Q7Z6J4 (FGD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
FYVE, RhoGEF and PH domain-containing protein 2

Alternative name(s):
Zinc finger FYVE domain-containing protein 4

Gene names

Name:	FGD2
Synonyms:	ZFYVE4

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	655 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Activates JNK1 via CDC42 but not RAC1. Binds to phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate By similarity.
Subcellular location	Cytoplasm › cytoskeleton Probable. Cytoplasm By similarity. Nucleus By similarity. Early endosome By similarity. Early endosome membrane By similarity. Cell projection › ruffle membrane By similarity. Note: Recruitment to the endosome and ruffle membrane requires the presence of phosphoinositides By similarity.
Domain	The FYVE-type zinc-finger is necessary for early endosome localization. Recruitment to endosomal membranes via this domain requires the presence of phosphatidylinositol 3-phosphate or other phosphatidylinositides By similarity. The PH domain is necessary for localization to the ruffle membrane. Recruitment to ruffle membrane occurs through binding of phosphoinositides by the PH domain. This domain also contributes to the lipid-binding properties of the protein By similarity. The DH domain is necessary for its ability to activate JNK1 via CDC42 By similarity.
Sequence similarities	Contains 1 DH (DBL-homology) domain. Contains 1 FYVE-type zinc finger. Contains 2 PH domains.
Sequence caution	The sequence BAB15746.1 differs from that shown. Reason: Erroneous initiation. The sequence BAC85129.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAC85129.1 differs from that shown. Reason: Frameshift at position 460. The sequence CAI20471.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cytoplasm Cytoskeleton Endosome Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Guanine-nucleotide releasing factor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Traceable author statement. Source: Reactome filopodium assembly Inferred from sequence or structural similarity. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome regulation of Cdc42 GTPase activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell shape Inferred from sequence or structural similarity. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome early endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell ruffle Inferred from sequence or structural similarity. Source: UniProtKB ruffle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro guanyl-nucleotide exchange factor activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro small GTPase binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z6J4-1)

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: Q7Z6J4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-423: Missing.
     424-442: NETFKAAAQGPEGDIQEQE → MGGRRSPRAHSCPTPLNPQ
     585-655: DMRAHTSIPL...SWPNDGDLSD → VRPPPARPPSGPGLPTACV

Note: No experimental confirmation available.

Isoform 3 (identifier: Q7Z6J4-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-372: Missing.
     488-655: VCARCSDYRA...SWPNDGDLSD → STPASTPASTCVTQASTCITQASTFPT

Note: No experimental confirmation available.

Isoform 4 (identifier: Q7Z6J4-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MKGASEEKLASVSNLVTVFENS → MFPKKARHPGAPALGICTRQPKSTPGTCCCFPCSPGRKPSGLSLLL
     101-104: EPEK → VPEG
     105-655: Missing.

Note: May be due to an intron retention. No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 655	655	FYVE, RhoGEF and PH domain-containing protein 2		PRO_0000080942
Regions
	Domain	102 – 290	189	DH
	Domain	319 – 418	100	PH 1
	Domain	544 – 641	98	PH 2
	Zinc finger	458 – 518	61	FYVE-type
Natural variations
	Alternative sequence	1 – 423	423	Missing in isoform 2.		VSP_013065
	Alternative sequence	1 – 372	372	Missing in isoform 3.		VSP_013066
	Alternative sequence	1 – 22	22	MKGAS…VFENS → MFPKKARHPGAPALGICTRQ PKSTPGTCCCFPCSPGRKPS GLSLLL in isoform 4.		VSP_013067
	Alternative sequence	101 – 104	4	EPEK → VPEG in isoform 4.		VSP_013068
	Alternative sequence	105 – 655	551	Missing in isoform 4.		VSP_038219
	Alternative sequence	424 – 442	19	NETFK…IQEQE → MGGRRSPRAHSCPTPLNPQ in isoform 2.		VSP_013070
	Alternative sequence	488 – 655	168	VCARC…GDLSD → STPASTPASTCVTQASTCIT QASTFPT in isoform 3.		VSP_013071
	Alternative sequence	585 – 655	71	DMRAH…GDLSD → VRPPPARPPSGPGLPTACV in isoform 2.		VSP_013072
	Natural variant	32	1	Q → H. Ref.4 Corresponds to variant rs831510 [ dbSNP | Ensembl ].		VAR_021491

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: DB60098249C2B340	FASTA	655	74,892
	10 20 30 40 50 60 MKGASEEKLA SVSNLVTVFE NSRTPEAAPR GQRLEDVHHR PECRPPESPG PREKTNVGEA 70 80 90 100 110 120 VGSEPRTVSR RYLNSLKNKL SSEAWRKSCQ PVTLSGSGTQ EPEKKIVQEL LETEQAYVAR 130 140 150 160 170 180 LHLLDQVFFQ ELLKTARSSK AFPEDVVRVI FSNISSIYQF HSQFFLPELQ RRLDDWTANP 190 200 210 220 230 240 RIGDVIQKLA PFLKMYSEYV KNFERAAELL ATWTDKSPLF QEVLTRIQSS EASGSLTLQH 250 260 270 280 290 300 HMLEPVQRIP RYELLLKEYI QKLPAQAPDQ ADAQKALDMI FSAAQHSNAA ITEMERLQDL 310 320 330 340 350 360 WEVYQRLGLE DDIVDPSNTL LREGPVLKIS FRRNDPMERY LFLFNNMLLY CVPRVIQVGA 370 380 390 400 410 420 QFQVRTRIDV AGMKVRELMD AEFPHSFLVS GKQRTLELQA RSQEEMISWM QAFQAAIDQI 430 440 450 460 470 480 EKRNETFKAA AQGPEGDIQE QELQSEELGL RAPQWVRDKM VTMCMRCQEP FNALTRRRHH 490 500 510 520 530 540 CRACGYVVCA RCSDYRAELK YDDNRPNRVC LHCYAFLTGN VLPEAKEDKR RGILEKGSSA 550 560 570 580 590 600 TPDQSLMCSF LQLIGDKWGK SGPRGWCVIP RDDPLVLYVY AAPQDMRAHT SIPLLGYQVT 610 620 630 640 650 VGPQGDPRVF QLQQSGQLYT FKAETEELKG RWVKAMERAA SGWSPSWPND GDLSD
	Isoform 2 [UniParc]. Checksum: 96FB2A2E1FE129C5	FASTA	180	20,193
	10 20 30 40 50 60 MGGRRSPRAH SCPTPLNPQL QSEELGLRAP QWVRDKMVTM CMRCQEPFNA LTRRRHHCRA 70 80 90 100 110 120 CGYVVCARCS DYRAELKYDD NRPNRVCLHC YAFLTGNVLP EAKEDKRRGI LEKGSSATPD 130 140 150 160 170 180 QSLMCSFLQL IGDKWGKSGP RGWCVIPRDD PLVLYVYAAP QVRPPPARPP SGPGLPTACV
	Isoform 3 [UniParc]. Checksum: 3BC622A79372D3FA	FASTA	142	16,086
	10 20 30 40 50 60 MKVRELMDAE FPHSFLVSGK QRTLELQARS QEEMISWMQA FQAAIDQIEK RNETFKAAAQ 70 80 90 100 110 120 GPEGDIQEQE LQSEELGLRA PQWVRDKMVT MCMRCQEPFN ALTRRRHHCR ACGYVSTPAS 130 140 TPASTCVTQA STCITQASTF PT
	Isoform 4 [UniParc]. Checksum: B6EB12FF70E7A602	FASTA	128	13,825
	10 20 30 40 50 60 MFPKKARHPG APALGICTRQ PKSTPGTCCC FPCSPGRKPS GLSLLLRTPE AAPRGQRLED 70 80 90 100 110 120 VHHRPECRPP ESPGPREKTN VGEAVGSEPR TVSRRYLNSL KNKLSSEAWR KSCQPVTLSG SGTQVPEG

References

[1]	"Characterization of long cDNA clones from human adult spleen." Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O. DNA Res. 7:357-366(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Spleen.
[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] (ISOFORMS 2 AND 3). Tissue: Spleen.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [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] (ISOFORM 1), VARIANT HIS-32. Tissue: Leukocyte and Lymph.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK024456 mRNA. Translation: BAB15746.1. Different initiation. AK097230 mRNA. Translation: BAC04982.1. AK131079 mRNA. Translation: BAC85129.1. Sequence problems. AL160264 Genomic DNA. Translation: CAI20471.1. Sequence problems. BC023645 mRNA. Translation: AAH23645.1. BC053655 mRNA. Translation: AAH53655.1.
IPI	IPI00217865. IPI00384678. IPI00386320. IPI00442361.
RefSeq	NP_775829.2. NM_173558.3.
UniGene	Hs.509664.
3D structure databases
ProteinModelPortal	Q7Z6J4.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000274963.
PTM databases
PhosphoSite	Q7Z6J4.
Polymorphism databases
DMDM	61213572.
Proteomic databases
PaxDb	Q7Z6J4.
PRIDE	Q7Z6J4.
Protocols and materials databases
DNASU	221472.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000274963; ENSP00000274963; ENSG00000146192.
GeneID	221472.
KEGG	hsa:221472.
UCSC	uc003ong.2. human. uc003onj.1. human.
Organism-specific databases
CTD	221472.
GeneCards	GC06P036973.
HGNC	HGNC:3664. FGD2.
HPA	HPA029145.
MIM	605091. gene.
neXtProt	NX_Q7Z6J4.
PharmGKB	PA28103.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG284234.
HOVERGEN	HBG007506.
KO	K05721.
OMA	YAAPQDM.
OrthoDB	EOG4R23TD.
PhylomeDB	Q7Z6J4.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q7Z6J4.
Bgee	Q7Z6J4.
CleanEx	HS_FGD2.
Genevestigator	Q7Z6J4.
GermOnline	ENSG00000146192. Homo sapiens.
Family and domain databases
Gene3D	1.20.900.10. 1 hit. 2.30.29.30. 2 hits. 3.30.40.10. 1 hit.
InterPro	IPR000219. DH-domain. IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR000306. Znf_FYVE. IPR017455. Znf_FYVE-rel. IPR011011. Znf_FYVE_PHD. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF01363. FYVE. 1 hit. PF00169. PH. 1 hit. PF00621. RhoGEF. 1 hit. [Graphical view]
SMART	SM00064. FYVE. 1 hit. SM00233. PH. 2 hits. SM00325. RhoGEF. 1 hit. [Graphical view]
SUPFAM	SSF48065. DH-domain. 1 hit. SSF57903. FYVE_PHD_ZnF. 1 hit.
PROSITE	PS50010. DH_2. 1 hit. PS50003. PH_DOMAIN. 2 hits. PS50178. ZF_FYVE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FGD2. human.
GenomeRNAi	221472.
NextBio	91355.
SOURCE	Search...

Entry information

Entry name

FGD2_HUMAN

Accession

Primary (citable) accession number: Q7Z6J4
Secondary accession number(s): Q5T8I1 , Q6P6A8, Q6ZNL5, Q8IZ32, Q8N868, Q9H7M2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	October 1, 2003
Last modified:	May 1, 2013
This is version 92 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.