A=285-366.
DR PDBsum; 2CP0; -.
DR AlphaFoldDB; Q96DZ5; -.
DR SMR; Q96DZ5; -.
DR BioGRID; 117475; 14.
DR IntAct; Q96DZ5; 10.
DR STRING; 9606.ENSP00000353732; -.
DR iPTMnet; Q96DZ5; -.
DR PhosphoSitePlus; Q96DZ5; -.
DR SwissPalm; Q96DZ5; -.
DR BioMuta; CLIP3; -.
DR DMDM; 116241302; -.
DR EPD; Q96DZ5; -.
DR jPOST; Q96DZ5; -.
DR MassIVE; Q96DZ5; -.
DR PaxDb; Q96DZ5; -.
DR PeptideAtlas; Q96DZ5; -.
DR PRIDE; Q96DZ5; -.
DR ProteomicsDB; 76346; -.
DR Antibodypedia; 48030; 133 antibodies from 23 providers.
DR DNASU; 25999; -.
DR Ensembl; ENST00000360535.9; ENSP00000353732.3; ENSG00000105270.15.
DR Ensembl; ENST00000593074.5; ENSP00000466832.1; ENSG00000105270.15.
DR GeneID; 25999; -.
DR KEGG; hsa:25999; -.
DR MANE-Select; ENST00000360535.9; ENSP00000353732.3; NM_015526.3; NP_056341.1.
DR UCSC; uc002ocz.3; human.
DR CTD; 25999; -.
DR GeneCards; CLIP3; -.
DR HGNC; HGNC:24314; CLIP3.
DR HPA; ENSG00000105270; Tissue enhanced (brain).
DR MIM; 607382; gene.
DR neXtProt; NX_Q96DZ5; -.
DR OpenTargets; ENSG00000105270; -.
DR PharmGKB; PA162382439; -.
DR VEuPathDB; HostDB:ENSG00000105270; -.
DR eggNOG; KOG4568; Eukaryota.
DR GeneTree; ENSGT00940000159557; -.
DR HOGENOM; CLU_023687_2_1_1; -.
DR InParanoid; Q96DZ5; -.
DR OMA; IELDHPT; -.
DR OrthoDB; 482616at2759; -.
DR PhylomeDB; Q96DZ5; -.
DR TreeFam; TF326096; -.
DR PathwayCommons; Q96DZ5; -.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR SignaLink; Q96DZ5; -.
DR BioGRID-ORCS; 25999; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; CLIP3; human.
DR EvolutionaryTrace; Q96DZ5; -.
DR GenomeRNAi; 25999; -.
DR Pharos; Q96DZ5; Tbio.
DR PRO; PR:Q96DZ5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96DZ5; protein.
DR Bgee; ENSG00000105270; Expressed in cortical plate and 157 other tissues.
DR ExpressionAtlas; Q96DZ5; baseline and differential.
DR Genevisible; Q96DZ5; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005795; C:Golgi stack; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0035371; C:microtubule plus-end; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0035594; F:ganglioside binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0051010; F:microtubule plus-end binding; IBA:GO_Central.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IBA:GO_Central.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0044091; P:membrane biogenesis; IMP:UniProtKB.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IMP:UniProtKB.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045807; P:positive regulation of endocytosis; IMP:UniProtKB.
DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; ISS:UniProtKB.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0098840; P:protein transport along microtubule; IMP:GO_Central.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 2.30.30.190; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR036859; CAP-Gly_dom_sf.
DR InterPro; IPR000938; CAP-Gly_domain.
DR InterPro; IPR030504; CLIP3.
DR PANTHER; PTHR18916:SF77; PTHR18916:SF77; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF01302; CAP_GLY; 2.
DR SMART; SM00248; ANK; 3.
DR SMART; SM01052; CAP_GLY; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF74924; SSF74924; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
DR PROSITE; PS00845; CAP_GLY_1; 2.
DR PROSITE; PS50245; CAP_GLY_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Cell membrane; Cytoplasm; Golgi apparatus;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..547
FT /note="CAP-Gly domain-containing linker protein 3"
FT /id="PRO_0000076212"
FT REPEAT 117..158
FT /note="ANK 1"
FT REPEAT 160..191
FT /note="ANK 2"
FT REPEAT 197..229
FT /note="ANK 3"
FT DOMAIN 314..356
FT /note="CAP-Gly 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00045"
FT DOMAIN 436..478
FT /note="CAP-Gly 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00045"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 365..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 488..547
FT /note="GoLD"
FT COMPBIAS 15..29
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 365..380
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 374
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:B9EHT4"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B9EHT4"
FT LIPID 534
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:24001771"
FT LIPID 535
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:24001771"
FT VARIANT 175
FT /note="D -> V (in dbSNP:rs17851002)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027962"
FT MUTAGEN 509
FT /note="P->A: Inhibits interaction with ZDHHC13 and
FT ZDHHC17."
FT /evidence="ECO:0000269|PubMed:26198635"
FT MUTAGEN 534..535
FT /note="CC->AA: Strongly reduced plasma membrane association
FT and decrease in the levels of Akt at the plasma membrane."
FT /evidence="ECO:0000269|PubMed:24001771"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:2CP0"
FT STRAND 299..302
FT /evidence="ECO:0007829|PDB:2CP0"
FT TURN 303..305
FT /evidence="ECO:0007829|PDB:2CP0"
FT STRAND 306..314
FT /evidence="ECO:0007829|PDB:2CP0"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:2CP0"
FT STRAND 323..331
FT /evidence="ECO:0007829|PDB:2CP0"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:2CP0"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:2CP0"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:2CP0"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:2CP0"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:2CP0"
SQ SEQUENCE 547 AA; 59560 MW; A718D9673EC1CF4B CRC64;
MTKTDPAPMA PPPRGEEEEE EEEDEPVPEA PSPTQERRQK PVVHPSAPAP LPKDYAFTFF
DPNDPACQEI LFDPQTTIPE LFAIVRQWVP QVQHKIDVIG NEILRRGCHV NDRDGLTDMT
LLHYACKAGA HGVGDPAAAV RLSQQLLALG ADVTLRSRWT NMNALHYAAY FDVPDLVRVL
LKGARPRVVN STCSDFNHGS ALHIAASSLC LGAAKCLLEH GANPALRNRK GQVPAEVVPD
PMDMSLDKAE AALVAKELRT LLEEAVPLSC ALPKVTLPNY DNVPGNLMLS ALGLRLGDRV
LLDGQKTGTL RFCGTTEFAS GQWVGVELDE PEGKNDGSVG GVRYFICPPK QGLFASVSKI
SKAVDAPPSS VTSTPRTPRM DFSRVTGKGR REHKGKKKTP SSPSLGSLQQ RDGAKAEVGD
QVLVAGQKQG IVRFYGKTDF APGYWYGIEL DQPTGKHDGS VFGVRYFTCP PRHGVFAPAS
RIQRIGGSTD SPGDSVGAKK VHQVTMTQPK RTFTTVRTPK DIASENSISR LLFCCWFPWM
LRAEMQS
