Q7L804 (RFIP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rab11 family-interacting protein 2
Short name=Rab11-FIP2

Alternative name(s):
NRip11

Gene names

Name:	RAB11FIP2
Synonyms:	KIAA0941

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

General annotation (Comments)

Function	A Rab11 effector protein acting in the regulation of the transport of vesicles from the endosomal recycling compartment (ERC) to the plasma membrane. Also involved in receptor-mediated endocytosis and membrane trafficking of recycling endosomes, probably originating from clathrin-coated vesicles. Binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and phosphatidic acid (PA). Required in a complex with MYO5B and RAB11 for the transport of NPC1L1 to the plasma membrane. Also acts as a regulator of cell polarity. Ref.10 Ref.12 Ref.13 Ref.16
Subunit structure	Homooligomerizes in a Rab11-independent manner. Forms an heterooligomeric complex with RAB11FIP4. Interacts with AP2A1, MYO5B, RAB11A, RAB11B, RAB25 and REPS1. Interacts with RAB11A/RAB11B that has been activated by GTP binding. Interacts with NPC1L1. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.16 Ref.17
Subcellular location	Cell membrane; Peripheral membrane protein. Recycling endosome membrane; Peripheral membrane protein. Note: Translocates with RAB11A from the vesicles of the endocytic recycling compartment (ERC) to the plasma membrane. Ref.6 Ref.9 Ref.10 Ref.12 Ref.17
Post-translational modification	Phosphorylation at Ser-227 by MARK2 regulates epithelial cell polarity.
Sequence similarities	Contains 1 C2 domain. Contains 1 FIP-RBD domain.
Sequence caution	The sequence BAA76785.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Polymorphism
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	establishment of cell polarity Inferred from mutant phenotype Ref.13. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell recycling endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein homodimerization activity Inferred from physical interaction Ref.17. Source: UniProtKB protein kinase binding Inferred from physical interaction Ref.13. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RAB11A	P62491	2	EBI-1049676,EBI-745098

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 512

512

Rab11 family-interacting protein 2

PRO_0000097306

Regions

Domain

1 – 102

102

C2

Domain

437 – 499

63

FIP-RBD

Region

15 – 102

88

Necessary for its cellular translocation to the plasma membrane

Region

465 – 512

48

Necessary for the interaction with AP2A1, RAB11A, subcellular location, endocytosis activity and homooligomerization

Amino acid modifications

Modified residue

150

1

Phosphoserine Ref.14

Modified residue

227

1

Phosphoserine; by MARK2 Ref.13

Modified residue

382

1

Phosphoserine Ref.15

Natural variations

Natural variant

152

1

F → V.
Corresponds to variant rs34028100 [ dbSNP | Ensembl ].

VAR_051316

Experimental info

Mutagenesis

223

1

S → A: No effect. Ref.13

Mutagenesis

224

1

S → A: No effect. Ref.13

Mutagenesis

227

1

S → A: Abolishes phosphorylation by MARK2 and induces defects in the reestablishment of junctional complexes. Ref.13

Mutagenesis

229

1

S → A: No effect. Ref.13

Mutagenesis

406 – 408

3

NPF → AAA: Severe reduction of the interaction with REPS1 and AP2A1. No effects on its subcellular location. Modifies the endocytosis activity. Ref.10

Mutagenesis

480 – 482

3

YID → AAA: Abolishes the interaction with REPS1 and AP2A1. Modifies its subcellular location and the endocytosis activity. Enhances homooligomerization. Ref.10 Ref.17

Mutagenesis

480

1

Y → F: No effect on the interaction with RAB11A. Abolishes the vesicular localization. Ref.17

Mutagenesis

481

1

I → E: Abolishes the interaction with RAB11A and the vesicular localization. Ref.17

Secondary structure

1

.

.

.

.

.

.

.

.

512

Helix Strand Turn

Details...

Helix

453 – 467

15

Helix

470 – 491

22

Helix

493 – 496

4

Beta strand

497 – 499

3

Sequences

	Sequence		Length	Mass (Da)
	Q7L804 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 9EC2DAB0A585BCD3	FASTA	512	58,279
	10 20 30 40 50 60 MMLSEQAQKW FPTHVQVTVL QAKDLKPKGK SGTNDTYTII QLGKEKYSTS VAEKTLEPVW 70 80 90 100 110 120 KEEASFELPG LLIQGSPEKY ILFLIVMHRS LVGLDKFLGQ VAINLNDIFE DKQRRKTEWF 130 140 150 160 170 180 RLESKQGKRI KNRGEIKVNI QFMRNNMTAS MFDLSMKDKT RSPFAKLKDK MKGRKNDGTF 190 200 210 220 230 240 SDTSSAIIPS THMPDANSEF SSGEIQMKSK PKKPFLLGPQ RLSSAHSMSD LSGSHMSSEK 250 260 270 280 290 300 LKAGTIGQTH LLGHQLDSFG TVPESGSLKS PHRRTLSFDT SKMNQPDSIV DEGELCFGRQ 310 320 330 340 350 360 NDPFTNVTAS LPQKFATLPR KKNPFEESSE TWDSSMNLFS KPIEIRKENK REKREKVSLF 370 380 390 400 410 420 ERVTGKKDSR RSDKLNNGGS DSPCDLKSPN AFSENRQDYF DYESTNPFTA KFRASNIMPS 430 440 450 460 470 480 SSFHMSPTSN EDLRKIPDSN PFDATAGYRS LTYEEVLQEL VKHKELLRRK DTHIRELEDY 490 500 510 IDNLLVRVME ETPSILRVPY EPSRKAGKFS NS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Rip11 and nRip11 are Rab11/25 interacting proteins." Prekeris R., Davies J.M., Scheller R.H. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed: 10231032] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"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].
[4]	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].
[5]	"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]. Tissue: Brain.
[6]	"Identification and characterization of a family of Rab11-interacting proteins." Hales C.M., Griner R., Hobdy-Henderson K.C., Dorn M.C., Hardy D., Kumar R., Navarre J., Chan E.K.L., Lapierre L.A., Goldenring J.R. J. Biol. Chem. 276:39067-39075(2001) [PubMed: 11495908] [Abstract] Cited for: INTERACTION WITH MYO5B; RAB11A; RAB11B AND RAB25, SUBCELLULAR LOCATION.
[7]	"The novel Rab11-FIP/Rip/RCP family of proteins displays extensive homo- and hetero-interacting abilities." Wallace D.M., Lindsay A.J., Hendrick A.G., McCaffrey M.W. Biochem. Biophys. Res. Commun. 292:909-915(2002) [PubMed: 11944901] [Abstract] Cited for: SUBUNIT.
[8]	"Rab11-FIP4 interacts with Rab11 in a GTP-dependent manner and its overexpression condenses the Rab11 positive compartment in HeLa cells." Wallace D.M., Lindsay A.J., Hendrick A.G., McCaffrey M.W. Biochem. Biophys. Res. Commun. 299:770-779(2002) [PubMed: 12470645] [Abstract] Cited for: SUBUNIT.
[9]	"Rab11-FIP2 functions in transferrin recycling and associates with endosomal membranes via its COOH-terminal domain." Lindsay A.J., McCaffrey M.W. J. Biol. Chem. 277:27193-27199(2002) [PubMed: 11994279] [Abstract] Cited for: SUBUNIT, INTERACTION WITH RAB11A, SUBCELLULAR LOCATION.
[10]	"Rab11-FIP2, an adaptor protein connecting cellular components involved in internalization and recycling of epidermal growth factor receptors." Cullis D.N., Philip B., Baleja J.D., Feig L.A. J. Biol. Chem. 277:49158-49166(2002) [PubMed: 12364336] [Abstract] Cited for: FUNCTION IN RECEPTOR-MEDIATED ENDOCYTOSIS, SUBUNIT, INTERACTION WITH REPS1 AND AP2A1, MUTAGENESIS OF 406-ASN--PHE-408 AND 480-TYR--ASP-482, SUBCELLULAR LOCATION.
[11]	"Molecular characterization of Rab11 interactions with members of the family of Rab11-interacting proteins." Junutula J.R., Schonteich E., Wilson G.M., Peden A.A., Scheller R.H., Prekeris R. J. Biol. Chem. 279:33430-33437(2004) [PubMed: 15173169] [Abstract] Cited for: SUBUNIT, INTERACTION WITH GTP-BOUND RAB11A AND GTP-BOUND RAB11B.
[12]	"The C2 domains of the class I Rab11 family of interacting proteins target recycling vesicles to the plasma membrane." Lindsay A.J., McCaffrey M.W. J. Cell Sci. 117:4365-4375(2004) [PubMed: 15304524] [Abstract] Cited for: FUNCTION IN ENDOSOME TRAFFICKING, INTERACTION WITH PTDINSP3 AND PA, SUBCELLULAR LOCATION.
[13]	"MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells." Ducharme N.A., Hales C.M., Lapierre L.A., Ham A.J., Oztan A., Apodaca G., Goldenring J.R. Mol. Biol. Cell 17:3625-3637(2006) [PubMed: 16775013] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-227, MUTAGENESIS OF SER-223; SER-224; SER-227 AND SER-229.
[14]	"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-150, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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-382, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[16]	"Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface." Chu B.-B., Ge L., Xie C., Zhao Y., Miao H.-H., Wang J., Li B.-L., Song B.-L. J. Biol. Chem. 284:22481-22490(2009) [PubMed: 19542231] [Abstract] Cited for: FUNCTION, INTERACTION WITH NPC1L1.
[17]	"Crystal structure of rab11 in complex with rab11 family interacting protein 2." Jagoe W.N., Lindsay A.J., Read R.J., McCoy A.J., McCaffrey M.W., Khan A.R. Structure 14:1273-1283(2006) [PubMed: 16905101] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 410-512, INTERACTION WITH RAB11A, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-480 AND ILE-481.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY037299 mRNA. Translation: AAK68635.1.
AB023158 mRNA. Translation: BAA76785.2. Different initiation.
AC022395 Genomic DNA. No translation available.
CH471066 Genomic DNA. Translation: EAW49423.1.
BC075073 mRNA. Translation: AAH75073.1.
BC075074 mRNA. Translation: AAH75074.1.

IPI

IPI00479368.

RefSeq

NP_055719.1. NM_014904.2.

UniGene

Hs.173656.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GZD	X-ray	2.44	C/D	410-512	[»]
2GZH	X-ray	2.47	B	410-512	[»]
2K6S	NMR	-	A/B	450-489	[»]

ProteinModelPortal

Q7L804.

SMR

Q7L804. Positions 14-125, 447-503.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29139N.

IntAct

Q7L804. 3 interactions.

MINT

MINT-1682199.

STRING

Q7L804.

PTM databases

PhosphoSite

Q7L804.

Polymorphism databases

DMDM

67472131.

Proteomic databases

PRIDE

Q7L804.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355624; ENSP00000347839; ENSG00000107560.

GeneID

22841.

KEGG

hsa:22841.

UCSC

uc001ldj.1. human.

Organism-specific databases

CTD

22841.

GeneCards

GC10M119754.

H-InvDB

HIX0009245.

HGNC

HGNC:29152. RAB11FIP2.

HPA

HPA037726.

MIM

608599. gene.

neXtProt

NX_Q7L804.

PharmGKB

PA134961225.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17474.

GeneTree

ENSGT00530000063203.

HOVERGEN

HBG054920.

OrthoDB

EOG4WQ12F.

Gene expression databases

ArrayExpress

Q7L804.

Bgee

Q7L804.

CleanEx

HS_RAB11FIP2.

Genevestigator

Q7L804.

GermOnline

ENSG00000107560. Homo sapiens.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR019018. Rab-bd_FIP-RBD.
[Graphical view]

KO

K12484.

Pfam

PF00168. C2. 1 hit.
PF09457. RBD-FIP. 1 hit.
[Graphical view]

SMART

SM00239. C2. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.

PROSITE

PS50004. C2. 1 hit.
PS51511. FIP_RBD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

43289.

SOURCE

Search...

Entry information

Entry name

RFIP2_HUMAN

Accession

Primary (citable) accession number: Q7L804
Secondary accession number(s): A6NEI4, Q9Y2F0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 87 of the entry and version 1 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.