NSE4A_HUMAN
ID NSE4A_HUMAN Reviewed; 385 AA.
AC Q9NXX6; Q5SQQ5; Q6P673; Q8WY66; Q9BS90;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Non-structural maintenance of chromosomes element 4 homolog A;
DE Short=NS4EA;
DE Short=Non-SMC element 4 homolog A;
GN Name=NSMCE4A; Synonyms=C10orf86; ORFNames=PP4762;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Adipose tissue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Adipose tissue;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 102-385 (ISOFORM 2).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-345 AND SER-377, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SMC6 AND NSMCE1, AND
RP IDENTIFICATION IN THE SMC5-SMC6 COMPLEX.
RX PubMed=18086888; DOI=10.1128/mcb.00767-07;
RA Taylor E.M., Copsey A.C., Hudson J.J., Vidot S., Lehmann A.R.;
RT "Identification of the proteins, including MAGEG1, that make up the human
RT SMC5-6 protein complex.";
RL Mol. Cell. Biol. 28:1197-1206(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP INTERACTION WITH NSMCE3.
RX PubMed=27427983; DOI=10.1172/jci82890;
RA van der Crabben S.N., Hennus M.P., McGregor G.A., Ritter D.I.,
RA Nagamani S.C., Wells O.S., Harakalova M., Chinn I.K., Alt A., Vondrova L.,
RA Hochstenbach R., van Montfrans J.M., Terheggen-Lagro S.W., van Lieshout S.,
RA van Roosmalen M.J., Renkens I., Duran K., Nijman I.J., Kloosterman W.P.,
RA Hennekam E., Orange J.S., van Hasselt P.M., Wheeler D.A., Palecek J.J.,
RA Lehmann A.R., Oliver A.W., Pearl L.H., Plon S.E., Murray J.M.,
RA van Haaften G.;
RT "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with
RT severe lung disease.";
RL J. Clin. Invest. 126:2881-2892(2016).
CC -!- FUNCTION: Component of the SMC5-SMC6 complex, a complex involved in DNA
CC double-strand breaks by homologous recombination. The complex may
CC promote sister chromatid homologous recombination by recruiting the
CC SMC1-SMC3 cohesin complex to double-strand breaks. The complex is
CC required for telomere maintenance via recombination in ALT (alternative
CC lengthening of telomeres) cell lines and mediates sumoylation of
CC shelterin complex (telosome) components which is proposed to lead to
CC shelterin complex disassembly in ALT-associated PML bodies (APBs). Is
CC involved in positive regulation of response to DNA damage stimulus.
CC {ECO:0000269|PubMed:18086888}.
CC -!- SUBUNIT: Component of the SMC5-SMC6 complex which consists at least of
CC SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3. NSMCE1, NSMCE4A
CC or EID3 and NSMCE3 probably form a subcomplex that bridges the head
CC domains of the SMC5:SMC6 heterodimer (PubMed:18086888). Interacts with
CC NSMCE3 (PubMed:27427983). {ECO:0000269|PubMed:18086888,
CC ECO:0000269|PubMed:27427983}.
CC -!- INTERACTION:
CC Q9NXX6; Q96MG7: NSMCE3; NbExp=4; IntAct=EBI-2557393, EBI-2557356;
CC Q9NXX6-2; O14901: KLF11; NbExp=3; IntAct=EBI-25905546, EBI-948266;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18086888}.
CC Chromosome, telomere {ECO:0000305|PubMed:18086888}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NXX6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NXX6-2; Sequence=VSP_014601, VSP_014602;
CC -!- SIMILARITY: Belongs to the NSE4 family. {ECO:0000305}.
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DR EMBL; AK000010; BAA90881.1; -; mRNA.
DR EMBL; AK222487; BAD96207.1; -; mRNA.
DR EMBL; AL731566; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005212; AAH05212.1; -; mRNA.
DR EMBL; BC062427; AAH62427.1; -; mRNA.
DR EMBL; AF258584; AAG23787.1; -; mRNA.
DR CCDS; CCDS7624.1; -. [Q9NXX6-1]
DR RefSeq; NP_001161337.1; NM_001167865.1.
DR RefSeq; NP_060085.2; NM_017615.2. [Q9NXX6-1]
DR AlphaFoldDB; Q9NXX6; -.
DR SMR; Q9NXX6; -.
DR BioGRID; 120147; 87.
DR ComplexPortal; CPX-6086; SMC5-SMC6 SUMO ligase complex, NSE4EA variant.
DR CORUM; Q9NXX6; -.
DR IntAct; Q9NXX6; 30.
DR MINT; Q9NXX6; -.
DR STRING; 9606.ENSP00000358019; -.
DR iPTMnet; Q9NXX6; -.
DR PhosphoSitePlus; Q9NXX6; -.
DR BioMuta; NSMCE4A; -.
DR DMDM; 68565328; -.
DR EPD; Q9NXX6; -.
DR jPOST; Q9NXX6; -.
DR MassIVE; Q9NXX6; -.
DR MaxQB; Q9NXX6; -.
DR PaxDb; Q9NXX6; -.
DR PeptideAtlas; Q9NXX6; -.
DR PRIDE; Q9NXX6; -.
DR ProteomicsDB; 83143; -. [Q9NXX6-1]
DR ProteomicsDB; 83144; -. [Q9NXX6-2]
DR Antibodypedia; 48679; 98 antibodies from 18 providers.
DR DNASU; 54780; -.
DR Ensembl; ENST00000369017.5; ENSP00000358013.5; ENSG00000107672.15. [Q9NXX6-2]
DR Ensembl; ENST00000369023.8; ENSP00000358019.3; ENSG00000107672.15. [Q9NXX6-1]
DR GeneID; 54780; -.
DR KEGG; hsa:54780; -.
DR MANE-Select; ENST00000369023.8; ENSP00000358019.3; NM_017615.3; NP_060085.2.
DR UCSC; uc001lfs.4; human. [Q9NXX6-1]
DR CTD; 54780; -.
DR GeneCards; NSMCE4A; -.
DR HGNC; HGNC:25935; NSMCE4A.
DR HPA; ENSG00000107672; Low tissue specificity.
DR MIM; 612987; gene.
DR neXtProt; NX_Q9NXX6; -.
DR OpenTargets; ENSG00000107672; -.
DR PharmGKB; PA162398205; -.
DR VEuPathDB; HostDB:ENSG00000107672; -.
DR eggNOG; KOG2866; Eukaryota.
DR GeneTree; ENSGT00390000011476; -.
DR HOGENOM; CLU_041037_3_0_1; -.
DR InParanoid; Q9NXX6; -.
DR OMA; TFMGINR; -.
DR OrthoDB; 935469at2759; -.
DR PhylomeDB; Q9NXX6; -.
DR TreeFam; TF313999; -.
DR PathwayCommons; Q9NXX6; -.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR SignaLink; Q9NXX6; -.
DR SIGNOR; Q9NXX6; -.
DR BioGRID-ORCS; 54780; 292 hits in 1081 CRISPR screens.
DR GeneWiki; NSMCE4A; -.
DR GenomeRNAi; 54780; -.
DR Pharos; Q9NXX6; Tdark.
DR PRO; PR:Q9NXX6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9NXX6; protein.
DR Bgee; ENSG00000107672; Expressed in oocyte and 197 other tissues.
DR Genevisible; Q9NXX6; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IC:ComplexPortal.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030915; C:Smc5-Smc6 complex; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IC:ComplexPortal.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IC:ComplexPortal.
DR GO; GO:0032204; P:regulation of telomere maintenance; IC:ComplexPortal.
DR InterPro; IPR027786; Nse4/EID.
DR InterPro; IPR014854; Nse4_C.
DR InterPro; IPR029225; Nse4_Nse3-bd.
DR PANTHER; PTHR16140; PTHR16140; 1.
DR Pfam; PF15412; Nse4-Nse3_bdg; 1.
DR Pfam; PF08743; Nse4_C; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosome; DNA damage; DNA recombination;
KW DNA repair; Nucleus; Phosphoprotein; Reference proteome; Telomere.
FT CHAIN 1..385
FT /note="Non-structural maintenance of chromosomes element 4
FT homolog A"
FT /id="PRO_0000214101"
FT REGION 1..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..29
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 345
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VAR_SEQ 282..316
FT /note="PDTPMSFFDFVVDPHSFPRTVENIFHVSFIIRDGF -> RDSLTLSPRLECS
FT GTISTHCNLHLLDSSNSPASAS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15498874"
FT /id="VSP_014601"
FT VAR_SEQ 317..385
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15498874"
FT /id="VSP_014602"
FT VARIANT 72
FT /note="S -> T (in dbSNP:rs1065683)"
FT /id="VAR_057657"
FT CONFLICT 145
FT /note="K -> I (in Ref. 1; BAA90881)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="Missing (in Ref. 4; AAH62427)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 385 AA; 44301 MW; 8BB8C54C8A6D0A1E CRC64;
MSGDSSGRGP EGRGRGRDPH RDRTRSRSRS RSPLSPRSRR GSARERREAP ERPSLEDTEP
SDSGDEMMDP ASLEAEADQG LCRQIRHQYR ALINSVQQNR EDILNAGDKL TEVLEEANTL
FNEVSRAREA VLDAHFLVLA SDLGKEKAKQ LRSDLSSFDM LRYVETLLTH MGVNPLEAEE
LIRDEDSPDF EFIVYDSWKI TGRTAENTFN KTHTFHFLLG SIYGECPVPK PRVDRPRKVP
VIQEERAMPA QLRRMEESHQ EATEKEVERI LGLLQTYFRE DPDTPMSFFD FVVDPHSFPR
TVENIFHVSF IIRDGFARIR LDQDRLPVIE PVSINEENEG FEHNTQVRNQ GIIALSYRDW
EEIVKTFEIS EPVITPSQRQ QKPSA
