CP131_MOUSE
ID CP131_MOUSE Reviewed; 1060 AA.
AC Q62036; B1AXJ0;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Centrosomal protein of 131 kDa;
DE AltName: Full=5-azacytidine-induced protein 1;
DE AltName: Full=Pre-acrosome localization protein 1;
GN Name=Cep131; Synonyms=Az1, Azi, Azi1;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8529672; DOI=10.1111/j.1432-1033.1995.008_c.x;
RA Aoto H., Tsuchida J., Nishina Y., Nishimune Y., Asano A., Tajima S.;
RT "Isolation of a novel cDNA that encodes a protein localized to the pre-
RT acrosome region of spermatids.";
RL Eur. J. Biochem. 234:8-15(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=9070930; DOI=10.1006/geno.1996.4546;
RA Aoto H., Miyake Y., Nakamura M., Tajima S.;
RT "Genomic organization of the mouse AZ1 gene that encodes the protein
RT localized to preacrosomes of spermatids.";
RL Genomics 40:138-141(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-47; THR-473 AND
RP SER-481, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, 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).
RN [6]
RP REVIEW, AND FUNCTION.
RX PubMed=24185901; DOI=10.1038/emboj.2013.241;
RA Chavali P.L., Gergely F.;
RT "Cilia born out of shock and stress.";
RL EMBO J. 32:3011-3013(2013).
RN [7]
RP FUNCTION IN SPERMIOGENESIS, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=24415959; DOI=10.1371/journal.pgen.1003928;
RA Hall E.A., Keighren M., Ford M.J., Davey T., Jarman A.P., Smith L.B.,
RA Jackson I.J., Mill P.;
RT "Acute versus chronic loss of mammalian Azi1/Cep131 results in distinct
RT ciliary phenotypes.";
RL PLoS Genet. 9:E1003928-E1003928(2013).
RN [8]
RP ASSOCIATION WITH THE BBSOME COMPLEX.
RX PubMed=24550735; DOI=10.1371/journal.pgen.1004083;
RA Chamling X., Seo S., Searby C.C., Kim G., Slusarski D.C., Sheffield V.C.;
RT "The centriolar satellite protein AZI1 interacts with BBS4 and regulates
RT ciliary trafficking of the BBSome.";
RL PLoS Genet. 10:E1004083-E1004083(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CEP152 AND PCM1.
RX PubMed=26297806; DOI=10.7554/elife.07519;
RA Kodani A., Yu T.W., Johnson J.R., Jayaraman D., Johnson T.L., Al-Gazali L.,
RA Sztriha L., Partlow J.N., Kim H., Krup A.L., Dammermann A., Krogan N.,
RA Walsh C.A., Reiter J.F.;
RT "Centriolar satellites assemble centrosomal microcephaly proteins to
RT recruit CDK2 and promote centriole duplication.";
RL Elife 4:0-0(2015).
CC -!- FUNCTION: Component of centriolar satellites contributing to the
CC building of a complex and dynamic network required to regulate
CC cilia/flagellum formation. In proliferating cells, MIB1-mediated
CC ubiquitination induces its sequestration within centriolar satellites,
CC precluding untimely cilia formation initiation. In contrast, during
CC normal and ultraviolet or heat shock cellular stress-induced
CC ciliogenesis, its non-ubiquitinated form is rapidly displaced from
CC centriolar satellites and recruited to centrosome/basal bodies in a
CC microtubule- and p38 MAPK-dependent manner. Acts also as a negative
CC regulator of BBSome ciliary trafficking (By similarity). Plays a role
CC in sperm flagellar formation; may be involved in the regulation of
CC intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking,
CC which are important for axoneme extension and/or cargo delivery to the
CC nascent sperm tail (PubMed:24415959). Required for optimal cell
CC proliferation and cell cycle progression; may play a role in the
CC regulation of genome stability and centriole duplication in non-
CC ciliogenic cells (By similarity). Involved in centriole duplication
CC (PubMed:26297806). Required for CEP152, WDR62 and CEP63 centrosomal
CC localization and promotes the centrosomal localization of CDK2 (By
CC similarity). Essential for maintaining proper centriolar satellite
CC integrity (By similarity). {ECO:0000250|UniProtKB:Q9UPN4,
CC ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24415959,
CC ECO:0000269|PubMed:26297806}.
CC -!- SUBUNIT: Self-associates (By similarity). Associates with the
CC centriolar satellite BBSome protein complex (PubMed:24550735) Interacts
CC with BBS4; the interaction limits BBS4 availability for association
CC with the BBSome complex, and hence negatively regulates ciliary
CC localization of the BBSome complex. Interacts with MIB1. Interacts with
CC PCM1; the interaction increases in response to ultraviolet light (UV)
CC radiation. Associates with microtubule; association to microtubule is
CC reduced in response to cellular stress, such as UV stimulation, in a
CC process that requires p38 MAP kinase signaling. Interacts with CEP290,
CC DCTN1, MAP1LC3B, PCNT, PCM1 and CEP152 (By similarity). Interacts with
CC 14-3-3 proteins following UV-induced phosphorylation by MAPKAPK2; this
CC inhibits formation of novel centriolar satellites (By similarity).
CC Interacts with SDCCAG8 (By similarity). Interacts with CCDC61 (By
CC similarity). Interacts with PLK4 (By similarity).
CC {ECO:0000250|UniProtKB:Q9UPN4, ECO:0000269|PubMed:24550735}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:24415959}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome, centriolar
CC satellite {ECO:0000269|PubMed:24415959}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome, centriole
CC {ECO:0000250|UniProtKB:Q9UPN4}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:24415959}. Cytoplasmic vesicle, secretory
CC vesicle, acrosome {ECO:0000269|PubMed:24415959}. Note=Ubiquitinated
CC form is sequestered and colocalized with BBS4, CEP290, PCM1 and PCNT at
CC centriolar satellites in proliferating cells. Traffics towards and away
CC from centriolar satellites and centrosome in a microtubule- and dynein-
CC dependent manner in interphase cells. Displaced from centriolar
CC satellites but still remained associated with centrosome in response to
CC cellular stress, such as ultraviolet light (UV) radiation or heat
CC shock, in a process that requires p38 MAPK signaling (By similarity).
CC Colocalized with pericentriolar material protein PCM1 at centriolar
CC satellites. During spermiogenesis, becomes enriched with nephrocystin
CC NPHP1 at the transition zone, a structure at the base of the ciliary
CC axoneme important for regulating traffic into the ciliary compartment.
CC Traffics towards and away from the centrosome/basal bodies and the
CC transition zone of the ciliary axoneme in a microtubule-dependent
CC manner. Localized at the Golgi-derived acrosome and the centrosome-
CC containing head-tail coupling apparatus (HTCA).
CC {ECO:0000250|UniProtKB:Q9UPN4}.
CC -!- TISSUE SPECIFICITY: Localized to the pre-acrosome region of round and
CC elongated spermatids in testis but also present in ovary, brain and
CC adipose tissue. {ECO:0000269|PubMed:8529672}.
CC -!- DEVELOPMENTAL STAGE: Widely expressed during development, with strong
CC expression in tissues with high levels of cilia-dependent developmental
CC signaling such as the limbs, eyes, somite derivatives and brain.
CC Significant amounts are found in the testis of 16 day old mice, at a
CC late stage of pachytene spermatocytes when meiosis occurs. The level
CC increases thereafter. {ECO:0000269|PubMed:24415959}.
CC -!- INDUCTION: By 5-azacytidine.
CC -!- PTM: Ubiquitinated. Undergoes monoubiquitination catalyzed by the E3
CC ubiquitin-protein ligase MIB1 in proliferating cells, preventing cilia
CC formation. Monoubiquitination by MIB1 is inhibited in response to
CC cellular stress, such as ultraviolet light (UV) radiation or heat
CC shock, resulting in ciliogenesis restoration (By similarity).
CC {ECO:0000250|UniProtKB:Q9UPN4}.
CC -!- PTM: MAPKAPK2-dependent phosphorylation at Ser-47 and Ser-78 occurs in
CC response to cellular stress such as exposure to ultraviolet irradiation
CC and promotes binding to 14-3-3 proteins which leads to cytoplasmic
CC sequestration of CEP131 and blocks formation of new centriolar
CC satellites (By similarity). Phosphorylation at Ser-78 mediated by PLK4
CC is essential for proper organization and integrity of centriolar
CC satellites but is dispensable for its localization to centrioles and
CC its function in ciliogenesis (By similarity).
CC {ECO:0000250|UniProtKB:Q9UPN4}.
CC -!- DISRUPTION PHENOTYPE: Females grow normally and are healthy. Males
CC display developing sperm flagella abnormalities resulting in
CC infertility. Post-meiotic defects during spermatogenesis with abnormal
CC morphology of elongating and elongated spermatids, including
CC teratozoospermia, premature apoptosis, but without increase in DNA
CC damage. Sperm are immotile with shortened and morphologically abnormal
CC flagella, and altered intraflagellar transport (IFT) and/or
CC intramanchette (IMT) trafficking. Displays normal postnatal
CC multiciliated airway epithelium. Lacks retinal degeneration and kidney
CC cysts formations. {ECO:0000269|PubMed:24415959}.
CC -!- MISCELLANEOUS: Transient cell cultured-based knock-down (by RNAi) of
CC CEP131 leads to a reduction in ciliogenesis (PubMed:24415959). However,
CC chronic absence of CEP131 following genetic deletion (knockout) shows
CC that cilia develop and function normally in vivo. This suggests that
CC CEP131 is not essential for ciliogenesis, except for the modified cilia
CC of the developing sperm flagella, and that there is an alternative
CC mechanism to compensate for the lack of CEP131 (PubMed:24415959).
CC {ECO:0000305|PubMed:24415959}.
CC -!- SIMILARITY: Belongs to the CEP131 family. {ECO:0000305}.
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DR EMBL; D43921; BAA07868.1; -; mRNA.
DR EMBL; D88509; BAA19002.1; -; Genomic_DNA.
DR EMBL; AL807824; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; S63993; S63993.
DR RefSeq; NP_033864.3; NM_009734.3.
DR RefSeq; XP_006532124.1; XM_006532061.3.
DR AlphaFoldDB; Q62036; -.
DR SMR; Q62036; -.
DR BioGRID; 198290; 47.
DR IntAct; Q62036; 45.
DR STRING; 10090.ENSMUSP00000101834; -.
DR iPTMnet; Q62036; -.
DR PhosphoSitePlus; Q62036; -.
DR EPD; Q62036; -.
DR MaxQB; Q62036; -.
DR PaxDb; Q62036; -.
DR PRIDE; Q62036; -.
DR ProteomicsDB; 283806; -.
DR Antibodypedia; 19799; 126 antibodies from 24 providers.
DR DNASU; 12009; -.
DR Ensembl; ENSMUST00000106229; ENSMUSP00000101836; ENSMUSG00000039781.
DR GeneID; 12009; -.
DR KEGG; mmu:12009; -.
DR CTD; 22994; -.
DR MGI; MGI:107440; Cep131.
DR VEuPathDB; HostDB:ENSMUSG00000039781; -.
DR eggNOG; ENOG502RZME; Eukaryota.
DR GeneTree; ENSGT00390000001758; -.
DR InParanoid; Q62036; -.
DR OrthoDB; 918776at2759; -.
DR PhylomeDB; Q62036; -.
DR Reactome; R-MMU-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-MMU-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-MMU-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-MMU-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-MMU-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-MMU-8854518; AURKA Activation by TPX2.
DR BioGRID-ORCS; 12009; 0 hits in 74 CRISPR screens.
DR PRO; PR:Q62036; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q62036; protein.
DR Bgee; ENSMUSG00000039781; Expressed in ventricular zone and 192 other tissues.
DR ExpressionAtlas; Q62036; baseline and differential.
DR Genevisible; Q62036; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:MGI.
DR GO; GO:0034451; C:centriolar satellite; IDA:MGI.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; ISO:MGI.
DR GO; GO:0035869; C:ciliary transition zone; IDA:MGI.
DR GO; GO:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0002177; C:manchette; IEA:GOC.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0120212; C:sperm head-tail coupling apparatus; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0060271; P:cilium assembly; IBA:GO_Central.
DR GO; GO:0042073; P:intraciliary transport; IMP:MGI.
DR GO; GO:0035735; P:intraciliary transport involved in cilium assembly; ISS:UniProtKB.
DR GO; GO:1990953; P:intramanchette transport; IMP:MGI.
DR GO; GO:1905198; P:manchette assembly; IMP:MGI.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0071539; P:protein localization to centrosome; ISO:MGI.
DR GO; GO:0010824; P:regulation of centrosome duplication; ISS:UniProtKB.
DR GO; GO:0007288; P:sperm axoneme assembly; IMP:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; TAS:UniProtKB.
DR InterPro; IPR030465; CEP131.
DR PANTHER; PTHR31540; PTHR31540; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell projection; Cilium biogenesis/degradation; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Developmental protein; Differentiation;
KW Phosphoprotein; Reference proteome; Spermatogenesis; Transport;
KW Ubl conjugation.
FT CHAIN 1..1060
FT /note="Centrosomal protein of 131 kDa"
FT /id="PRO_0000064782"
FT DOMAIN 263..283
FT /note="IQ"
FT REGION 1..244
FT /note="Interaction with PLK4"
FT /evidence="ECO:0000250|UniProtKB:Q9UPN4"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 217..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 314..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 71..91
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 228..242
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..329
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..363
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPN4"
FT MOD_RES 47
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 78
FT /note="Phosphoserine; by MAPKAPK2 and PLK4"
FT /evidence="ECO:0000250|UniProtKB:Q9UPN4"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPN4"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPN4"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPN4"
FT MOD_RES 146
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPN4"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPN4"
FT MOD_RES 473
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 336
FT /note="V -> E (in Ref. 1; BAA07868 and 2; BAA19002)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1060 AA; 120313 MW; FAAC3F922EB83A96 CRC64;
MKGSRTITAT PEGSPEAVDL SLIGLPPPMS QRPGSASATR SIFRSMSVAT GSEPRKKALE
ATGPGGPRAI NNLRRSNSTT QVNQSWTGSP RPAEPTDFLM LFEGSTSGRR RVASLSKASS
EKEATWNVLD EQPRGLALPA SAQSPSTLDS ALGPRRKECP LAPSFTANNR SNKGAVGNCV
TTMVHNHYAS SKMVSPPKSS NQTAPSLNNI VKAAAREGGE GSDLGKPRKN LSSASQSARG
TTGLLRRREV TEEEAERFIH QVNQAAVTIQ RWYRCQVQRR RAGAAALEHL LASKREGQRQ
RLGGGNLLEL HRQEEAARKK AREEKARQAR QAAIQVLQQK RAQKASEAEH RRPKDRPETR
APEQPRPMQE PGCVTHPKAN NAGASIYPTG PADPCPPASE SSPEQWQSPE DKPQDIHSQG
EARQDLAVSG SSRGKARARA TLDDLLDTLK LLEEEPEPLP HPKAYHKDRY AWTDEEEDAN
SLTADNLEKF GKLSAAPGPP DDGTLLSEAK LQSIMTFLDE MEKSGQERPA PWRESLVLEA
GSGSEGSTSV MRLKLELEEK KQAMALLQRA LAQQRDLTVR RVKETEKELT RQLRQQKEQY
EATIQRHLSF IDQLIEDKKV LSEKCEAVVA ELKHGDQRCR ERVAQMQEQH ELEIKKLKEL
MSATEKIRRE KWINEKTKKI KEITVRGLEP EIQKLIAKHK QEVRRLRGLH EAELQQREEQ
AAQRHLRQAE ELRQHLDRER EVLGQQERER AQQRFEQHLE QEQRALEQQR RRLYNEVAEE
KERLGQQAAR QRAELEELRQ QLEESSAALT RALRAEFERS REEQERRHQM ELKALKDQLE
AERQAWVASC AKKEEAWLLT RERELKEEIR KGRDQEIELV IHRLEADMTL AKEESERAAE
SRVKRVRDKY ETELSELEQS ERKLQERCSE LKGRLGEAEG EKERLQSLVR QKEKELEDLR
AVNTQMCSER ASLAQVVRQE FAEQLAASQE ETQRVKVELA ELQARQQVEL DEVHRRVKTA
LARKEAAVNS LRKQHEAAVK RADHLEELLE QHKGSSLSSK
