ACSF4_HUMAN
ID ACSF4_HUMAN Reviewed; 1098 AA.
AC Q4L235; A5D8V3; A5PL22; Q63HK2; Q63HR7; Q6IPP8; Q6TFZ6; Q7Z5Y3; Q96BW4;
AC Q9P064;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Beta-alanine-activating enzyme {ECO:0000250|UniProtKB:Q80WC9};
DE EC=6.2.1.-;
DE AltName: Full=Acyl-CoA synthetase family member 4;
DE AltName: Full=Protein NRPS998;
GN Name=AASDH; Synonyms=ACSF4, U26; ORFNames=HSPC318;
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] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP ASP-1030.
RC TISSUE=Fetal brain;
RX PubMed=15865210; DOI=10.1007/s11033-003-2716-4;
RA Wang L., Jil C., Xu Y., Xu J., Dai J., Wu Q., Wu M., Zou X., Sun L., Gu S.,
RA Xie Y., Mao Y.;
RT "Cloning and characterization of a novel human homolog of mouse U26, a
RT putative PQQ-dependent AAS dehydrogenase.";
RL Mol. Biol. Rep. 32:47-53(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT VAL-747.
RA Paliga K., Bauer K.;
RT "Identification and preliminary characterization of a human protein with
RT similarity to microbial peptide synthetases.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 96-1098.
RC TISSUE=Liver, and Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND VARIANT
RP VAL-747.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-164, AND VARIANTS VAL-61 AND
RP ARG-93.
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649, 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).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649 AND SER-724, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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).
CC -!- FUNCTION: Covalently binds beta-alanine in an ATP-dependent manner to
CC form a thioester bond with its phosphopantetheine group and transfers
CC it to an, as yet, unknown acceptor. May be required for a post-
CC translational protein modification or for post-transcriptional
CC modification of an RNA. {ECO:0000250|UniProtKB:Q80WC9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q4L235-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4L235-2; Sequence=VSP_030707;
CC Name=3;
CC IsoId=Q4L235-3; Sequence=VSP_030711, VSP_030712;
CC Name=4;
CC IsoId=Q4L235-4; Sequence=VSP_030710, VSP_030713;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in adult tissues.
CC {ECO:0000269|PubMed:15865210}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH56482.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY314787; AAQ83120.1; -; mRNA.
DR EMBL; AF516672; AAP76519.1; -; mRNA.
DR EMBL; AY422212; AAR31184.1; -; mRNA.
DR EMBL; BX640635; CAH56482.1; ALT_INIT; Transcribed_RNA.
DR EMBL; BX648853; CAH56130.1; -; mRNA.
DR EMBL; AC068620; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC071815; AAH71815.1; -; mRNA.
DR EMBL; BC141824; AAI41825.1; -; mRNA.
DR EMBL; BC142709; AAI42710.1; -; mRNA.
DR EMBL; AF161436; AAF28996.1; -; mRNA.
DR CCDS; CCDS3504.1; -. [Q4L235-1]
DR CCDS; CCDS68705.1; -. [Q4L235-2]
DR CCDS; CCDS68706.1; -. [Q4L235-4]
DR CCDS; CCDS75127.1; -. [Q4L235-3]
DR RefSeq; NP_001273597.1; NM_001286668.1. [Q4L235-2]
DR RefSeq; NP_001273598.1; NM_001286669.1.
DR RefSeq; NP_001273599.1; NM_001286670.1.
DR RefSeq; NP_001273600.1; NM_001286671.1. [Q4L235-4]
DR RefSeq; NP_001273601.1; NM_001286672.1. [Q4L235-3]
DR RefSeq; NP_001310819.1; NM_001323890.1.
DR RefSeq; NP_001310821.1; NM_001323892.1.
DR RefSeq; NP_001310822.1; NM_001323893.1.
DR RefSeq; NP_001310828.1; NM_001323899.1.
DR RefSeq; NP_861522.2; NM_181806.3. [Q4L235-1]
DR AlphaFoldDB; Q4L235; -.
DR SMR; Q4L235; -.
DR BioGRID; 126342; 10.
DR IntAct; Q4L235; 4.
DR STRING; 9606.ENSP00000205214; -.
DR iPTMnet; Q4L235; -.
DR PhosphoSitePlus; Q4L235; -.
DR BioMuta; AASDH; -.
DR DMDM; 269849683; -.
DR EPD; Q4L235; -.
DR jPOST; Q4L235; -.
DR MassIVE; Q4L235; -.
DR MaxQB; Q4L235; -.
DR PaxDb; Q4L235; -.
DR PeptideAtlas; Q4L235; -.
DR PRIDE; Q4L235; -.
DR ProteomicsDB; 62225; -. [Q4L235-1]
DR ProteomicsDB; 62226; -. [Q4L235-2]
DR ProteomicsDB; 62227; -. [Q4L235-3]
DR ProteomicsDB; 62228; -. [Q4L235-4]
DR Antibodypedia; 24007; 57 antibodies from 16 providers.
DR DNASU; 132949; -.
DR Ensembl; ENST00000205214.11; ENSP00000205214.6; ENSG00000157426.14. [Q4L235-1]
DR Ensembl; ENST00000451613.5; ENSP00000409656.1; ENSG00000157426.14. [Q4L235-4]
DR Ensembl; ENST00000502617.1; ENSP00000421171.1; ENSG00000157426.14. [Q4L235-3]
DR Ensembl; ENST00000513376.5; ENSP00000423760.1; ENSG00000157426.14. [Q4L235-2]
DR GeneID; 132949; -.
DR KEGG; hsa:132949; -.
DR MANE-Select; ENST00000205214.11; ENSP00000205214.6; NM_181806.4; NP_861522.2.
DR UCSC; uc003hbn.5; human. [Q4L235-1]
DR CTD; 132949; -.
DR DisGeNET; 132949; -.
DR GeneCards; AASDH; -.
DR HGNC; HGNC:23993; AASDH.
DR HPA; ENSG00000157426; Low tissue specificity.
DR MIM; 614365; gene.
DR neXtProt; NX_Q4L235; -.
DR OpenTargets; ENSG00000157426; -.
DR PharmGKB; PA162375178; -.
DR VEuPathDB; HostDB:ENSG00000157426; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG4649; Eukaryota.
DR GeneTree; ENSGT00440000033811; -.
DR InParanoid; Q4L235; -.
DR OMA; GEKPIFA; -.
DR OrthoDB; 881306at2759; -.
DR PhylomeDB; Q4L235; -.
DR TreeFam; TF314245; -.
DR BRENDA; 1.2.1.31; 2681.
DR PathwayCommons; Q4L235; -.
DR SignaLink; Q4L235; -.
DR BioGRID-ORCS; 132949; 3 hits in 1075 CRISPR screens.
DR ChiTaRS; AASDH; human.
DR GenomeRNAi; 132949; -.
DR Pharos; Q4L235; Tbio.
DR PRO; PR:Q4L235; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q4L235; protein.
DR Bgee; ENSG00000157426; Expressed in kidney epithelium and 186 other tissues.
DR ExpressionAtlas; Q4L235; baseline and differential.
DR Genevisible; Q4L235; HS.
DR GO; GO:0016878; F:acid-thiol ligase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043041; P:amino acid activation for nonribosomal peptide biosynthetic process; IBA:GO_Central.
DR GO; GO:0019482; P:beta-alanine metabolic process; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR025666; PQQ-like_dom.
DR InterPro; IPR018391; PQQ_beta_propeller_repeat.
DR InterPro; IPR002372; PQQ_repeat.
DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF13360; PQQ_2; 1.
DR Pfam; PF13570; PQQ_3; 1.
DR SMART; SM00564; PQQ; 6.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50998; SSF50998; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Fatty acid metabolism; Ligase;
KW Lipid metabolism; Nucleotide-binding; Phosphopantetheine; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1098
FT /note="Beta-alanine-activating enzyme"
FT /id="PRO_0000315803"
FT DOMAIN 553..630
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT BINDING 198..206
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 428
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 442
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 527
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 589
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 724
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_030707"
FT VAR_SEQ 831..857
FT /note="CYNGLVYVLKSNSGEKYWMFTTEDAVK -> LAVLYQWTNLFIPVYLTIRAK
FT NIFWFP (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030710"
FT VAR_SEQ 831..841
FT /note="CYNGLVYVLKS -> KFLNLRFVELN (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_030711"
FT VAR_SEQ 842..1098
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_030712"
FT VAR_SEQ 858..1098
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030713"
FT VARIANT 61
FT /note="I -> V (in dbSNP:rs34543011)"
FT /evidence="ECO:0000269|PubMed:11042152"
FT /id="VAR_061008"
FT VARIANT 93
FT /note="P -> R (in dbSNP:rs34228795)"
FT /evidence="ECO:0000269|PubMed:11042152"
FT /id="VAR_061009"
FT VARIANT 368
FT /note="K -> R (in dbSNP:rs3796543)"
FT /id="VAR_038309"
FT VARIANT 747
FT /note="A -> V (in dbSNP:rs3796544)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_038310"
FT VARIANT 774
FT /note="V -> I (in dbSNP:rs3796545)"
FT /id="VAR_038311"
FT VARIANT 865
FT /note="T -> A (in dbSNP:rs12498340)"
FT /id="VAR_038312"
FT VARIANT 1030
FT /note="Y -> D (in dbSNP:rs8340)"
FT /evidence="ECO:0000269|PubMed:15865210"
FT /id="VAR_038313"
FT CONFLICT 167
FT /note="I -> R (in Ref. 5; AAI41825/AAI42710)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="T -> A (in Ref. 3; CAH56130)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="D -> G (in Ref. 1; AAQ83120 and 3; CAH56482)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="E -> V (in Ref. 3; CAH56482)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="K -> Q (in Ref. 3; CAH56482)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="F -> L (in Ref. 3; CAH56482)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1098 AA; 122597 MW; 067ACB7C020AD4F1 CRC64;
MTLQELVHKA ASCYMDRVAV CFDECNNQLP VYYTYKTVVN AASELSNFLL LHCDFQGIRE
IGLYCQPGID LPSWILGILQ VPAAYVPIEP DSPPSLSTHF MKKCNLKYIL VEKKQINKFK
SFHETLLNYD TFTVEHNDLV LFRLHWKNTE VNLMLNDGKE KYEKEKIKSI SSEHVNEEKA
EEHMDLRLKH CLAYVLHTSG TTGIPKIVRV PHKCIVPNIQ HFRVLFDITQ EDVLFLASPL
TFDPSVVEIF LALSSGASLL IVPTSVKLLP SKLASVLFSH HRVTVLQATP TLLRRFGSQL
IKSTVLSATT SLRVLALGGE AFPSLTVLRS WRGEGNKTQI FNVYGITEVS SWATIYRIPE
KTLNSTLKCE LPVQLGFPLL GTVVEVRDTN GFTIQEGSGQ VFLGGRNRVC FLDDEVTVPL
GTMRATGDFV TVKDGEIFFL GRKDSQIKRH GKRLNIELVQ QVAEELQQVE SCAVTWYNQE
KLILFMVSKD ASVKEYIFKE LQKYLPSHAV PDELVLIDSL PFTSHGKIDV SELNKIYLNY
INLKSENKLS GKEDLWEKLQ YLWKSTLNLP EDLLRVPDES LFLNSGGDSL KSIRLLSEIE
KLVGTSVPGL LEIILSSSIL EIYNHILQTV VPDEDVTFRK SCATKRKLSD INQEEASGTS
LHQKAIMTFT CHNEINAFVV LSRGSQILSL NSTRFLTKLG HCSSACPSDS VSQTNIQNLK
GLNSPVLIGK SKDPSCVAKV SEEGKPAIGT QKMELHVRWR SDTGKCVDAS PLVVIPTFDK
SSTTVYIGSH SHRMKAVDFY SGKVKWEQIL GDRIESSACV SKCGNFIVVG CYNGLVYVLK
SNSGEKYWMF TTEDAVKSSA TMDPTTGLIY IGSHDQHAYA LDIYRKKCVW KSKCGGTVFS
SPCLNLIPHH LYFATLGGLL LAVNPATGNV IWKHSCGKPL FSSPQCCSQY ICIGCVDGNL
LCFTHFGEQV WQFSTSGPIF SSPCTSPSEQ KIFFGSHDCF IYCCNMKGHL QWKFETTSRV
YATPFAFHNY NGSNEMLLAA ASTDGKVWIL ESQSGQLQSV YELPGEVFSS PVVLESMLII
GCRDNYVYCL DLLGGNQK
