eF-site ID 5a63-ABCD
PDB Code 5a63
Chain A, B, C, D

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Title Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution.
Classification HYDROLASE
Compound Nicastrin
Source (PEN2_HUMAN)
Sequence A:  NSVERKIYIPLNKTAPCVRLLNATHQIGCQSSISGDTGVI
HVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKG
RTSRIAGLAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYG
PEFAHCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIK
QCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRR
SSIQSTFSINPEIVCDPLSDYNVWSMLKPINTTGTLKPDD
RVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQ
KAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFP
VQLENVDSFVELGQVALRTSLELWMHTDPVSQKNESVRNQ
VEDLLATLEKSGAGVPAVILRRPNQSQPLPPSSLQRFLRA
RNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSP
EEDLNFVTDTAKALADVATVLGRALYELAGGTNFSDTVQA
DPQTVTRLLYGFLIKANNSWFQSILRQDLRSYLGDGPLQH
YIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVP
SENKDLYEYSWVQGPLHSNETDRLPRCVRSTARLARALSP
AFELSQWSSTEYSTWTESRWKDIRARIFLIASKELELITL
TVGFGILIFSLIVTYCINAKADVLF
B:  GAKHVIMLFVPVTLCMVVVVATIKSVSFYTRIISSLLLLF
FFSFIYLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHW
KGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISV
YDLVAVVKLGLGDFIFYSVLVGKASATASGDWNTTIACFV
AILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYL
VQPFMDQLAFHQFYI
C:  GAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFF
WLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVL
LQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYVS
GLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSA
FLTAAIILLHTFWGVVFFDACERRRYWALGLVVGSHLLTS
GLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQR
SLL
D:  NLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREA
FLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIFQIY
RPRWGALGDYLSFTIPLGTP
Description (1)  NICASTRIN, PRESENILIN-1 (E.C.3.4.23.-), GAMMA-SECRETASE SUBUNIT APH-1A, GAMMA-SECRETASE SUBUNIT PEN-2


Functional site

1) chain D
residue 37-57
type TOPO_DOM
sequence FFREAFLVPAYTEQSQIKGYV
description Cytoplasmic => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI1

2) chain C
residue 140-158
type TOPO_DOM
sequence DALGPGVVGIHGDSPYYFL
description Cytoplasmic => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI1

3) chain C
residue 208-213
type TOPO_DOM
sequence PWYEAS
description Cytoplasmic => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI1

4) chain B
residue 429-432
type TOPO_DOM
sequence KKAL
description Cytoplasmic => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI1

5) chain D
residue 18-36
type INTRAMEM
sequence YYLGGFAFLPFLWLVNIFW
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI2

6) chain B
residue 167-189
type INTRAMEM
sequence IISSLLLLFFFSFIYLGEVFKTY
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI2

7) chain B
residue 195-216
type INTRAMEM
sequence YITVALLIWNFGVVGMISIHWK
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI2

8) chain B
residue 221-241
type INTRAMEM
sequence LQQAYLIMISALMALVFIKYL
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI2

9) chain B
residue 381-401
type INTRAMEM
sequence LGLGDFIFYSVLVGKASATAS
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI2

10) chain B
residue 408-428
type INTRAMEM
sequence IACFVAILIGLCLTLLLLAIF
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI2

11) chain B
residue 433-453
type INTRAMEM
sequence PALPISITFGLVFYFATDYLV
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI2

12) chain D
residue 58-78
type TRANSMEM
sequence WRSAVGFLFWVIVLTSWITIF
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI3

13) chain C
residue 90-118
type TRANSMEM
sequence YYKLLKKADEGLASLSEDGRSPISIRQMA
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI3

14) chain C
residue 180-186
type TRANSMEM
sequence DACERRR
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI3

15) chain B
residue 454-467
type TRANSMEM
sequence QPFMDQLAFHQFYI
description Helical => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI3

16) chain D
residue 79-101
type TOPO_DOM
sequence QIYRPRWGALGDYLSFTIPLGTP
description Lumenal => ECO:0000269|PubMed:26280335, ECO:0000305|PubMed:12639958
source Swiss-Prot : SWS_FT_FI4

17) chain A
residue 187
type TOPO_DOM
sequence N
description Lumenal => ECO:0000269|PubMed:26280335, ECO:0000305|PubMed:12639958
source Swiss-Prot : SWS_FT_FI4

18) chain C
residue 69-89
type TRANSMEM
sequence YGLLIFGAAVSVLLQEVFRFA
description Helical; Name=3 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI5

19) chain A
residue 264
type TRANSMEM
sequence N
description Helical; Name=3 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI5

20) chain A
residue 435
type TRANSMEM
sequence N
description Helical; Name=3 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI5

21) chain A
residue 464
type TRANSMEM
sequence N
description Helical; Name=3 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI5

22) chain A
residue 506
type TRANSMEM
sequence N
description Helical; Name=3 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI5

23) chain A
residue 530
type TRANSMEM
sequence N
description Helical; Name=3 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI5

24) chain A
residue 562
type TRANSMEM
sequence N
description Helical; Name=3 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI5

25) chain A
residue 573
type TRANSMEM
sequence N
description Helical; Name=3 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI5

26) chain C
residue 119-139
type TRANSMEM
sequence YVSGLSFGIISGVFSVINILA
description Helical; Name=4 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI6

27) chain A
residue 417
type TRANSMEM
sequence N
description Helical; Name=4 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI6

28) chain C
residue 159-179
type TRANSMEM
sequence TSAFLTAAIILLHTFWGVVFF
description Helical; Name=5 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI7

29) chain C
residue 187-207
type TRANSMEM
sequence YWALGLVVGSHLLTSGLTFLN
description Helical; Name=6 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI8

30) chain C
residue 214-234
type TRANSMEM
sequence LLPIYAVTVSMGLWAFITAGG
description Helical; Name=7 => ECO:0000269|PubMed:26280335
source Swiss-Prot : SWS_FT_FI9

31) chain A
residue 277-291
type prosite
sequence VAATRLDSRSFFWNV
description WD_REPEATS_1 Trp-Asp (WD) repeats signature. VAATrlDsRSFFWNV
source prosite : PS00678


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