9RX6: VPS34-CII

VPS34-CII (VPS34 199-REIE-202 to 199-ERIR-202 mutant) bound to RAB5A (Q79L) on the VPS15 subunit. Determined by electron microscopy at 3.52 Å resolution. Released 3 Jun 2026.

Method: Electron microscopy
Resolution: 3.52 Å
Organism: Homo sapiens
Chains: 5
Atoms: 24,058
Mol. weight: 411.25 kDa
Ligands: ZN, MG, GDP, MYR
Released: 3 Jun 2026

Explore 9RX6 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9RX6 contains 152 α-helices and 121 β-strands across 5 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 40 helices, 29 β-strands

Element	Residues	Length	Sheet
β-strand	6-10	5	1
β-strand	18-27	10	2
α-helix	30-33	4
α-helix	35-40	6
α-helix	42-46	5
β-strand	58-65	8	3
β-strand	68-69	2	3
β-strand	74-75	2	3
α-helix	76-78	3
β-strand	86-96	11	2
α-helix	97-99	3
β-strand	105-115	11	3
β-strand	118-128	11	3
β-strand	130	1	4
β-strand	135	1	5
β-strand	136	1	4
α-helix	137	1
β-strand	140-145	6	2
β-strand	146-147	2	3
α-helix	173-183	11
α-helix	191-211	21
β-strand	215-221	7	2
β-strand	223-226	4	6
β-strand	229-231	3	6
β-strand	232-233	2	1
β-strand	234	1	5
α-helix	265-274	10
α-helix	281-283	3
α-helix	290-300	11
α-helix	310-318	9
α-helix	322-325	4
α-helix	330-334	5
α-helix	342-353	12
α-helix	356-359	4
α-helix	362-367	6
α-helix	374-387	14
α-helix	396-401	6
α-helix	402-405	4
α-helix	409-412	4
α-helix	477-483	7
α-helix	487-501	15
α-helix	504-509	6
α-helix	511-528	18
α-helix	533-560	28
α-helix	566-577	12
α-helix	580-583	4
β-strand	591-592	2	7
β-strand	600-611	12	7
α-helix	618	1
β-strand	619-625	7	7
β-strand	630-637	8	7
α-helix	642-659	18
β-strand	672-674	3	7
β-strand	679-683	5	7
β-strand	688-689	2	8
α-helix	690-696	7
α-helix	700-707	8
β-strand	709	1	9
α-helix	714-716	3
β-strand	717	1	9
α-helix	719-739	21
β-strand	749-751	3	8
β-strand	757-759	3	8
α-helix	781-785	5
α-helix	793-810	18
α-helix	813-821	9
α-helix	838-843	6
α-helix	852-867	16
α-helix	868-870	3

Chain B: 68 helices, 53 β-strands

Element	Residues	Length	Sheet
β-strand	31-34	4	10
β-strand	39-44	6	10
β-strand	49-56	8	10
α-helix	65-77	13
β-strand	84	1	11
β-strand	89-91	3	10
β-strand	98-104	7	10
β-strand	108-109	2	11
α-helix	110-114	5
α-helix	119-120	2
α-helix	122-141	20
α-helix	151-153	3
β-strand	154-156	3	11
β-strand	162-164	3	11
β-strand	175-176	2	12
α-helix	183-186	4
α-helix	199-201	3
β-strand	202-203	2	12
α-helix	205-212	8
α-helix	229-232	4
α-helix	237-239	3
α-helix	241-252	12
α-helix	261-268	8
α-helix	277-280	4
α-helix	284-293	10
α-helix	298-300	3
α-helix	304-310	7
β-strand	312	1	13
β-strand	316	1	13
α-helix	318-319	2
α-helix	320-324	5
α-helix	325-328	4
α-helix	329-332	4
α-helix	339-348	10
α-helix	350-357	8
α-helix	375-383	9
α-helix	392-405	14
α-helix	406-408	3
α-helix	411-413	3
α-helix	414-418	5
α-helix	419-423	5
α-helix	431-445	15
α-helix	451-452	2
α-helix	459-463	5
α-helix	464-467	4
α-helix	468-472	5
α-helix	476-505	30
α-helix	523-544	22
α-helix	550-558	9
α-helix	561-568	8
α-helix	570-572	3
α-helix	573-577	5
α-helix	578-580	3
α-helix	583-586	4
α-helix	591-599	9
α-helix	601-608	8
α-helix	610-612	3
α-helix	613-623	11
α-helix	629-645	17
α-helix	651-660	10
α-helix	661-665	5
α-helix	669-685	17
α-helix	688-690	3
α-helix	691-695	5
α-helix	696-698	3
β-strand	703	1	14
α-helix	715-718	4
β-strand	720	1	14
α-helix	721-725	5
α-helix	726-734	9
α-helix	738-752	15
α-helix	759-762	4
α-helix	765-777	13
α-helix	781-789	9
α-helix	791-808	18
α-helix	809-812	4
β-strand	818-820	3	6
α-helix	821-824	4
β-strand	829-832	4	1
α-helix	940-965	26
α-helix	974-976	3
β-strand	985	1	15
β-strand	990	1	15
β-strand	998-1001	4	16
β-strand	1007-1011	5	16
β-strand	1017-1021	5	16
α-helix	1022-1024	3
β-strand	1037-1038	2	16
β-strand	1045-1050	6	17
β-strand	1057-1061	5	17
β-strand	1065-1068	4	17
β-strand	1072	1	18
β-strand	1081	1	18
β-strand	1088-1089	2	17
β-strand	1097-1103	7	19
β-strand	1111-1116	6	19
β-strand	1120-1125	6	19
β-strand	1131-1136	6	19
α-helix	1139-1141	3
β-strand	1144-1146	3	20
β-strand	1149	1	20
β-strand	1155-1160	6	20
β-strand	1164-1169	6	20
β-strand	1175-1180	6	20
β-strand	1187-1192	6	21
β-strand	1199-1204	6	21
β-strand	1210-1214	5	21
β-strand	1219-1225	7	21
α-helix	1230	1
β-strand	1242	1	22
β-strand	1246-1247	2	23
β-strand	1255-1258	4	23
β-strand	1260	1	22
β-strand	1264-1269	6	23
α-helix	1273-1275	3
β-strand	1279-1281	3	23
β-strand	1290-1295	6	21
β-strand	1298-1303	6	21
β-strand	1332-1339	8	15
β-strand	1343-1349	7	15
β-strand	1354-1357	4	15

Chain C: 18 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	16-17	2	24
β-strand	24-25	2	24
α-helix	29-32	4
α-helix	36-42	7
β-strand	79	1	25
α-helix	111-127	17
α-helix	138-168	31
α-helix	169-171	3
α-helix	177-266	90
β-strand	276-279	4	26
β-strand	282-285	4	26
β-strand	288	1	26
α-helix	311-315	5
α-helix	318-321	4
β-strand	328-331	4	27
α-helix	334-336	3
β-strand	338-341	4	27
β-strand	348-350	3	27
α-helix	356-361	6
α-helix	364-367	4
α-helix	370-373	4
α-helix	377-380	4
β-strand	394-397	4	28
β-strand	402-405	4	28
β-strand	414	1	28
α-helix	422-424	3
α-helix	426-428	3
α-helix	430-438	9
α-helix	439-442	4
α-helix	443-447	5

Chain D: 18 helices, 19 β-strands

Element	Residues	Length	Sheet
α-helix	42-44	3
β-strand	47-50	4	29
α-helix	58-60	3
β-strand	63-69	7	25
β-strand	72	1	30
β-strand	76	1	30
β-strand	81-82	2	25
β-strand	86	1	25
β-strand	93	1	29
α-helix	95-97	3
β-strand	112-121	10	25
β-strand	124-134	11	25
α-helix	135-137	3
α-helix	138	1
β-strand	139-142	4	29
β-strand	153-156	4	29
β-strand	161-163	3	29
β-strand	188	1	24
α-helix	193-223	31
α-helix	228-323	96
α-helix	326-328	3
β-strand	331-332	2	31
β-strand	340-341	2	31
β-strand	344	1	31
α-helix	352-354	3
α-helix	360-363	4
α-helix	365-377	13
α-helix	380-382	3
β-strand	386-387	2	32
α-helix	390-392	3
β-strand	394-396	3	32
α-helix	401-403	3
β-strand	409-411	3	32
α-helix	421-423	3
α-helix	424-433	10
α-helix	435-438	4
α-helix	444-446	3

Chain F: 8 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	20-27	8	33
α-helix	33-41	9
α-helix	49-52	4
β-strand	58-64	7	33
β-strand	67-75	9	33
α-helix	80-85	6
α-helix	87-90	4
β-strand	95-101	7	33
α-helix	105-120	16
β-strand	127-133	7	33
α-helix	135-140	6
α-helix	145-154	10
β-strand	158-161	4	33
β-strand	163	1	34
β-strand	168	1	34
α-helix	172-180	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Phosphatidylinositol 3-kinase catalytic subunit type 3	A	protein	887	Homo sapiens	Q8NEB9 (AlphaFold model)
Phosphoinositide 3-kinase regulatory subunit 4	B	protein	1370	Homo sapiens	Q99570 (AlphaFold model)
Beclin-1	C	protein	450	Homo sapiens	Q14457 (AlphaFold model)
UV radiation resistance associated protein	D	protein	699	Homo sapiens	Q6P1X0 (AlphaFold model)
Ras-related protein Rab-5A	F	protein	212	Homo sapiens	P20339

Sequence of entity 1 (A), FASTA

>9RX6_1 Phosphatidylinositol 3-kinase catalytic subunit type 3 (chains A)
MGEAEKFHYIYSCDLDINVQLKIGSLEGKREQKSYKAVLEDPMLKFSGLYQETCSDLYVT
CQVFAEGKPLALPVRTSYKAFSTRWNWNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKAV
PVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTKTPGRTSSTLSEDQMSRLAKLTK
AHRQGHMVKVDWLDRLTFERIRMINESEKRSSNFMYLMVEFRCVKCDDKEYGIVYYEKDG
DESSPILTSFELVKVPDPQMSMENLVESKHHKLARSLRSGPSDHDLKPNAATRDQLNIIV
SYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDV
EDSLELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKNGLEPTKK
DSQSSVSENVSNSGINSAEIDSSQIITSPLPSVSSPPPASKTKEVPDGENLEQDLCTFLI
SRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLNVMRRFSQALLKGDKSVRVMRS
LLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMNLSDVELIPLPLEPQVK
IRGIIPETATLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRK
ENLDLKLTPYKVLATSTKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSENGPNGISAE
VMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPMKLN
KEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEPDKTVK
KVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQYWRK

Sequence of entity 2 (B), FASTA

>9RX6_2 Phosphoinositide 3-kinase regulatory subunit 4 (chains B)
GNQLAGIAPSQILSVESYFSDIHDFEYDKSLGSTRFFKVARAKHREGLVVVKVFAIQDPT
LPLTSYKQELEELKIRLNSAQNCLPFQKASEKASEKAAMLFRQYVRDNLYDRISTRPFLN
NIEKRWIAFQILTAVDQAHKSGVRHGDIKTENVMVTSWNWVLLTDFASFKPTYLPEDNPA
DFNYFFDTSRRRTCYIAPERFVDGGMFATELEYMRDPSTPLVDLNSNQRTRGELKRAMDI
FSAGCVIAELFTEGVPLFDLSQLLAYRNGHFFPEQVLNKIEDHSIRELVTQMIHREPDKR
LEAEDYLKQQRGNAFPEIFYTFLQPYMAQFAKETFLSADERILVIRKDLGNIIHNLCGHD
LPEKAEGEPKENGLVILVSVITSCLQTLKYCDSKLAALELILHLAPRLSVEILLDRITPY
LLHFSNDSVPRVRAEALRTLTKVLALVKEVPRNDINIYPEYILPGIAHLAQDDATIVRLA
YAENIALLAETALRFLELVQLKNLNMENDPNNEEIDEVTHPNGNYDTELQALHEMVQQKV
VTLLSDPENIVKQTLMENGITRLCVFFGRQKANDVLLSHMITFLNDKNDWHLRGAFFDSI
VGVAAYVGWQSSSILKPLLQQGLSDAEEFVIVKALYALTCMCQLGLLQKPHVYEFASDIA
PFLCHPNLWIRYGAVGFITVVARQISTADVYCKLMPYLDPYITQPIIQIERKLVLLSVLK
EPVSRSIFDYALRSKDITSLFRHLHMRQKKRNGSLPDCPPPEDPAIAQLLKKLLSQGMTE
EEEDKLLALKDFMMKSNKAKANIVDQSHLHDSSQKGVIDLAALGITGRQVDLVKTKQEPD
DKRARKHVKQDSNVNEEWKSMFGSLDPPNMPQALPKGSDQEVIQTGKPPRSESSAGICVP
LSTSSQVPEVTTVQNKKPVIPVLSSTILPSTYQIRITTCKTELQQLIQQKREQCNAERIA
KQMMENAEWESKPPPPGWRPKGLLVAHLHEHKSAVNRIRVSDEHSLFATCSNDGTVKIWN
SQKMEGKTTTTRSILTYSRIGGRVKTLTFCQGSHYLAIASDNGAVQLLGIEASKLPKSPK
IHPLQSRILDQKEDGCVVDMHHFNSGAQSVLAYATVNGSLVGWDLRSSSNAWTLKHDLKS
GLITSFAVDIHQCWLCIGTSSGTMACWDMRFQLPISSHCHPSRARIRRLSMHPLYQSWVI
AAVQGNNEVSMWDMETGDRRFTLWASSAPPLSELQPSPHSVHGIYCSPADGNPILLTAGS
DMKIRFWDLAYPERSYVVAGSTSSPSVSYYRKIIEGTEVVQEIQNKQKVGPSDDTPRRGP
ESLPVGHHDIITDVATFQTTQGFIVTASRDGIVKVWKSRPTTASENLYFQ

Sequence of entity 3 (C), FASTA

>9RX6_3 Beclin-1 (chains C)
MEGSKTSNNSTMQVSFVCQRCSQPLKLDTSFKILDRVTIQELTAPLLTTAQAKPGETQEE
ETNSGEEPFIETPRQDGVSRRFIPPARMMSTESANSFTLIGEASDGGTMENLSRRLKVTG
DLFDIMSGQTDVDHPLCEECTDTLLDQLDTQLNVTENECQNYKRCLEILEQMNEDDSEQL
QMELKELALEEERLIQELEDVEKNRKIVAENLEKVQAEAERLDQEEAQYQREYSEFKRQQ
LELDDELKSVENQMRYAQTQLDKLKKTNVFNATFHIWHSGQFGTINNFRLGRLPSVPVEW
NEINAAWGQTVLLLHALANKMGLKFQRYRLVPYGNHSYLESLTDKSKELPLYCSGGLRFF
WDNKFDHAMVAFLDCVQQFKEEVEKGETRFCLPYRMDVEKGKIEDTGGSGGSYSIKTQFN
SEEQWTKALKFMLTNLKWGLAWVSSQFYNK

Sequence of entity 4 (D), FASTA

>9RX6_4 UV radiation resistance associated protein (chains D)
MSASASVGGQVPQPPPGPAAALPPGSAARALHVELPSQQRRLRHLRNIAARNIVNRNGHQ
LLDTYFTLHLCSTEKIYKEFYRSEVIKNSLNPTWRSLDFGIMPDRLDTSVSCFVVKIWGG
KENIYQLLIEWKVCLDGLKYLGQQIHARNQNEIIFGLNDGYYGAPFEHKGYSNAQKTILL
QVDQNCVRNSYDVFSLLRLHRAQCAIKQTQVTVQKIGKEIEEKLRLTSTSNELKKKSECL
QLKILVLQNELERQKKALGREVALLHKQQIALQDKGSAFSAEHLKLQLQKESLNELRKEC
TAKRELFLKTNAQLTIRCRQLLSELSYIYPIDLNEHKDYFVCGVKLPNSEDFQAKDDGSI
AVALGYTAHLVSMISFFLQVPLRYPIIHKGSRSTIKDNINDKLTEKEREFPLYPKGGEKL
QFDYGVYLLNKNIAQLRYQHGLGTPDLRQTLPNLKNFMEHGLMVRCDRHHTSSAIPVPKR
QSSIFGGADVGFSGGIPSPDKGHRKRASSENERLQYKTPPPSYNSALAQPVTTVPSMGET
ERKITSLSSSLDTSLDFSKENKKKGEDLVGSLNGGHANVHPSQEQGEALSGHRATVNGTL
LPSEQAGSASVQLPGEFHPVSEAELCCTVEQAEEIIGLEATGFASGDQLEAFNCIPVDSA
VAVECDEQVLGEFEEFSRRIYALNENVSSFRRPRRSSDK

Sequence of entity 5 (F), FASTA

>9RX6_5 Ras-related protein Rab-5A (chains F)
MASRGATRPNGPNTGNKISQFKLVLLGESAVGKSSLVLRFVKGQFHEFQESTIGAAFLTQ
TVSLDDTTVKFEIWDTAGLERYHSLAPMYYRGAQAAIVVYDITNEESFARAKNWVKELQR
QASPNIVIALSGNKADLANKRAVDFQEAQSYADDNSLLFMETSAKTSMNVNEIFMAIAKK
LPKNEPQNPGANSARGRGVDLTEPTQPTRNQC

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	1
MG	Magnesium ion	Mg	2
GDP	Guanosine-5'-diphosphate	C10 H15 N5 O11 P2	1
MYR	Myristic acid	C14 H28 O2	1
GTP	Guanosine-5'-triphosphate	C10 H16 N5 O14 P3	1

Primary citation

A novel RAB5 binding site in human VPS34-CII that is likely the primordial site in eukaryotic evolution. Spokaite, S., Ohashi, Y., Bourguet, M. et al. Elife (2026) 15. DOI 10.7554/eLife.110040 · PubMed

Other PDB entries of the same protein (UniProt Q8NEB9 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6HOG 1.26 Å, Structure of VPS34 LIR motif bound to GABARAP
7RSP 1.67 Å, Structure of the VPS34 kinase domain with compound 14
7RSV 1.78 Å, Structure of the VPS34 kinase domain with compound 5
7RSJ 1.88 Å, Structure of the VPS34 kinase domain with compound 14
4UWH 1.93 Å, Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo-…
9NIN 2.01 Å, The structure of human Vacuolar Protein Sorting 34 catalytic domain bound to RD-I-86
8RXR 2.06 Å, Crystal structure of VPS34 in complex with inhibitor SB02024
9ORM 2.06 Å, The structure of human Vacuolar Protein Sorting 34 catalytic domain bound to RD-I-137
6I3U 2.09 Å, Optimization of potent and selective ATM inhibitors suitable for a proof-of-concept…
9ZF4 2.09 Å, The structure of human Vacuolar Protein Sorting 34 catalytic domain bound to RD-II-83
9DKP 2.16 Å, The structure of human vacuolar protein sorting 34 catalytic domain bound to RD-I-53
3LS8 2.25 Å, Crystal structure of human PIK3C3 in complex with 3-[4-(4-Morpholinyl)thieno[3,2-d]pyrimi…

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