PKHA8_CANLF
ID PKHA8_CANLF Reviewed; 519 AA.
AC D2KC46; E2R9N6;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 65.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, FUNCTION, AND MUTAGENESIS OF ARG-18
RP AND TRP-407.
RX PubMed=19940249; DOI=10.1073/pnas.0911789106;
RA Cao X., Coskun U., Rossle M., Buschhorn S.B., Grzybek M., Dafforn T.R.,
RA Lenoir M., Overduin M., Simons K.;
RT "Golgi protein FAPP2 tubulates membranes.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:21121-21125(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHOLIPID-BINDING.
RX PubMed=16103222; DOI=10.1083/jcb.200503078;
RA Vieira O.V., Verkade P., Manninen A., Simons K.;
RT "FAPP2 is involved in the transport of apical cargo in polarized MDCK
RT cells.";
RL J. Cell Biol. 170:521-526(2005).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19794145; DOI=10.1152/ajpcell.00098.2009;
RA Yui N., Okutsu R., Sohara E., Rai T., Ohta A., Noda Y., Sasaki S.,
RA Uchida S.;
RT "FAPP2 is required for aquaporin-2 apical sorting at trans-Golgi network in
RT polarized MDCK cells.";
RL Am. J. Physiol. 297:C1389-C1396(2009).
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.
CC {ECO:0000269|PubMed:16103222, ECO:0000269|PubMed:19794145,
CC ECO:0000269|PubMed:19940249}.
CC -!- SUBUNIT: Homodimer. Interacts with ARF1; the interaction together with
CC phosphatidylinositol 4-phosphate binding is required for FAPP2 GlcCer
CC transfer ability (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC D2KC46; D2KC46: PLEKHA8; NbExp=4; IntAct=EBI-15817088, EBI-15817088;
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; GU204956; ACZ98822.1; -; mRNA.
DR RefSeq; NP_001161170.1; NM_001167698.1.
DR AlphaFoldDB; D2KC46; -.
DR SMR; D2KC46; -.
DR DIP; DIP-49023N; -.
DR STRING; 9615.ENSCAFP00000052497; -.
DR PaxDb; D2KC46; -.
DR Ensembl; ENSCAFT00030013452; ENSCAFP00030011750; ENSCAFG00030007125.
DR GeneID; 482381; -.
DR KEGG; cfa:482381; -.
DR CTD; 84725; -.
DR eggNOG; KOG3221; Eukaryota.
DR HOGENOM; CLU_039839_0_0_1; -.
DR InParanoid; D2KC46; -.
DR OrthoDB; 952122at2759; -.
DR Reactome; R-CFA-1660499; Synthesis of PIPs at the plasma membrane.
DR Proteomes; UP000002254; Unplaced.
DR Bgee; ENSCAFG00000003056; Expressed in testis and 46 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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:0042802; F:identical protein binding; IPI:IntAct.
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..519
FT /note="Pleckstrin homology domain-containing family A
FT member 8"
FT /id="PRO_0000419607"
FT DOMAIN 1..93
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 274..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 310..519
FT /note="Glycolipid transfer protein homology domain"
FT COMPBIAS 280..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 139
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:D3ZY60"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:D3ZY60"
FT MOD_RES 153
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:D3ZY60"
FT MUTAGEN 18
FT /note="R->L: No binding of PtdIns4P. Very little induction
FT of membrane tubulation."
FT /evidence="ECO:0000269|PubMed:19940249"
FT MUTAGEN 407
FT /note="W->A: Abolishes GlcCer binding. No effect on
FT membrane tubulation."
FT /evidence="ECO:0000269|PubMed:19940249"
FT CONFLICT 296
FT /note="P -> S (in Ref. 1; ACZ98822)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 58082 MW; 584C3F68BC0B9E43 CRC64;
MEGVLYKWTN YLSGWQPRWF LLCGGILSYY DSPEDAWKGC KGSIQMAVCE IQVHSVDNTR
MDLIIPGEQY FYLKARSVAE RQRWLVALGS AKACLTDSRT QKEKEFAENT ENLKTKMSEL
RLYCDLLVQQ VDKTKEVTTT GVSNSEEGID VGTLLKSTCN TFLKTLEECM QIANAAFTSE
LLYRTPPGSP QLAMLKSSKM KHPIIPIHNS LERQMELNSC ENGSLHMEIN DGEEILMKNK
SSLYLKPEID CSISSEENTD DNITVQGEIM KEEGEDNLGN HDSSLAQPAS DSSSSPPESH
WEEGQEIIPT FFSTMNTSFS DIELLEDSGI PTEAFLASCY AVVPVLDKLG PTVFAPVKMD
LVGNIKKVNQ KYITNKEEFT TLQKIVLHEV EADVAQVRNS ATEALLWLKR GLKFLKGFLT
EVKNGEKDIQ TALNNAYGKT LRQHHGWVVR GVFALALRAA PSYEDFVAAL TIKEGDHQKA
AFSVGMQRDL SLYLPAMEKQ LAILDTLYEV HGLESDEVV
