ASB4_HUMAN
ID ASB4_HUMAN Reviewed; 426 AA.
AC Q9Y574; A4D1H6; O14586; Q14D68; Q8TBT2;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Ankyrin repeat and SOCS box protein 4;
DE Short=ASB-4;
GN Name=ASB4;
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).
RX PubMed=11111040; DOI=10.1016/s0378-1119(00)00402-9;
RA Kile B.T., Viney E.M., Willson T.A., Brodnicki T.C., Cancilla M.R.,
RA Herlihy A.S., Croker B.A., Baca M., Nicola N.A., Hilton D.J.,
RA Alexander W.S.;
RT "Cloning and characterization of the genes encoding the ankyrin repeat and
RT SOCS box-containing proteins Asb-1, Asb-2, Asb-3 and Asb-4.";
RL Gene 258:31-41(2000).
RN [2]
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 [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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 32-426 (ISOFORM 2).
RC TISSUE=Adrenal cortex;
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: Probable substrate-recognition component of a SCF-like ECS
CC (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex
CC which mediates the ubiquitination and subsequent proteasomal
CC degradation of target proteins. Promotes differentiation and maturation
CC of the vascular lineage by an oxygen-dependent mechanism (By
CC similarity). {ECO:0000250}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with HIF1AN. Component of an ECS (Elongin BC-CUL2/5-
CC SOCS-box protein) E3 ubiquitin-protein ligase complex formed of CUL2 or
CC CUL5, Elongin BC (ELOB and ELOC), RBX1 and ASB4.
CC -!- INTERACTION:
CC Q9Y574-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-25911000, EBI-748974;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y574-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y574-2; Sequence=VSP_042668;
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin-protein ligase
CC complexes. {ECO:0000250}.
CC -!- PTM: Hydroxylation at Asn-246 by HIF1AN may provide an oxygen-dependent
CC regulation mechanism for the function of ASB4 in promoting vascular
CC differentiation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ankyrin SOCS box (ASB) family.
CC {ECO:0000305}.
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DR EMBL; AF156779; AAD41896.1; -; mRNA.
DR EMBL; AC002451; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC003079; AAB83943.2; -; Genomic_DNA.
DR EMBL; CH471091; EAW76761.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76762.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24129.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24130.1; -; Genomic_DNA.
DR EMBL; BC113479; AAI13480.1; -; mRNA.
DR EMBL; BC113481; AAI13482.1; -; mRNA.
DR EMBL; BC025024; AAH25024.1; -; mRNA.
DR CCDS; CCDS5641.1; -. [Q9Y574-1]
DR CCDS; CCDS5642.1; -. [Q9Y574-2]
DR RefSeq; NP_057200.1; NM_016116.2. [Q9Y574-1]
DR RefSeq; NP_665879.1; NM_145872.2. [Q9Y574-2]
DR AlphaFoldDB; Q9Y574; -.
DR SMR; Q9Y574; -.
DR BioGRID; 119669; 34.
DR IntAct; Q9Y574; 4.
DR STRING; 9606.ENSP00000321388; -.
DR iPTMnet; Q9Y574; -.
DR PhosphoSitePlus; Q9Y574; -.
DR BioMuta; ASB4; -.
DR DMDM; 20532003; -.
DR MassIVE; Q9Y574; -.
DR PaxDb; Q9Y574; -.
DR PeptideAtlas; Q9Y574; -.
DR PRIDE; Q9Y574; -.
DR ProteomicsDB; 86304; -. [Q9Y574-1]
DR ProteomicsDB; 86305; -. [Q9Y574-2]
DR Antibodypedia; 30158; 170 antibodies from 21 providers.
DR DNASU; 51666; -.
DR Ensembl; ENST00000325885.6; ENSP00000321388.5; ENSG00000005981.13. [Q9Y574-1]
DR Ensembl; ENST00000428113.5; ENSP00000397070.1; ENSG00000005981.13. [Q9Y574-2]
DR GeneID; 51666; -.
DR KEGG; hsa:51666; -.
DR MANE-Select; ENST00000325885.6; ENSP00000321388.5; NM_016116.3; NP_057200.1.
DR UCSC; uc003unx.3; human. [Q9Y574-1]
DR CTD; 51666; -.
DR DisGeNET; 51666; -.
DR GeneCards; ASB4; -.
DR HGNC; HGNC:16009; ASB4.
DR HPA; ENSG00000005981; Tissue enhanced (adrenal gland, skeletal muscle).
DR MIM; 605761; gene.
DR neXtProt; NX_Q9Y574; -.
DR OpenTargets; ENSG00000005981; -.
DR PharmGKB; PA25032; -.
DR VEuPathDB; HostDB:ENSG00000005981; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000158874; -.
DR HOGENOM; CLU_035721_1_0_1; -.
DR InParanoid; Q9Y574; -.
DR OMA; PIQYVLK; -.
DR OrthoDB; 529398at2759; -.
DR PhylomeDB; Q9Y574; -.
DR TreeFam; TF331836; -.
DR PathwayCommons; Q9Y574; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9Y574; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 51666; 143 hits in 1109 CRISPR screens.
DR GenomeRNAi; 51666; -.
DR Pharos; Q9Y574; Tbio.
DR PRO; PR:Q9Y574; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9Y574; protein.
DR Bgee; ENSG00000005981; Expressed in adrenal tissue and 128 other tissues.
DR Genevisible; Q9Y574; HS.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0031466; C:Cul5-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF07525; SOCS_box; 1.
DR SMART; SM00248; ANK; 6.
DR SMART; SM00969; SOCS_box; 1.
DR SUPFAM; SSF158235; SSF158235; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 5.
DR PROSITE; PS50225; SOCS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Hydroxylation; Reference proteome;
KW Repeat; Ubl conjugation pathway.
FT CHAIN 1..426
FT /note="Ankyrin repeat and SOCS box protein 4"
FT /id="PRO_0000066928"
FT REPEAT 74..103
FT /note="ANK 1"
FT REPEAT 106..135
FT /note="ANK 2"
FT REPEAT 139..168
FT /note="ANK 3"
FT REPEAT 174..203
FT /note="ANK 4"
FT REPEAT 207..247
FT /note="ANK 5"
FT REPEAT 251..280
FT /note="ANK 6"
FT DOMAIN 371..423
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 238..239
FT /note="Essential for interaction with HIF1AN"
FT /evidence="ECO:0000250"
FT REGION 244..246
FT /note="Essential for interaction with HIF1AN"
FT /evidence="ECO:0000250"
FT SITE 256
FT /note="Essential for interaction with HIF1AN"
FT /evidence="ECO:0000250"
FT MOD_RES 246
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT /evidence="ECO:0000250"
FT VAR_SEQ 328..426
FT /note="IQACHSCPKAIEVVVNAYEHIRWNTKWRRAIPDDDLEKYWDFYHSLFTVCCN
FT SPRTLMHLSRCAIRRTLHNRCHRAIPLLSLPLSLKKYLLLEPEGIIY -> RLCPVVSR
FT LRKIQMAALSEISK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042668"
FT VARIANT 17
FT /note="V -> L (in dbSNP:rs35047380)"
FT /id="VAR_033512"
SQ SEQUENCE 426 AA; 48195 MW; 4027F109A6C264A5 CRC64;
MDGTTAPVTK SGAAKLVKRN FLEALKSNDF GKLKAILIQR QIDVDTVFEV EDENMVLASY
KQGYWLPSYK LKSSWATGLH LSVLFGHVEC LLVLLDHNAT INCRPNGKTP LHVACEMANV
DCVKILCDRG AKLNCYSLSG HTALHFCTTP SSILCAKQLV WRGANVNMKT NNQDEETPLH
TAAHFGLSEL VAFYVEHGAI VDSVNAHMET PLAIAAYWAL RFKEQEYSTE HHLVCRMLLD
YKAEVNARDD DFKSPLHKAA WNCDHVLMHM MLEAGAEANL MDINGCAAIQ YVLKVTSVRP
AAQPEICYQL LLNHGAARIY PPQFHKVIQA CHSCPKAIEV VVNAYEHIRW NTKWRRAIPD
DDLEKYWDFY HSLFTVCCNS PRTLMHLSRC AIRRTLHNRC HRAIPLLSLP LSLKKYLLLE
PEGIIY
