Q92738 (US6NL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
USP6 N-terminal-like protein

Alternative name(s):
Related to the N-terminus of tre
Short name=RN-tre

Gene names

Name:	USP6NL
Synonyms:	KIAA0019

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	828 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a GTPase-activating protein for RAB5A. Involved in receptor trafficking. In complex with EPS8 inhibits internalization of EGFR. Ref.9
Subunit structure	Interacts with EPS8. Ref.1
Tissue specificity	Widely expressed. Ref.1
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Sequence similarities	Contains 1 Rab-GAP TBC domain.
Sequence caution	The sequence BAA02807.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular function	Rab GTPase activator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q92738-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q92738-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: MN → MRTEAVVNSQGQTDYLTKD

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 828	828	USP6 N-terminal-like protein		PRO_0000208056
Regions
	Domain	100 – 292	193	Rab-GAP TBC
Amino acid modifications
	Modified residue	391	1	Phosphoserine Ref.13
	Modified residue	396	1	Phosphoserine Ref.13
	Modified residue	546	1	Phosphoserine By similarity
	Modified residue	582	1	Phosphotyrosine Ref.10
	Modified residue	585	1	Phosphoserine Ref.10
	Modified residue	617	1	Phosphoserine Ref.12
	Modified residue	673	1	Phosphoserine By similarity
	Modified residue	680	1	Phosphoserine Ref.11
	Modified residue	710	1	Phosphotyrosine Ref.10
	Modified residue	716	1	Phosphoserine Ref.10 Ref.13 Ref.14 Ref.15
	Modified residue	729	1	Phosphotyrosine Ref.10
Natural variations
	Alternative sequence	1 – 2	2	MN → MRTEAVVNSQGQTDYLTKD in isoform 2.		VSP_040850
Experimental info
	Mutagenesis	106	1	R → A: Loss of GAP activity on RAB5A. Ref.9
	Mutagenesis	147	1	D → A: Loss of GAP activity on RAB5A. Ref.9
	Mutagenesis	150	1	R → A: Loss of GAP activity on RAB5A. Ref.9
	Sequence conflict	622	1	E → D in BAF85633. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 30, 2004. Version 3. Checksum: A5E3DBF0FEE04E78	FASTA	828	94,104
	10 20 30 40 50 60 MNSDQDVALK LAQERAEIVA KYDRGREGAE IEPWEDADYL VYKVTDRFGF LHEEELPDHN 70 80 90 100 110 120 VAVERQKHLE IERTTKWLKM LKGWEKYKNT EKFHRRIYKG IPLQLRGEVW ALLLEIPKMK 130 140 150 160 170 180 EETRDLYSKL KHRARGCSPD IRQIDLDVNR TFRDHIMFRD RYGVKQQSLF HVLAAYSIYN 190 200 210 220 230 240 TEVGYCQGMS QITALLLMYM NEEDAFWALV KLFSGPKHAM HGFFVQGFPK LLRFQEHHEK 250 260 270 280 290 300 ILNKFLSKLK QHLDSQEIYT SFYTMKWFFQ CFLDRTPFTL NLRIWDIYIF EGERVLTAMS 310 320 330 340 350 360 YTILKLHKKH LMKLSMEELV EFFQETLAKD FFFEDDFVIE QLQISMTELK RAKLDLPEPG 370 380 390 400 410 420 KEDEYPKKPL GQLPPELQSW GVHHLSNGQR SVGRPSPLAS GRRESGAPHR RHEHSPHPQS 430 440 450 460 470 480 RTGTPERAQP PRRKSVEEES KKLKDEADFQ RKLPSGPQDS SRQYNHAAAN QNSNATSNIR 490 500 510 520 530 540 KEFVPKWNKP SDVSATERTA KYTMEGKGRA AHPALAVTVP GPAEVRVSNV RPKMKALDAE 550 560 570 580 590 600 DGKRGSTASQ YDNVPGPELD SGASVEEALE RAYSQSPRHA LYPPSPRKHA EPSSSPSKVS 610 620 630 640 650 660 NKFTFKVQPP SHARYPSQLD GEARGLAHPP SYSNPPVYHG NSPKHFPTAN SSFASPQFSP 670 680 690 700 710 720 GTQLNPSRRP HGSTLSVSAS PEKSYSRPSP LVLPSSRIEV LPVDTGAGGY SGNSGSPKNG 730 740 750 760 770 780 KLIIPPVDYL PDNRTWSEVS YTYRPETQGQ SWTRDASRGN LPKYSAFQLA PFQDHGLPAV 790 800 810 820 SVDSPVRYKA SPAAEDASPS GYPYSGPPPP AYHYRNRDGL SIQESVLL
	Isoform 2 [UniParc]. Checksum: 3C174D986C902346	FASTA	845	95,997
	10 20 30 40 50 60 MRTEAVVNSQ GQTDYLTKDS DQDVALKLAQ ERAEIVAKYD RGREGAEIEP WEDADYLVYK 70 80 90 100 110 120 VTDRFGFLHE EELPDHNVAV ERQKHLEIER TTKWLKMLKG WEKYKNTEKF HRRIYKGIPL 130 140 150 160 170 180 QLRGEVWALL LEIPKMKEET RDLYSKLKHR ARGCSPDIRQ IDLDVNRTFR DHIMFRDRYG 190 200 210 220 230 240 VKQQSLFHVL AAYSIYNTEV GYCQGMSQIT ALLLMYMNEE DAFWALVKLF SGPKHAMHGF 250 260 270 280 290 300 FVQGFPKLLR FQEHHEKILN KFLSKLKQHL DSQEIYTSFY TMKWFFQCFL DRTPFTLNLR 310 320 330 340 350 360 IWDIYIFEGE RVLTAMSYTI LKLHKKHLMK LSMEELVEFF QETLAKDFFF EDDFVIEQLQ 370 380 390 400 410 420 ISMTELKRAK LDLPEPGKED EYPKKPLGQL PPELQSWGVH HLSNGQRSVG RPSPLASGRR 430 440 450 460 470 480 ESGAPHRRHE HSPHPQSRTG TPERAQPPRR KSVEEESKKL KDEADFQRKL PSGPQDSSRQ 490 500 510 520 530 540 YNHAAANQNS NATSNIRKEF VPKWNKPSDV SATERTAKYT MEGKGRAAHP ALAVTVPGPA 550 560 570 580 590 600 EVRVSNVRPK MKALDAEDGK RGSTASQYDN VPGPELDSGA SVEEALERAY SQSPRHALYP 610 620 630 640 650 660 PSPRKHAEPS SSPSKVSNKF TFKVQPPSHA RYPSQLDGEA RGLAHPPSYS NPPVYHGNSP 670 680 690 700 710 720 KHFPTANSSF ASPQFSPGTQ LNPSRRPHGS TLSVSASPEK SYSRPSPLVL PSSRIEVLPV 730 740 750 760 770 780 DTGAGGYSGN SGSPKNGKLI IPPVDYLPDN RTWSEVSYTY RPETQGQSWT RDASRGNLPK 790 800 810 820 830 840 YSAFQLAPFQ DHGLPAVSVD SPVRYKASPA AEDASPSGYP YSGPPPPAYH YRNRDGLSIQ ESVLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"RN-tre identifies a family of tre-related proteins displaying a novel potential protein binding domain." Wong W.T., Seki N., Nagase T., Nomura N., Robbins K.C., Di Fiore P.P., Matoskova B. Oncogene 12:2563-2571(1996) [PubMed: 8700515] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH EPS8.
[2]	"Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC) protein that possesses Rab3A-GAP activity." Ishibashi K., Kanno E., Itoh T., Fukuda M. Genes Cells 14:41-52(2009) [PubMed: 19077034] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1." Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S. DNA Res. 1:27-35(1994) [PubMed: 7584026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Trachea.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[8]	"Normalization and subtraction: two approaches to facilitate gene discovery." Bonaldo M.F., Lennon G., Soares M.B. Genome Res. 6:791-806(1996) [PubMed: 8889548] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-202 (ISOFORM 2).
[9]	"The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5." Lanzetti L., Rybin V., Malabarba M.G., Christoforidis S., Scita G., Zerial M., Di Fiore P.P. Nature 408:374-377(2000) [PubMed: 11099046] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ARG-106; ASP-147 AND ARG-150.
[10]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-582; SER-585; TYR-710; SER-716 AND TYR-729, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-680, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-391; SER-396 AND SER-716, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-716, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[15]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-716, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB449916 mRNA. Translation: BAH16659.1. D13644 mRNA. Translation: BAA02807.2. Different initiation. AK292944 mRNA. Translation: BAF85633.1. AL512631, AL590416 Genomic DNA. Translation: CAH70484.1. AL590416, AL512631 Genomic DNA. Translation: CAI16966.1. CH471072 Genomic DNA. Translation: EAW86344.1. BC042943 mRNA. Translation: AAH42943.1. CF121539 mRNA. No translation available.
IPI	IPI00400875. IPI00921527.
RefSeq	NP_001073960.1. NM_001080491.2. NP_055503.1. NM_014688.2.
UniGene	Hs.498661.
3D structure databases
ProteinModelPortal	Q92738.
SMR	Q92738. Positions 72-341.
ModBase	Search...
Protein-protein interaction databases
STRING	Q92738.
PTM databases
PhosphoSite	Q92738.
Polymorphism databases
DMDM	50897492.
Proteomic databases
PRIDE	Q92738.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379237; ENSP00000368539; ENSG00000148429.
GeneID	9712.
KEGG	hsa:9712.
UCSC	uc001ikt.2. human.
Organism-specific databases
CTD	9712.
GeneCards	GC10M011542.
H-InvDB	HIX0008637.
HGNC	HGNC:16858. USP6NL.
HPA	HPA039196.
MIM	605405. gene.
neXtProt	NX_Q92738.
PharmGKB	PA134955568.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08583.
GeneTree	ENSGT00550000074322.
HOVERGEN	HBG059159.
InParanoid	Q92738.
OMA	HGNSPKH.
OrthoDB	EOG4NKBVT.
PhylomeDB	Q92738.
Gene expression databases
ArrayExpress	Q92738.
Bgee	Q92738.
CleanEx	HS_USP6NL.
Genevestigator	Q92738.
GermOnline	ENSG00000148429. Homo sapiens.
Family and domain databases
InterPro	IPR000195. RabGAP/TBC_dom. [Graphical view]
Pfam	PF00566. TBC. 1 hit. [Graphical view]
SMART	SM00164. TBC. 1 hit. [Graphical view]
SUPFAM	SSF47923. RabGAP_TBC. 2 hits.
PROSITE	PS50086. TBC_RABGAP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

US6NL_HUMAN

Accession

Primary (citable) accession number: Q92738
Secondary accession number(s): A8KA79 , Q15400, Q5VV10, Q7L0K9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 30, 2004
Last sequence update:	July 30, 2004
Last modified:	January 25, 2012
This is version 88 of the entry and version 3 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.