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Q0JRZ9 (FCHO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
FCH domain only protein 2
Gene names
Name:FCHO2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length810 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a lipid-binding activity with a preference for membranes enriched in phosphatidylserine and phosphoinositides (Pi(4,5) biphosphate) like the plasma membrane. Its membrane-bending activity might be important for the subsequent action of clathrin and adaptors in the formation of clathrin-coated vesicles. Involved in adaptor protein complex AP-2-dependent endocytosis of the transferin receptor, it also functions in the AP-2-independent endocytosis of the LDL receptor. Ref.9 Ref.11 Ref.13 Ref.15

Subunit structure

Homodimer; disulfide-linked. May form homotetramer. Interacts with AP2A1. Interacts with EPS15, EPS15R, ITSN1 and ITSN2; recruit those scaffolding proteins which in turn may interact with the adaptor protein complex AP-2 at the plasma membrane. Interacts with DAB2 (via DPF motifs); mediates LDL receptor/LDLR endocytosis. Ref.9 Ref.11 Ref.13 Ref.14 Ref.15

Subcellular location

Membraneclathrin-coated pit; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Associated with forming but not mature clathrin-coated vesicles. The recruitment to coated-pits precede the one of clathrin and the adaptor protein complex AP-2 By similarity. Ref.11 Ref.13

Post-translational modification

Ubiquitinated. Mainly undergoes monoubiquitination but also polyubiquitination By similarity.

Miscellaneous

Deforms liposomes into a range of tubule diameters from 20 to 130 nm in vitro.

Sequence similarities

Belongs to the FCHO family.

Contains 1 FCH domain.

Contains 1 MHD (mu homology) domain.

Sequence caution

The sequence AAH14311.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dab2P980784EBI-2609756,EBI-1391846From a different organism.
EPS15P425663EBI-2609756,EBI-396684

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q0JRZ9-1)

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: Q0JRZ9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     306-373: ECPDADSLNI...PNNSHHTMAS → WSFTVVAQVG...PYWPGWSRTP
     374-810: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q0JRZ9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     200-232: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 810810FCH domain only protein 2
PRO_0000266005

Regions

Domain4 – 8582FCH
Domain542 – 809268MHD
Region3 – 274272Mediates dimerization and binding to membranes enriched in Pi(4,5)-P2 and induces their tubulation
Region521 – 810290Mediates interaction with DAB2, EPS15, EPS15R and ITSN1
Coiled coil87 – 15670 Potential
Compositional bias434 – 51986Ser-rich

Amino acid modifications

Modified residue3851Phosphothreonine Ref.8
Modified residue3871Phosphoserine Ref.6 Ref.8
Modified residue3941Phosphoserine Ref.8
Modified residue4031Phosphoserine Ref.6 Ref.8 Ref.12
Modified residue4881Phosphoserine Ref.7 Ref.8
Modified residue5111Phosphoserine Ref.7
Modified residue5331Phosphoserine Ref.8
Disulfide bond147Interchain (with C-273) Ref.15
Disulfide bond273Interchain (with C-147) Ref.15

Natural variations

Alternative sequence200 – 23233Missing in isoform 3.
VSP_044812
Alternative sequence306 – 37368ECPDA…HTMAS → WSFTVVAQVGMQWRDLGLLH SPPPRFKRFSSYLSLPSSWN YGAHHHIWLIFCIFSRDRVS PYWPGWSRTP in isoform 2.
VSP_021910
Alternative sequence374 – 810437Missing in isoform 2.
VSP_021911
Natural variant3711M → V.
Corresponds to variant rs185435 [ dbSNP | Ensembl ].
VAR_029636

Experimental info

Mutagenesis101F → E: Binds preferentially to larger liposomes. Ref.15
Sequence conflict61F → L in AL831971. Ref.2
Sequence conflict2861K → E in BAG58162. Ref.1
Sequence conflict4391S → P in BAF84471. Ref.1
Sequence conflict4621P → Q in AL831971. Ref.2
Sequence conflict6171D → Y in BAG58162. Ref.1

Secondary structure

................. 810
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 12, 2006. Version 2.
Checksum: 0FCFBC5D814B5242

FASTA81088,924
        10         20         30         40         50         60 
MVMAYFVENF WGEKNSGFDV LYHNMKHGQI STKELADFVR ERATIEEAYS RSMTKLAKSA 

        70         80         90        100        110        120 
SNYSQLGTFA PVWDVFKTST EKLANCHLDL VRKLQELIKE VQKYGEEQVK SHKKTKEEVA 

       130        140        150        160        170        180 
GTLEAVQTIQ SITQALQKSK ENYNAKCVEQ ERLKKEGATQ REIEKAAVKS KKATDTYKLY 

       190        200        210        220        230        240 
VEKYALAKAD FEQKMTETAQ KFQDIEETHL IHIKEIIGSL SNAIKEIHLQ IGQVHEEFIN 

       250        260        270        280        290        300 
NMANTTVESL IQKFAESKGT GKERPGLIEF EECDTASAVE GIKPRKRKTF ALPGIIKKEK 

       310        320        330        340        350        360 
DAESVECPDA DSLNIPDVDE EGYSIKPETN QNDTKENHFY SSSDSDSEDE EPKKYRIEIK 

       370        380        390        400        410        420 
PMHPNNSHHT MASLDELKVS IGNITLSPAI SRHSPVQMNR NLSNEELTKS KPSAPPNEKG 

       430        440        450        460        470        480 
TSDLLAWDPL FGPSLDSSSS SSLTSSSSAR PTTPLSVGTI VPPPRPASRP KLTSGKLSGI 

       490        500        510        520        530        540 
NEIPRPFSPP VTSNTSPPPA APLARAESSS SISSSASLSA ANTPTVGVSR GPSPVSLGNQ 

       550        560        570        580        590        600 
DTLPVAVALT ESVNAYFKGA DPTKCIVKIT GDMTMSFPSG IIKVFTSNPT PAVLCFRVKN 

       610        620        630        640        650        660 
ISRLEQILPN AQLVFSDPSQ CDSNTKDFWM NMQAVTVYLK KLSEQNPAAS YYNVDVLKYQ 

       670        680        690        700        710        720 
VSSNGIQSTP LNLATYWKCS ASTTDLRVDY KYNPEAMVAP SVLSNIQVVV PVDGGVTNMQ 

       730        740        750        760        770        780 
SLPPAIWNAE QMKAFWKLSS ISEKSENGGS GSLRAKFDLS EGPSKPTTLA VQFLSEGSTL 

       790        800        810 
SGVDFELVGT GYRLSLIKKR FATGRYLADC 

« Hide

Isoform 2 [UniParc].

Checksum: 070F5C2EE86C95CF
Show »

FASTA37543,036
Isoform 3 [UniParc].

Checksum: D316D1D723C3698A
Show »

FASTA77785,146

References

« Hide 'large scale' references
[1]"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. expand/collapse author list , 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] (ISOFORMS 1 AND 3).
Tissue: Brain and Placenta.
[2]"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] (ISOFORM 1).
Tissue: Skeletal muscle.
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORMS 1 AND 2).
Tissue: Lung and Urinary bladder.
[5]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387 AND SER-403, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"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-488 AND SER-511, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"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 THR-385; SER-387; SER-394; SER-403; SER-488 AND SER-533, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"FCHo proteins are nucleators of clathrin-mediated endocytosis."
Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y., Mittal R., McMahon H.T.
Science 328:1281-1284(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CLATHRIN-COATED PITS NUCLEATION, INTERACTION WITH EPS15; EPS15R; ITSN1 AND ITSN2.
[10]"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].
[11]"Characterization of the EFC/F-BAR domain protein, FCHO2."
Uezu A., Umeda K., Tsujita K., Suetsugu S., Takenawa T., Nakanishi H.
Genes Cells 16:868-878(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CLATHRIN-MEDIATED ENDOCYTOSIS, INTERACTION WITH EPS15 AND AP2A1, SUBCELLULAR LOCATION.
[12]"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-403, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"FCH domain only-2 organizes clathrin-coated structures and interacts with Disabled-2 for low-density lipoprotein receptor endocytosis."
Mulkearns E.E., Cooper J.A.
Mol. Biol. Cell 23:1330-1342(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DAB2-MEDIATED ENDOCYTOSIS, INTERACTION WITH DAB2, SUBCELLULAR LOCATION.
[14]"Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning."
Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B., Tsang M., Traub L.M.
Nat. Cell Biol. 14:488-501(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: LIPID-BINDING, INTERACTION WITH DAB2; EPS15; EPS15R AND ITSN1.
[15]"Structure and analysis of FCHo2 F-BAR domain: a dimerizing and membrane recruitment module that effects membrane curvature."
Henne W.M., Kent H.M., Ford M.G., Hegde B.G., Daumke O., Butler P.J., Mittal R., Langen R., Evans P.R., McMahon H.T.
Structure 15:839-852(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 3-274, FUNCTION, SUBUNIT, DISULFIDE BOND, MUTAGENESIS OF PHE-10.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK291782 mRNA. Translation: BAF84471.1.
AK295141 mRNA. Translation: BAG58162.1.
AL831971 mRNA. No translation available.
AC008972 Genomic DNA. No translation available.
AC020893 Genomic DNA. No translation available.
AC020942 Genomic DNA. No translation available.
BC014311 mRNA. Translation: AAH14311.1. Different initiation.
BC137070 mRNA. Translation: AAI37071.1.
RefSeqNP_001139504.1. NM_001146032.1.
NP_620137.2. NM_138782.2.
UniGeneHs.165762.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2V0OX-ray2.30A/B/C3-274[»]
ProteinModelPortalQ0JRZ9.
SMRQ0JRZ9. Positions 3-274.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125437. 4 interactions.
DIPDIP-29488N.
IntActQ0JRZ9. 10 interactions.
STRING9606.ENSP00000393776.

PTM databases

PhosphoSiteQ0JRZ9.

Polymorphism databases

DMDM119369487.

Proteomic databases

PaxDbQ0JRZ9.
PRIDEQ0JRZ9.

Protocols and materials databases

DNASU115548.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000430046; ENSP00000393776; ENSG00000157107. [Q0JRZ9-1]
ENST00000512348; ENSP00000427296; ENSG00000157107. [Q0JRZ9-3]
GeneID115548.
KEGGhsa:115548.
UCSCuc003kcl.3. human. [Q0JRZ9-1]

Organism-specific databases

CTD115548.
GeneCardsGC05P072287.
H-InvDBHIX0004941.
HGNCHGNC:25180. FCHO2.
HPAHPA037685.
HPA037686.
MIM613438. gene.
neXtProtNX_Q0JRZ9.
PharmGKBPA134911830.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG324072.
HOGENOMHOG000231544.
HOVERGENHBG081524.
InParanoidQ0JRZ9.
OMAFNCEGTT.
OrthoDBEOG712TVK.
PhylomeDBQ0JRZ9.
TreeFamTF328986.

Gene expression databases

ArrayExpressQ0JRZ9.
BgeeQ0JRZ9.
CleanExHS_FCHO2.
GenevestigatorQ0JRZ9.

Family and domain databases

InterProIPR001060. FCH_dom.
IPR028565. MHD.
IPR018808. Muniscin_C.
[Graphical view]
PfamPF00611. FCH. 1 hit.
PF10291. muHD. 1 hit.
[Graphical view]
SMARTSM00055. FCH. 1 hit.
[Graphical view]
PROSITEPS50133. FCH. 1 hit.
PS51072. MHD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFCHO2. human.
EvolutionaryTraceQ0JRZ9.
GeneWikiFCHO2.
GenomeRNAi115548.
NextBio79607.
PROQ0JRZ9.
SOURCESearch...

Entry information

Entry nameFCHO2_HUMAN
AccessionPrimary (citable) accession number: Q0JRZ9
Secondary accession number(s): A8K6W7 expand/collapse secondary AC list , B2RNQ9, B4DHK0, E9PG79, Q0JTJ3, Q96CF5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: December 12, 2006
Last modified: April 16, 2014
This is version 74 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM