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Protein

E3 ubiquitin-protein ligase HUWE1

Gene

HUWE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1. Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair. Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4. Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN. May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation. Mediates polyubiquitination of isoform 2 of PA2G4.8 Publications

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.

Pathwayi: protein ubiquitination

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 keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei4341Glycyl thioester intermediate1

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • base-excision repair Source: UniProtKB
  • cell differentiation Source: UniProtKB-KW
  • histone ubiquitination Source: UniProtKB
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • protein monoubiquitination Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Differentiation, DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase HUWE1 (EC:2.3.2.26)
Alternative name(s):
ARF-binding protein 1
Short name:
ARF-BP1
HECT, UBA and WWE domain-containing protein 1
HECT-type E3 ubiquitin transferase HUWE1
Homologous to E6AP carboxyl terminus homologous protein 9
Short name:
HectH9
Large structure of UREB1
Short name:
LASU1
Mcl-1 ubiquitin ligase E3
Short name:
Mule
Upstream regulatory element-binding protein 1
Short name:
URE-B1
Short name:
URE-binding protein 1
Gene namesi
Name:HUWE1
Synonyms:KIAA0312, KIAA1578, UREB1
ORF Names:HSPC272
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:30892. HUWE1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked, syndromic, Turner type (MRXST)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by the association of mental retardation with macrocephaly and variable contractures.
See also OMIM:300706
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0456702981R → H in MRXST. 1 PublicationCorresponds to variant rs121918526dbSNPEnsembl.1
Natural variantiVAR_0456714013R → W in MRXST. 1 PublicationCorresponds to variant rs121918525dbSNPEnsembl.1
Natural variantiVAR_0456724187R → C in MRXST. 1 PublicationCorresponds to variant rs121918527dbSNPEnsembl.1
Mental retardation, X-linked 17 (MRX17)1 Publication
The gene represented in this entry is involved in disease pathogenesis. A chromosomal microduplication involving HSD17B10 and HUWE1 has been found in patients with mental retardation.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.
See also OMIM:300705

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi4268Y → S: Loss of activity. 1 Publication1
Mutagenesisi4341C → A or D: Loss of activity. 4 Publications1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi10075.
MalaCardsiHUWE1.
MIMi300705. phenotype.
300706. phenotype.
OpenTargetsiENSG00000086758.
Orphaneti85328. X-linked intellectual disability, Turner type.
PharmGKBiPA128394567.

Polymorphism and mutation databases

BioMutaiHUWE1.
DMDMi73915353.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203401 – 4374E3 ubiquitin-protein ligase HUWE1Add BLAST4374

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei648PhosphoserineBy similarity1
Modified residuei649PhosphoserineBy similarity1
Modified residuei740PhosphoserineCombined sources1
Modified residuei1084PhosphoserineCombined sources1
Modified residuei1368PhosphoserineCombined sources1
Modified residuei1370PhosphoserineCombined sources1
Modified residuei1382PhosphoserineCombined sources1
Modified residuei1395PhosphoserineCombined sources1
Modified residuei1722PhosphothreonineCombined sources1
Modified residuei1907PhosphoserineCombined sources1
Modified residuei2035PhosphothreonineCombined sources1
Modified residuei2266PhosphoserineCombined sources1
Modified residuei2267N6-acetyllysineBy similarity1
Modified residuei2362PhosphoserineCombined sources1
Modified residuei2365PhosphoserineCombined sources1
Modified residuei2391PhosphoserineCombined sources1
Modified residuei2527PhosphoserineCombined sources1
Modified residuei2532PhosphoserineCombined sources1
Modified residuei2535PhosphoserineCombined sources1
Modified residuei2554PhosphothreonineCombined sources1
Modified residuei2584PhosphoserineCombined sources1
Modified residuei2595PhosphoserineCombined sources1
Modified residuei2619PhosphoserineCombined sources1
Modified residuei2751PhosphothreonineCombined sources1
Modified residuei2826PhosphoserineCombined sources1
Modified residuei2833PhosphoserineCombined sources1
Modified residuei2835PhosphoserineCombined sources1
Modified residuei2861PhosphoserineCombined sources1
Modified residuei2887PhosphoserineCombined sources1
Modified residuei2888PhosphoserineCombined sources1
Modified residuei2889PhosphothreonineCombined sources1
Modified residuei2918PhosphoserineCombined sources1
Modified residuei3116PhosphoserineCombined sources1
Modified residuei3117PhosphoserineCombined sources1
Modified residuei3122PhosphoserineCombined sources1
Modified residuei3127PhosphoserineCombined sources1
Modified residuei3135PhosphoserineCombined sources1
Modified residuei3149Omega-N-methylarginineBy similarity1
Modified residuei3555PhosphoserineCombined sources1
Modified residuei3662PhosphoserineCombined sources1
Modified residuei3752PhosphoserineCombined sources1
Modified residuei3757PhosphoserineCombined sources1
Modified residuei3759PhosphoserineCombined sources1
Modified residuei3760PhosphoserineCombined sources1
Modified residuei3808PhosphoserineCombined sources1
Modified residuei3816PhosphoserineCombined sources1
Modified residuei3827PhosphoserineCombined sources1
Modified residuei3830PhosphothreonineCombined sources1
Modified residuei3906PhosphoserineCombined sources1
Modified residuei3919PhosphoserineCombined sources1
Modified residuei3924PhosphothreonineCombined sources1
Modified residuei3927PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine; phosphorylation is probably required for its ability to inhibit TP53 transactivation.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ7Z6Z7.
MaxQBiQ7Z6Z7.
PaxDbiQ7Z6Z7.
PeptideAtlasiQ7Z6Z7.
PRIDEiQ7Z6Z7.

PTM databases

iPTMnetiQ7Z6Z7.
PhosphoSitePlusiQ7Z6Z7.

Expressioni

Tissue specificityi

Weakly expressed in heart, brain and placenta but not in other tissues. Expressed in a number of cell lines, predominantly in those from colorectal carcinomas.1 Publication

Gene expression databases

BgeeiENSG00000086758.
ExpressionAtlasiQ7Z6Z7. baseline and differential.
GenevisibleiQ7Z6Z7. HS.

Organism-specific databases

HPAiCAB022718.
HPA002548.

Interactioni

Subunit structurei

Interacts with isoform p14ARF of CDKN2A which strongly inhibits HUWE1 ubiquitin ligase activity. Interacts with MYCN, POLB and CDC6. Interacts with isoform 2 of PA2G4.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDKN2AQ8N7265EBI-625934,EBI-625922
HSPB1P047923EBI-625934,EBI-352682
TP53P046373EBI-625934,EBI-366083
USP4Q131074EBI-625934,EBI-723290

Protein-protein interaction databases

BioGridi115385. 459 interactors.
DIPiDIP-34362N.
IntActiQ7Z6Z7. 79 interactors.
MINTiMINT-1576525.
STRINGi9606.ENSP00000262854.

Structurei

Secondary structure

14374
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1319 – 1329Combined sources11
Helixi1332 – 1341Combined sources10
Helixi1345 – 1353Combined sources9
Helixi1976 – 1991Combined sources16
Helixi2958 – 2960Combined sources3
Helixi2970 – 2975Combined sources6
Helixi2978 – 2988Combined sources11
Helixi3994 – 4008Combined sources15
Turni4009 – 4011Combined sources3
Beta strandi4016 – 4021Combined sources6
Helixi4023 – 4025Combined sources3
Helixi4026 – 4034Combined sources9
Helixi4041 – 4043Combined sources3
Beta strandi4044 – 4050Combined sources7
Helixi4061 – 4072Combined sources12
Helixi4076 – 4078Combined sources3
Beta strandi4080 – 4083Combined sources4
Turni4085 – 4087Combined sources3
Beta strandi4088 – 4093Combined sources6
Helixi4095 – 4099Combined sources5
Helixi4103 – 4120Combined sources18
Helixi4130 – 4137Combined sources8
Helixi4143 – 4145Combined sources3
Helixi4146 – 4149Combined sources4
Helixi4151 – 4162Combined sources12
Helixi4165 – 4167Combined sources3
Beta strandi4168 – 4170Combined sources3
Beta strandi4172 – 4175Combined sources4
Turni4176 – 4178Combined sources3
Beta strandi4181 – 4183Combined sources3
Helixi4186 – 4189Combined sources4
Beta strandi4193 – 4197Combined sources5
Turni4200 – 4202Combined sources3
Helixi4203 – 4215Combined sources13
Helixi4217 – 4219Combined sources3
Helixi4220 – 4233Combined sources14
Helixi4236 – 4239Combined sources4
Helixi4244 – 4252Combined sources9
Helixi4259 – 4264Combined sources6
Beta strandi4266 – 4271Combined sources6
Helixi4276 – 4287Combined sources12
Helixi4290 – 4301Combined sources12
Beta strandi4302 – 4304Combined sources3
Helixi4311 – 4313Combined sources3
Beta strandi4317 – 4320Combined sources4
Beta strandi4323 – 4328Combined sources6
Beta strandi4337 – 4339Combined sources3
Helixi4340 – 4342Combined sources3
Beta strandi4344 – 4348Combined sources5
Helixi4353 – 4365Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EKKNMR-A1317-1356[»]
2MULNMR-A2951-3003[»]
3G1NX-ray2.60A/B4005-4374[»]
3H1DX-ray1.89A3993-4374[»]
5C6HX-ray2.05B/D/F/H/J/L/N/P/R/T/V/X1969-1994[»]
ProteinModelPortaliQ7Z6Z7.
SMRiQ7Z6Z7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ7Z6Z7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1316 – 1355UBAPROSITE-ProRule annotationAdd BLAST40
Domaini1370 – 1389UIMCuratedAdd BLAST20
Domaini1603 – 1680WWEPROSITE-ProRule annotationAdd BLAST78
Domaini4038 – 4374HECTPROSITE-ProRule annotationAdd BLAST337

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2295 – 2469Glu-richAdd BLAST175
Compositional biasi2427 – 2490Asp-richAdd BLAST64
Compositional biasi3483 – 3550Thr-richAdd BLAST68

Domaini

The HECT domain mediates inhibition of the transcriptional activity of p53.

Sequence similaritiesi

Belongs to the UPL family. TOM1/PTR1 subfamily.Curated
Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation
Contains 1 WWE domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0939. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00850000132302.
HOVERGENiHBG080254.
InParanoidiQ7Z6Z7.
KOiK10592.
OMAiHAFEFIF.
OrthoDBiEOG091G01V1.
PhylomeDBiQ7Z6Z7.
TreeFamiTF323417.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
InterProiIPR016024. ARM-type_fold.
IPR025527. DUF4414.
IPR010309. E3_Ub_ligase_DUF908.
IPR010314. E3_Ub_ligase_DUF913.
IPR000569. HECT_dom.
IPR015940. UBA.
IPR009060. UBA-like.
IPR004170. WWE-dom.
[Graphical view]
PfamiPF14377. DUF4414. 1 hit.
PF06012. DUF908. 1 hit.
PF06025. DUF913. 1 hit.
PF00632. HECT. 1 hit.
PF00627. UBA. 1 hit.
PF02825. WWE. 1 hit.
[Graphical view]
SMARTiSM00119. HECTc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF48371. SSF48371. 3 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50237. HECT. 1 hit.
PS50030. UBA. 1 hit.
PS50918. WWE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7Z6Z7-1) [UniParc]FASTAAdd to basket
Also known as: LASU1, Large structure of UREB1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKVDRTKLKK TPTEAPADCR ALIDKLKVCN DEQLLLELQQ IKTWNIGKCE
60 70 80 90 100
LYHWVDLLDR FDGILADAGQ TVENMSWMLV CDRPEREQLK MLLLAVLNFT
110 120 130 140 150
ALLIEYSFSR HLYSSIEHLT TLLASSDMQV VLAVLNLLYV FSKRSNYITR
160 170 180 190 200
LGSDKRTPLL TRLQHLAESW GGKENGFGLA ECCRDLHMMK YPPSATTLHF
210 220 230 240 250
EFYADPGAEV KIEKRTTSNT LHYIHIEQLD KISESPSEIM ESLTKMYSIP
260 270 280 290 300
KDKQMLLFTH IRLAHGFSNH RKRLQAVQAR LHAISILVYS NALQESANSI
310 320 330 340 350
LYNGLIEELV DVLQITDKQL MEIKAASLRT LTSIVHLERT PKLSSIIDCT
360 370 380 390 400
GTASYHGFLP VLVRNCIQAM IDPSMDPYPH QFATALFSFL YHLASYDAGG
410 420 430 440 450
EALVSCGMME ALLKVIKFLG DEQDQITFVT RAVRVVDLIT NLDMAAFQSH
460 470 480 490 500
SGLSIFIYRL EHEVDLCRKE CPFVIKPKIQ RPNTTQEGEE METDMDGVQC
510 520 530 540 550
IPQRAALLKS MLNFLKKAIQ DPAFSDGIRH VMDGSLPTSL KHIISNAEYY
560 570 580 590 600
GPSLFLLATE VVTVFVFQEP SLLSSLQDNG LTDVMLHALL IKDVPATREV
610 620 630 640 650
LGSLPNVFSA LCLNARGLQS FVQCQPFERL FKVLLSPDYL PAMRRRRSSD
660 670 680 690 700
PLGDTASNLG SAVDELMRHQ PTLKTDATTA IIKLLEEICN LGRDPKYICQ
710 720 730 740 750
KPSIQKADGT ATAPPPRSNH AAEEASSEDE EEEEVQAMQS FNSTQQNETE
760 770 780 790 800
PNQQVVGTEE RIPIPLMDYI LNVMKFVESI LSNNTTDDHC QEFVNQKGLL
810 820 830 840 850
PLVTILGLPN LPIDFPTSAA CQAVAGVCKS ILTLSHEPKV LQEGLLQLDS
860 870 880 890 900
ILSSLEPLHR PIESPGGSVL LRELACAGNV ADATLSAQAT PLLHALTAAH
910 920 930 940 950
AYIMMFVHTC RVGQSEIRSI SVNQWGSQLG LSVLSKLSQL YCSLVWESTV
960 970 980 990 1000
LLSLCTPNSL PSGCEFGQAD MQKLVPKDEK AGTTQGGKRS DGEQDGAAGS
1010 1020 1030 1040 1050
MDASTQGLLE GIGLDGDTLA PMETDEPTAS DSKGKSKITP AMAARIKQIK
1060 1070 1080 1090 1100
PLLSASSRLG RALAELFGLL VKLCVGSPVR QRRSHHAAST TTAPTPAARS
1110 1120 1130 1140 1150
TASALTKLLT KGLSWQPPPY TPTPRFRLTF FICSVGFTSP MLFDERKYPY
1160 1170 1180 1190 1200
HLMLQKFLCS GGHNALFETF NWALSMGGKV PVSEGLEHSD LPDGTGEFLD
1210 1220 1230 1240 1250
AWLMLVEKMV NPTTVLESPH SLPAKLPGGV QNFPQFSALR FLVVTQKAAF
1260 1270 1280 1290 1300
TCIKNLWNRK PLKVYGGRMA ESMLAILCHI LRGEPVIRER LSKEKEGSRG
1310 1320 1330 1340 1350
EEDTGQEEGG SRREPQVNQQ QLQQLMDMGF TREHAMEALL NTSTMEQATE
1360 1370 1380 1390 1400
YLLTHPPPIM GGVVRDLSMS EEDQMMRAIA MSLGQDIPMD QRAESPEEVA
1410 1420 1430 1440 1450
CRKEEEERKA REKQEEEEAK CLEKFQDADP LEQDELHTFT DTMLPGCFHL
1460 1470 1480 1490 1500
LDELPDTVYR VCDLIMTAIK RNGADYRDMI LKQVVNQVWE AADVLIKAAL
1510 1520 1530 1540 1550
PLTTSDTKTV SEWISQMATL PQASNLATRI LLLTLLFEEL KLPCAWVVES
1560 1570 1580 1590 1600
SGILNVLIKL LEVVQPCLQA AKEQKEVQTP KWITPVLLLI DFYEKTAISS
1610 1620 1630 1640 1650
KRRAQMTKYL QSNSNNWRWF DDRSGRWCSY SASNNSTIDS AWKSGETSVR
1660 1670 1680 1690 1700
FTAGRRRYTV QFTTMVQVNE ETGNRRPVML TLLRVPRLNK NSKNSNGQEL
1710 1720 1730 1740 1750
EKTLEESKEM DIKRKENKGN DTPLALESTN TEKETSLEET KIGEILIQGL
1760 1770 1780 1790 1800
TEDMVTVLIR ACVSMLGVPV DPDTLHATLR LCLRLTRDHK YAMMFAELKS
1810 1820 1830 1840 1850
TRMILNLTQS SGFNGFTPLV TLLLRHIIED PCTLRHTMEK VVRSAATSGA
1860 1870 1880 1890 1900
GSTTSGVVSG SLGSREINYI LRVLGPAACR NPDIFTEVAN CCIRIALPAP
1910 1920 1930 1940 1950
RGSGTASDDE FENLRIKGPN AVQLVKTTPL KPSPLPVIPD TIKEVIYDML
1960 1970 1980 1990 2000
NALAAYHAPE EADKSDPKPG VMTQEVGQLL QDMGDDVYQQ YRSLTRQSSD
2010 2020 2030 2040 2050
FDTQSGFSIN SQVFAADGAS TETSASGTSQ GEASTPEESR DGKKDKEGDR
2060 2070 2080 2090 2100
ASEEGKQKGK GSKPLMPTST ILRLLAELVR SYVGIATLIA NYSYTVGQSE
2110 2120 2130 2140 2150
LIKEDCSVLA FVLDHLLPHT QNAEDKDTPA LARLFLASLA AAGSGTDAQV
2160 2170 2180 2190 2200
ALVNEVKAAL GRALAMAEST EKHARLQAVM CIISTIMESC PSTSSFYSSA
2210 2220 2230 2240 2250
TAKTQHNGMN NIIRLFLKKG LVNDLARVPH SLDLSSPNMA NTVNAALKPL
2260 2270 2280 2290 2300
ETLSRIVNQP SSLFGSKSAS SKNKSEQDAQ GASQDSSSNQ QDPGEPGEAE
2310 2320 2330 2340 2350
VQEEDHDVTQ TEVADGDIMD GEAETDSVVI AGQPEVLSSQ EMQVENELED
2360 2370 2380 2390 2400
LIDELLERDG GSGNSTIIVS RSGEDESQED VLMDEAPSNL SQASTLQANR
2410 2420 2430 2440 2450
EDSMNILDPE DEEEHTQEED SSGSNEDEDD SQDEEEEEEE DEEDDQEDDE
2460 2470 2480 2490 2500
GEEGDEDDDD DGSEMELDED YPDMNASPLV RFERFDREDD LIIEFDNMFS
2510 2520 2530 2540 2550
SATDIPPSPG NIPTTHPLMV RHADHSSLTL GSGSSTTRLT QGIGRSQRTL
2560 2570 2580 2590 2600
RQLTANTGHT IHVHYPGNRQ PNPPLILQRL LGPSAAADIL QLSSSLPLQS
2610 2620 2630 2640 2650
RGRARLLVGN DDVHIIARSD DELLDDFFHD QSTATSQAGT LSSIPTALTR
2660 2670 2680 2690 2700
WTEECKVLDA ESMHDCVSVV KVSIVNHLEF LRDEELEERR EKRRKQLAEE
2710 2720 2730 2740 2750
ETKITDKGKE DKENRDQSAQ CTASKSNDST EQNLSDGTPM PDSYPTTPSS
2760 2770 2780 2790 2800
TDAATSESKE TLGTLQSSQQ QPTLPTPPAL GEVPQELQSP AGEGGSSTQL
2810 2820 2830 2840 2850
LMPVEPEELG PTRPSGEAET TQMELSPAPT ITSLSPERAE DSDALTAVSS
2860 2870 2880 2890 2900
QLEGSPMDTS SLASCTLEEA VGDTSAAGSS EQPRAGSSTP GDAPPAVAEV
2910 2920 2930 2940 2950
QGRSDGSGES AQPPEDSSPP ASSESSSTRD SAVAISGADS RGILEEPLPS
2960 2970 2980 2990 3000
TSSEEEDPLA GISLPEGVDP SFLAALPDDI RREVLQNQLG IRPPTRTAPS
3010 3020 3030 3040 3050
TNSSAPAVVG NPGVTEVSPE FLAALPPAIQ EEVLAQQRAE QQRRELAQNA
3060 3070 3080 3090 3100
SSDTPMDPVT FIQTLPSDLR RSVLEDMEDS VLAVMPPDIA AEAQALRREQ
3110 3120 3130 3140 3150
EARQRQLMHE RLFGHSSTSA LSAILRSPAF TSRLSGNRGV QYTRLAVQRG
3160 3170 3180 3190 3200
GTFQMGGSSS HNRPSGSNVD TLLRLRGRLL LDHEALSCLL VLLFVDEPKL
3210 3220 3230 3240 3250
NTSRLHRVLR NLCYHAQTRH WVIRSLLSIL QRSSESELCI ETPKLTTSEE
3260 3270 3280 3290 3300
KGKKSSKSCG SSSHENRPLD LLHKMESKSS NQLSWLSVSM DAALGCRTNI
3310 3320 3330 3340 3350
FQIQRSGGRK HTEKHASGGS TVHIHPQAAP VVCRHVLDTL IQLAKVFPSH
3360 3370 3380 3390 3400
FTQQRTKETN CESDRERGNK ACSPCSSQSS SSGICTDFWD LLVKLDNMNV
3410 3420 3430 3440 3450
SRKGKNSVKS VPVSAGGEGE TSPYSLEASP LGQLMNMLSH PVIRRSSLLT
3460 3470 3480 3490 3500
EKLLRLLSLI SIALPENKVS EAQANSGSGA SSTTTATSTT STTTTTAAST
3510 3520 3530 3540 3550
TPTPPTAPTP VTSAPALVAA TAISTIVVAA STTVTTPTTA TTTVSISPTT
3560 3570 3580 3590 3600
KGSKSPAKVS DGGSSSTDFK MVSSGLTENQ LQLSVEVLTS HSCSEEGLED
3610 3620 3630 3640 3650
AANVLLQLSR GDSGTRDTVL KLLLNGARHL GYTLCKQIGT LLAELREYNL
3660 3670 3680 3690 3700
EQQRRAQCET LSPDGLPEEQ PQTTKLKGKM QSRFDMAENV VIVASQKRPL
3710 3720 3730 3740 3750
GGRELQLPSM SMLTSKTSTQ KFFLRVLQVI IQLRDDTRRA NKKAKQTGRL
3760 3770 3780 3790 3800
GSSGLGSASS IQAAVRQLEA EADAIIQMVR EGQRARRQQQ AATSESSQSE
3810 3820 3830 3840 3850
ASVRREESPM DVDQPSPSAQ DTQSIASDGT PQGEKEKEER PPELPLLSEQ
3860 3870 3880 3890 3900
LSLDELWDML GECLKELEES HDQHAVLVLQ PAVEAFFLVH ATERESKPPV
3910 3920 3930 3940 3950
RDTRESQLAH IKDEPPPLSP APLTPATPSS LDPFFSREPS SMHISSSLPP
3960 3970 3980 3990 4000
DTQKFLRFAE THRTVLNQIL RQSTTHLADG PFAVLVDYIR VLDFDVKRKY
4010 4020 4030 4040 4050
FRQELERLDE GLRKEDMAVH VRRDHVFEDS YRELHRKSPE EMKNRLYIVF
4060 4070 4080 4090 4100
EGEEGQDAGG LLREWYMIIS REMFNPMYAL FRTSPGDRVT YTINPSSHCN
4110 4120 4130 4140 4150
PNHLSYFKFV GRIVAKAVYD NRLLECYFTR SFYKHILGKS VRYTDMESED
4160 4170 4180 4190 4200
YHFYQGLVYL LENDVSTLGY DLTFSTEVQE FGVCEVRDLK PNGANILVTE
4210 4220 4230 4240 4250
ENKKEYVHLV CQMRMTGAIR KQLAAFLEGF YEIIPKRLIS IFTEQELELL
4260 4270 4280 4290 4300
ISGLPTIDID DLKSNTEYHK YQSNSIQIQW FWRALRSFDQ ADRAKFLQFV
4310 4320 4330 4340 4350
TGTSKVPLQG FAALEGMNGI QKFQIHRDDR STDRLPSAHT CFNQLDLPAY
4360 4370
ESFEKLRHML LLAIQECSEG FGLA
Length:4,374
Mass (Da):481,891
Last modified:August 30, 2005 - v3
Checksum:iFA9D3A7712F6393B
GO
Isoform 2 (identifier: Q7Z6Z7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     3016-3031: Missing.

Note: No experimental confirmation available.
Show »
Length:4,358
Mass (Da):480,198
Checksum:iD30775B19F710F6F
GO
Isoform 3 (identifier: Q7Z6Z7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     982-990: Missing.

Show »
Length:4,365
Mass (Da):481,018
Checksum:iE8A8FFC3C7EB9B24
GO

Sequence cautioni

The sequence AAC62492 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAF28950 differs from that shown. Reason: Frameshift at position 4356.Curated
The sequence AAF28950 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAB13404 differs from that shown. Chimeric cDNA, contains the C-terminal part of ATP5I.Curated
The sequence BAC06833 differs from that shown. Reason: Frameshift at positions 982 and 1055.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1111K → N in BAC06833 (Ref. 5) Curated1
Sequence conflicti1124P → L in AAV90838 (PubMed:15989956).Curated1
Sequence conflicti1124P → L in BAC06833 (Ref. 5) Curated1
Sequence conflicti1190D → H in BAC06833 (Ref. 5) Curated1
Sequence conflicti1962Missing in BAA20771 (PubMed:9205841).Curated1
Sequence conflicti2525H → Y in BAC06833 (Ref. 5) Curated1
Sequence conflicti2525H → Y in AAF28950 (PubMed:11042152).Curated1
Sequence conflicti4022R → L in AAH02602 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_061986483N → S.Corresponds to variant rs41307640dbSNPEnsembl.1
Natural variantiVAR_076253950V → D Found in patients with autism spectrum disorders; unknown pathological significance. 1 Publication1
Natural variantiVAR_0456702981R → H in MRXST. 1 PublicationCorresponds to variant rs121918526dbSNPEnsembl.1
Natural variantiVAR_0456714013R → W in MRXST. 1 PublicationCorresponds to variant rs121918525dbSNPEnsembl.1
Natural variantiVAR_0456724187R → C in MRXST. 1 PublicationCorresponds to variant rs121918527dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015272982 – 990Missing in isoform 3. 1 Publication9
Alternative sequenceiVSP_0111463016 – 3031Missing in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY772009 mRNA. Translation: AAV90838.1.
DQ097177 mRNA. Translation: AAY98258.1.
AY929612 mRNA. Translation: AAX24125.1.
AL592046, Z94044, Z97054 Genomic DNA. Translation: CAI39580.1.
Z94044, AL592046, Z97054 Genomic DNA. Translation: CAI42354.1.
Z97054, AL592046, Z94044 Genomic DNA. Translation: CAI42654.1.
AB071605 mRNA. Translation: BAC06833.1. Frameshift.
AB002310 mRNA. Translation: BAA20771.3.
AB046798 mRNA. Translation: BAB13404.1. Sequence problems.
AF161390 mRNA. Translation: AAF28950.1. Sequence problems.
BC002602 mRNA. Translation: AAH02602.2.
BC063505 mRNA. Translation: AAH63505.1.
AF057569 mRNA. Translation: AAC62492.1. Different initiation.
CR456813 mRNA. Translation: CAG33094.1.
AL162050 mRNA. Translation: CAB82393.1.
CCDSiCCDS35301.1. [Q7Z6Z7-1]
PIRiT47165.
RefSeqiNP_113584.3. NM_031407.6. [Q7Z6Z7-1]
XP_005262022.1. XM_005261965.3. [Q7Z6Z7-1]
UniGeneiHs.136905.

Genome annotation databases

EnsembliENST00000262854; ENSP00000262854; ENSG00000086758. [Q7Z6Z7-1]
ENST00000342160; ENSP00000340648; ENSG00000086758. [Q7Z6Z7-1]
ENST00000612484; ENSP00000479451; ENSG00000086758. [Q7Z6Z7-3]
GeneIDi10075.
KEGGihsa:10075.
UCSCiuc033eew.2. human. [Q7Z6Z7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY772009 mRNA. Translation: AAV90838.1.
DQ097177 mRNA. Translation: AAY98258.1.
AY929612 mRNA. Translation: AAX24125.1.
AL592046, Z94044, Z97054 Genomic DNA. Translation: CAI39580.1.
Z94044, AL592046, Z97054 Genomic DNA. Translation: CAI42354.1.
Z97054, AL592046, Z94044 Genomic DNA. Translation: CAI42654.1.
AB071605 mRNA. Translation: BAC06833.1. Frameshift.
AB002310 mRNA. Translation: BAA20771.3.
AB046798 mRNA. Translation: BAB13404.1. Sequence problems.
AF161390 mRNA. Translation: AAF28950.1. Sequence problems.
BC002602 mRNA. Translation: AAH02602.2.
BC063505 mRNA. Translation: AAH63505.1.
AF057569 mRNA. Translation: AAC62492.1. Different initiation.
CR456813 mRNA. Translation: CAG33094.1.
AL162050 mRNA. Translation: CAB82393.1.
CCDSiCCDS35301.1. [Q7Z6Z7-1]
PIRiT47165.
RefSeqiNP_113584.3. NM_031407.6. [Q7Z6Z7-1]
XP_005262022.1. XM_005261965.3. [Q7Z6Z7-1]
UniGeneiHs.136905.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EKKNMR-A1317-1356[»]
2MULNMR-A2951-3003[»]
3G1NX-ray2.60A/B4005-4374[»]
3H1DX-ray1.89A3993-4374[»]
5C6HX-ray2.05B/D/F/H/J/L/N/P/R/T/V/X1969-1994[»]
ProteinModelPortaliQ7Z6Z7.
SMRiQ7Z6Z7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115385. 459 interactors.
DIPiDIP-34362N.
IntActiQ7Z6Z7. 79 interactors.
MINTiMINT-1576525.
STRINGi9606.ENSP00000262854.

PTM databases

iPTMnetiQ7Z6Z7.
PhosphoSitePlusiQ7Z6Z7.

Polymorphism and mutation databases

BioMutaiHUWE1.
DMDMi73915353.

Proteomic databases

EPDiQ7Z6Z7.
MaxQBiQ7Z6Z7.
PaxDbiQ7Z6Z7.
PeptideAtlasiQ7Z6Z7.
PRIDEiQ7Z6Z7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262854; ENSP00000262854; ENSG00000086758. [Q7Z6Z7-1]
ENST00000342160; ENSP00000340648; ENSG00000086758. [Q7Z6Z7-1]
ENST00000612484; ENSP00000479451; ENSG00000086758. [Q7Z6Z7-3]
GeneIDi10075.
KEGGihsa:10075.
UCSCiuc033eew.2. human. [Q7Z6Z7-1]

Organism-specific databases

CTDi10075.
DisGeNETi10075.
GeneCardsiHUWE1.
HGNCiHGNC:30892. HUWE1.
HPAiCAB022718.
HPA002548.
MalaCardsiHUWE1.
MIMi300697. gene.
300705. phenotype.
300706. phenotype.
neXtProtiNX_Q7Z6Z7.
OpenTargetsiENSG00000086758.
Orphaneti85328. X-linked intellectual disability, Turner type.
PharmGKBiPA128394567.
HUGEiSearch...
Search...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0939. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00850000132302.
HOVERGENiHBG080254.
InParanoidiQ7Z6Z7.
KOiK10592.
OMAiHAFEFIF.
OrthoDBiEOG091G01V1.
PhylomeDBiQ7Z6Z7.
TreeFamiTF323417.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiHUWE1. human.
EvolutionaryTraceiQ7Z6Z7.
GeneWikiiHUWE1.
GenomeRNAii10075.
PROiQ7Z6Z7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000086758.
ExpressionAtlasiQ7Z6Z7. baseline and differential.
GenevisibleiQ7Z6Z7. HS.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
InterProiIPR016024. ARM-type_fold.
IPR025527. DUF4414.
IPR010309. E3_Ub_ligase_DUF908.
IPR010314. E3_Ub_ligase_DUF913.
IPR000569. HECT_dom.
IPR015940. UBA.
IPR009060. UBA-like.
IPR004170. WWE-dom.
[Graphical view]
PfamiPF14377. DUF4414. 1 hit.
PF06012. DUF908. 1 hit.
PF06025. DUF913. 1 hit.
PF00632. HECT. 1 hit.
PF00627. UBA. 1 hit.
PF02825. WWE. 1 hit.
[Graphical view]
SMARTiSM00119. HECTc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF48371. SSF48371. 3 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50237. HECT. 1 hit.
PS50030. UBA. 1 hit.
PS50918. WWE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHUWE1_HUMAN
AccessioniPrimary (citable) accession number: Q7Z6Z7
Secondary accession number(s): O15029
, Q4G2Z2, Q5H961, Q6P4D0, Q8NG67, Q9BUI0, Q9HCJ4, Q9NSL6, Q9P0A9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: August 30, 2005
Last modified: November 30, 2016
This is version 152 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.