NED4L_PONAB
ID NED4L_PONAB Reviewed; 959 AA.
AC Q5RBF2;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 108.
DE RecName: Full=E3 ubiquitin-protein ligase NEDD4-like;
DE EC=2.3.2.26 {ECO:0000250|UniProtKB:P46934};
DE AltName: Full=HECT-type E3 ubiquitin transferase NED4L;
GN Name=NEDD4L;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an
CC E2 ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates. Inhibits TGF-
CC beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and
CC proteasome-dependent degradation. Promotes ubiquitination and
CC internalization of various plasma membrane channels such as ENaC,
CC Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, KCNH2, EAAT1 or CLC5.
CC Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates
CC BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1.
CC Plays a role in dendrite formation by melanocytes (By similarity).
CC Involved in the regulation of TOR signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000250|UniProtKB:Q96PU5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26; Evidence={ECO:0000250|UniProtKB:P46934};
CC -!- ACTIVITY REGULATION: Activated by NDFIP1- and NDFIP2-binding.
CC {ECO:0000250|UniProtKB:Q96PU5}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with UBE2E3 (By similarity). Interacts with NDFIP1;
CC this interaction activates the E3 ubiquitin-protein ligase (By
CC similarity). Interacts with NDFIP2; this interaction activates the E3
CC ubiquitin-protein ligase (By similarity). Interacts (via WW domains)
CC with SCNN1A (By similarity). Interacts (via WW domains) with SCNN1B (By
CC similarity). Interacts (via WW domains) with SCNN1G (By similarity).
CC Interacts (via WW domains) with SCN1A (By similarity). Interacts (via
CC WW domains) with SCN2A (By similarity). Interacts (via WW domains) with
CC SCN3A (By similarity). Interacts (via WW domains) with SCN5A (By
CC similarity). Interacts (via WW domains) with SCN8A (By similarity).
CC Interacts (via WW domains) with SCN9A (By similarity). Interacts (via
CC WW domains) with SCN10A (By similarity). Interacts (via WW domains)
CC with CLCN5 (By similarity). Interacts with SMAD2 (By similarity).
CC Interacts with SMAD3 (By similarity). Interacts with SMAD6 (By
CC similarity). Interacts with SMAD7 (By similarity). The phosphorylated
CC form interacts with 14-3-3 proteins (By similarity). Interacts with
CC TNK2 (By similarity). Interacts with WNK1 (By similarity). Interacts
CC with SGK1 (By similarity). Interacts (via C2 domain) with NPC2 (By
CC similarity). Interacts with ARRDC4 (By similarity). Interacts with
CC KCNQ1; promotes internalization of KCNQ1 (By similarity). Interacts
CC (via domains WW1, 3 and 4) with USP36; the interaction inhibits
CC ubiquitination of, at least, NTRK1, KCNQ2 and KCNQ3 by NEDD4L (By
CC similarity). Interacts with PRRG4 (via cytoplasmic domain) (By
CC similarity). Interacts with LDLRAD3; the interaction is direct (By
CC similarity). {ECO:0000250|UniProtKB:Q8CFI0,
CC ECO:0000250|UniProtKB:Q96PU5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96PU5}. Golgi
CC apparatus {ECO:0000250|UniProtKB:Q96PU5}. Endosome, multivesicular body
CC {ECO:0000250|UniProtKB:Q96PU5}.
CC -!- PTM: Phosphorylated; which impairs interaction with SCNN. Interaction
CC with YWHAH inhibits dephosphorylation (By similarity). {ECO:0000250}.
CC -!- PTM: Auto-ubiquitinated. {ECO:0000250|UniProtKB:Q96PU5}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR858697; CAH90908.1; -; mRNA.
DR RefSeq; NP_001125518.1; NM_001132046.1.
DR AlphaFoldDB; Q5RBF2; -.
DR BMRB; Q5RBF2; -.
DR SMR; Q5RBF2; -.
DR STRING; 9601.ENSPPYP00000010317; -.
DR GeneID; 100172429; -.
DR KEGG; pon:100172429; -.
DR CTD; 23327; -.
DR eggNOG; KOG0940; Eukaryota.
DR InParanoid; Q5RBF2; -.
DR OrthoDB; 271539at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005771; C:multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 4.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR024928; E3_ub_ligase_SMURF1.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00397; WW; 4.
DR PIRSF; PIRSF001569; E3_ub_ligase_SMURF1; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR SMART; SM00239; C2; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00456; WW; 4.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 4.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 4.
DR PROSITE; PS50020; WW_DOMAIN_2; 4.
PE 2: Evidence at transcript level;
KW Cytoplasm; Differentiation; Endosome; Golgi apparatus; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..959
FT /note="E3 ubiquitin-protein ligase NEDD4-like"
FT /id="PRO_0000120325"
FT DOMAIN 10..130
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 197..230
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 369..402
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 481..514
FT /note="WW 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 532..565
FT /note="WW 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 624..958
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 183..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 248..275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 408..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 248..265
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..439
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 926
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 322
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 346
FT /note="Phosphoserine; by WNK1 and WNK4"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 432
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 433
FT /note="Phosphoserine; by WNK1 and WNK4"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 448
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 459
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PU5"
SQ SEQUENCE 959 AA; 110511 MW; E328E83DC8EEB79B CRC64;
MAPLSAALLP WHGVCVPVCY GESRILRVKV VSGIDLAKKD IFGASDPYVK LSLYVADENR
ELALVQTKTI KKTLNPKWNE EFYFRVNPSN HRLLFEVFDE NRLTRDDFLG QVDVPLSHLP
TEDPTMERPY TFKDFLLRPR SHKSRVKGFL RLKMAYMPKN GGQEEENSEQ RDDMEHGWEV
VDSNDSASQH QEELPPPPLP PGWEEKVDNL GRTYYVNHNN RTTQWHRPSL MDVSSESDNN
IRQINQEAAH RRFRSRRHIS EDLEPEPSEG GDVPEPWETI SEEVNIAGDS LGLALPPPPA
SPGSRTSPQE LSEELSRRLQ ITPDSNGEQF SSLIQREPSS RLRSCSVTDA VAEQGHLPPP
SVAYVHTTPG LPSGWEERKD AKGRTYYVNH NNRTTTWTRP IMQLAEDGAS GSATNSNNHL
IEPQIRRPRS LSSPTVTLSA PLEGAKDSPV RRAVKDTLSN PQSPQPSPYN SPKPQHKVTQ
SFLPPGWEMR IAPNGRPFFI DHNTKTTTWE DPRLKFPVHM RSKTSLNPND LGPLPPGWEE
RIHLDGRTFY IDHNSKITQW EDPRLQNPAI TGPAVPYSRE FKQKYDYFRK KLKKPADIPN
RFEMKLHRNN IFEESYRRIM SVKRPDVLKA RLWIEFESEK GLDYGGVARE WFFLLSKEMF
NPYYGLFEYS ATDNYTLQIN PNSGLCNEDH LSYFTFIGRV AGLAVFHGKL LDGFFIRPFY
KMMLGKQITL NDMESVDSEY YNSLKWILEN DPTELDLMFC IDEENFGQTY QVDLEPNGSE
IMVTNENKRE YIDLVIQWRF VNRVQKQMNA FLEGFTELLP IDLIKIFDEN ELELLMCGLG
DVDVNDWRQH SIYKNGYCPN HPVIQWFWKA VLLMDAEKRI RLLQFVTGTS RVPMNGFAEL
YGSNGPQLFT IEQWGSPEKL PRAHTCFNRL DLPPYETFED LREKLLMAVE NAQGFEGVD
