PP4P1_HUMAN
ID PP4P1_HUMAN Reviewed; 277 AA.
AC Q86T03; B2RA35; Q86U09; Q8WUC0; Q9BU67; Q9NSU8;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase;
DE Short=Type 1 PtdIns-4,5-P2 4-Ptase;
DE EC=3.1.3.78 {ECO:0000269|PubMed:16365287};
DE AltName: Full=PtdIns-4,5-P2 4-Ptase I;
DE AltName: Full=Transmembrane protein 55B;
GN Name=PIP4P1 {ECO:0000312|HGNC:HGNC:19299};
GN Synonyms=C14orf9 {ECO:0000312|HGNC:HGNC:19299},
GN TMEM55B {ECO:0000312|HGNC:HGNC:19299};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Neuroblastoma, and T-cell;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Substantia nigra;
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] (ISOFORM 3).
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Lung;
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=16365287; DOI=10.1073/pnas.0509740102;
RA Ungewickell A., Hugge C., Kisseleva M., Chang S.-C., Zou J., Feng Y.,
RA Galyov E.E., Wilson M., Majerus P.W.;
RT "The identification and characterization of two phosphatidylinositol-4,5-
RT bisphosphate 4-phosphatases.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:18854-18859(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP FUNCTION, AND INDUCTION.
RX PubMed=25035345; DOI=10.1161/atvbaha.113.302806;
RA Medina M.W., Bauzon F., Naidoo D., Theusch E., Stevens K., Schilde J.,
RA Schubert C., Mangravite L.M., Rudel L.L., Temel R.E., Runz H., Krauss R.M.;
RT "Transmembrane protein 55B is a novel regulator of cellular cholesterol
RT metabolism.";
RL Arterioscler. Thromb. Vasc. Biol. 34:1917-1923(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH JIP4, AND INDUCTION.
RX PubMed=29146937; DOI=10.1038/s41467-017-01871-z;
RA Willett R., Martina J.A., Zewe J.P., Wills R., Hammond G.R.V.,
RA Puertollano R.;
RT "TFEB regulates lysosomal positioning by modulating TMEM55B expression and
RT JIP4 recruitment to lysosomes.";
RL Nat. Commun. 8:1580-1580(2017).
RN [10]
RP FUNCTION, AND INTERACTION WITH ATP6V0D1 AND LAMTOR1.
RX PubMed=29644770; DOI=10.1111/gtc.12583;
RA Hashimoto Y., Shirane M., Nakayama K.I.;
RT "TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1
RT activation.";
RL Genes Cells 23:418-434(2018).
CC -!- FUNCTION: Catalyzes the hydrolysis of phosphatidylinositol-4,5-
CC bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate
CC (PtdIns-4-P) (PubMed:16365287). Does not hydrolyze phosphatidylinositol
CC 3,4,5-trisphosphate, phosphatidylinositol 3,4-bisphosphate, inositol
CC 3,5-bisphosphate, inositol 3,4-bisphosphate, phosphatidylinositol 5-
CC monophosphate, phosphatidylinositol 4-monophosphate and
CC phosphatidylinositol 3-monophosphate (PubMed:16365287). Regulates
CC lysosomal positioning by recruiting JIP4 to lysosomal membranes, thus
CC inducing retrograde transport of lysosomes along microtubules
CC (PubMed:29146937). Contributes to assembly of the V-ATPase complex in
CC lipid rafts of the lysosomal membrane and to subsequent amino acid-
CC dependent activation of mTORC1 (PubMed:29644770). May play a role in
CC the regulation of cellular cholesterol metabolism (PubMed:25035345).
CC {ECO:0000269|PubMed:16365287, ECO:0000269|PubMed:25035345,
CC ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:29644770}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:25674,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57795,
CC ChEBI:CHEBI:58456; EC=3.1.3.78;
CC Evidence={ECO:0000269|PubMed:16365287};
CC -!- SUBUNIT: Interacts (via transmembrane domain) with ATP6V0D1
CC (PubMed:29644770). Interacts with LAMTOR1 (PubMed:29644770). Interacts
CC with RRAGA and RRAGC (By similarity). {ECO:0000250|UniProtKB:Q3TWL2,
CC ECO:0000269|PubMed:29644770}.
CC -!- INTERACTION:
CC Q86T03; O95208-2: EPN2; NbExp=3; IntAct=EBI-6164623, EBI-12135243;
CC Q86T03; Q92993: KAT5; NbExp=3; IntAct=EBI-6164623, EBI-399080;
CC Q86T03; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-6164623, EBI-11742507;
CC Q86T03; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-6164623, EBI-373552;
CC Q86T03; Q5EBL4-3: RILPL1; NbExp=5; IntAct=EBI-6164623, EBI-12072024;
CC Q86T03; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-6164623, EBI-9090795;
CC Q86T03; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-6164623, EBI-18159983;
CC Q86T03; P61981: YWHAG; NbExp=3; IntAct=EBI-6164623, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:16365287}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:16365287}; Multi-
CC pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, phagosome
CC membrane {ECO:0000250|UniProtKB:Q3TWL2}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q3TWL2}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q86T03-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86T03-2; Sequence=VSP_007815;
CC Name=3;
CC IsoId=Q86T03-3; Sequence=VSP_007816, VSP_007817;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:16365287}.
CC -!- INDUCTION: By sterol depletion. {ECO:0000269|PubMed:25035345,
CC ECO:0000269|PubMed:29146937}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be due to intron retention.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB70896.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAD62347.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BX161490; CAD61939.1; -; mRNA.
DR EMBL; BX248025; CAD62347.1; ALT_INIT; mRNA.
DR EMBL; AK314021; BAG36732.1; -; mRNA.
DR EMBL; AL137727; CAB70896.1; ALT_INIT; mRNA.
DR EMBL; CH471078; EAW66461.1; -; Genomic_DNA.
DR EMBL; BC002867; AAH02867.2; -; mRNA.
DR EMBL; BC020947; AAH20947.1; -; mRNA.
DR CCDS; CCDS41911.1; -. [Q86T03-2]
DR CCDS; CCDS9551.1; -. [Q86T03-1]
DR PIR; T46382; T46382.
DR RefSeq; NP_001094284.1; NM_001100814.2. [Q86T03-2]
DR RefSeq; NP_653169.2; NM_144568.3. [Q86T03-1]
DR AlphaFoldDB; Q86T03; -.
DR BioGRID; 124764; 63.
DR IntAct; Q86T03; 30.
DR MINT; Q86T03; -.
DR STRING; 9606.ENSP00000381102; -.
DR SwissLipids; SLP:000000850; -.
DR DEPOD; PIP4P1; -.
DR iPTMnet; Q86T03; -.
DR PhosphoSitePlus; Q86T03; -.
DR SwissPalm; Q86T03; -.
DR BioMuta; PIP4P1; -.
DR DMDM; 33112243; -.
DR EPD; Q86T03; -.
DR jPOST; Q86T03; -.
DR MassIVE; Q86T03; -.
DR MaxQB; Q86T03; -.
DR PaxDb; Q86T03; -.
DR PeptideAtlas; Q86T03; -.
DR PRIDE; Q86T03; -.
DR ProteomicsDB; 69653; -. [Q86T03-1]
DR ProteomicsDB; 69654; -. [Q86T03-2]
DR ProteomicsDB; 69655; -. [Q86T03-3]
DR Antibodypedia; 64010; 55 antibodies from 17 providers.
DR DNASU; 90809; -.
DR Ensembl; ENST00000250489.9; ENSP00000250489.4; ENSG00000165782.11. [Q86T03-1]
DR Ensembl; ENST00000398020.6; ENSP00000381102.4; ENSG00000165782.11. [Q86T03-2]
DR GeneID; 90809; -.
DR KEGG; hsa:90809; -.
DR MANE-Select; ENST00000250489.9; ENSP00000250489.4; NM_144568.4; NP_653169.2.
DR UCSC; uc001vxk.4; human. [Q86T03-1]
DR CTD; 90809; -.
DR DisGeNET; 90809; -.
DR GeneCards; PIP4P1; -.
DR HGNC; HGNC:19299; PIP4P1.
DR HPA; ENSG00000165782; Low tissue specificity.
DR MIM; 609865; gene.
DR neXtProt; NX_Q86T03; -.
DR OpenTargets; ENSG00000165782; -.
DR PharmGKB; PA134919069; -.
DR VEuPathDB; HostDB:ENSG00000165782; -.
DR eggNOG; KOG4684; Eukaryota.
DR GeneTree; ENSGT00390000003680; -.
DR HOGENOM; CLU_087485_0_0_1; -.
DR InParanoid; Q86T03; -.
DR OMA; APYGVPN; -.
DR OrthoDB; 1346704at2759; -.
DR PhylomeDB; Q86T03; -.
DR TreeFam; TF316367; -.
DR BioCyc; MetaCyc:HS15363-MON; -.
DR BRENDA; 3.1.3.78; 2681.
DR PathwayCommons; Q86T03; -.
DR Reactome; R-HSA-6811555; PI5P Regulates TP53 Acetylation.
DR Reactome; R-HSA-8847453; Synthesis of PIPs in the nucleus.
DR SignaLink; Q86T03; -.
DR BioGRID-ORCS; 90809; 14 hits in 1082 CRISPR screens.
DR ChiTaRS; TMEM55B; human.
DR GenomeRNAi; 90809; -.
DR Pharos; Q86T03; Tbio.
DR PRO; PR:Q86T03; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q86T03; protein.
DR Bgee; ENSG00000165782; Expressed in ileal mucosa and 165 other tissues.
DR ExpressionAtlas; Q86T03; baseline and differential.
DR Genevisible; Q86T03; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; IDA:FlyBase.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0030670; C:phagocytic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0034597; F:phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity; IDA:FlyBase.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; IMP:UniProtKB.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:FlyBase.
DR GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0070070; P:proton-transporting V-type ATPase complex assembly; ISS:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0006991; P:response to sterol depletion; IDA:UniProtKB.
DR InterPro; IPR019178; PtdIns-P2-Ptase.
DR PANTHER; PTHR21014; PTHR21014; 1.
DR Pfam; PF09788; Tmemb_55A; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasmic vesicle; Endosome;
KW Hydrolase; Lipid metabolism; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..277
FT /note="Type 1 phosphatidylinositol 4,5-bisphosphate 4-
FT phosphatase"
FT /id="PRO_0000072579"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 242..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 133..139
FT /note="CX5R motif"
FT COMPBIAS 44..73
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 133
FT /evidence="ECO:0000250"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3TWL2"
FT VAR_SEQ 47
FT /note="A -> AGKHAPPQ (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_007815"
FT VAR_SEQ 48..224
FT /note="AFPPFPEGHPAVLPGEDPPPYSPLTSPDSGSAPMITCRVCQSLINVEGKMHQ
FT HVVKCGVCNEATPIKNAPPGKKYVRCPCNCLLICKVTSQRIACPRPYCKRIINLGPVHP
FT GPLSPEPQPMGVRVICGHCKNTFLWTEFTDRTLARCPHCRKVSSIGRRYPRKRCICCFL
FT LGLLLAV -> GKHAPPQGKPGRVRGAPRGTLKAGEGAGPRAEAGPSRQVRDCCTCDWA
FT RLPSLRNRDHSLGTEGGSEQPDRSANYEKPSELGQRVEDQKDFPTTVEHQWGCK (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_007816"
FT VAR_SEQ 225..277
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_007817"
FT CONFLICT 208
FT /note="P -> T (in Ref. 5; AAH20947)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 277 AA; 29470 MW; A85FE1F736366CBC CRC64;
MAADGERSPL LSEPIDGGAG GNGLVGPGGS GAGPGGGLTP SAPPYGAAFP PFPEGHPAVL
PGEDPPPYSP LTSPDSGSAP MITCRVCQSL INVEGKMHQH VVKCGVCNEA TPIKNAPPGK
KYVRCPCNCL LICKVTSQRI ACPRPYCKRI INLGPVHPGP LSPEPQPMGV RVICGHCKNT
FLWTEFTDRT LARCPHCRKV SSIGRRYPRK RCICCFLLGL LLAVTATGLA FGTWKHARRY
GGIYAAWAFV ILLAVLCLGR ALYWACMKVS HPVQNFS
