HERC4_MOUSE
ID HERC4_MOUSE Reviewed; 1057 AA.
AC Q6PAV2; Q3UL34; Q3UPX2; Q810A0; Q811C9; Q8R315; Q9D797;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Probable E3 ubiquitin-protein ligase HERC4;
DE EC=2.3.2.26;
DE AltName: Full=HECT domain and RCC1-like domain-containing protein 4;
DE AltName: Full=HECT-type E3 ubiquitin transferase HERC4;
GN Name=Herc4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Blastocyst, Eye, Melanocyte, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, FVB/N, and FVB/N-3;
RC TISSUE=Brain, Colon, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=129/Ola, and C57BL/6J;
RX PubMed=17967448; DOI=10.1016/j.ydbio.2007.09.053;
RA Rodriguez C.I., Stewart C.L.;
RT "Disruption of the ubiquitin ligase HERC4 causes defects in spermatozoon
RT maturation and impaired fertility.";
RL Dev. Biol. 312:501-508(2007).
RN [4]
RP MISCELLANEOUS.
RX PubMed=19819847; DOI=10.3724/sp.j.1005.2009.00941;
RA Huang D., Li J., He L.Q.;
RT "Influence of Tripterygium wilfordii on the expression of spermiogenesis
RT related genes Herc4, Ipo11 and Mrto4 in mice.";
RL Yi Chuan 31:941-946(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Probable E3 ubiquitin-protein ligase involved in either
CC protein trafficking or in the distribution of cellular structures.
CC Required for spermatozoon maturation and fertility, and for the removal
CC of the cytoplasmic droplet of the spermatozoon. E3 ubiquitin-protein
CC ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the
CC form of a thioester and then directly transfer it to targeted
CC substrates. {ECO:0000269|PubMed:17967448}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q5GLZ8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6PAV2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PAV2-2; Sequence=VSP_023182;
CC Name=3;
CC IsoId=Q6PAV2-3; Sequence=VSP_023180, VSP_023181;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, highest expression is found
CC in testis during spermiogenesis. It is specifically found in
CC spermatogonia, spermatocytes, and spermatids with little or no
CC expression detectable in the spermatozoa, or interstitial cells.
CC {ECO:0000269|PubMed:17967448}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in testis during spermiogenesis.
CC Expression was almost undetectable in testes at postnatal day 14 (P14).
CC However, by P23, a strong increase in mRNA levels was observed with
CC expression persisting to P40 when spermatozoa were first observed. Up-
CC regulated in the uterine luminal epithelium at the time of embryo
CC implantation. {ECO:0000269|PubMed:17967448}.
CC -!- DISRUPTION PHENOTYPE: Disruption causes defects in spermatozoon
CC maturation and impaired fertility in males; females display normal
CC fertility. Males produce litter sizes some 50% smaller, as well 50% of
CC mature spermatozoa have reduced mobility.
CC {ECO:0000269|PubMed:17967448}.
CC -!- MISCELLANEOUS: T.wilfordii induces abnormal expression of
CC spermiogenesis genes including Herc4, the spermatogenic cells in the
CC convoluted seminiferous tubules decrease and the lumen is obstructed by
CC large deciduous spermatogenic cells. T.wilfordii has apparent
CC antifertility effects.
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DR EMBL; AK009436; BAB26286.1; -; mRNA.
DR EMBL; AK143111; BAE25272.1; -; mRNA.
DR EMBL; AK145735; BAE26617.1; -; mRNA.
DR EMBL; AK147723; BAE28095.1; -; mRNA.
DR EMBL; BC026855; AAH26855.1; -; mRNA.
DR EMBL; BC043082; AAH43082.1; -; mRNA.
DR EMBL; BC047157; AAH47157.1; -; mRNA.
DR EMBL; BC060033; AAH60033.1; -; mRNA.
DR CCDS; CCDS23897.1; -. [Q6PAV2-2]
DR CCDS; CCDS88014.1; -. [Q6PAV2-1]
DR RefSeq; NP_080377.2; NM_026101.4. [Q6PAV2-2]
DR RefSeq; NP_084390.1; NM_030114.2. [Q6PAV2-1]
DR AlphaFoldDB; Q6PAV2; -.
DR SMR; Q6PAV2; -.
DR BioGRID; 212125; 15.
DR IntAct; Q6PAV2; 1.
DR MINT; Q6PAV2; -.
DR STRING; 10090.ENSMUSP00000020258; -.
DR iPTMnet; Q6PAV2; -.
DR PhosphoSitePlus; Q6PAV2; -.
DR SwissPalm; Q6PAV2; -.
DR EPD; Q6PAV2; -.
DR MaxQB; Q6PAV2; -.
DR PaxDb; Q6PAV2; -.
DR PeptideAtlas; Q6PAV2; -.
DR PRIDE; Q6PAV2; -.
DR ProteomicsDB; 269738; -. [Q6PAV2-1]
DR ProteomicsDB; 269739; -. [Q6PAV2-2]
DR ProteomicsDB; 269740; -. [Q6PAV2-3]
DR Antibodypedia; 28396; 173 antibodies from 27 providers.
DR DNASU; 67345; -.
DR Ensembl; ENSMUST00000020258; ENSMUSP00000020258; ENSMUSG00000020064. [Q6PAV2-2]
DR Ensembl; ENSMUST00000219577; ENSMUSP00000151886; ENSMUSG00000020064. [Q6PAV2-1]
DR GeneID; 67345; -.
DR KEGG; mmu:67345; -.
DR UCSC; uc007fka.2; mouse. [Q6PAV2-3]
DR UCSC; uc007fkc.2; mouse. [Q6PAV2-2]
DR UCSC; uc007fkd.2; mouse. [Q6PAV2-1]
DR CTD; 26091; -.
DR MGI; MGI:1914595; Herc4.
DR VEuPathDB; HostDB:ENSMUSG00000020064; -.
DR eggNOG; KOG0941; Eukaryota.
DR GeneTree; ENSGT00940000158924; -.
DR HOGENOM; CLU_002173_5_3_1; -.
DR InParanoid; Q6PAV2; -.
DR OMA; TIPFAKC; -.
DR OrthoDB; 1062377at2759; -.
DR PhylomeDB; Q6PAV2; -.
DR TreeFam; TF315189; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 67345; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Herc4; mouse.
DR PRO; PR:Q6PAV2; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q6PAV2; protein.
DR Bgee; ENSMUSG00000020064; Expressed in granulocyte and 263 other tissues.
DR ExpressionAtlas; Q6PAV2; baseline and differential.
DR Genevisible; Q6PAV2; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd00078; HECTc; 1.
DR Gene3D; 2.130.10.30; -; 2.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00415; RCC1; 7.
DR PRINTS; PR00633; RCCNDNSATION.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS00626; RCC1_2; 3.
DR PROSITE; PS50012; RCC1_3; 7.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Differentiation; Reference proteome;
KW Repeat; Spermatogenesis; Transferase; Ubl conjugation pathway.
FT CHAIN 1..1057
FT /note="Probable E3 ubiquitin-protein ligase HERC4"
FT /id="PRO_0000278217"
FT REPEAT 1..51
FT /note="RCC1 1"
FT REPEAT 52..101
FT /note="RCC1 2"
FT REPEAT 102..154
FT /note="RCC1 3"
FT REPEAT 156..207
FT /note="RCC1 4"
FT REPEAT 208..259
FT /note="RCC1 5"
FT REPEAT 261..311
FT /note="RCC1 6"
FT REPEAT 313..366
FT /note="RCC1 7"
FT DOMAIN 730..1057
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT ACT_SITE 1025
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT VAR_SEQ 229..233
FT /note="DRYVP -> GRCAL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023180"
FT VAR_SEQ 234..1057
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023181"
FT VAR_SEQ 643..650
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_023182"
FT CONFLICT 299
FT /note="V -> A (in Ref. 2; AAH60033)"
FT /evidence="ECO:0000305"
FT CONFLICT 800
FT /note="V -> I (in Ref. 1; BAE25272)"
FT /evidence="ECO:0000305"
FT CONFLICT 898
FT /note="D -> N (in Ref. 1; BAE26617)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1057 AA; 118412 MW; FCFFC9481AB0D4AE CRC64;
MLCWGNASYG QLGLGGIDEE IVLEPRRSDF FVNKKVRDVG CGLRHTVFVL DDGTVYTCGC
NDLGQLGHEK SRKKPEQVVA LDAQNIVAVA CGEAHTLALN DKGQVYAWGL DSDGQLGLQG
SEECIRVPRN IKSLSDIQIV QVACGYYHSL ALSKASEVFC WGQNKYGQLG LGIDCQKQTS
PQLIKSLLGI PFMQVAAGGA HSFVLTLSGA IFGWGRNKFG QLGLNDENDR YVPNLLKSLR
SQKIVYICCG EDHTAALTKE GGVFTFGAGG YGQLGHNSTS HEINPRKVFE LMGSIVTQVA
CGRQHTSAFV PSSGRIYSFG LGGNGQLGTG STSNRKSPFT VKGNWFSYNG QCPQDIGSED
YFCVKRIFSG GDQSFSHYSS PQNCGPPDDF RCSDPSKQIW TVNEALIQKW LSYPSGRFPV
EIANEIDGTF SSSGCLNGSF LAISNDDHYR TGTRFSGVDM NAARLLFHKL IQPDHPQISQ
QVAASLEKNL IPKLTSSLPD VEALRFYLTL PECPLMSDCN NFTTIAIPFG TALVNLEKAP
LKVLENWWSV LEPPLFLKIV ELFKEVVVHL LKLYKIGIPP SERRIFNSFL HTALKVLEIL
HRVNEKTGQL IQYDKFYIHE VQELIDIRND YINWVQQQAY GVDVSHGVTE LADIPVTICT
YPFVFDAQAK TTLLQTDAVL QMQMAIDQAH RQNVSSLFLP VIESVNPCLI LVVRRENIVG
DAMEVLRKTK NIDYKKPLKV IFVGEDAVDA GGVRKEFFLL IMRELLDPKY GMFRYYEDSR
LIWFSDKTFE DSDLFHLIGV ICGLAIYNFT IVDLHFPLAL YKKLLKRKPS LDDLKELMPA
VGRSMQQLLD YPEDDIEETF CLNFTITVEN FGATEVKELV LNGADTAVNR QNRQEFVDAY
VDYIFNKSVA SLFDAFHAGF HKVCGGKVLL LFQPNELQAM VIGNTNYDWK ELEKNTEYKG
EYWADHPTIK IFWEVFHELP LEKKKQFLLF LTGSDRIPIL GMKSLKLVIQ STGGGESYLP
VSHTCFNLLD LPKYTEKETL RCKLIQAIDH NEGFSLI
