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Protein

Probable E3 ubiquitin-protein ligase HERC4

Gene

Herc4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable E3 ubiquitin-protein ligase involved in either protein trafficking or in the distribution of cellular structures. Required for spermatozoon maturation and fertility, and for the removal of the cytoplasmic droplet of the spermatozoon. E3 ubiquitin-protein ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer it to targeted substrates.1 Publication

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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei1025 – 10251Glycyl thioester intermediatePROSITE-ProRule annotation

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • protein ubiquitination Source: UniProtKB
  • spermatogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Differentiation, Spermatogenesis, Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Probable E3 ubiquitin-protein ligase HERC4 (EC:6.3.2.-)
Alternative name(s):
HECT domain and RCC1-like domain-containing protein 4
Gene namesi
Name:Herc4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1914595. Herc4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Disruption causes defects in spermatozoon maturation and impaired fertility in males; females display normal fertility. Males produce litter sizes some 50% smaller, as well 50% of mature spermatozoa have reduced mobility.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10571057Probable E3 ubiquitin-protein ligase HERC4PRO_0000278217Add
BLAST

Proteomic databases

EPDiQ6PAV2.
MaxQBiQ6PAV2.
PaxDbiQ6PAV2.
PRIDEiQ6PAV2.

PTM databases

iPTMnetiQ6PAV2.
PhosphoSiteiQ6PAV2.
SwissPalmiQ6PAV2.

Expressioni

Tissue specificityi

Ubiquitously expressed, highest expression is found in testis during spermiogenesis. It is specifically found in spermatogonia, spermatocytes, and spermatids with little or no expression detectable in the spermatozoa, or interstitial cells.1 Publication

Developmental stagei

Highly expressed in testis during spermiogenesis. Expression was almost undetectable in testes at postnatal day 14 (P14). However, by P23, a strong increase in mRNA levels was observed with expression persisting to P40 when spermatozoa were first observed. Up-regulated in the uterine luminal epithelium at the time of embryo implantation.1 Publication

Gene expression databases

BgeeiQ6PAV2.
CleanExiMM_HERC4.
GenevisibleiQ6PAV2. MM.

Interactioni

Protein-protein interaction databases

IntActiQ6PAV2. 1 interaction.
MINTiMINT-8174110.
STRINGi10090.ENSMUSP00000020258.

Structurei

3D structure databases

ProteinModelPortaliQ6PAV2.
SMRiQ6PAV2. Positions 34-395, 706-1050.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati1 – 5151RCC1 1Add
BLAST
Repeati52 – 10150RCC1 2Add
BLAST
Repeati102 – 15453RCC1 3Add
BLAST
Repeati156 – 20752RCC1 4Add
BLAST
Repeati208 – 25952RCC1 5Add
BLAST
Repeati261 – 31151RCC1 6Add
BLAST
Repeati313 – 36654RCC1 7Add
BLAST
Domaini730 – 1057328HECTPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
Contains 7 RCC1 repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0941. Eukaryota.
COG5021. LUCA.
COG5184. LUCA.
GeneTreeiENSGT00830000128260.
HOVERGENiHBG050878.
InParanoidiQ6PAV2.
KOiK10615.
OMAiPYNGQCP.
OrthoDBiEOG71VSRW.
PhylomeDBiQ6PAV2.
TreeFamiTF315189.

Family and domain databases

Gene3Di2.130.10.30. 1 hit.
InterProiIPR000569. HECT_dom.
IPR009091. RCC1/BLIP-II.
IPR000408. Reg_chr_condens.
[Graphical view]
PfamiPF00632. HECT. 1 hit.
PF00415. RCC1. 7 hits.
[Graphical view]
PRINTSiPR00633. RCCNDNSATION.
SMARTiSM00119. HECTc. 1 hit.
[Graphical view]
SUPFAMiSSF50985. SSF50985. 1 hit.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50237. HECT. 1 hit.
PS00626. RCC1_2. 3 hits.
PS50012. RCC1_3. 7 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q6PAV2-1) [UniParc]FASTAAdd to basket

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
MLCWGNASYG QLGLGGIDEE IVLEPRRSDF FVNKKVRDVG CGLRHTVFVL
60 70 80 90 100
DDGTVYTCGC NDLGQLGHEK SRKKPEQVVA LDAQNIVAVA CGEAHTLALN
110 120 130 140 150
DKGQVYAWGL DSDGQLGLQG SEECIRVPRN IKSLSDIQIV QVACGYYHSL
160 170 180 190 200
ALSKASEVFC WGQNKYGQLG LGIDCQKQTS PQLIKSLLGI PFMQVAAGGA
210 220 230 240 250
HSFVLTLSGA IFGWGRNKFG QLGLNDENDR YVPNLLKSLR SQKIVYICCG
260 270 280 290 300
EDHTAALTKE GGVFTFGAGG YGQLGHNSTS HEINPRKVFE LMGSIVTQVA
310 320 330 340 350
CGRQHTSAFV PSSGRIYSFG LGGNGQLGTG STSNRKSPFT VKGNWFSYNG
360 370 380 390 400
QCPQDIGSED YFCVKRIFSG GDQSFSHYSS PQNCGPPDDF RCSDPSKQIW
410 420 430 440 450
TVNEALIQKW LSYPSGRFPV EIANEIDGTF SSSGCLNGSF LAISNDDHYR
460 470 480 490 500
TGTRFSGVDM NAARLLFHKL IQPDHPQISQ QVAASLEKNL IPKLTSSLPD
510 520 530 540 550
VEALRFYLTL PECPLMSDCN NFTTIAIPFG TALVNLEKAP LKVLENWWSV
560 570 580 590 600
LEPPLFLKIV ELFKEVVVHL LKLYKIGIPP SERRIFNSFL HTALKVLEIL
610 620 630 640 650
HRVNEKTGQL IQYDKFYIHE VQELIDIRND YINWVQQQAY GVDVSHGVTE
660 670 680 690 700
LADIPVTICT YPFVFDAQAK TTLLQTDAVL QMQMAIDQAH RQNVSSLFLP
710 720 730 740 750
VIESVNPCLI LVVRRENIVG DAMEVLRKTK NIDYKKPLKV IFVGEDAVDA
760 770 780 790 800
GGVRKEFFLL IMRELLDPKY GMFRYYEDSR LIWFSDKTFE DSDLFHLIGV
810 820 830 840 850
ICGLAIYNFT IVDLHFPLAL YKKLLKRKPS LDDLKELMPA VGRSMQQLLD
860 870 880 890 900
YPEDDIEETF CLNFTITVEN FGATEVKELV LNGADTAVNR QNRQEFVDAY
910 920 930 940 950
VDYIFNKSVA SLFDAFHAGF HKVCGGKVLL LFQPNELQAM VIGNTNYDWK
960 970 980 990 1000
ELEKNTEYKG EYWADHPTIK IFWEVFHELP LEKKKQFLLF LTGSDRIPIL
1010 1020 1030 1040 1050
GMKSLKLVIQ STGGGESYLP VSHTCFNLLD LPKYTEKETL RCKLIQAIDH

NEGFSLI
Length:1,057
Mass (Da):118,412
Last modified:February 20, 2007 - v2
Checksum:iFCFFC9481AB0D4AE
GO
Isoform 2 (identifier: Q6PAV2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     643-650: Missing.

Show »
Length:1,049
Mass (Da):117,587
Checksum:i1D07E1D4F12DDAC1
GO
Isoform 3 (identifier: Q6PAV2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     229-233: DRYVP → GRCAL
     234-1057: Missing.

Show »
Length:233
Mass (Da):25,123
Checksum:i83A08E79DE5C5CFD
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti299 – 2991V → A in AAH60033 (PubMed:15489334).Curated
Sequence conflicti800 – 8001V → I in BAE25272 (PubMed:16141072).Curated
Sequence conflicti898 – 8981D → N in BAE26617 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei229 – 2335DRYVP → GRCAL in isoform 3. 1 PublicationVSP_023180
Alternative sequencei234 – 1057824Missing in isoform 3. 1 PublicationVSP_023181Add
BLAST
Alternative sequencei643 – 6508Missing in isoform 2. 2 PublicationsVSP_023182

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK009436 mRNA. Translation: BAB26286.1.
AK143111 mRNA. Translation: BAE25272.1.
AK145735 mRNA. Translation: BAE26617.1.
AK147723 mRNA. Translation: BAE28095.1.
BC026855 mRNA. Translation: AAH26855.1.
BC043082 mRNA. Translation: AAH43082.1.
BC047157 mRNA. Translation: AAH47157.1.
BC060033 mRNA. Translation: AAH60033.1.
CCDSiCCDS23897.1. [Q6PAV2-2]
RefSeqiNP_080377.2. NM_026101.4. [Q6PAV2-2]
NP_084390.1. NM_030114.2. [Q6PAV2-1]
UniGeneiMm.234437.
Mm.422789.
Mm.441725.
Mm.487274.

Genome annotation databases

EnsembliENSMUST00000020258; ENSMUSP00000020258; ENSMUSG00000020064. [Q6PAV2-2]
GeneIDi67345.
KEGGimmu:67345.
UCSCiuc007fka.2. mouse. [Q6PAV2-3]
uc007fkc.2. mouse. [Q6PAV2-2]
uc007fkd.2. mouse. [Q6PAV2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK009436 mRNA. Translation: BAB26286.1.
AK143111 mRNA. Translation: BAE25272.1.
AK145735 mRNA. Translation: BAE26617.1.
AK147723 mRNA. Translation: BAE28095.1.
BC026855 mRNA. Translation: AAH26855.1.
BC043082 mRNA. Translation: AAH43082.1.
BC047157 mRNA. Translation: AAH47157.1.
BC060033 mRNA. Translation: AAH60033.1.
CCDSiCCDS23897.1. [Q6PAV2-2]
RefSeqiNP_080377.2. NM_026101.4. [Q6PAV2-2]
NP_084390.1. NM_030114.2. [Q6PAV2-1]
UniGeneiMm.234437.
Mm.422789.
Mm.441725.
Mm.487274.

3D structure databases

ProteinModelPortaliQ6PAV2.
SMRiQ6PAV2. Positions 34-395, 706-1050.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ6PAV2. 1 interaction.
MINTiMINT-8174110.
STRINGi10090.ENSMUSP00000020258.

PTM databases

iPTMnetiQ6PAV2.
PhosphoSiteiQ6PAV2.
SwissPalmiQ6PAV2.

Proteomic databases

EPDiQ6PAV2.
MaxQBiQ6PAV2.
PaxDbiQ6PAV2.
PRIDEiQ6PAV2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020258; ENSMUSP00000020258; ENSMUSG00000020064. [Q6PAV2-2]
GeneIDi67345.
KEGGimmu:67345.
UCSCiuc007fka.2. mouse. [Q6PAV2-3]
uc007fkc.2. mouse. [Q6PAV2-2]
uc007fkd.2. mouse. [Q6PAV2-1]

Organism-specific databases

CTDi26091.
MGIiMGI:1914595. Herc4.

Phylogenomic databases

eggNOGiKOG0941. Eukaryota.
COG5021. LUCA.
COG5184. LUCA.
GeneTreeiENSGT00830000128260.
HOVERGENiHBG050878.
InParanoidiQ6PAV2.
KOiK10615.
OMAiPYNGQCP.
OrthoDBiEOG71VSRW.
PhylomeDBiQ6PAV2.
TreeFamiTF315189.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

ChiTaRSiHerc4. mouse.
NextBioi324318.
PROiQ6PAV2.
SOURCEiSearch...

Gene expression databases

BgeeiQ6PAV2.
CleanExiMM_HERC4.
GenevisibleiQ6PAV2. MM.

Family and domain databases

Gene3Di2.130.10.30. 1 hit.
InterProiIPR000569. HECT_dom.
IPR009091. RCC1/BLIP-II.
IPR000408. Reg_chr_condens.
[Graphical view]
PfamiPF00632. HECT. 1 hit.
PF00415. RCC1. 7 hits.
[Graphical view]
PRINTSiPR00633. RCCNDNSATION.
SMARTiSM00119. HECTc. 1 hit.
[Graphical view]
SUPFAMiSSF50985. SSF50985. 1 hit.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50237. HECT. 1 hit.
PS00626. RCC1_2. 3 hits.
PS50012. RCC1_3. 7 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
    Strain: C57BL/6J.
    Tissue: Blastocyst, Eye, Melanocyte and Tongue.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J, FVB/N and FVB/N-3.
    Tissue: Brain, Colon and Mammary tumor.
  3. "Disruption of the ubiquitin ligase HERC4 causes defects in spermatozoon maturation and impaired fertility."
    Rodriguez C.I., Stewart C.L.
    Dev. Biol. 312:501-508(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
    Strain: 129/Ola and C57BL/6.
  4. "Influence of Tripterygium wilfordii on the expression of spermiogenesis related genes Herc4, Ipo11 and Mrto4 in mice."
    Huang D., Li J., He L.Q.
    Yi Chuan 31:941-946(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: MISCELLANEOUS.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiHERC4_MOUSE
AccessioniPrimary (citable) accession number: Q6PAV2
Secondary accession number(s): Q3UL34
, Q3UPX2, Q810A0, Q811C9, Q8R315, Q9D797
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: May 11, 2016
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

T.wilfordii induces abnormal expression of spermiogenesis genes including Herc4, the spermatogenic cells in the convoluted seminiferous tubules decrease and the lumen is obstructed by large deciduous spermatogenic cells. T.wilfordii has apparent antifertility effects.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.