NACAD_HUMAN
ID NACAD_HUMAN Reviewed; 1562 AA.
AC O15069;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=NAC-alpha domain-containing protein 1;
GN Name=NACAD; Synonyms=KIAA0363;
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 GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 41-1562.
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1068, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: May prevent inappropriate targeting of non-secretory
CC polypeptides to the endoplasmic reticulum (ER). May bind to nascent
CC polypeptide chains as they emerge from the ribosome and block their
CC interaction with the signal recognition particle (SRP), which normally
CC targets nascent secretory peptides to the ER. May also reduce the
CC inherent affinity of ribosomes for protein translocation sites in the
CC ER membrane (M sites) (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O15069; Q13216-2: ERCC8; NbExp=3; IntAct=EBI-7108375, EBI-16466949;
CC O15069; P28799: GRN; NbExp=3; IntAct=EBI-7108375, EBI-747754;
CC O15069; P42858: HTT; NbExp=15; IntAct=EBI-7108375, EBI-466029;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NAC-alpha family. {ECO:0000305}.
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DR EMBL; AC013416; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB002361; BAA20818.1; -; mRNA.
DR CCDS; CCDS47582.1; -.
DR RefSeq; NP_001139806.1; NM_001146334.1.
DR AlphaFoldDB; O15069; -.
DR SMR; O15069; -.
DR BioGRID; 116763; 19.
DR IntAct; O15069; 19.
DR MINT; O15069; -.
DR STRING; 9606.ENSP00000420477; -.
DR iPTMnet; O15069; -.
DR PhosphoSitePlus; O15069; -.
DR BioMuta; NACAD; -.
DR EPD; O15069; -.
DR jPOST; O15069; -.
DR MassIVE; O15069; -.
DR MaxQB; O15069; -.
DR PaxDb; O15069; -.
DR PeptideAtlas; O15069; -.
DR PRIDE; O15069; -.
DR ProteomicsDB; 48426; -.
DR Antibodypedia; 56503; 77 antibodies from 21 providers.
DR DNASU; 23148; -.
DR Ensembl; ENST00000490531.3; ENSP00000420477.2; ENSG00000136274.9.
DR GeneID; 23148; -.
DR KEGG; hsa:23148; -.
DR MANE-Select; ENST00000490531.3; ENSP00000420477.2; NM_001146334.2; NP_001139806.1.
DR UCSC; uc003tmt.4; human.
DR CTD; 23148; -.
DR GeneCards; NACAD; -.
DR HGNC; HGNC:22196; NACAD.
DR HPA; ENSG00000136274; Group enriched (brain, pituitary gland).
DR MIM; 619419; gene.
DR neXtProt; NX_O15069; -.
DR OpenTargets; ENSG00000136274; -.
DR PharmGKB; PA162396706; -.
DR VEuPathDB; HostDB:ENSG00000136274; -.
DR eggNOG; KOG2239; Eukaryota.
DR GeneTree; ENSGT00940000161501; -.
DR HOGENOM; CLU_005021_0_0_1; -.
DR InParanoid; O15069; -.
DR OMA; WADPGEG; -.
DR OrthoDB; 1331328at2759; -.
DR PhylomeDB; O15069; -.
DR TreeFam; TF313348; -.
DR PathwayCommons; O15069; -.
DR SignaLink; O15069; -.
DR BioGRID-ORCS; 23148; 21 hits in 1077 CRISPR screens.
DR ChiTaRS; NACAD; human.
DR GenomeRNAi; 23148; -.
DR Pharos; O15069; Tdark.
DR PRO; PR:O15069; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O15069; protein.
DR Bgee; ENSG00000136274; Expressed in inferior vagus X ganglion and 140 other tissues.
DR Genevisible; O15069; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005854; C:nascent polypeptide-associated complex; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0006612; P:protein targeting to membrane; IBA:GO_Central.
DR CDD; cd14416; UBA_NACAD; 1.
DR Gene3D; 2.20.70.30; -; 1.
DR InterPro; IPR016641; EGD2/NACA.
DR InterPro; IPR044034; NAC-like_UBA.
DR InterPro; IPR038187; NAC_A/B_dom_sf.
DR InterPro; IPR041907; NACAD_UBA.
DR InterPro; IPR002715; Nas_poly-pep-assoc_cplx_dom.
DR PANTHER; PTHR21713; PTHR21713; 3.
DR Pfam; PF19026; HYPK_UBA; 1.
DR Pfam; PF01849; NAC; 1.
DR SMART; SM01407; NAC; 1.
DR PROSITE; PS51151; NAC_AB; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..1562
FT /note="NAC-alpha domain-containing protein 1"
FT /id="PRO_0000280748"
FT DOMAIN 1411..1476
FT /note="NAC-A/B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00507"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 56..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 249..288
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 327..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 381..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..941
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 953..1423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..288
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..350
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 506..536
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..561
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..650
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 668..690
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 708..730
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 748..770
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 788..810
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 828..850
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 868..890
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 908..930
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1044..1074
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1134..1158
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1281..1296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1407..1421
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1068
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1354
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SWP3"
FT VARIANT 438
FT /note="D -> E (in dbSNP:rs3735495)"
FT /id="VAR_031195"
FT VARIANT 498
FT /note="V -> A (in dbSNP:rs3735494)"
FT /id="VAR_031196"
FT VARIANT 591
FT /note="K -> E (in dbSNP:rs7777835)"
FT /id="VAR_031197"
FT VARIANT 1105
FT /note="D -> E (in dbSNP:rs10243185)"
FT /id="VAR_031198"
FT VARIANT 1152
FT /note="C -> F (in dbSNP:rs3735493)"
FT /id="VAR_031199"
FT CONFLICT 1086
FT /note="P -> L (in Ref. 2; BAA20818)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1562 AA; 161101 MW; 790B73CAF05D7D93 CRC64;
MPGEAARAEL LLPEADRPGP RTDLSCDAAA ATTILGGDRR EPCALTPGPS HLALTFLPSK
PGARPQPEGA SWDAGPGGAP SAWADPGEGG PSPMLLPEGL SSQALSTEAP LPATLEPRIV
MGEETCQALL SPRAARTALR DQEGGHASPD PPPELCSQGD LSVPSPPPDP DSFFTPPSTP
TKTTYALLPA CGPHGDARDS EAELRDELLD SPPASPSGSY ITADGDSWAS SPSCSLSLLA
PAEGLDFPSG WGLSPQGSMV DERELHPAGT PEPPSSESSL SADSSSSWGQ EGHFFDLDFL
ANDPMIPAAL LPFQGSLIFQ VEAVEVTPLS PEEEEEEAVA DPDPGGDLAG EGEEDSTSAS
FLQSLSDLSI TEGMDEAFAF RDDTSAASSD SDSASYAEAD DERLYSGEPH AQATLLQDSV
QKTEEESGGG AKGLQAQDGT VSWAVEAAPQ TSDRGAYLSQ RQELISEVTE EGLALGQEST
ATVTPHTLQV APGLQVEVAT RVTPQAGEEE TDSTAGQESA AMAMPQPSQE GISEILGQES
VTAEKLPTPQ EETSLTLCPD SPQNLKEEGG LDLPSGRKPV AAATIVPRQA KEDLTLPQDS
AMTPPLPLQD TDLSSAPKPV AAATIVSQQA EEGLTLPQDS VMTPPLPLQD TELSSAPKPV
AAATLVSQQA EEGLTLPQDS AMTPPLPLQD TDLSSAPKPV AAATLVSQQA EEGLTLPQDS
AMTPPLPLQD TDLSSAPKPV AAATLVSQQA EEGLTLPQDS AMTPPLPLQD TDLSSAPKPV
AAATIVSQQA EEGLTLPQDS AMTPPLPLQD TDLSSAPKPV AAATIVSQQA EEGLTLPQDS
AMTPPLPLQD TDLSSAPKPV AAATPVSQQA EEGLTLPQDS AMTPPLPLQD TDLSSAPKPV
AAATPVSQQA EEGLTLPQDS AMTAPLPLQD TGPTSGPEPL AVATPQTLQA EAGCAPGTEP
VATMAQQEVG EALGPRPAPE EKNAALPTVP EPAALDQVQQ DDPQPAAEAG TPWAAQEDAD
STLGMEALSL PEPASGAGEE IAEALSRPGR EACLEARAHT GDGAKPDSPQ KETLEVENQQ
EGGLKPLAQE HGPRSALGGA REVPDAPPAA CPEVSQARLL SPAREERGLS GKSTPEPTLP
SAVATEASLD SCPESSVGAV SSLDRGCPDA PAPTSAPTSQ QPEPVLGLGS VEQPHEVPSV
LGTPLLQPPE NLAKGQPSTP VDRPLGPDPS APGTLAGAAL PPLEPPAPCL CQDPQEDSVE
DEEPPGSLGL PPPQAGVQPA AAAVSGTTQP LGTGPRVSLS PHSPLLSPKV ASMDAKDLAL
QILPPCQVPP PSGPQSPAGP QGLSAPEQQE DEDSLEEDSP RALGSGQHSD SHGESSAELD
EQDILAPQTV QCPAQAPAGG SEETIAKAKQ SRSEKKARKA MSKLGLRQIQ GVTRITIQKS
KNILFVIAKP DVFKSPASDT YVVFGEAKIE DLSQQVHKAA AEKFKVPSEP SALVPESAPR
PRVRLECKEE EEEEEEEVDE AGLELRDIEL VMAQANVSRA KAVRALRDNH SDIVNAIMEL
TM
