UniProtKB - Q5RBF2 (NED4L_PONAB)
Protein
E3 ubiquitin-protein ligase NEDD4-like
Gene
NEDD4L
Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Functioni
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, KCNH2, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1. Plays a role in dendrite formation by melanocytes (By similarity). Involved in the regulation of TOR signaling (By similarity).By similarity
Catalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. EC:2.3.2.26
Activity regulationi
Activated by NDFIP1- and NDFIP2-binding. Interacts (via C2 domain) with NPC2.By similarity
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 926 | Glycyl thioester intermediatePROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- ubiquitin protein ligase activity Source: InterPro
GO - Biological processi
- cell differentiation Source: UniProtKB-KW
- ubiquitin-dependent protein catabolic process Source: InterPro
Keywordsi
Molecular function | Transferase |
Biological process | Differentiation, Ubl conjugation pathway |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase NEDD4-like (EC:2.3.2.26)Alternative name(s): HECT-type E3 ubiquitin transferase NED4L |
Gene namesi | Name:NEDD4L |
Organismi | Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) |
Taxonomic identifieri | 9601 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Pongo |
Proteomesi |
|
Subcellular locationi
Golgi apparatus
- Golgi apparatus By similarity
Endosome
- multivesicular body By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Endosome
- multivesicular body Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, Endosome, Golgi apparatusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000120325 | 1 – 959 | E3 ubiquitin-protein ligase NEDD4-likeAdd BLAST | 959 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 316 | PhosphoserineBy similarity | 1 | |
Modified residuei | 322 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 346 | Phosphoserine; by WNK1 and WNK4By similarity | 1 | |
Modified residuei | 430 | PhosphoserineBy similarity | 1 | |
Modified residuei | 432 | Phosphoserine; by SGK1By similarity | 1 | |
Modified residuei | 433 | Phosphoserine; by WNK1 and WNK4By similarity | 1 | |
Modified residuei | 448 | Phosphoserine; by SGK1By similarity | 1 | |
Modified residuei | 459 | PhosphoserineBy similarity | 1 | |
Modified residuei | 463 | PhosphoserineBy similarity | 1 | |
Modified residuei | 467 | PhosphoserineBy similarity | 1 | |
Modified residuei | 471 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Phosphorylated; which impairs interaction with SCNN. Interaction with YWHAH inhibits dephosphorylation (By similarity).By similarity
Auto-ubiquitinated.By similarity
Keywords - PTMi
Phosphoprotein, Ubl conjugationInteractioni
Subunit structurei
Interacts with SMAD2, SMAD3, SMAD6 and SMAD7. The phosphorylated form interacts with 14-3-3 proteins.
Interacts via its WW domains with SCNN1A, SCNN1B, SCNN1G, SCN1A, SCN2A, SCN3A, SCN5A, SCN8A, SCN9A, SCN10A and CLCN5.
Interacts with UBE2E3.
Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase.
Interacts with TNK2.
Interacts with SGK1.
Interacts with ARRDC4.
Interacts with KCNQ1; promotes internalization of KCNQ1.
Interacts with PRRG4 (via cytoplasmic domain) (By similarity).
By similarityProtein-protein interaction databases
STRINGi | 9601.ENSPPYP00000010317 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 10 – 130 | C2PROSITE-ProRule annotationAdd BLAST | 121 | |
Domaini | 197 – 230 | WW 1PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 369 – 402 | WW 2PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 481 – 514 | WW 3PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 532 – 565 | WW 4PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 624 – 958 | HECTPROSITE-ProRule annotationAdd BLAST | 335 |
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0940, Eukaryota |
InParanoidi | Q5RBF2 |
OrthoDBi | 271539at2759 |
Family and domain databases
CDDi | cd00078, HECTc, 1 hit cd00201, WW, 4 hits |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR024928, E3_ub_ligase_SMURF1 IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR001202, WW_dom IPR036020, WW_dom_sf |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF00397, WW, 4 hits |
PIRSFi | PIRSF001569, E3_ub_ligase_SMURF1, 1 hit |
PRINTSi | PR00360, C2DOMAIN |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 4 hits |
SUPFAMi | SSF51045, SSF51045, 4 hits SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 4 hits PS50020, WW_DOMAIN_2, 4 hits |
i Sequence
Sequence statusi: Complete.
Q5RBF2-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAPLSAALLP WHGVCVPVCY GESRILRVKV VSGIDLAKKD IFGASDPYVK
60 70 80 90 100
LSLYVADENR ELALVQTKTI KKTLNPKWNE EFYFRVNPSN HRLLFEVFDE
110 120 130 140 150
NRLTRDDFLG QVDVPLSHLP TEDPTMERPY TFKDFLLRPR SHKSRVKGFL
160 170 180 190 200
RLKMAYMPKN GGQEEENSEQ RDDMEHGWEV VDSNDSASQH QEELPPPPLP
210 220 230 240 250
PGWEEKVDNL GRTYYVNHNN RTTQWHRPSL MDVSSESDNN IRQINQEAAH
260 270 280 290 300
RRFRSRRHIS EDLEPEPSEG GDVPEPWETI SEEVNIAGDS LGLALPPPPA
310 320 330 340 350
SPGSRTSPQE LSEELSRRLQ ITPDSNGEQF SSLIQREPSS RLRSCSVTDA
360 370 380 390 400
VAEQGHLPPP SVAYVHTTPG LPSGWEERKD AKGRTYYVNH NNRTTTWTRP
410 420 430 440 450
IMQLAEDGAS GSATNSNNHL IEPQIRRPRS LSSPTVTLSA PLEGAKDSPV
460 470 480 490 500
RRAVKDTLSN PQSPQPSPYN SPKPQHKVTQ SFLPPGWEMR IAPNGRPFFI
510 520 530 540 550
DHNTKTTTWE DPRLKFPVHM RSKTSLNPND LGPLPPGWEE RIHLDGRTFY
560 570 580 590 600
IDHNSKITQW EDPRLQNPAI TGPAVPYSRE FKQKYDYFRK KLKKPADIPN
610 620 630 640 650
RFEMKLHRNN IFEESYRRIM SVKRPDVLKA RLWIEFESEK GLDYGGVARE
660 670 680 690 700
WFFLLSKEMF NPYYGLFEYS ATDNYTLQIN PNSGLCNEDH LSYFTFIGRV
710 720 730 740 750
AGLAVFHGKL LDGFFIRPFY KMMLGKQITL NDMESVDSEY YNSLKWILEN
760 770 780 790 800
DPTELDLMFC IDEENFGQTY QVDLEPNGSE IMVTNENKRE YIDLVIQWRF
810 820 830 840 850
VNRVQKQMNA FLEGFTELLP IDLIKIFDEN ELELLMCGLG DVDVNDWRQH
860 870 880 890 900
SIYKNGYCPN HPVIQWFWKA VLLMDAEKRI RLLQFVTGTS RVPMNGFAEL
910 920 930 940 950
YGSNGPQLFT IEQWGSPEKL PRAHTCFNRL DLPPYETFED LREKLLMAVE
NAQGFEGVD
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | CR858697 mRNA Translation: CAH90908.1 |
RefSeqi | NP_001125518.1, NM_001132046.1 |
Genome annotation databases
GeneIDi | 100172429 |
KEGGi | pon:100172429 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | CR858697 mRNA Translation: CAH90908.1 |
RefSeqi | NP_001125518.1, NM_001132046.1 |
3D structure databases
BMRBi | Q5RBF2 |
SMRi | Q5RBF2 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9601.ENSPPYP00000010317 |
Genome annotation databases
GeneIDi | 100172429 |
KEGGi | pon:100172429 |
Organism-specific databases
CTDi | 23327 |
Phylogenomic databases
eggNOGi | KOG0940, Eukaryota |
InParanoidi | Q5RBF2 |
OrthoDBi | 271539at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Family and domain databases
CDDi | cd00078, HECTc, 1 hit cd00201, WW, 4 hits |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR024928, E3_ub_ligase_SMURF1 IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR001202, WW_dom IPR036020, WW_dom_sf |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF00397, WW, 4 hits |
PIRSFi | PIRSF001569, E3_ub_ligase_SMURF1, 1 hit |
PRINTSi | PR00360, C2DOMAIN |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 4 hits |
SUPFAMi | SSF51045, SSF51045, 4 hits SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 4 hits PS50020, WW_DOMAIN_2, 4 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NED4L_PONAB | |
Accessioni | Q5RBF2Primary (citable) accession number: Q5RBF2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 30, 2005 |
Last sequence update: | December 21, 2004 | |
Last modified: | February 10, 2021 | |
This is version 104 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways