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  6. Probable E3 ubiquitin-protein ligase HERC1

Tbio Probable E3 ubiquitin-protein ligase HERC1

Involved in membrane trafficking via some guanine nucleotide exchange factor (GEF) activity and its ability to bind clathrin. Acts as a GEF for Arf and Rab, by exchanging bound GDP for free GTP. Binds phosphatidylinositol 4,5-bisphosphate, which is required for GEF activity. May also act as a 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.

This gen encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. [provided by RefSeq, Mar 2012]

 Comments

Property Summary

NCBI Gene PubMed Count 17
Grant Count 5
R01 Count 5
Funding $358,915
PubMed Score 5.25
PubTator Score 21.27

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Relevance (15)

Disease Z-score Confidence
Chromosome 1q41-q42 deletion syndrome 3 5.023 2.5
Carcinoma 2,147 1.0
Intellectual disability 573 4.0
Pick disease 1,893
adult high grade glioma 2,148
atypical teratoid / rhabdoid tumor 4,369
ependymoma 2,514
glioblastoma 5,572
hereditary spastic paraplegia 313
lung cancer 4,466
medulloblastoma, large-cell 6,234
osteosarcoma 7,933
ovarian cancer 8,484
pilocytic astrocytoma 3,086
subependymal giant cell astrocytoma 2,287

Expression

  Differential Expression (12)

Disease log2 FC p
glioblastoma -1.700 0.000
osteosarcoma -1.239 0.000
ependymoma -1.600 0.000
atypical teratoid / rhabdoid tumor -1.400 0.000
medulloblastoma, large-cell -1.200 0.000
hereditary spastic paraplegia -1.140 0.007
lung cancer -1.400 0.011
adult high grade glioma -1.500 0.000
pilocytic astrocytoma -1.200 0.000
subependymal giant cell astrocytoma -1.097 0.047
Pick disease -1.100 0.013
ovarian cancer -1.800 0.000

Synonym

Accession Q15751 Q8IW65
Symbols p532
p619
MDFPMR

Gene

HERC1

PANTHER Protein Class (3)

 Grant Application (5)

PDB

4O2W   4QT6  

 GO Function (2)

 GO Component (4)

 GO Process (5)

 Compartment GO Term (15)

 MGI Term (4)

 GWAS Trait (1)

Pathway (7)

 UniProt Keyword (14)

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Gene RIF (7)

PMID Text
26138117 Biallelic sequence variants in a novel gene (HERC1) are linked to a syndromic form of overgrowth and intellectual disability.
25408501 Data show that E3 ubiquitin-protein ligase HERC1 interacts with bcl-2 homologous antagonist-killer protein BAK in HPV5 E6-expressing cells that have been damaged by UV.
19618402 global frequency distributions of 4 single nucleotide polymorphisms in the HERC1 gene; 12 population groups included
19618402 Observational study of genotype prevalence. (HuGE Navigator)
15642342 HERC1, through its RLD1 (RCC1-like domain), stimulates GDP release from ARF6 but it inhibits GDP/GTP exchange on ARF6 under conditions where ARNO stimulates it.
14960311 HERC1 overexpression does not stimulate protrusion formation in the absence of AlF(4)(-), in conditions where ARNO does, indicating that HERC1 is not acting as an ARF6-GEF, but instead its recruitment takes place downstream of ARF6 activation
12650930 physical interaction between the HECT domain of HERC1, a giant protein involved in intracellular membrane traffic, and the M2 isoform of glycolytic enzyme pyruvate kinase (M2-PK)

AA Sequence 

MATMIPPVKLKWLEHLNSSWITEDSESIATREGVAVLYSKLVSNKEVVPLPQQVLCLKGPQLPDFERESL      1 - 70
SSDEQDHYLDALLSSQLALAKMVCSDSPFAGALRKRLLVLQRVFYALSNKYHDKGKVKQQQHSPESSSGS     71 - 140
ADVHSVSERPRSSTDALIEMGVRTGLSLLFALLRQSWMMPVSGPGLSLCNDVIHTAIEVVSSLPPLSLAN    141 - 210
ESKIPPMGLDCLSQVTTFLKGVTIPNSGADTLGRRLASELLLGLAAQRGSLRYLLEWIEMALGASAVVHT    211 - 280
MEKGKLLSSQEGMISFDCFMTILMQMRRSLGSSADRSQWREPTRTSDGLCSLYEAALCLFEEVCRMASDY    281 - 350
SRTCASPDSIQTGDAPIVSETCEVYVWGSNSSHQLVEGTQEKILQPKLAPSFSDAQTIEAGQYCTFVIST    351 - 420
DGSVRACGKGSYGRLGLGDSNNQSTLKKLTFEPHRSIKKVSSSKGSDGHTLAFTTEGEVFSWGDGDYGKL    421 - 490
GHGNSSTQKYPKLIQGPLQGKVVVCVSAGYRHSAAVTEDGELYTWGEGDFGRLGHGDSNSRNIPTLVKDI    491 - 560
SNVGEVSCGSSHTIALSKDGRTVWSFGGGDNGKLGHGDTNRVYKPKVIEALQGMFIRKVCAGSQSSLALT    561 - 630
STGQVYAWGCGACLGCGSSEATALRPKLIEELAATRIVDVSIGDSHCLALSHDNEVYAWGNNSMGQCGQG    631 - 700
NSTGPITKPKKVSGLDGIAIQQISAGTSHSLAWTALPRDRQVVAWHRPYCVDLEESTFSHLRSFLERYCD    701 - 770
KINSEIPPLPFPSSREHHSFLKLCLKLLSNHLALALAGGVATSILGRQAGPLRNLLFRLMDSTVPDEIQE    771 - 840
VVIETLSVGATMLLPPLRERMELLHSLLPQGPDRWESLSKGQRMQLDIILTSLQDHTHVASLLGYSSPSD    841 - 910
AADLSSVCTGYGNLSDQPYGTQSCHPDTHLAEILMKTLLRNLGFYTDQAFGELEKNSDKFLLGTSSSENS    911 - 980
QPAHLHELLCSLQKQLLAFCHINNISENSSSVALLHKHLQLLLPHATDIYSRSANLLKESPWNGSVGEKL    981 - 1050
RDVIYVSAAGSMLCQIVNSLLLLPVSVARPLLSYLLDLLPPLDCLNRLLPAADLLEDQELQWPLHGGPEL   1051 - 1120
IDPAGLPLPQPAQSWVWLVDLERTIALLIGRCLGGMLQGSPVSPEEQDTAYWMKTPLFSDGVEMDTPQLD   1121 - 1190
KCMSCLLEVALSGNEEQKPFDYKLRPEIAVYVDLALGCSKEPARSLWISMQDYAVSKDWDSATLSNESLL   1191 - 1260
DTVSRFVLAALLKHTNLLSQACGESRYQPGKHLSEVYRCVYKVRSRLLACKNLELIQTRSSSRDRWISEN   1261 - 1330
QDSADVDPQEHSFTRTIDEEAEMEEQAERDREEGHPEPEDEEEEREHEVMTAGKIFQCFLSAREVARSRD   1331 - 1400
RDRMNSGAGSGARADDPPPQSQQERRVSTDLPEGQDVYTAACNSVIHRCALLILGVSPVIDELQKRREEG   1401 - 1470
QLQQPSTSASEGGGLMTRSESLTAESRLVHTSPNYRLIKSRSESDLSQPESDEEGYALSGRRNVDLDLAA   1471 - 1540
SHRKRGPMHSQLESLSDSWARLKHSRDWLCNSSYSFESDFDLTKSLGVHTLIENVVSFVSGDVGNAPGFK   1541 - 1610
EPEESMSTSPQASIIAMEQQQLRAELRLEALHQILVLLSGMEEKGSISLAGSRLSSGFQSSTLLTSVRLQ   1611 - 1680
FLAGCFGLGTVGHTGGKGESGRLHHYQDGIRAAKRNIQIEIQVAVHKIYQQLSATLERALQANKHHIEAQ   1681 - 1750
QRLLLVTVFALSVHYQPVDVSLAISTGLLNVLSQLCGTDTMLGQPLQLLPKTGVSQLSTALKVASTRLLQ   1751 - 1820
ILAITTGTYADKLSPKVVQSLLDLLCSQLKNLLSQTGVLHMASFGEGEQEDGEEEEKKVDSSGETEKKDF   1821 - 1890
RAALRKQHAAELHLGDFLVFLRRVVSSKAIQSKMASPKWTEVLLNIASQKCSSGIPLVGNLRTRLLALHV   1891 - 1960
LEAVLPACESGVEDDQMAQIVERLFSLLSDCMWETPIAQAKHAIQIKEKEQEIKLQKQGELEEEDENLPI   1961 - 2030
QEVSFDPEKAQCCLVENGQILTHGSGGKGYGLASTGVTSGCYQWKFYIVKENRGNEGTCVGVSRWPVHDF   2031 - 2100
NHRTTSDMWLYRAYSGNLYHNGEQTLTLSSFTQGDFITCVLDMEARTISFGKNGEEPKLAFEDVDAAELY   2101 - 2170
PCVMFYSSNPGEKVKICDMQMRGTPRDLLPGDPICSPVAAVLAEATIQLIRILHRTDRWTYCINKKMMER   2171 - 2240
LHKIKICIKESGQKLKKSRSVQSREENEMREEKESKEEEKGKHTRHGLADLSELQLRTLCIEVWPVLAVI   2241 - 2310
GGVDAGLRVGGRCVHKQTGRHATLLGVVKEGSTSAKVQWDEAEITISFPTFWSPSDTPLYNLEPCEPLPF   2311 - 2380
DVARFRGLTASVLLDLTYLTGVHEDMGKQSTKRHEKKHRHESEEKGDVEQKPESESALDMRTGLTSDDVK   2381 - 2450
SQSTTSSKSENEIASFSLDPTLPSVESQHQITEGKRKNHEHMSKNHDVAQSEIRAVQLSYLYLGAMKSLS   2451 - 2520
ALLGCSKYAELLLIPKVLAENGHNSDCASSPVVHEDVEMRAALQFLMRHMVKRAVMRSPIKRALGLADLE   2521 - 2590
RAQAMIYKLVVHGLLEDQFGGKIKQEIDQQAEESDPAQQAQTPVTTSPSASSTTSFMSSSLEDTTTATTP   2591 - 2660
VTDTETVPASESPGVMPLSLLRQMFSSYPTTTVLPTRRAQTPPISSLPTSPSDEVGRRQSLTSPDSQSAR   2661 - 2730
PANRTALSDPSSRLSTSPPPPAIAVPLLEMGFSLRQIAKAMEATGARGEADAQNITVLAMWMIEHPGHED   2731 - 2800
EEEPQSGSTADSRPGAAVLGSGGKSNDPCYLQSPGDIPSADAAEMEEGFSESPDNLDHTENAASGSGPSA   2801 - 2870
RGRSAVTRRHKFDLAARTLLARAAGLYRSVQAHRNQSRREGISLQQDPGALYDFNLDEELEIDLDDEAME   2871 - 2940
AMFGQDLTSDNDILGMWIPEVLDWPTWHVCESEDREEVVVCELCECSVVSFNQHMKRNHPGCGRSANRQG   2941 - 3010
YRSNGSYVDGWFGGECGSGNPYYLLCGTCREKYLAMKTKSKSTSSERYKGQAPDLIGKQDSVYEEDWDML   3011 - 3080
DVDEDEKLTGEEEFELLAGPLGLNDRRIVPEPVQFPDSDPLGASVAMVTATNSMEETLMQIGCHGSVEKS   3081 - 3150
SSGRITLGEQAAALANPHDRVVALRRVTAAAQVLLARTMVMRALSLLSVSGSSCSLAAGLESLGLTDIRT   3151 - 3220
LVRLMCLAAAGRAGLSTSPSAMASTSERSRGGHSKANKPISCLAYLSTAVGCLASNAPSAAKLLVQLCTQ   3221 - 3290
NLISAATGVNLTTVDDSIQRKFLPSFLRGIAEENKLVTSPNFVVTQALVALLADKGAKLRPNYDKSEVEK   3291 - 3360
KGPLELANALAACCLSSRLSSQHRQWAAQQLVRTLAAHDRDNQTTLQTLADMGGDLRKCSFIKLEAHQNR   3361 - 3430
VMTCVWCNKKGLLATSGNDGTIRVWNVTKKQYSLQQTCVFNRLEGDAEESLGSPSDPSFSPVSWSISGKY   3431 - 3500
LAGALEKMVNIWQVNGGKGLVDIQPHWVSALAWPEEGPATAWSGESPELLLVGRMDGSLGLIEVVDVSTM   3501 - 3570
HRRELEHCYRKDVSVTCIAWFSEDRPFAVGYFDGKLLLGTKEPLEKGGIVLIDAHKDTLISMKWDPTGHI   3571 - 3640
LMTCAKEDSVKLWGSISGCWCCLHSLCHPSIVNGIAWCRLPGKGSKLQLLMATGCQSGLVCVWRIPQDTT   3641 - 3710
QTNVTSAEGWWEQESNCQDGYRKSSGAKCVYQLRGHITPVRTVAFSSDGLALVSGGLGGLMNIWSLRDGS   3711 - 3780
VLQTVVIGSGAIQTTVWIPEVGVAACSNRSKDVLVVNCTAEWAAANHVLATCRTALKQQGVLGLNMAPCM   3781 - 3850
RAFLERLPMMLQEQYAYEKPHVVCGDQLVHSPYMQCLASLAVGLHLDQLLCNPPVPPHHQNCLPDPASWN   3851 - 3920
PNEWAWLECFSTTIKAAEALTNGAQFPESFTVPDLEPVPEDELVFLMDNSKWINGMDEQIMSWATSRPED   3921 - 3990
WHLGGKCDVYLWGAGRHGQLAEAGRNVMVPAAAPSFSQAQQVICGQNCTFVIQANGTVLACGEGSYGRLG   3991 - 4060
QGNSDDLHVLTVISALQGFVVTQLVTSCGSDGHSMALTESGEVFSWGDGDYGKLGHGNSDRQRRPRQIEA   4061 - 4130
LQGEEVVQMSCGFKHSAVVTSDGKLFTFGNGDYGRLGLGNTSNKKLPERVTALEGYQIGQVACGLNHTLA   4131 - 4200
VSADGSMVWAFGDGDYGKLGLGNSTAKSSPQKIDVLCGIGIKKVACGTQFSVALTKDGHVYTFGQDRLIG   4201 - 4270
LPEGRARNHNRPQQIPVLAGVIIEDVAVGAEHTLALASNGDVYAWGSNSEGQLGLGHTNHVREPTLVTGL   4271 - 4340
QGKNVRQISAGRCHSAAWTAPPVPPRAPGVSVPLQLGLPDTVPPQYGALREVSIHTVRARLRLLYHFSDL   4341 - 4410
MYSSWRLLNLSPNNQNSTSHYNAGTWGIVQGQLRPLLAPRVYTLPMVRSIGKTMVQGKNYGPQITVKRIS   4411 - 4480
TRGRKCKPIFVQIARQVVKLNASDLRLPSRAWKVKLVGEGADDAGGVFDDTITEMCQELETGIVDLLIPS   4481 - 4550
PNATAEVGYNRDRFLFNPSACLDEHLMQFKFLGILMGVAIRTKKPLDLHLAPLVWKQLCCVPLTLEDLEE   4551 - 4620
VDLLYVQTLNSILHIEDSGITEESFHEMIPLDSFVGQSADGKMVPIIPGGNSIPLTFSNRKEYVERAIEY   4621 - 4690
RLHEMDRQVAAVREGMSWIVPVPLLSLLTAKQLEQMVCGMPEISVEVLKKVVRYREVDEQHQLVQWFWHT   4691 - 4760
LEEFSNEERVLFMRFVSGRSRLPANTADISQRFQIMKVDRPYDSLPTSQTCFFQLRLPPYSSQLVMAERL   4761 - 4830
RYAINNCRSIDMDNYMLSRNVDNAEGSDTDY                                          4831 - 4861
//

Text Mined References (30)

PMID Year Title
26138117 2015 Biallelic HERC1 mutations in a syndromic form of overgrowth and intellectual disability.
25408501 2015 Resistance to UV-induced apoptosis by ?-HPV5 E6 involves targeting of activated BAK for proteolysis by recruitment of the HERC1 ubiquitin ligase.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
21835309 2011 GWAS findings for human iris patterns: associations with variants in genes that influence normal neuronal pattern development.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21269460 2011 Initial characterization of the human central proteome.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19618402 2009 HERC1 polymorphisms: population-specific variations in haplotype composition.
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