HERC1

Protein identityUniProt · HPA

UniProt accession

Q15751

Gene

HERC1

Ensembl

ENSG00000103657

Chromosome

15

Canonical length

4861 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

4861 residues, UniProt reviewed canonical sequence.

>Q15751|HERC1
     1  MATMIPPVKL KWLEHLNSSW ITEDSESIAT REGVAVLYSK LVSNKEVVPL PQQVLCLKGP
    61  QLPDFERESL SSDEQDHYLD ALLSSQLALA KMVCSDSPFA GALRKRLLVL QRVFYALSNK
   121  YHDKGKVKQQ QHSPESSSGS ADVHSVSERP RSSTDALIEM GVRTGLSLLF ALLRQSWMMP
   181  VSGPGLSLCN DVIHTAIEVV SSLPPLSLAN ESKIPPMGLD CLSQVTTFLK GVTIPNSGAD
   241  TLGRRLASEL LLGLAAQRGS LRYLLEWIEM ALGASAVVHT MEKGKLLSSQ EGMISFDCFM
   301  TILMQMRRSL GSSADRSQWR EPTRTSDGLC SLYEAALCLF EEVCRMASDY SRTCASPDSI
   361  QTGDAPIVSE TCEVYVWGSN SSHQLVEGTQ EKILQPKLAP SFSDAQTIEA GQYCTFVIST
   421  DGSVRACGKG SYGRLGLGDS NNQSTLKKLT FEPHRSIKKV SSSKGSDGHT LAFTTEGEVF
   481  SWGDGDYGKL GHGNSSTQKY PKLIQGPLQG KVVVCVSAGY RHSAAVTEDG ELYTWGEGDF
   541  GRLGHGDSNS RNIPTLVKDI SNVGEVSCGS SHTIALSKDG RTVWSFGGGD NGKLGHGDTN
   601  RVYKPKVIEA LQGMFIRKVC AGSQSSLALT STGQVYAWGC GACLGCGSSE ATALRPKLIE
   661  ELAATRIVDV SIGDSHCLAL SHDNEVYAWG NNSMGQCGQG NSTGPITKPK KVSGLDGIAI
   721  QQISAGTSHS LAWTALPRDR QVVAWHRPYC VDLEESTFSH LRSFLERYCD KINSEIPPLP
   781  FPSSREHHSF LKLCLKLLSN HLALALAGGV ATSILGRQAG PLRNLLFRLM DSTVPDEIQE
   841  VVIETLSVGA TMLLPPLRER MELLHSLLPQ GPDRWESLSK GQRMQLDIIL TSLQDHTHVA
   901  SLLGYSSPSD AADLSSVCTG YGNLSDQPYG TQSCHPDTHL AEILMKTLLR NLGFYTDQAF
   961  GELEKNSDKF LLGTSSSENS QPAHLHELLC SLQKQLLAFC HINNISENSS SVALLHKHLQ
  1021  LLLPHATDIY SRSANLLKES PWNGSVGEKL RDVIYVSAAG SMLCQIVNSL LLLPVSVARP
  1081  LLSYLLDLLP PLDCLNRLLP AADLLEDQEL QWPLHGGPEL IDPAGLPLPQ PAQSWVWLVD
  1141  LERTIALLIG RCLGGMLQGS PVSPEEQDTA YWMKTPLFSD GVEMDTPQLD KCMSCLLEVA
  1201  LSGNEEQKPF DYKLRPEIAV YVDLALGCSK EPARSLWISM QDYAVSKDWD SATLSNESLL
  1261  DTVSRFVLAA LLKHTNLLSQ ACGESRYQPG KHLSEVYRCV YKVRSRLLAC KNLELIQTRS
  1321  SSRDRWISEN QDSADVDPQE HSFTRTIDEE AEMEEQAERD REEGHPEPED EEEEREHEVM
  1381  TAGKIFQCFL SAREVARSRD RDRMNSGAGS GARADDPPPQ SQQERRVSTD LPEGQDVYTA
  1441  ACNSVIHRCA LLILGVSPVI DELQKRREEG QLQQPSTSAS EGGGLMTRSE SLTAESRLVH
  1501  TSPNYRLIKS RSESDLSQPE SDEEGYALSG RRNVDLDLAA SHRKRGPMHS QLESLSDSWA
  1561  RLKHSRDWLC NSSYSFESDF DLTKSLGVHT LIENVVSFVS GDVGNAPGFK EPEESMSTSP
  1621  QASIIAMEQQ QLRAELRLEA LHQILVLLSG MEEKGSISLA GSRLSSGFQS STLLTSVRLQ
  1681  FLAGCFGLGT VGHTGGKGES GRLHHYQDGI RAAKRNIQIE IQVAVHKIYQ QLSATLERAL
  1741  QANKHHIEAQ QRLLLVTVFA LSVHYQPVDV SLAISTGLLN VLSQLCGTDT MLGQPLQLLP
  1801  KTGVSQLSTA LKVASTRLLQ ILAITTGTYA DKLSPKVVQS LLDLLCSQLK NLLSQTGVLH
  1861  MASFGEGEQE DGEEEEKKVD SSGETEKKDF RAALRKQHAA ELHLGDFLVF LRRVVSSKAI
  1921  QSKMASPKWT EVLLNIASQK CSSGIPLVGN LRTRLLALHV LEAVLPACES GVEDDQMAQI
  1981  VERLFSLLSD CMWETPIAQA KHAIQIKEKE QEIKLQKQGE LEEEDENLPI QEVSFDPEKA
  2041  QCCLVENGQI LTHGSGGKGY GLASTGVTSG CYQWKFYIVK ENRGNEGTCV GVSRWPVHDF
  2101  NHRTTSDMWL YRAYSGNLYH NGEQTLTLSS FTQGDFITCV LDMEARTISF GKNGEEPKLA
  2161  FEDVDAAELY PCVMFYSSNP GEKVKICDMQ MRGTPRDLLP GDPICSPVAA VLAEATIQLI
  2221  RILHRTDRWT YCINKKMMER LHKIKICIKE SGQKLKKSRS VQSREENEMR EEKESKEEEK
  2281  GKHTRHGLAD LSELQLRTLC IEVWPVLAVI GGVDAGLRVG GRCVHKQTGR HATLLGVVKE
  2341  GSTSAKVQWD EAEITISFPT FWSPSDTPLY NLEPCEPLPF DVARFRGLTA SVLLDLTYLT
  2401  GVHEDMGKQS TKRHEKKHRH ESEEKGDVEQ KPESESALDM RTGLTSDDVK SQSTTSSKSE
  2461  NEIASFSLDP TLPSVESQHQ ITEGKRKNHE HMSKNHDVAQ SEIRAVQLSY LYLGAMKSLS
  2521  ALLGCSKYAE LLLIPKVLAE NGHNSDCASS PVVHEDVEMR AALQFLMRHM VKRAVMRSPI
  2581  KRALGLADLE RAQAMIYKLV VHGLLEDQFG GKIKQEIDQQ AEESDPAQQA QTPVTTSPSA
  2641  SSTTSFMSSS LEDTTTATTP VTDTETVPAS ESPGVMPLSL LRQMFSSYPT TTVLPTRRAQ
  2701  TPPISSLPTS PSDEVGRRQS LTSPDSQSAR PANRTALSDP SSRLSTSPPP PAIAVPLLEM
  2761  GFSLRQIAKA MEATGARGEA DAQNITVLAM WMIEHPGHED EEEPQSGSTA DSRPGAAVLG
  2821  SGGKSNDPCY LQSPGDIPSA DAAEMEEGFS ESPDNLDHTE NAASGSGPSA RGRSAVTRRH
  2881  KFDLAARTLL ARAAGLYRSV QAHRNQSRRE GISLQQDPGA LYDFNLDEEL EIDLDDEAME
  2941  AMFGQDLTSD NDILGMWIPE VLDWPTWHVC ESEDREEVVV CELCECSVVS FNQHMKRNHP
  3001  GCGRSANRQG YRSNGSYVDG WFGGECGSGN PYYLLCGTCR EKYLAMKTKS KSTSSERYKG
  3061  QAPDLIGKQD SVYEEDWDML DVDEDEKLTG EEEFELLAGP LGLNDRRIVP EPVQFPDSDP
  3121  LGASVAMVTA TNSMEETLMQ IGCHGSVEKS SSGRITLGEQ AAALANPHDR VVALRRVTAA
  3181  AQVLLARTMV MRALSLLSVS GSSCSLAAGL ESLGLTDIRT LVRLMCLAAA GRAGLSTSPS
  3241  AMASTSERSR GGHSKANKPI SCLAYLSTAV GCLASNAPSA AKLLVQLCTQ NLISAATGVN
  3301  LTTVDDSIQR KFLPSFLRGI AEENKLVTSP NFVVTQALVA LLADKGAKLR PNYDKSEVEK
  3361  KGPLELANAL AACCLSSRLS SQHRQWAAQQ LVRTLAAHDR DNQTTLQTLA DMGGDLRKCS
  3421  FIKLEAHQNR VMTCVWCNKK GLLATSGNDG TIRVWNVTKK QYSLQQTCVF NRLEGDAEES
  3481  LGSPSDPSFS PVSWSISGKY LAGALEKMVN IWQVNGGKGL VDIQPHWVSA LAWPEEGPAT
  3541  AWSGESPELL LVGRMDGSLG LIEVVDVSTM HRRELEHCYR KDVSVTCIAW FSEDRPFAVG
  3601  YFDGKLLLGT KEPLEKGGIV LIDAHKDTLI SMKWDPTGHI LMTCAKEDSV KLWGSISGCW
  3661  CCLHSLCHPS IVNGIAWCRL PGKGSKLQLL MATGCQSGLV CVWRIPQDTT QTNVTSAEGW
  3721  WEQESNCQDG YRKSSGAKCV YQLRGHITPV RTVAFSSDGL ALVSGGLGGL MNIWSLRDGS
  3781  VLQTVVIGSG AIQTTVWIPE VGVAACSNRS KDVLVVNCTA EWAAANHVLA TCRTALKQQG
  3841  VLGLNMAPCM RAFLERLPMM LQEQYAYEKP HVVCGDQLVH SPYMQCLASL AVGLHLDQLL
  3901  CNPPVPPHHQ NCLPDPASWN PNEWAWLECF STTIKAAEAL TNGAQFPESF TVPDLEPVPE
  3961  DELVFLMDNS KWINGMDEQI MSWATSRPED WHLGGKCDVY LWGAGRHGQL AEAGRNVMVP
  4021  AAAPSFSQAQ QVICGQNCTF VIQANGTVLA CGEGSYGRLG QGNSDDLHVL TVISALQGFV
  4081  VTQLVTSCGS DGHSMALTES GEVFSWGDGD YGKLGHGNSD RQRRPRQIEA LQGEEVVQMS
  4141  CGFKHSAVVT SDGKLFTFGN GDYGRLGLGN TSNKKLPERV TALEGYQIGQ VACGLNHTLA
  4201  VSADGSMVWA FGDGDYGKLG LGNSTAKSSP QKIDVLCGIG IKKVACGTQF SVALTKDGHV
  4261  YTFGQDRLIG LPEGRARNHN RPQQIPVLAG VIIEDVAVGA EHTLALASNG DVYAWGSNSE
  4321  GQLGLGHTNH VREPTLVTGL QGKNVRQISA GRCHSAAWTA PPVPPRAPGV SVPLQLGLPD
  4381  TVPPQYGALR EVSIHTVRAR LRLLYHFSDL MYSSWRLLNL SPNNQNSTSH YNAGTWGIVQ
  4441  GQLRPLLAPR VYTLPMVRSI GKTMVQGKNY GPQITVKRIS TRGRKCKPIF VQIARQVVKL
  4501  NASDLRLPSR AWKVKLVGEG ADDAGGVFDD TITEMCQELE TGIVDLLIPS PNATAEVGYN
  4561  RDRFLFNPSA CLDEHLMQFK FLGILMGVAI RTKKPLDLHL APLVWKQLCC VPLTLEDLEE
  4621  VDLLYVQTLN SILHIEDSGI TEESFHEMIP LDSFVGQSAD GKMVPIIPGG NSIPLTFSNR
  4681  KEYVERAIEY RLHEMDRQVA AVREGMSWIV PVPLLSLLTA KQLEQMVCGM PEISVEVLKK
  4741  VVRYREVDEQ HQLVQWFWHT LEEFSNEERV LFMRFVSGRS RLPANTADIS QRFQIMKVDR
  4801  PYDSLPTSQT CFFQLRLPPY SSQLVMAERL RYAINNCRSI DMDNYMLSRN VDNAEGSDTD
  4861  Y

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HERC1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

29 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HERC1.

Disease | AllUniProt

Conditions HERC1 is implicated in, by any mechanism.

• Macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR) MIM:617011

Disease | GeneticClinVar

52 pathogenic / likely-pathogenic of 1,815 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Macrocephaly, dysmorphic facies, and psychomotor retardation
• Inborn genetic diseases
• Megalencephaly with thick corpus callosum, cerebellar atrophy, and intellectual disability
• HERC1-related disorder
• See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.24

gnomAD pLI

1

gnomAD missense Z

4.96

DepMap mean gene effect

-0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autophagy
• bone mineralization
• bone remodeling
• cerebellar Purkinje cell differentiation
• corpus callosum development
• gene expression
• negative regulation of autophagy
• neuromuscular process controlling balance
• neuron projection development
• protein ubiquitination

Molecular functions

• guanyl-nucleotide exchange factor activity
• ubiquitin protein ligase activity

Cellular components

• cytoplasm
• cytosol
• Golgi apparatus
• membrane

Protein domainsUniProt · Pfam · InterPro

• Regulator of chromosome condensation, RCC1
• HECT domain
• WD40 repeat
• B30.2/SPRY domain
• SPRY domain
• Regulator of chromosome condensation 1/beta-lactamase-inhibitor protein II
• Concanavalin A-like lectin/glucanase domain superfamily
• WD40/YVTN repeat-like-containing domain superfamily
• WD40 repeat, conserved site
• HECT, E3 ligase catalytic domain
• WD40-repeat-containing domain superfamily
• B30.2/SPRY domain superfamily
• Diverse Signaling and Regulatory Domain-Containing Protein
• RCC1-like domain
• WD domain, G-beta repeat
• Regulator of chromosome condensation (RCC1) repeat
• SPRY domain
• HECT-domain (ubiquitin-transferase)
• RCC1-like domain
• HERC1, SPRY domain

KeywordsUniProt

• Cytoplasm
• Golgi apparatus
• Guanine-nucleotide releasing factor
• Intellectual disability
• Membrane
• Phosphoprotein
• Repeat
• Transferase
• Transport
• Ubl conjugation pathway
• WD repeat

InteractionsUniProt · HPA

Protein binding partners of HERC1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARF1
• ARF6
• PKM
• TSC2