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 01-MAY-2013, entry version 72.
DE RecName: Full=Probable E3 ubiquitin-protein ligase HERC4;
DE EC=6.3.2.-;
DE AltName: Full=HECT domain and RCC1-like domain-containing protein 4;
GN Name=Herc4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; 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.,
RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA 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.,
RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA 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/6, 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
RT project: 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/6;
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
RT spermatozoon maturation and impaired fertility.";
RL Dev. Biol. 312:501-508(2007).
RN [4]
RP MISCELLANEOUS.
RX PubMed=19819847;
RA Huang D., Li J., He L.Q.;
RT "Influence of Tripterygium wilfordii on the expression of
RT spermiogenesis related genes Herc4, Ipo11 and Mrto4 in mice.";
RL Yi Chuan 31:941-946(2009).
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
CC removal of the cytoplasmic droplet of the spermatozoon. E3
CC ubiquitin-protein ligases accept ubiquitin from an E2 ubiquitin-
CC conjugating enzyme in the form of a thioester and then directly
CC transfer it to targeted substrates.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol (By similarity).
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
CC found 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 -!- DEVELOPMENTAL STAGE: Highly expressed in testis during
CC spermiogenesis. Expression was almost undetectable in testes at
CC postnatal day 14 (P14). However, by P23, a strong increase in mRNA
CC levels was observed with expression persisting to P40 when
CC spermatozoa were first observed. Up-regulated in the uterine
CC luminal epithelium at the time of embryo implantation.
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
CC 50% of mature spermatozoa have reduced mobility.
CC -!- MISCELLANEOUS: T.wilfordii induces abnormal expression of
CC spermiogenesis genes including Herc4, the spermatogenic cells in
CC the convoluted seminiferous tubules decrease and the lumen is
CC obstructed by large deciduous spermatogenic cells. T.wilfordii has
CC apparent antifertility effects.
CC -!- SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein
CC ligase) domain.
CC -!- SIMILARITY: Contains 7 RCC1 repeats.
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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 IPI; IPI00453903; -.
DR IPI; IPI00554980; -.
DR IPI; IPI00828240; -.
DR RefSeq; NP_080377.2; NM_026101.4.
DR RefSeq; NP_084390.1; NM_030114.2.
DR UniGene; Mm.234437; -.
DR UniGene; Mm.422789; -.
DR UniGene; Mm.441725; -.
DR UniGene; Mm.487274; -.
DR HSSP; Q9UEP9; 1C4Z.
DR ProteinModelPortal; Q6PAV2; -.
DR SMR; Q6PAV2; 4-342, 706-1050.
DR PhosphoSite; Q6PAV2; -.
DR PaxDb; Q6PAV2; -.
DR PRIDE; Q6PAV2; -.
DR Ensembl; ENSMUST00000020258; ENSMUSP00000020258; ENSMUSG00000020064.
DR GeneID; 67345; -.
DR KEGG; mmu:67345; -.
DR UCSC; uc007fka.2; mouse.
DR UCSC; uc007fkc.2; mouse.
DR UCSC; uc007fkd.2; mouse.
DR CTD; 26091; -.
DR MGI; MGI:1914595; Herc4.
DR eggNOG; COG5021; -.
DR GeneTree; ENSGT00660000095216; -.
DR HOVERGEN; HBG050878; -.
DR InParanoid; Q6PAV2; -.
DR KO; K10615; -.
DR OMA; KLVIQPT; -.
DR OrthoDB; EOG44XJG1; -.
DR UniPathway; UPA00143; -.
DR NextBio; 324318; -.
DR Bgee; Q6PAV2; -.
DR CleanEx; MM_HERC4; -.
DR Genevestigator; Q6PAV2; -.
DR GO; GO:0005737; C:cytoplasm; IBA:RefGenome.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:RefGenome.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; TAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR Gene3D; 2.130.10.30; -; 1.
DR InterPro; IPR000569; HECT.
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; SSF56204; HECT; 1.
DR SUPFAM; SSF50985; RCC1/BLIP-II; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS00625; RCC1_1; FALSE_NEG.
DR PROSITE; PS00626; RCC1_2; 3.
DR PROSITE; PS50012; RCC1_3; 7.
PE 2: Evidence at transcript level;
KW Alternative splicing; Complete proteome; Cytoplasm; Differentiation;
KW Ligase; Reference proteome; Repeat; Spermatogenesis;
KW Ubl conjugation pathway.
FT CHAIN 1 1057 Probable E3 ubiquitin-protein ligase
FT HERC4.
FT /FTId=PRO_0000278217.
FT REPEAT 1 51 RCC1 1.
FT REPEAT 52 101 RCC1 2.
FT REPEAT 102 154 RCC1 3.
FT REPEAT 156 207 RCC1 4.
FT REPEAT 208 259 RCC1 5.
FT REPEAT 261 311 RCC1 6.
FT REPEAT 313 366 RCC1 7.
FT DOMAIN 730 1057 HECT.
FT ACT_SITE 1025 1025 Glycyl thioester intermediate (By
FT similarity).
FT VAR_SEQ 229 233 DRYVP -> GRCAL (in isoform 3).
FT /FTId=VSP_023180.
FT VAR_SEQ 234 1057 Missing (in isoform 3).
FT /FTId=VSP_023181.
FT VAR_SEQ 643 650 Missing (in isoform 2).
FT /FTId=VSP_023182.
FT CONFLICT 299 299 V -> A (in Ref. 2; AAH60033).
FT CONFLICT 800 800 V -> I (in Ref. 1; BAE25272).
FT CONFLICT 898 898 D -> N (in Ref. 1; BAE26617).
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
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