PKHA8_RAT
ID PKHA8_RAT Reviewed; 520 AA.
AC D3ZY60;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Pleckstrin homology domain-containing family A member 8;
DE Short=PH domain-containing family A member 8;
DE AltName: Full=Phosphatidylinositol-four-phosphate adapter protein 2;
DE Short=FAPP-2;
DE Short=Phosphoinositol 4-phosphate adapter protein 2;
GN Name=Plekha8; Synonyms=Fapp2;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-139; SER-145 AND THR-153, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
CC -!- FUNCTION: Cargo transport protein that is required for apical transport
CC from the trans-Golgi network (TGN). Transports AQP2 from the trans-
CC Golgi network (TGN) to sites of AQP2 phosphorylation. Mediates the non-
CC vesicular transport of glucosylceramide (GlcCer) from the trans-Golgi
CC network (TGN) to the plasma membrane and plays a pivotal role in the
CC synthesis of complex glycosphingolipids. Binding of both
CC phosphatidylinositol 4-phosphate (PIP) and ARF1 are essential for the
CC GlcCer transfer ability. Also required for primary cilium formation,
CC possibly by being involved in the transport of raft lipids to the
CC apical membrane, and for membrane tubulation (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with ARF1; the interaction together with
CC phosphatidylinositol 4-phosphate binding is required for FAPP2 GlcCer
CC transfer ability. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:Q96JA3}. Membrane
CC {ECO:0000250|UniProtKB:Q96JA3}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q96JA3}. Note=Binds through its PH domain to
CC PtdIns(4)P and ARF1, and subsequently localizes to TGN exit sites.
CC {ECO:0000250|UniProtKB:Q96JA3}.
CC -!- DOMAIN: The PH domain of FAPPS binds the small GTPase ARF1 and
CC phosphatidylinositol-4-phosphate (PtdIns4P) with high selectivity, and
CC is required for recruitment of FAPPs to the trans-Golgi network (TGN).
CC {ECO:0000250}.
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DR EMBL; CH474011; EDL88113.1; -; Genomic_DNA.
DR RefSeq; NP_001102705.1; NM_001109235.2.
DR AlphaFoldDB; D3ZY60; -.
DR SMR; D3ZY60; -.
DR STRING; 10116.ENSRNOP00000013528; -.
DR iPTMnet; D3ZY60; -.
DR PhosphoSitePlus; D3ZY60; -.
DR PaxDb; D3ZY60; -.
DR PeptideAtlas; D3ZY60; -.
DR Ensembl; ENSRNOT00000013528; ENSRNOP00000013528; ENSRNOG00000009971.
DR GeneID; 500132; -.
DR KEGG; rno:500132; -.
DR UCSC; RGD:1563940; rat.
DR CTD; 84725; -.
DR RGD; 1563940; Plekha8.
DR eggNOG; KOG3221; Eukaryota.
DR GeneTree; ENSGT00940000157288; -.
DR HOGENOM; CLU_039839_0_0_1; -.
DR InParanoid; D3ZY60; -.
DR OMA; SKMKHPV; -.
DR OrthoDB; 952122at2759; -.
DR PhylomeDB; D3ZY60; -.
DR TreeFam; TF317467; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR PRO; PR:D3ZY60; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Proteomes; UP000234681; Chromosome 4.
DR Bgee; ENSRNOG00000009971; Expressed in duodenum and 20 other tissues.
DR Genevisible; D3ZY60; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:1902387; F:ceramide 1-phosphate binding; IBA:GO_Central.
DR GO; GO:1902388; F:ceramide 1-phosphate transfer activity; IBA:GO_Central.
DR GO; GO:0097001; F:ceramide binding; ISS:UniProtKB.
DR GO; GO:0051861; F:glycolipid binding; ISS:UniProtKB.
DR GO; GO:0017089; F:glycolipid transfer activity; ISS:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR GO; GO:0035627; P:ceramide transport; IBA:GO_Central.
DR GO; GO:0035621; P:ER to Golgi ceramide transport; ISS:UniProtKB.
DR GO; GO:0120009; P:intermembrane lipid transfer; IBA:GO_Central.
DR GO; GO:0006869; P:lipid transport; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.10.3520.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR036497; GLTP_sf.
DR InterPro; IPR014830; Glycolipid_transfer_prot_dom.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF08718; GLTP; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF110004; SSF110004; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Golgi apparatus; Lipid transport; Lipid-binding; Membrane; Phosphoprotein;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..520
FT /note="Pleckstrin homology domain-containing family A
FT member 8"
FT /id="PRO_0000419608"
FT DOMAIN 1..93
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 255..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..520
FT /note="Glycolipid transfer protein homology domain"
FT COMPBIAS 268..288
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 139
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 153
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
SQ SEQUENCE 520 AA; 58096 MW; 580D1B4A5C163F4D CRC64;
MEGVLYKWTN YLSGWQPRWF LLCGGILSYY DSPEDAWKGC KGSIQMAVCE IQVHSVDNTR
MDLIIPGEQY FYLKARSVAE RQRWLVALGS AKACLTDSRT QKEKEFAENT ENLKTKMSEL
RLYCDLLVQQ VDKTKEVATA GVADSEEGID VGTLLRSTCN TFLKTLEECM QIANAAFTSE
LLYHTPPGSP QLAVLKSSKM KHPIIPIHNS LERPIELNSC ENGSLSVEVN GDEELLMKTK
KSSLYLKSTK ADCNISSEEN TDGNTTVQGE RMKEDGEENL ESHDRDLAQP GSDSVCSPES
PWEDSEEVIP TFFSTMNTSF SDIELLEDSG IPTEAFLASC YAVVPVLDKL GPTVFAPVKM
DLVGNIKKVN QKYITNKEEF TTLQKIVLHE VEADVARVRN SATEALLWLK RGLKFLKGFL
TEVKNGEKDI QTALNNAYGK TLRQHHGWVV RGVFALALRA APSYEDFVAA LTIKEGDHQK
EAFSAGMQRD LSLYLPAMEK QLAILDTLYE IHGLESDEVV
