dbPTM

NEP_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	NEP_HUMAN
UniProt AC	P08473
Protein Name	Neprilysin
Gene Name	MME
Organism	Homo sapiens (Human).
Sequence Length	750
Subcellular Localization	Cell membrane Single-pass type II membrane protein.
Protein Description	Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. [PubMed: 15283675]
Protein Sequence	MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSSDCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKDVLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGASWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKEACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLYNKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILTKYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERIGYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAAVVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYRAYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIGTLQNSAEFSEAFHCRKNSYMNPEKKCRVW

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	N-myristoyl glycine	------MGKSESQMD ------CCCCHHHCC	42.04	-
2	Myristoylation	------MGKSESQMD ------CCCCHHHCC	42.04	19756956
4	Phosphorylation	----MGKSESQMDIT ----CCCCHHHCCCC	36.43	23927012
6	Phosphorylation	--MGKSESQMDITDI --CCCCHHHCCCCCC	37.59	28355574
11	Phosphorylation	SESQMDITDINTPKP CHHHCCCCCCCCCCC	26.94	23927012
15	Phosphorylation	MDITDINTPKPKKKQ CCCCCCCCCCCCCCC	32.78	23927012
76	Phosphorylation	LIQNMDATTEPCTDF HHHCCCCCCCCCCHH	27.68	28450419
77	Phosphorylation	IQNMDATTEPCTDFF HHCCCCCCCCCCHHH	39.38	28450419
85	Acetylation	EPCTDFFKYACGGWL CCCCHHHHHHHCHHH	31.75	7483887
93	Acetylation	YACGGWLKRNVIPET HHHCHHHHHCCCCCC	35.10	7483897
93	Ubiquitination	YACGGWLKRNVIPET HHHCHHHHHCCCCCC	35.10	21963094
145	N-linked_Glycosylation	ALYRSCINESAIDSR HHHHHHCCHHHHHCC	41.31	10669592
207	Phosphorylation	LINLFVGTDDKNSVN EEEEEECCCCCCCEE	35.41	24719451
285	N-linked_Glycosylation	ELEKEIANATAKPED HHHHHHHHCCCCCCC	43.41	12754519
325	N-linked_Glycosylation	GKPFSWLNFTNEIMS CEECCEEECCCCCHH	35.12	10669592
387	Phosphorylation	VSSLSRTYKESRNAF HHHHHHHHHHHHHHH	16.20	22817900
399	Phosphorylation	NAFRKALYGTTSETA HHHHHHHHCCCCCCH	19.79	20068231
401	Phosphorylation	FRKALYGTTSETATW HHHHHHCCCCCCHHH	17.37	28509920
402	Phosphorylation	RKALYGTTSETATWR HHHHHCCCCCCHHHH	21.87	20068231
403	Phosphorylation	KALYGTTSETATWRR HHHHCCCCCCHHHHH	32.56	28509920
405	Phosphorylation	LYGTTSETATWRRCA HHCCCCCCHHHHHHH	29.20	20068231
407	Phosphorylation	GTTSETATWRRCANY CCCCCCHHHHHHHHH	27.24	20068231
482	Phosphorylation	AIKERIGYPDDIVSN HHHHHHCCCHHHCCC	10.91	-
497	Phosphorylation	DNKLNNEYLELNYKE CCCCCHHHHHHHCCC	13.96	-
502	Phosphorylation	NEYLELNYKEDEYFE HHHHHHHCCCHHHHH	28.51	-
507	Phosphorylation	LNYKEDEYFENIIQN HHCCCHHHHHHHHHH	28.63	-
628	N-linked_Glycosylation	CMVYQYGNFSWDLAG EEEEEECCEEEECCC	23.89	22766194
713	Phosphorylation	SIKTDVHSPGNFRII CCCCEECCCCCEEEE	34.06	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
6	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
628	N	Glycosylation		22766194
Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of NEP_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
LYN_HUMAN	LYN	physical	8943850
NHRF1_HUMAN	SLC9A3R1	physical	17342744
NDUA9_HUMAN	NDUFA9	physical	17342744
UBAC2_HUMAN	UBAC2	physical	17342744
AT12A_HUMAN	ATP12A	physical	17342744
RS10_HUMAN	RPS10	physical	17342744
RUVB2_HUMAN	RUVBL2	physical	17342744
UTRO_HUMAN	UTRN	physical	17342744
RM44_HUMAN	MRPL44	physical	17342744
CAB45_HUMAN	SDF4	physical	17342744
FAHD1_HUMAN	FAHD1	physical	17342744
FAAH1_HUMAN	FAAH	physical	17342744
F234A_HUMAN	ITFG3	physical	17342744
CPSF6_HUMAN	CPSF6	physical	17342744
RT25_HUMAN	MRPS25	physical	17342744
SRS11_HUMAN	SRSF11	physical	17342744
DJB12_HUMAN	DNAJB12	physical	17342744
LTOR1_HUMAN	LAMTOR1	physical	17342744
RAP2B_HUMAN	RAP2B	physical	17342744
SSRD_HUMAN	SSR4	physical	17342744
RUVB1_HUMAN	RUVBL1	physical	17342744
LMNA_HUMAN	LMNA	physical	17342744
PCNA_HUMAN	PCNA	physical	17342744
NUCKS_HUMAN	NUCKS1	physical	17342744
MET7A_HUMAN	METTL7A	physical	17342744
VDAC2_HUMAN	VDAC2	physical	17342744
TNPO1_HUMAN	TNPO1	physical	17342744
MOT1_HUMAN	SLC16A1	physical	17342744
HSPB1_HUMAN	HSPB1	physical	17342744
FACE1_HUMAN	ZMPSTE24	physical	17342744
HEMH_HUMAN	FECH	physical	17342744
FOLH1_HUMAN	FOLH1	physical	17342744
FLOT2_HUMAN	FLOT2	physical	17342744
PDIA5_HUMAN	PDIA5	physical	17342744
HSP7C_HUMAN	HSPA8	physical	17342744
TM9S1_HUMAN	TM9SF1	physical	17342744
NDUAA_HUMAN	NDUFA10	physical	17342744
RBM39_HUMAN	RBM39	physical	17342744
NDUB4_HUMAN	NDUFB4	physical	17342744
KBTB3_HUMAN	KBTBD3	physical	17342744
C1TC_HUMAN	MTHFD1	physical	17342744
RS23_HUMAN	RPS23	physical	17342744
RL30_HUMAN	RPL30	physical	17342744
ATPK_HUMAN	ATP5J2	physical	17342744
ARL1_HUMAN	ARL1	physical	17342744
XRCC5_HUMAN	XRCC5	physical	17342744
IMDH2_HUMAN	IMPDH2	physical	17342744
NOLC1_HUMAN	NOLC1	physical	17342744
TBB8_HUMAN	TUBB8	physical	17342744
ARM10_HUMAN	ARMC10	physical	17342744
MRVI1_HUMAN	MRVI1	physical	17342744
CK5P3_HUMAN	CDK5RAP3	physical	17342744
IRAK2_HUMAN	IRAK2	physical	17342744
LYRIC_HUMAN	MTDH	physical	17342744
MYH9_HUMAN	MYH9	physical	17342744
AL3A2_HUMAN	ALDH3A2	physical	17342744
LONM_HUMAN	LONP1	physical	17342744
FA83F_HUMAN	FAM83F	physical	17342744
POTEI_HUMAN	POTEI	physical	17342744
OPA1_HUMAN	OPA1	physical	17342744
CLC4M_HUMAN	CLEC4M	physical	17342744
EF1A1_HUMAN	EEF1A1	physical	17342744
K1C10_HUMAN	KRT10	physical	17342744
NNTM_HUMAN	NNT	physical	17342744
SHIP1_HUMAN	INPP5D	physical	17342744
HSP74_HUMAN	HSPA4	physical	17342744
ANGT_HUMAN	AGT	physical	15283675
ANF_HUMAN	NPPA	physical	2531377
NEP_HUMAN	MME	physical	21515054
GL8D2_HUMAN	GLT8D2	physical	28514442
MAN1_HUMAN	LEMD3	physical	28514442
PXMP2_HUMAN	PXMP2	physical	28514442
PMGT1_HUMAN	POMGNT1	physical	28514442
NTCP7_HUMAN	SLC10A7	physical	28514442
STAR3_HUMAN	STARD3	physical	28514442
MANEL_HUMAN	MANEAL	physical	28514442
TEN3_HUMAN	TENM3	physical	28514442
TM223_HUMAN	TMEM223	physical	28514442
ACSL4_HUMAN	ACSL4	physical	28514442
B4GT1_HUMAN	B4GALT1	physical	28514442
EPHB4_HUMAN	EPHB4	physical	28514442
LEMD2_HUMAN	LEMD2	physical	28514442
S22AI_HUMAN	SLC22A18	physical	28514442
PLD6_HUMAN	PLD6	physical	28514442
TIM16_HUMAN	PAM16	physical	28514442
MANEA_HUMAN	MANEA	physical	28514442
F213A_HUMAN	FAM213A	physical	28514442
GALT7_HUMAN	GALNT7	physical	28514442

Drug and Disease Associations

Kegg Disease
H00001	Acute lymphoblastic leukemia (ALL) (precursor B lymphoblastic leukemia)
H00002	Acute lymphoblastic leukemia (ALL) (precursor T lymphoblastic leukemia)
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D01070	Candoxatril (JAN/USAN/INN)
D03349	Candoxatrilat (USAN/INN)
D03929	Ecadotril (USAN/INN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of NEP_HUMAN

Related Literatures of Post-Translational Modification

Myristoylation
Reference	PubMed
"Neutral endopeptidase is a myristoylated protein."; Zheng R., Horiguchi A., Iida K., Lee J., Shen R., Goodman O.B. Jr.,Nanus D.M.; Mol. Cell. Biochem. 335:173-180(2010). Cited for: MYRISTOYLATION AT GLY-2.	19756956 [Abstract]
N-linked Glycosylation
Reference	PubMed
"Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV."; Oefner C., Pierau S., Schulz H., Dale G.E.; Acta Crystallogr. D 63:975-981(2007). Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 55-750 IN COMPLEX WITH ZINCIONS AND THE SYNTHETIC INHIBITOR MCB3937, DISULFIDE BONDS, COFACTOR,AND GLYCOSYLATION AT ASN-145; ASN-325 AND ASN-628.	17704566 [Abstract]
"Structural analysis of neprilysin with various specific and potentinhibitors."; Oefner C., Roques B.P., Fournie-Zaluski M.-C., Dale G.E.; Acta Crystallogr. D 60:392-396(2004). Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 55-750 IN COMPLEXES WITHZINC IONS AND SYNTHETIC INHIBITORS, DISULFIDE BONDS, COFACTOR, ANDGLYCOSYLATION AT ASN-145; ASN-325 AND ASN-628.	14747736 [Abstract]
"Structure of human neutral endopeptidase (Neprilysin) complexed withphosphoramidon."; Oefner C., D'Arcy A., Hennig M., Winkler F.K., Dale G.E.; J. Mol. Biol. 296:341-349(2000). Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), AND GLYCOSYLATION AT ASN-145;ASN-325 AND ASN-628.	10669592 [Abstract]
"Identification and quantification of N-linked glycoproteins usinghydrazide chemistry, stable isotope labeling and mass spectrometry."; Zhang H., Li X.-J., Martin D.B., Aebersold R.; Nat. Biotechnol. 21:660-666(2003). Cited for: GLYCOSYLATION AT ASN-145 AND ASN-285.	12754519 [Abstract]

show