NIPBL_CAEEL
ID NIPBL_CAEEL Reviewed; 2176 AA.
AC Q95XZ5; A0A0K3AU30;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 3.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Nipped-B-like protein scc-2 {ECO:0000305};
DE AltName: Full=Prion-like-(Q/N-rich) domain-bearing protein 85;
DE AltName: Full=SCC2 homolog;
GN Name=scc-2 {ECO:0000303|PubMed:21856158};
GN Synonyms=pqn-85 {ECO:0000312|WormBase:Y43H11AL.3a};
GN ORFNames=Y43H11AL.3 {ECO:0000312|WormBase:Y43H11AL.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15146185; DOI=10.1038/ng1363;
RA Tonkin E.T., Wang T.-J., Lisgo S., Bamshad M.J., Strachan T.;
RT "NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion
RT proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.";
RL Nat. Genet. 36:636-641(2004).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16802858; DOI=10.1371/journal.pbio.0040242;
RA Seitan V.C., Banks P., Laval S., Majid N.A., Dorsett D., Rana A., Smith J.,
RA Bateman A., Krpic S., Hostert A., Rollins R.A., Erdjument-Bromage H.,
RA Tempst P., Benard C.Y., Hekimi S., Newbury S.F., Strachan T.;
RT "Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon
RT migration guidance.";
RL PLoS Biol. 4:E242-E242(2006).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP HIS-112.
RX PubMed=21856158; DOI=10.1016/j.cub.2011.07.007;
RA Lightfoot J., Testori S., Barroso C., Martinez-Perez E.;
RT "Loading of meiotic cohesin by SCC-2 is required for early processing of
RT DSBs and for the DNA damage checkpoint.";
RL Curr. Biol. 21:1421-1430(2011).
CC -!- FUNCTION: Plays an important role in the loading of the cohesin complex
CC on to meiotic chromosomes (PubMed:21856158). Forms a heterodimeric
CC complex (also known as cohesin loading complex) with mau-2/SCC4 which
CC mediates the loading of the cohesin complex onto chromatin (By
CC similarity). Plays an essential role in cell division during embryonic
CC development (PubMed:15146185, PubMed:16802858). Promotes normal
CC chromosome organization during meiosis (PubMed:21856158). Required for
CC the assembly of the synaptonemal complex between homologous chromosomes
CC to promote sister chromatid cohesion during meiosis (PubMed:21856158).
CC Required for chromosome segregation during mitosis and meiosis
CC (PubMed:16802858). Plays a role in DNA double-strand break (DSB) repair
CC during meiotic recombination and promotes the assembly of the 9-1-1
CC cell-cycle checkpoint response complex which is required for inducing
CC apoptosis in response to DNA damage, at DNA damage sites
CC (PubMed:21856158). {ECO:0000250|UniProtKB:Q6KC79,
CC ECO:0000269|PubMed:15146185, ECO:0000269|PubMed:16802858,
CC ECO:0000269|PubMed:21856158}.
CC -!- SUBUNIT: May heterodimerize with mau-2/SCC4 to form the cohesin loading
CC complex. {ECO:0000250|UniProtKB:Q6KC79}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21856158}. Chromosome
CC {ECO:0000269|PubMed:21856158}. Note=Localizes to pachytene nuclei in
CC germlines (PubMed:21856158). Localizes to the axial element of meiotic
CC chromosomes in germlines (PubMed:21856158).
CC {ECO:0000269|PubMed:21856158}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:Y43H11AL.3a};
CC IsoId=Q95XZ5-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y43H11AL.3b};
CC IsoId=Q95XZ5-2; Sequence=VSP_061056;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in 100% embryonic
CC lethality (PubMed:15146185, PubMed:16802858). Any survivors display a
CC paralyzed uncoordinated phenotype, body morphology defects and
CC sometimes a vulval defect (PubMed:15146185). RNAi-mediated knockdown
CC results in chromosome segregation defects in early embryos with lagging
CC chromosomes at the anaphase phase of mitosis (PubMed:16802858). RNAi-
CC mediated knockdown results in cytological defects in the pachytene and
CC diakinesis phases of meiosis in the germline (PubMed:21856158). RNAi-
CC mediated knockdown abolishes loading of cohesin complex components smc-
CC 1, smc-3 and rec-8 onto the to the axial element of meiotic chromosomes
CC in the germline, however these subunits do accumulate in the mitotic
CC nuclei and the meiotic S phase nuclei that precede the start of meiotic
CC prophase (PubMed:21856158). RNAi-mediated knockdown results in
CC defective DNA double-strand break repair during meiosis resulting in an
CC accumulation of rad-51-positive recombination intermediates and
CC elongated rad-51-positive recombination structures in the mid and late
CC pachytene region of the germline (PubMed:21856158). There is an
CC increase in apoptosis in response to the accumulation of recombination
CC intermediates, but only in the presence of smc-1, indicative of a
CC defective DNA damage response (PubMed:21856158).
CC {ECO:0000269|PubMed:15146185, ECO:0000269|PubMed:16802858,
CC ECO:0000269|PubMed:21856158}.
CC -!- SIMILARITY: Belongs to the SCC2/Nipped-B family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BX284602; CCD71490.2; -; Genomic_DNA.
DR EMBL; BX284602; CTQ86543.1; -; Genomic_DNA.
DR RefSeq; NP_001300604.1; NM_001313675.1. [Q95XZ5-2]
DR RefSeq; NP_493687.2; NM_061286.3.
DR AlphaFoldDB; Q95XZ5; -.
DR SMR; Q95XZ5; -.
DR BioGRID; 38788; 3.
DR IntAct; Q95XZ5; 2.
DR STRING; 6239.Y43H11AL.3; -.
DR iPTMnet; Q95XZ5; -.
DR EPD; Q95XZ5; -.
DR PaxDb; Q95XZ5; -.
DR PeptideAtlas; Q95XZ5; -.
DR PRIDE; Q95XZ5; -.
DR EnsemblMetazoa; Y43H11AL.3a.1; Y43H11AL.3a.1; WBGene00004166. [Q95XZ5-1]
DR EnsemblMetazoa; Y43H11AL.3a.2; Y43H11AL.3a.2; WBGene00004166. [Q95XZ5-1]
DR EnsemblMetazoa; Y43H11AL.3b.1; Y43H11AL.3b.1; WBGene00004166. [Q95XZ5-2]
DR GeneID; 173410; -.
DR UCSC; Y43H11AL.3; c. elegans. [Q95XZ5-1]
DR CTD; 173410; -.
DR WormBase; Y43H11AL.3a; CE53800; WBGene00004166; scc-2. [Q95XZ5-1]
DR WormBase; Y43H11AL.3b; CE50846; WBGene00004166; scc-2. [Q95XZ5-2]
DR eggNOG; KOG1020; Eukaryota.
DR GeneTree; ENSGT00390000010427; -.
DR HOGENOM; CLU_000763_1_1_1; -.
DR InParanoid; Q95XZ5; -.
DR OrthoDB; 608077at2759; -.
DR PhylomeDB; Q95XZ5; -.
DR Reactome; R-CEL-2470946; Cohesin Loading onto Chromatin.
DR PRO; PR:Q95XZ5; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00004166; Expressed in adult organism and 4 other tissues.
DR ExpressionAtlas; Q95XZ5; baseline and differential.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090694; C:Scc2-Scc4 cohesin loading complex; IBA:GO_Central.
DR GO; GO:0032116; C:SMC loading complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0070192; P:chromosome organization involved in meiotic cell cycle; IMP:UniProtKB.
DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; IMP:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0034087; P:establishment of mitotic sister chromatid cohesion; IBA:GO_Central.
DR GO; GO:0071169; P:establishment of protein localization to chromatin; IBA:GO_Central.
DR GO; GO:0034088; P:maintenance of mitotic sister chromatid cohesion; ISS:UniProtKB.
DR GO; GO:0051177; P:meiotic sister chromatid cohesion; IMP:UniProtKB.
DR GO; GO:0061780; P:mitotic cohesin loading; IEA:InterPro.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:WormBase.
DR GO; GO:1905309; P:positive regulation of cohesin loading; IMP:UniProtKB.
DR GO; GO:1905088; P:positive regulation of synaptonemal complex assembly; IMP:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IEA:InterPro.
DR GO; GO:1990414; P:replication-born double-strand break repair via sister chromatid exchange; IBA:GO_Central.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR026003; Cohesin_HEAT.
DR InterPro; IPR024986; Nipped-B_C.
DR InterPro; IPR033031; Scc2/Nipped-B.
DR PANTHER; PTHR21704; PTHR21704; 2.
DR Pfam; PF12765; Cohesin_HEAT; 1.
DR Pfam; PF12830; Nipped-B_C; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Chromosome; Nucleus; Reference proteome;
KW Repeat.
FT CHAIN 1..2176
FT /note="Nipped-B-like protein scc-2"
FT /id="PRO_0000218598"
FT REPEAT 1280..1312
FT /note="HEAT 1"
FT REPEAT 1320..1351
FT /note="HEAT 2"
FT REPEAT 1353..1388
FT /note="HEAT 3"
FT REPEAT 1393..1426
FT /note="HEAT 4"
FT REPEAT 1692..1723
FT /note="HEAT 5"
FT REPEAT 1803..1834
FT /note="HEAT 6"
FT REPEAT 1840..1871
FT /note="HEAT 7"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 464..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 495..514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 523..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 585..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 669..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2149..2176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 534..551
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 586..615
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..1761
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_061056"
FT MUTAGEN 112
FT /note="H->Y: In fq1; cytological defects in the pachytene
FT and diakinesis phases of meiotic prophase in the germline.
FT Abolishes loading of cohesin complex components smc-1, smc-
FT 3 and rec-8 onto the to the axial element of meiotic
FT chromosomes in the germline, however these subunits do
FT accumulate in the mitotic nuclei and the meiotic S phase
FT nuclei that precede the start of meiotic prophase.
FT Abrogates assembly of the synaptonemal complex between
FT homologous chromosomes. Does not affect the loading of
FT condensin and the smc-5/6 complex onto meiotic chromosomes.
FT Defective DNA double-strand break repair during meiosis
FT resulting in an accumulation of rad-51-positive
FT recombination intermediates and elongated rad-51-positive
FT recombination structures in the mid and late pachytene
FT region of the germline. No increase in apoptosis in
FT response to the accumulation of recombination
FT intermediates, indicative of a defective DNA damage
FT response. Furthermore, hus-1, a component of the 9-1-1
FT cell-cycle checkpoint response complex which is required
FT for inducing apoptosis in response to DNA damage, does not
FT accumulate on the recombination intermediates."
FT /evidence="ECO:0000269|PubMed:21856158"
SQ SEQUENCE 2176 AA; 249784 MW; AB58B2406273EA9D CRC64;
MDPNNLQNSL NGTGNPNFQP VQTNAGGFGH QMAQTGAAAA AAATGQYNPM LLQQQYLNFG
FGMNYNNQLF DFQAQQQQQQ QYLMQQQQQQ QQLHHQQQQQ HQNIAQPQAQ HHQMNMFTQH
QMLQLMQQQQ QQQQQQPVQQ IQRQQPIAQP IPQHTIPPST SNQFQQQIQS AASSIFDSSV
ISSHQKLYEE QCRQIEKERK EQEERKRKQE LEEQRKRNEE LKRLRIAEEK RLLEEQQRLR
EQMERERLAE IKRLEEAARL EDERRIAADI EAQKQAMLQK MQAEQNKHIA EVERQRSELE
ERFARVSQPM TLVGTHFLPN FLDMIPFPYE SMVDSTLPQV FDMERDSAIL ESCDPQMVAT
ISNILNATNI DDIITRMDKL RPDDKETNDL FLDKLPPIIQ AVVNYNTSAL DVDSHNDMEL
LENEDVMMTE DITRTTAPST SSSSYNNHHQ NSIVMMTSSS VSMSEATQSS SVTMNHHDVD
EEGPAPISIE KRRQMMSVGK APKAGGGGGQ NQRKKRDMVE NLYDSLTDNF VPTDTGRRGR
RRGRGSDDDE DELLQRDLKL IEEMEKGVKL PASVTGFTTT EEDVQHFFGS QKKRRKEDRI
RKDRSPTPED VIESRDAEWQ ERLRLKMERE KSRKADEESQ NAWSLQALAD NETFTRFCQT
VDGVLEQGDS LDTELKMPKN KKRRSGGDHH HKGDENSDES DEEEEMDEID PDLRIELYIL
EELRRGSARL RENHALQAVG ADKLLKLVAM LDRNIRDAIS ADNQRLLVPC DDDVDVGDVL
EKEICEERVK RASDAAVVAL NIMSSHRMHK QVIIEDVIDR CVGLTRLLLI HLIYPASDSI
YKSVNSKKKD RAPEEARRRK KAGVCTRDKF SEYIYERITE AIGLLAVLVK SESMTDTSVH
NVASVALTPF FVANVGSLQI TAMLLASNIF SRAEDSLRFS MITDLLSSLH RAPQFTQKNS
NNGYSLPDGS WISTTTALFI QLVQSTIKIP KFKKHADEDE LAKRSKKEEA MVKEGFLKAS
KVTNAFLNGF LAKCSQKGNK MDGEEDYRIL FSNFLQELLS ALYSPEWPAA EMILTALGSL
LVKNFRSKSS DMTIRQASLD YLGNITAKLR KDQKEAIAGE RRLDAVVKKS FLLLSDKGVE
DYESVDISNL KQNDKLKVLE TSLIDYLVIT NSSDIIVYAC NFYVGEWYKE VAEDLESARS
KLKQTVDTNE SEKDVKKAER KYEKIQYRGA EMKVFLSKIL DKKEIKRRLE KSNKVKMLDS
DAFWAVKFLA QSREFTHSFD TYLKHIVFGA GSETIVALRS KALKCLSSII EADSSVLILE
DVQQAVHTRM VDSHAQVRES AVELIGRFVL YDEEYVRKYY SQIAERILDT GVAVRKRVIR
IMREICEKFP TFEMIPDMLA RMIRRVTDEE GVKKLVFETF TTLWFQPVDT RIYTNAVATK
VTTMCSVAQH CIKDAMSDYL EQLILHIVKN GQEGSGMSVA VKQIIDSLVD HILNLEQHKS
SENVSEVELM RRKEQEEKYM AYLSTLAVFS KIRPLLLTSH VEVLLPYLTF SGAKTNAENQ
VTKEMIGMLE RVIPLVPFPS NIVLDSIDEN LCKVIMFNGM ALVVSAVSCV ASIYKKFKRG
ATKTIDVFST YLKHLEVIKR NFDSNPRYDL DPKLFPILSR SIFTLGVLSR YFQFEEFVKE
DPTEEKVEAL KEKVFITLEF FSRYHKGGLR QKALTAMGHF CAQHSTYLTK RQLTNTYLEI
LNAANSPQQQ QQRILVLQNL EMFLQCEEQK LAASHDKWDE NKEAQNLKEM ELSGSGLGSS
VIQKYWKAVL ESYVDADIQL RRAAVQVVWL TLNQGLVTPG ASIPTLIAMT TDPVDVIRNR
IDILLKEIDS KYSGMVQSKA MQGVRLSYKL HLKLRMLQQE KFVRGFRFCD FHLNTLPNAL
PEKTHDGMAV LSGLYQSLRT NRQQRRSFLQ SMVKLFSEEF SHDKPQLMEY IFIADNLAMF
PYQMIDEPLY VMRQIDQNIA QTGQSLLVQY KLQLRMQESE DEDIVFLDEN MMSRLSQLGQ
IETFHQLFLD SQVPSLLLYV RTFLMQLYGF NETKVAEYQP SEAAKVYEKA VTRRNIHMFK
PITALEALNF PFEWGSFQHT AFLAEKICSF RKMLLSLDQV EEVEVSNTIT AANDDYDEEE
DGGEDSRGPI MEQMEH
