PHAX_HUMAN
ID PHAX_HUMAN Reviewed; 394 AA.
AC Q9H814; Q9H8W1;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Phosphorylated adapter RNA export protein;
DE AltName: Full=RNA U small nuclear RNA export adapter protein;
GN Name=PHAX; Synonyms=RNUXA;
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].
RC TISSUE=Retinoblastoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 FUNCTION IN U3 SNORNA TRANSPORT, RNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=15574332; DOI=10.1016/j.molcel.2004.11.013;
RA Boulon S., Verheggen C., Jady B.E., Girard C., Pescia C., Paul C.,
RA Ospina J.K., Kiss T., Matera A.G., Bordonne R., Bertrand E.;
RT "PHAX and CRM1 are required sequentially to transport U3 snoRNA to
RT nucleoli.";
RL Mol. Cell 16:777-787(2004).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=11333016; DOI=10.1017/s1355838201002278;
RA Segref A., Mattaj I.W., Ohno M.;
RT "The evolutionarily conserved region of the U snRNA export mediator PHAX is
RT a novel RNA-binding domain that is essential for U snRNA export.";
RL RNA 7:351-360(2001).
RN [6]
RP FUNCTION IN SNORNA TRANSPORT, AND IDENTIFICATION IN A COMPLEX WITH U3
RP SNORNA.
RX PubMed=15574333; DOI=10.1016/j.molcel.2004.11.012;
RA Watkins N.J., Lemm I., Ingelfinger D., Schneider C., Hossbach M.,
RA Urlaub H., Luehrmann R.;
RT "Assembly and maturation of the U3 snoRNP in the nucleoplasm in a large
RT dynamic multiprotein complex.";
RL Mol. Cell 16:789-798(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356, AND IDENTIFICATION BY
RP 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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT THR-296, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-14, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-16, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP INTERACTION WITH NCBP2.
RX PubMed=26382858; DOI=10.1038/ncomms9192;
RA Gebhardt A., Habjan M., Benda C., Meiler A., Haas D.A., Hein M.Y., Mann A.,
RA Mann M., Habermann B., Pichlmair A.;
RT "mRNA export through an additional cap-binding complex consisting of NCBP1
RT and NCBP3.";
RL Nat. Commun. 6:8192-8192(2015).
RN [14]
RP STRUCTURE BY NMR OF 223-323, AND RNA-BINDING REGION.
RX PubMed=20430857; DOI=10.1261/rna.2009910;
RA Mourao A., Varrot A., Mackereth C.D., Cusack S., Sattler M.;
RT "Structure and RNA recognition by the snRNA and snoRNA transport factor
RT PHAX.";
RL RNA 16:1205-1216(2010).
CC -!- FUNCTION: A phosphoprotein adapter involved in the XPO1-mediated U
CC snRNA export from the nucleus. Bridge components required for U snRNA
CC export, the cap binding complex (CBC)-bound snRNA on the one hand and
CC the GTPase Ran in its active GTP-bound form together with the export
CC receptor XPO1 on the other. Its phosphorylation in the nucleus is
CC required for U snRNA export complex assembly and export, while its
CC dephosphorylation in the cytoplasm causes export complex disassembly.
CC It is recycled back to the nucleus via the importin alpha/beta
CC heterodimeric import receptor. The directionality of nuclear export is
CC thought to be conferred by an asymmetric distribution of the GTP- and
CC GDP-bound forms of Ran between the cytoplasm and nucleus. Its
CC compartmentalized phosphorylation cycle may also contribute to the
CC directionality of export. Binds strongly to m7G-capped U1 and U5 small
CC nuclear RNAs (snRNAs) in a sequence-unspecific manner and
CC phosphorylation-independent manner (By similarity). Also plays a role
CC in the biogenesis of U3 small nucleolar RNA (snoRNA). Involved in the
CC U3 snoRNA transport from nucleoplasm to Cajal bodies. Binds strongly to
CC m7G-capped U3, U8 and U13 precursor snoRNAs and weakly to trimethylated
CC (TMG)-capped U3, U8 and U13 snoRNAs. Binds also to telomerase RNA.
CC {ECO:0000250, ECO:0000269|PubMed:15574332,
CC ECO:0000269|PubMed:15574333}.
CC -!- SUBUNIT: Found in a U snRNA export complex with PHAX/RNUXA,
CC NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Part of a
CC precomplex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20 and m7G-capped
CC RNA. Interacts with NCBP1/CBP80 (By similarity). Found in a complex
CC with snoRNA. Interacts with NCBP2/CBP20 (PubMed:26382858).
CC {ECO:0000250|UniProtKB:Q9JJT9, ECO:0000269|PubMed:15574333,
CC ECO:0000269|PubMed:26382858}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:11333016, ECO:0000269|PubMed:15574332}. Nucleus,
CC Cajal body {ECO:0000269|PubMed:15574332}. Cytoplasm
CC {ECO:0000269|PubMed:11333016}. Note=Located in the nucleoplasm and
CC Cajal bodies. Shuttles between the nucleus and the cytoplasm. Shuttles
CC between the nucleoplasm and Cajal bodies. {ECO:0000269|PubMed:11333016,
CC ECO:0000269|PubMed:15574332}.
CC -!- PTM: Phosphorylated in the nucleus. Dephosphorylated in the cytoplasm
CC (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PHAX family. {ECO:0000305}.
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DR EMBL; AK023255; BAB14489.1; -; mRNA.
DR EMBL; AK024065; BAB14809.1; -; mRNA.
DR EMBL; CR457305; CAG33586.1; -; mRNA.
DR EMBL; BC021161; AAH21161.1; -; mRNA.
DR CCDS; CCDS4138.1; -.
DR RefSeq; NP_115553.2; NM_032177.3.
DR PDB; 2XC7; NMR; -; A=223-323.
DR PDBsum; 2XC7; -.
DR AlphaFoldDB; Q9H814; -.
DR SMR; Q9H814; -.
DR BioGRID; 119734; 138.
DR CORUM; Q9H814; -.
DR IntAct; Q9H814; 46.
DR MINT; Q9H814; -.
DR STRING; 9606.ENSP00000297540; -.
DR TCDB; 9.A.60.1.1; the small nuclear rna exporter (snrna-e).
DR GlyGen; Q9H814; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H814; -.
DR PhosphoSitePlus; Q9H814; -.
DR BioMuta; PHAX; -.
DR DMDM; 74752718; -.
DR EPD; Q9H814; -.
DR jPOST; Q9H814; -.
DR MassIVE; Q9H814; -.
DR MaxQB; Q9H814; -.
DR PaxDb; Q9H814; -.
DR PeptideAtlas; Q9H814; -.
DR PRIDE; Q9H814; -.
DR ProteomicsDB; 81168; -.
DR Antibodypedia; 45036; 202 antibodies from 27 providers.
DR DNASU; 51808; -.
DR Ensembl; ENST00000297540.5; ENSP00000297540.4; ENSG00000164902.14.
DR GeneID; 51808; -.
DR KEGG; hsa:51808; -.
DR MANE-Select; ENST00000297540.5; ENSP00000297540.4; NM_032177.4; NP_115553.2.
DR UCSC; uc003kua.3; human.
DR CTD; 51808; -.
DR DisGeNET; 51808; -.
DR GeneCards; PHAX; -.
DR HGNC; HGNC:10241; PHAX.
DR HPA; ENSG00000164902; Low tissue specificity.
DR MIM; 604924; gene.
DR neXtProt; NX_Q9H814; -.
DR OpenTargets; ENSG00000164902; -.
DR PharmGKB; PA164724444; -.
DR VEuPathDB; HostDB:ENSG00000164902; -.
DR eggNOG; KOG3948; Eukaryota.
DR GeneTree; ENSGT00390000011084; -.
DR HOGENOM; CLU_058840_1_0_1; -.
DR InParanoid; Q9H814; -.
DR OMA; EEGCIKK; -.
DR OrthoDB; 1223195at2759; -.
DR PhylomeDB; Q9H814; -.
DR TreeFam; TF321050; -.
DR PathwayCommons; Q9H814; -.
DR Reactome; R-HSA-191859; snRNP Assembly.
DR Reactome; R-HSA-6807505; RNA polymerase II transcribes snRNA genes.
DR SignaLink; Q9H814; -.
DR BioGRID-ORCS; 51808; 741 hits in 1081 CRISPR screens.
DR ChiTaRS; PHAX; human.
DR GeneWiki; RNUXA; -.
DR GenomeRNAi; 51808; -.
DR Pharos; Q9H814; Tbio.
DR PRO; PR:Q9H814; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9H814; protein.
DR Bgee; ENSG00000164902; Expressed in buccal mucosa cell and 195 other tissues.
DR Genevisible; Q9H814; HS.
DR GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:FlyBase.
DR GO; GO:0140262; F:mRNA cap binding complex binding; IDA:FlyBase.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0015643; F:toxic substance binding; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0043489; P:RNA stabilization; IMP:FlyBase.
DR GO; GO:0006408; P:snRNA export from nucleus; IBA:GO_Central.
DR Gene3D; 1.10.10.1440; -; 1.
DR InterPro; IPR039047; PHAX.
DR InterPro; IPR019385; PHAX_RNA-binding_domain.
DR InterPro; IPR038092; PHAX_RNA-binding_sf.
DR PANTHER; PTHR13135; PTHR13135; 1.
DR Pfam; PF10258; RNA_GG_bind; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; RNA-binding; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT CHAIN 2..394
FT /note="Phosphorylated adapter RNA export protein"
FT /id="PRO_0000239775"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..329
FT /note="Necessary for interaction with CBP80"
FT /evidence="ECO:0000250"
FT REGION 83..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 183..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..328
FT /note="Sufficient for poly U RNA-binding"
FT REGION 279..287
FT /note="Necessary for poly U RNA-binding and snRNA export"
FT /evidence="ECO:0000250"
FT MOTIF 81..84
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 130..139
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 198..201
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 183..198
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63068"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63068"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63068"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63068"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63068"
FT MOD_RES 296
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 82
FT /note="R -> C (in dbSNP:rs3734173)"
FT /id="VAR_051871"
FT CONFLICT 141
FT /note="G -> A (in Ref. 1; BAB14489)"
FT /evidence="ECO:0000305"
FT CONFLICT 346
FT /note="D -> A (in Ref. 1; BAB14489)"
FT /evidence="ECO:0000305"
FT HELIX 227..237
FT /evidence="ECO:0007829|PDB:2XC7"
FT HELIX 243..253
FT /evidence="ECO:0007829|PDB:2XC7"
FT HELIX 255..271
FT /evidence="ECO:0007829|PDB:2XC7"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:2XC7"
FT HELIX 285..295
FT /evidence="ECO:0007829|PDB:2XC7"
FT HELIX 301..308
FT /evidence="ECO:0007829|PDB:2XC7"
SQ SEQUENCE 394 AA; 44403 MW; 3513FA5081C6F7CA CRC64;
MALEVGDMED GQLSDSDSDM TVAPSDRPLQ LPKVLGGDSA MRAFQNTATA CAPVSHYRAV
ESVDSSEESF SDSDDDSCLW KRKRQKCFNP PPKPEPFQFG QSSQKPPVAG GKKINNIWGA
VLQEQNQDAV ATELGILGME GTIDRSRQSE TYNYLLAKKL RKESQEHTKD LDKELDEYMH
GGKKMGSKEE ENGQGHLKRK RPVKDRLGNR PEMNYKGRYE ITAEDSQEKV ADEISFRLQE
PKKDLIARVV RIIGNKKAIE LLMETAEVEQ NGGLFIMNGS RRRTPGGVFL NLLKNTPSIS
EEQIKDIFYI ENQKEYENKK AARKRRTQVL GKKMKQAIKS LNFQEDDDTS RETFASDTNE
ALASLDESQE GHAEAKLEAE EAIEVDHSHD LDIF
