iUUCD 2.0 - integrated annotations for ubiquitin and ubiquitin-like conjugation database

Cancer Mutation
TCGA	ICGC	COSMIC	CGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEO	ArrayExpress	TCGA	ICGC
COSMIC	THPA	HPM
DNA & RNA Element
UTRdb	circBase	circRNADb	CircNet
miRTarBase	microRNA	TRANSFAC	TargetScan
RepTar	SomamiR	miRcode	RAID2
Protein-protein Interaction
IID	iRefIndex	HINT	Mentha
InWeb_IM
Disease-associated Information
GWASdb	OMIM
Post-translational Modifications (PTMs)
CPLM	dbPAF	PhosphositePlus	dbPTM
HPRD	BioGRID	mUbiSiDa
DNA Methylation
MethyCancer	TCGA	ICGC	COSMIC
Protein Expression/Proteomics
THPA	HPM	GPMDB

Status

Reviewed

Details

Family	Domain	References (PMIDs)
E3 activity/HECT	HECT	15331633; 20175895; 18535780

Classification

Family	E-value	Score	Start	End
E3 activity/HECT	1.30e-90	305.9	703	1024

Active Site

Position(s)	Description	Evidence
994	Glycyl thioester intermediate	{ECO:0000255\|PROSITE-ProRule:PRU00104}

Domain Profile

E3 activity/HECT

   S: 2    ksdlkkrlevefvgEegldlgGvtreflallskelqnpdlglflysendketlqpnpdsglknpehlklFeflGrllgkalqdgrlldlp 91
           ++dl+k+l+v+f+gE g dlgGv++ef+++l++e+ +p++g+f+y e+ +++++p + ++    e+ ++F f+G+l+g++l++ ++ +lp
   Q: 703  NEDLRKELWVSFSGEIGYDLGGVKKEFFYCLFAEMIQPEYGMFMYPEGASCMWFPVKPKF----EKKRYF-FFGVLCGLSLFNCNVANLP 787
           689********************************************************9....567888.99***************** PP
   S: 92   lsksfyklllgkklsledleevdpelykslkeikenaesdieelgldltfsvseeilgetkeeeLkpgGenipVtneNkeeYvklvveyr 181
           ++ +++k+ll++  sledl+e+ p+l k+l+ +++ + ++ e       f ++ ++  ++++++L+p+G++i V+++Nk++Yv+++++y+
   Q: 788  FPLALFKKLLDQMPSLEDLKELSPDLGKNLQTLLDDEGDNFE-----EVFYIHFNVHWDRNDTNLIPNGSSITVNQTNKRDYVSKYINYI 872
           **********************************87544444.....455555667779999**************************** PP
   S: 182  lkegikeqveafreGfneviplellslFteeelellicGeeeidvedlkketkykggytedspaiqwFwevleefsseerkafLqFvTgs 271
           +++++k  +e+fr+Gf++++++++++lF++eel+ +i G++++d+++++k+++y+ gy++++p+i +Fw+++++++ ee+k+fL F+Tg+
   Q: 873  FNDSVKAVYEEFRRGFYKMCDEDIIKLFHPEELKDVIVGNTDYDWKTFEKNARYEPGYNSSHPTIVMFWKAFHKLTLEEKKKFLVFLTGT 962
           ****************************************************************************************** PP
   S: 272  srlPlgGfaelkprlfvirkdasddrlPssnTCfnyLkLPeYsskeilkekLlyAieetkgFe 334
           +rl ++ ++++k   f+++++ ++++ +++ TCf++L LP+Ys++e+++e L+ Ai++++gF+
   Q: 963  DRLQMKDLNNMK-ITFCCPESWNERDPIRALTCFSVLFLPKYSTMETVEEALQEAINNNRGFG 1024
           ************.77999999****************************************96 PP

Organism

Homo sapiens

Functional Description
(View)

Major E3 ligase for ISG15 conjugation. Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant-negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15.

Protein Sequence
(Fasta)

MERRSRRKSR RNGRSTAGKA AATQPAKSPG AQLWLFPSAA GLHRALLRRV EVTRQLCCSP 60
GRLAVLERGG AGVQVHQLLA GSGGARTPKC IKLGKNMKIH SVDQGAEHML ILSSDGKPFE 120

It may take some time, please wait.

Nucleotide Sequence
(Fasta)

TCAGTAGCTG AGGCTGCGGT TCCCCGACGC CACGCAGCTG CGCGCAGCTG GTTCCCGCTC 60
TGCAGCGCAA CGCCTGAGGC AGTGGGCGCG CTCAGTCCCG GGACCAGGCG TTCTCTCCTC 120

It may take some time, please wait.

Sequence Source

Ensembl

Keyword

KW-0051--Antiviral defense
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0391--Immunity
KW-0399--Innate immunity
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0677--Repeat
KW-0808--Transferase
KW-0832--Ubl conjugation
KW-0833--Ubl conjugation pathway

Interpro

IPR000569--HECT_dom
IPR009091--RCC1/BLIP-II
IPR000408--Reg_chr_condens

PROSITE

PS50237--HECT
PS00626--RCC1_2
PS50012--RCC1_3

Pfam

PF00632--HECT
PF00415--RCC1

PRINTS

PR00633--RCCNDNSATION

SMART

SM00119--HECTc

Gene Ontology

GO:0005829--C:cytosol
GO:0048471--C:perinuclear region of cytoplasm
GO:0042296--F:ISG15 transferase activity
GO:0003723--F:RNA binding
GO:0004842--F:ubiquitin-protein transferase activity
GO:0051607--P:defense response to virus
GO:0045087--P:innate immune response
GO:0032020--P:ISG15-protein conjugation
GO:0032480--P:negative regulation of type I interferon production
GO:0000209--P:protein polyubiquitination
GO:0000079--P:regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0050688--P:regulation of defense response to virus

KEGG

hsa:51191

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-001676	Ailuropoda melanoleuca	77.14	0.00e+00	1596.00
IUUC-Bta-012422	Bos taurus	68.78	0.00e+00	1283.00
IUUC-Cja-018751	Callithrix jacchus	90.78	0.00e+00	1896.00
IUUC-Cfa-020247	Canis familiaris	76.58	0.00e+00	1504.00
IUUC-Csa-023204	Chlorocebus sabaeus	95.15	0.00e+00	1723.00
IUUC-Cho-025101	Choloepus hoffmanni	62.78	4.00e-178	618.00
IUUC-Dno-029795	Dasypus novemcinctus	70.26	0.00e+00	1145.00
IUUC-Dor-030862	Dipodomys ordii	66.16	0.00e+00	1284.00
IUUC-Ete-032585	Echinops telfairi	59.86	0.00e+00	842.00
IUUC-Eca-034358	Equus caballus	76.01	0.00e+00	1489.00
IUUC-Eeu-035282	Erinaceus europaeus	65.58	0.00e+00	733.00
IUUC-Fca-036505	Felis catus	77.60	0.00e+00	1569.00
IUUC-Ggo-045445	Gorilla gorilla	95.44	0.00e+00	1865.00
IUUC-Itr-049004	Ictidomys tridecemlineatus	70.67	0.00e+00	1426.00
IUUC-Laf-053921	Loxodonta africana	72.19	0.00e+00	1469.00
IUUC-Mcc-054850	Macaca mulatta	95.26	0.00e+00	1729.00
IUUC-Mmr-060783	Microcebus murinus	66.92	0.00e+00	1211.00
IUUC-Mpu-066123	Mustela putorius furo	76.71	0.00e+00	1581.00
IUUC-Mlu-067914	Myotis lucifugus	76.07	0.00e+00	1420.00
IUUC-Nle-069986	Nomascus leucogenys	96.98	0.00e+00	1954.00
IUUC-Opr-070513	Ochotona princeps	69.80	0.00e+00	1052.00
IUUC-Ocu-074305	Oryctolagus cuniculus	72.52	0.00e+00	1386.00
IUUC-Oar-089456	Ovis aries	76.61	0.00e+00	1518.00
IUUC-Ptr-091216	Pan troglodytes	89.00	0.00e+00	1743.00
IUUC-Pan-091706	Papio anubis	93.87	0.00e+00	1858.00
IUUC-Pab-097883	Pongo abelii	96.65	0.00e+00	795.00
IUUC-Pca-100320	Procavia capensis	66.20	0.00e+00	1348.00
IUUC-Pva-102646	Pteropus vampyrus	77.98	0.00e+00	1580.00
IUUC-Sar-113605	Sorex araneus	75.38	2.00e-150	526.00
IUUC-Tsy-119240	Tarsius syrichta	66.38	0.00e+00	1239.00
IUUC-Tbe-127787	Tupaia belangeri	71.09	0.00e+00	1352.00
IUUC-Ttr-128191	Tursiops truncatus	74.70	0.00e+00	1490.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence