Q9C0E2 (XPO4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Exportin-4
Short name=Exp4

Gene names

Name:	XPO4
Synonyms:	KIAA1721

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1151 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the nuclear export of proteins (cargos) with broad substrate specificity. In the nucleus binds cooperatively to its cargo and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. XPO4 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Ref.5 Ref.7
Subunit structure	Found in a complex with XPO4, Ran and EIF5A. Found in a complex with XPO4, Ran and SMAD3. Interacts with SMAD3. Interacts with Ran and cargo proteins in a GTP-dependent manner. Ref.5 Ref.7
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between the nucleus and the cytoplasm. Ref.7
Sequence similarities	Belongs to the exportin family.
Sequence caution	The sequence BAB14409.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of protein export from nucleus Inferred from mutant phenotype Ref.7. Source: BHF-UCL protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1151	1151	Exportin-4		PRO_0000204711
Amino acid modifications
	Modified residue	464	1	Phosphoserine Ref.8 Ref.9
	Modified residue	521	1	Phosphoserine Ref.6 Ref.8 Ref.10 Ref.11 Ref.13
Natural variations
	Natural variant	149	1	N → S. Corresponds to variant rs17320607 [ dbSNP | Ensembl ].		VAR_048958
	Natural variant	451	1	T → A. Corresponds to variant rs9552285 [ dbSNP | Ensembl ].		VAR_048959
Experimental info
	Sequence conflict	511	1	L → S in BAB14409. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9C0E2 [UniParc]. Last modified November 2, 2001. Version 2. Checksum: 38E7EEFC938B07C5	FASTA	1,151	130,139
	10 20 30 40 50 60 MMAAALGPPE VIAQLENAAK VLMAPPSMVN NEQRQHAEHI FLSFRKSKSP FAVCKHILET 70 80 90 100 110 120 SKVDYVLFQA ATAIMEAVVR EWILLEKGSI ESLRTFLLTY VLQRPNLQKY VREQILLAVA 130 140 150 160 170 180 VIVKRGSLDK SIDCKSIFHE VSQLISSGNP TVQTLACSIL TALLSEFSSS SKTSNIGLSM 190 200 210 220 230 240 EFHGNCKRVF QEEDLRQIFM LTVEVLQEFS RRENLNAQMS SVFQRYLALA NQVLSWNFLP 250 260 270 280 290 300 PNLGRHYIAM FESSQNVLLK PTESWRETLL DSRVMELFFT VHRKIREDSD MAQDSLQCLA 310 320 330 340 350 360 QLASLHGPIF PDEGSQVDYL AHFIEGLLNT INGIEIEDSE AVGISSIISN LITVFPRNVL 370 380 390 400 410 420 TAIPSELFSS FVNCLTHLTC SFGRSAALEE VLDKDDMVYM EAYDKLLESW LTLVQDDKHF 430 440 450 460 470 480 HKGFFTQHAV QVFNSYIQCH LAAPDGTRNL TANGVASREE EEISELQEDD RDQFSDQLAS 490 500 510 520 530 540 VGMLGRIAAE HCIPLLTSLL EERVTRLHGQ LQRHQQQLLA SPGSSTVDNK MLDDLYEDIH 550 560 570 580 590 600 WLILVTGYLL ADDTQGETPL IPPEIMEYSI KHSSEVDINT TLQILGSPGE KASSIPGYNR 610 620 630 640 650 660 TDSVIRLLSA ILRVSEVESR AIRADLTHLL SPQMGKDIVW FLKRWAKTYL LVDEKLYDQI 670 680 690 700 710 720 SLPFSTAFGA DTEGSQWIIG YLLQKVISNL SVWSSEQDLA NDTVQLLVTL VERRERANLV 730 740 750 760 770 780 IQCENWWNLA KQFASRSPPL NFLSSPVQRT LMKALVLGGF AHMDTETKQQ YWTEVLQPLQ 790 800 810 820 830 840 QRFLRVINQE NFQQMCQQEE VKQEITATLE ALCGIAEATQ IDNVAILFNF LMDFLTNCIG 850 860 870 880 890 900 LMEVYKNTPE TVNLIIEVFV EVAHKQICYL GESKAMNLYE ACLTLLQVYS KNNLGRQRID 910 920 930 940 950 960 VTAEEEQYQD LLLIMELLTN LLSKEFIDFS DTDEVFRGHE PGQAANRSVS AADVVLYGVN 970 980 990 1000 1010 1020 LILPLMSQDL LKFPTLCNQY YKLITFICEI FPEKIPQLPE DLFKSLMYSL ELGMTSMSSE 1030 1040 1050 1060 1070 1080 VCQLCLEALT PLAEQCAKAQ ETDSPLFLAT RHFLKLVFDM LVLQKHNTEM TTAAGEAFYT 1090 1100 1110 1120 1130 1140 LVCLHQAEYS ELVETLLSSQ QDPVIYQRLA DAFNKLTASS TPPTLDRKQK MAFLKSLEEF 1150 MANVGGLLCV K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O. DNA Res. 7:347-355(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 337-1151.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 888-1151. Tissue: Skeletal muscle.
[5]	"Exportin 4: a mediator of a novel nuclear export pathway in higher eukaryotes." Lipowsky G., Bischoff F.R., Schwarzmaier P., Kraft R., Kostka S., Hartmann E., Kutay U., Goerlich D. EMBO J. 19:4362-4371(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION IN NUCLEAR PROTEIN EXPORT, IDENTIFICATION IN A COMPLEX WITH RAN AND EIF5A.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"The mechanism of nuclear export of Smad3 involves exportin 4 and Ran." Kurisaki A., Kurisaki K., Kowanetz M., Sugino H., Yoneda Y., Heldin C.-H., Moustakas A. Mol. Cell. Biol. 26:1318-1332(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NUCLEAR PROTEIN EXPORT, IDENTIFICATION IN A COMPLEX WITH RAN AND SMAD3, INTERACTION WITH SMAD3, SUBCELLULAR LOCATION.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-464 AND SER-521, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-464, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB051508 mRNA. Translation: BAB21812.1. AL512652, AL356285 Genomic DNA. Translation: CAH71795.1. AL356285, AL512652 Genomic DNA. Translation: CAI15862.1. AK023108 mRNA. Translation: BAB14409.1. Different initiation. AL831819 mRNA. Translation: CAD38533.2.
IPI	IPI00028357.
RefSeq	NP_071904.4. NM_022459.4.
UniGene	Hs.744023.
3D structure databases
ProteinModelPortal	Q9C0E2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9C0E2. 1 interaction.
STRING	9606.ENSP00000255305.
PTM databases
PhosphoSite	Q9C0E2.
Polymorphism databases
DMDM	17368720.
Proteomic databases
PaxDb	Q9C0E2.
PRIDE	Q9C0E2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000255305; ENSP00000255305; ENSG00000132953.
GeneID	64328.
KEGG	hsa:64328.
UCSC	uc001unq.4. human.
Organism-specific databases
CTD	64328.
GeneCards	GC13M021351.
H-InvDB	HIX0011162.
HGNC	HGNC:17796. XPO4.
MIM	611449. gene.
neXtProt	NX_Q9C0E2.
PharmGKB	PA134866468.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG273883.
HOGENOM	HOG000154878.
HOVERGEN	HBG023214.
OMA	CKRIFQE.
OrthoDB	EOG4Z36CX.
Gene expression databases
ArrayExpress	Q9C0E2.
Bgee	Q9C0E2.
CleanEx	HS_XPO4.
Genevestigator	Q9C0E2.
GermOnline	ENSG00000132953. Homo sapiens.
Family and domain databases
InterPro	IPR016024. ARM-type_fold. IPR014877. CRM1_C_dom. [Graphical view]
Pfam	PF08767. CRM1_C. 1 hit. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	64328.
NextBio	66257.
SOURCE	Search...

Entry information

Entry name

XPO4_HUMAN

Accession

Primary (citable) accession number: Q9C0E2
Secondary accession number(s): Q5VUZ5, Q8N3V6, Q9H934

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 2, 2001
Last sequence update:	November 2, 2001
Last modified:	May 29, 2013
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.