Q96T51 (RUFY1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RUN and FYVE domain-containing protein 1

Alternative name(s):
FYVE-finger protein EIP1
La-binding protein 1
Rab4-interacting protein
Zinc finger FYVE domain-containing protein 12

Gene names

Name:	RUFY1
Synonyms:	RABIP4, ZFYVE12

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	708 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in early endosomal trafficking. Ref.1
Subunit structure	Interacts with BMX. May interact with SSB. Interacts with RAB4 and RAB5 that have been activated by GTP-binding. Ref.1 Ref.4
Subcellular location	Cytoplasm. Early endosome membrane; Peripheral membrane protein Ref.1 Ref.4.
Tissue specificity	Broadly expressed, with highest levels in lung, testis, kidney and brain. Ref.4
Domain	The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns3P-enriched membranes is substantially increased in acidic conditions. Ref.6
Post-translational modification	Phosphorylation on Tyr-389 and/or Tyr-400 is required for interaction with BMX and endosomal targeting.
Sequence similarities	Contains 1 FYVE-type zinc finger. Contains 1 RUN domain.
Sequence caution	The sequence AAK50771.1 differs from that shown. Reason: Frameshift at positions 47 and 88. The sequence BAB15276.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Endocytosis Protein transport Transport
Cellular component	Cytoplasm Endosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	Lipid-binding Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW regulation of endocytosis Inferred from electronic annotation. Source: Compara
Cellular_component	early endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	lipid binding Inferred from electronic annotation. Source: UniProtKB-KW protein transporter activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PIAS2	O75928	3	EBI-3941207,EBI-348555

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96T51-1)

Also known as: rabip4';

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: Q96T51-2)

Also known as: rabip4;

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Isoform 3 (identifier: Q96T51-3)

The sequence of this isoform differs from the canonical sequence as follows:
     343-412: LSAATDRICS...VWKQLKEEKK → EERMKGQDKG...RRTAAVKRTK
     413-708: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 708

708

RUN and FYVE domain-containing protein 1

PRO_0000097530

Regions

Domain

139 – 271

133

RUN

Zinc finger

642 – 700

59

FYVE-type

Region

615 – 625

11

Interaction with RAB4 By similarity

Coiled coil

321 – 374

54

Potential

Coiled coil

405 – 617

213

Potential

Amino acid modifications

Modified residue

389

1

Phosphotyrosine Ref.4

Modified residue

400

1

Phosphotyrosine Ref.4

Natural variations

Alternative sequence

1 – 108

108

Missing in isoform 2.

VSP_019785

Alternative sequence

343 – 412

70

LSAAT…KEEKK → EERMKGQDKGGLSRGRELAA SCPAVSLLDTSCLLLAGGGC SALLRLSTAFSCNRPNLLTS RRTAAVKRTK in isoform 3.

VSP_019786

Alternative sequence

413 – 708

296

Missing in isoform 3.

VSP_019787

Natural variant

267

1

C → F in a breast cancer sample; somatic mutation. Ref.9

VAR_035985

Natural variant

298

1

H → Q.
Corresponds to variant rs6879322 [ dbSNP | Ensembl ].

VAR_051327

Experimental info

Mutagenesis

389

1

Y → F: Abolishes phosphorylation and endosomal targeting; when associated with F-400. Ref.4

Mutagenesis

400

1

Y → F: Abolishes phosphorylation and endosomal targeting; when associated with F-389. Ref.4

Sequence conflict

519 – 528

10

SHKLQQELGG → TTSCSRSWAV in AAQ14554. Ref.1

Sequence conflict

570

1

D → N in AAQ14554. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

708

Helix Strand Turn

Details...

Turn

649 – 651

3

Beta strand

657 – 659

3

Beta strand

661 – 663

3

Turn

665 – 667

3

Beta strand

670 – 672

3

Helix

674 – 676

3

Beta strand

678 – 680

3

Beta strand

683 – 687

5

Beta strand

689 – 691

3

Helix

693 – 698

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (rabip4') [UniParc]. Last modified July 11, 2006. Version 2. Checksum: 6697B4BC108AD54F	FASTA	708	79,818
	10 20 30 40 50 60 MADREGGCAA GRGRELEPEL EPGPGPGSAL EPGEEFEIVD RSQLPGPGDL RSATRPRAAE 70 80 90 100 110 120 GWSAPILTLA RRATGNLSAS CGSALRAAAG LGGGDSGDGT ARAASKCQMM EERANLMHMM 130 140 150 160 170 180 KLSIKVLLQS ALSLGRSLDA DHAPLQQFFV VMEHCLKHGL KVKKSFIGQN KSFFGPLELV 190 200 210 220 230 240 EKLCPEASDI ATSVRNLPEL KTAVGRGRAW LYLALMQKKL ADYLKVLIDN KHLLSEFYEP 250 260 270 280 290 300 EALMMEEEGM VIVGLLVGLN VLDANLCLKG EDLDSQVGVI DFSLYLKDVQ DLDGGKEHER 310 320 330 340 350 360 ITDVLDQKNY VEELNRHLSC TVGDLQTKID GLEKTNSKLQ EELSAATDRI CSLQEEQQQL 370 380 390 400 410 420 REQNELIRER SEKSVEITKQ DTKVELETYK QTRQGLDEMY SDVWKQLKEE KKVRLELEKE 430 440 450 460 470 480 LELQIGMKTE MEIAMKLLEK DTHEKQDTLV ALRQQLEEVK AINLQMFHKA QNAESSLQQK 490 500 510 520 530 540 NEAITSFEGK TNQVMSSMKQ MEERLQHSER ARQGAEERSH KLQQELGGRI GALQLQLSQL 550 560 570 580 590 600 HEQCSSLEKE LKSEKEQRQA LQRELQHEKD TSSLLRMELQ QVEGLKKELR ELQDEKAELQ 610 620 630 640 650 660 KICEEQEQAL QEMGLHLSQS KLKMEDIKEV NQALKGHAWL KDDEATHCRQ CEKEFSISRR 670 680 690 700 KHHCRNCGHI FCNTCSSNEL ALPSYPKPVR VCDSCHTLLL QRCSSTAS
	Isoform 2 (rabip4) [UniParc]. Checksum: 44EEEB383C18FC47	FASTA	600	69,078
	10 20 30 40 50 60 MMEERANLMH MMKLSIKVLL QSALSLGRSL DADHAPLQQF FVVMEHCLKH GLKVKKSFIG 70 80 90 100 110 120 QNKSFFGPLE LVEKLCPEAS DIATSVRNLP ELKTAVGRGR AWLYLALMQK KLADYLKVLI 130 140 150 160 170 180 DNKHLLSEFY EPEALMMEEE GMVIVGLLVG LNVLDANLCL KGEDLDSQVG VIDFSLYLKD 190 200 210 220 230 240 VQDLDGGKEH ERITDVLDQK NYVEELNRHL SCTVGDLQTK IDGLEKTNSK LQEELSAATD 250 260 270 280 290 300 RICSLQEEQQ QLREQNELIR ERSEKSVEIT KQDTKVELET YKQTRQGLDE MYSDVWKQLK 310 320 330 340 350 360 EEKKVRLELE KELELQIGMK TEMEIAMKLL EKDTHEKQDT LVALRQQLEE VKAINLQMFH 370 380 390 400 410 420 KAQNAESSLQ QKNEAITSFE GKTNQVMSSM KQMEERLQHS ERARQGAEER SHKLQQELGG 430 440 450 460 470 480 RIGALQLQLS QLHEQCSSLE KELKSEKEQR QALQRELQHE KDTSSLLRME LQQVEGLKKE 490 500 510 520 530 540 LRELQDEKAE LQKICEEQEQ ALQEMGLHLS QSKLKMEDIK EVNQALKGHA WLKDDEATHC 550 560 570 580 590 600 RQCEKEFSIS RRKHHCRNCG HIFCNTCSSN ELALPSYPKP VRVCDSCHTL LLQRCSSTAS
	Isoform 3 [UniParc]. Checksum: DB0F4DA2BD8EEA83	FASTA	412	44,489
	10 20 30 40 50 60 MADREGGCAA GRGRELEPEL EPGPGPGSAL EPGEEFEIVD RSQLPGPGDL RSATRPRAAE 70 80 90 100 110 120 GWSAPILTLA RRATGNLSAS CGSALRAAAG LGGGDSGDGT ARAASKCQMM EERANLMHMM 130 140 150 160 170 180 KLSIKVLLQS ALSLGRSLDA DHAPLQQFFV VMEHCLKHGL KVKKSFIGQN KSFFGPLELV 190 200 210 220 230 240 EKLCPEASDI ATSVRNLPEL KTAVGRGRAW LYLALMQKKL ADYLKVLIDN KHLLSEFYEP 250 260 270 280 290 300 EALMMEEEGM VIVGLLVGLN VLDANLCLKG EDLDSQVGVI DFSLYLKDVQ DLDGGKEHER 310 320 330 340 350 360 ITDVLDQKNY VEELNRHLSC TVGDLQTKID GLEKTNSKLQ EEEERMKGQD KGGLSRGREL 370 380 390 400 410 AASCPAVSLL DTSCLLLAGG GCSALLRLST AFSCNRPNLL TSRRTAAVKR TK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Rabip4' is an effector of rab5 and rab4 and regulates transport through early endosomes." Fouraux M.A., Deneka M., Ivan V., van der Heijden A., Raymackers J., van Suylekom D., van Venrooij W.J., van der Sluijs P., Pruijn G.J.M. Mol. Biol. Cell 15:611-624(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SSB; RAB4 AND RAB5, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, FUNCTION.
[2]	"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] (ISOFORM 2).
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Interaction between tyrosine kinase Etk and a RUN-domain and FYVE-domain containing protein RUFY1. A possible role of Etk in regulation of vesicle trafficking." Yang J., Kim O., Wu J., Qiu Y. J. Biol. Chem. 277:30219-30226(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-708 (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH BMX, PHOSPHORYLATION AT TYR-389 AND TYR-400, MUTAGENESIS OF TYR-389 AND TYR-400.
[5]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 90-708 (ISOFORM 3). Tissue: Brain.
[6]	"Membrane insertion of the FYVE domain is modulated by pH." He J., Vora M., Haney R.M., Filonov G.S., Musselman C.A., Burd C.G., Kutateladze A.G., Verkhusha V.V., Stahelin R.V., Kutateladze T.G. Proteins 76:852-860(2009) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN FYVE-TYPE ZINC FINGER.
[7]	"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].
[8]	"Solution structure of the FYVE domain in zinc finger FYVE domain-containing protein 12." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 627-708.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-267.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF312367 mRNA. Translation: AAQ14554.1.
AK025904 mRNA. Translation: BAB15276.1. Different initiation.
AK075021 mRNA. No translation available.
BC032571 mRNA. Translation: AAH32571.1.
AF361055 mRNA. Translation: AAK50771.1. Frameshift.
AB209507 mRNA. Translation: BAD92744.1.

IPI

IPI00465429.
IPI00556586.
IPI00744637.

RefSeq

NP_001035541.1. NM_001040451.2.
NP_001035542.1. NM_001040452.2.
NP_079434.3. NM_025158.4.

UniGene

Hs.306769.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YQM	NMR	-	A	627-708	[»]
2YW8	X-ray	3.00	A	627-708	[»]

ProteinModelPortal

Q96T51.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96T51. 2 interactions.

STRING

9606.ENSP00000377094.

PTM databases

PhosphoSite

Q96T51.

Polymorphism databases

DMDM

110282993.

Proteomic databases

PaxDb

Q96T51.

PRIDE

Q96T51.

Protocols and materials databases

DNASU

80230.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000319449; ENSP00000325594; ENSG00000176783.
ENST00000377001; ENSP00000366200; ENSG00000176783.
ENST00000393438; ENSP00000377087; ENSG00000176783.
ENST00000437570; ENSP00000390025; ENSG00000176783.

GeneID

80230.

KEGG

hsa:80230.

UCSC

uc003mka.1. human.

Organism-specific databases

CTD

80230.

GeneCards

GC05P178977.

HGNC

HGNC:19760. RUFY1.

HPA

HPA038804.

MIM

610327. gene.

neXtProt

NX_Q96T51.

PharmGKB

PA134944787.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG270133.

HOVERGEN

HBG057053.

InParanoid

Q96T51.

KO

K12482.

OMA

AITSFEG.

Gene expression databases

Bgee

Q96T51.

CleanEx

HS_RUFY1.

Genevestigator

Q96T51.

GermOnline

ENSG00000176783. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR004012. Run.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Pfam

PF01363. FYVE. 1 hit.
PF02759. RUN. 1 hit.
[Graphical view]

SMART

SM00064. FYVE. 1 hit.
SM00593. RUN. 1 hit.
[Graphical view]

SUPFAM

SSF57903. FYVE_PHD_ZnF. 1 hit.

PROSITE

PS50826. RUN. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

RUFY1. human.

EvolutionaryTrace

Q96T51.

GenomeRNAi

80230.

NextBio

70661.

SOURCE

Search...

Entry information

Entry name

RUFY1_HUMAN

Accession

Primary (citable) accession number: Q96T51
Secondary accession number(s): Q59FF3, Q71S93, Q9H6I3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	July 11, 2006
Last modified:	May 1, 2013
This is version 106 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.