UN5CL_HUMAN
ID UN5CL_HUMAN Reviewed; 518 AA.
AC Q8IV45; Q5TGU1;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=UNC5C-like protein;
DE AltName: Full=Protein unc-5 homolog C-like;
DE AltName: Full=ZU5 and death domain-containing protein;
GN Name=UNC5CL; Synonyms=ZUD;
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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INTERACTION WITH RELA AND NFKB1, AND VARIANT GLY-432.
RX PubMed=14769797; DOI=10.1074/jbc.m310737200;
RA Zhang J., Xu L.-G., Han K.-J., Shu H.-B.;
RT "Identification of a ZU5 and death domain-containing inhibitor of NF-
RT kappaB.";
RL J. Biol. Chem. 279:17819-17825(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-432.
RC TISSUE=Colon;
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).
CC -!- FUNCTION: Inhibits NF-kappa-B-dependent transcription by impairing NF-
CC kappa-B binding to its targets. {ECO:0000269|PubMed:14769797}.
CC -!- SUBUNIT: Interacts with p65/RELA and NFKB1.
CC {ECO:0000269|PubMed:14769797}.
CC -!- INTERACTION:
CC Q8IV45; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12238241, EBI-3867333;
CC Q8IV45; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-12238241, EBI-11953846;
CC Q8IV45; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-12238241, EBI-12111050;
CC Q8IV45; P18669: PGAM1; NbExp=3; IntAct=EBI-12238241, EBI-717905;
CC Q8IV45; Q96NM4-3: TOX2; NbExp=3; IntAct=EBI-12238241, EBI-12815137;
CC Q8IV45; Q9H0C1: ZMYND12; NbExp=5; IntAct=EBI-12238241, EBI-12030590;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type III
CC membrane protein {ECO:0000305}. Cytoplasm
CC {ECO:0000269|PubMed:14769797}.
CC -!- TISSUE SPECIFICITY: Expressed in pancreas, liver and kidney.
CC {ECO:0000269|PubMed:14769797}.
CC -!- SIMILARITY: Belongs to the unc-5 family. {ECO:0000305}.
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DR EMBL; AY510109; AAS80165.1; -; mRNA.
DR EMBL; AL031778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04007.1; -; Genomic_DNA.
DR EMBL; BC035284; AAH35284.1; -; mRNA.
DR CCDS; CCDS4847.1; -.
DR RefSeq; NP_775832.2; NM_173561.2.
DR AlphaFoldDB; Q8IV45; -.
DR SMR; Q8IV45; -.
DR BioGRID; 128808; 39.
DR IntAct; Q8IV45; 19.
DR STRING; 9606.ENSP00000244565; -.
DR iPTMnet; Q8IV45; -.
DR PhosphoSitePlus; Q8IV45; -.
DR BioMuta; UNC5CL; -.
DR DMDM; 160358941; -.
DR MassIVE; Q8IV45; -.
DR PaxDb; Q8IV45; -.
DR PeptideAtlas; Q8IV45; -.
DR PRIDE; Q8IV45; -.
DR ProteomicsDB; 70658; -.
DR Antibodypedia; 29981; 149 antibodies from 30 providers.
DR DNASU; 222643; -.
DR Ensembl; ENST00000244565.8; ENSP00000244565.3; ENSG00000124602.10.
DR Ensembl; ENST00000373164.1; ENSP00000362258.1; ENSG00000124602.10.
DR GeneID; 222643; -.
DR KEGG; hsa:222643; -.
DR MANE-Select; ENST00000244565.8; ENSP00000244565.3; NM_173561.3; NP_775832.2.
DR UCSC; uc003opi.4; human.
DR CTD; 222643; -.
DR DisGeNET; 222643; -.
DR GeneCards; UNC5CL; -.
DR HGNC; HGNC:21203; UNC5CL.
DR HPA; ENSG00000124602; Group enriched (intestine, kidney, liver, pancreas, stomach).
DR MIM; 617464; gene.
DR neXtProt; NX_Q8IV45; -.
DR OpenTargets; ENSG00000124602; -.
DR PharmGKB; PA134906657; -.
DR VEuPathDB; HostDB:ENSG00000124602; -.
DR eggNOG; KOG1480; Eukaryota.
DR GeneTree; ENSGT00950000182815; -.
DR HOGENOM; CLU_040040_0_0_1; -.
DR InParanoid; Q8IV45; -.
DR OMA; QLAIFCS; -.
DR OrthoDB; 452660at2759; -.
DR PhylomeDB; Q8IV45; -.
DR TreeFam; TF316767; -.
DR PathwayCommons; Q8IV45; -.
DR SignaLink; Q8IV45; -.
DR BioGRID-ORCS; 222643; 13 hits in 1016 CRISPR screens.
DR GenomeRNAi; 222643; -.
DR Pharos; Q8IV45; Tbio.
DR PRO; PR:Q8IV45; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8IV45; protein.
DR Bgee; ENSG00000124602; Expressed in epithelial cell of pancreas and 119 other tissues.
DR ExpressionAtlas; Q8IV45; baseline and differential.
DR Genevisible; Q8IV45; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005042; F:netrin receptor activity; IEA:InterPro.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:MGI.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR037936; UNC5.
DR InterPro; IPR033772; UPA.
DR InterPro; IPR000906; ZU5_dom.
DR PANTHER; PTHR12582; PTHR12582; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF17217; UPA; 1.
DR Pfam; PF00791; ZU5; 1.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00218; ZU5; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS51145; ZU5; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..518
FT /note="UNC5C-like protein"
FT /id="PRO_0000309567"
FT TOPO_DOM 1..10
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 11..31
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..518
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 102..237
FT /note="ZU5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT DOMAIN 415..494
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 186..400
FT /note="Interaction with RELA and NFKB1"
FT /evidence="ECO:0000269|PubMed:14769797"
FT REGION 208..235
FT /note="Peptidase S68"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT REGION 492..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 227
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT ACT_SITE 229
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485"
FT VARIANT 432
FT /note="R -> G (in dbSNP:rs742493)"
FT /evidence="ECO:0000269|PubMed:14769797,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_036979"
SQ SEQUENCE 518 AA; 57818 MW; A90218B4453E0937 CRC64;
MCPQESSFQP SQFLLLVGVP VASVLLLAQC LRWHCPRRLL GACWTLNGQE EPVSQPTPQL
ENEVSRQHLP ATLPEMVAFY QELHTPTQGQ TMVRQLMHKL LVFSAREVDH RGGCLMLQDT
GISLLIPPGA VAVGRQERVS LILVWDLSDA PSLSQAQGLV SPVVACGPHG ASFLKPCTLT
FKHCAEQPSH ARTYSSNTTL LDAKVWRPLG RPGAHASRDE CRIHLSHFSL YTCVLEAPVG
REARKWLQLA VFCSPLVPGQ SHLQLRIYFL NNTPCALQWA LTNEQPHGGR LRGPCQLFDF
NGARGDQCLK LTYISEGWEN VDDSSCQLVP HLHIWHGKCP FRSFCFRRKA ADENEDCSAL
TNEIIVTMHT FQDGLETKYM EILRFQASEE ESWAAPPPVS QPPPCNRLPP ELFEQLRMLL
EPNSITGNDW RRLASHLGLC GMKIRFLSCQ RSPAAAILEL FEEQNGSLQE LHYLMTVMER
LDCASAIQNY LSGTHGGSPG PERGGARDNQ GLELDEKL
