ASB4_MOUSE
ID ASB4_MOUSE Reviewed; 426 AA.
AC Q9WV71; Q3UZE1; Q3V070;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Ankyrin repeat and SOCS box protein 4;
DE Short=ASB-4;
GN Name=Asb4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
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 MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, Embryonic lung, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP PROTEIN SEQUENCE OF 237-248, FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, INTERACTION WITH ELOB; CUL5; RBX1; CUL2 AND HIF1AN, HYDROXYLATION AT
RP ASN-246, AND MUTAGENESIS OF LEU-238; LEU-239; GLU-244; 244-GLU--ASN-246;
RP VAL-245; ASN-246 AND LEU-256.
RX PubMed=17636018; DOI=10.1128/mcb.00511-07;
RA Ferguson J.E. III, Wu Y., Smith K., Charles P., Powers K., Wang H.,
RA Patterson C.;
RT "ASB4 is a hydroxylation substrate of FIH and promotes vascular
RT differentiation via an oxygen-dependent mechanism.";
RL Mol. Cell. Biol. 27:6407-6419(2007).
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.
CC {ECO:0000269|PubMed:17636018}.
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 {ECO:0000269|PubMed:17636018}.
CC -!- TISSUE SPECIFICITY: Highest expression detected in testis, with some
CC expression detected in ovary and heart. Not detected in lung, kidney,
CC liver, spleen and bone marrow. {ECO:0000269|PubMed:11111040,
CC ECO:0000269|PubMed:17636018}.
CC -!- DEVELOPMENTAL STAGE: Differentially expressed in the vascular lineage
CC during embryonic stem (ES) cell differentiation, with expression
CC increasing when the cells differentiate. At 7.5 dpc, no remarkable
CC expression is detected. At 9.5 dpc, expressed in intersomitic vessels,
CC dorsal aorta, forelimb buds, allantois/umbilical vessels, vitelline
CC vessels, septum transversum, proepicardium, capillary plexi of the head
CC and branchial arches, endocardium, yolk sac vasculature and placenta.
CC At 10.5 dpc, expressed in forelimb and hind limb buds, intersomitic
CC vessels, peripheral liver cells and umbilical vessels, with expression
CC in the capillary plexi of the head and branchial arches no longer
CC detected. At 11.5 dpc, high expression levels are limited to forelimbs
CC and hind limbs and the most caudal intersomitic vessels.
CC {ECO:0000269|PubMed:17636018}.
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:0000269|PubMed:17636018}.
CC -!- SIMILARITY: Belongs to the ankyrin SOCS box (ASB) family.
CC {ECO:0000305}.
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DR EMBL; AF155355; AAD38811.1; -; mRNA.
DR EMBL; AK018373; BAB31183.1; -; mRNA.
DR EMBL; AK133400; BAE21634.1; -; mRNA.
DR EMBL; AK133894; BAE21916.1; -; mRNA.
DR EMBL; BC054745; AAH54745.1; -; mRNA.
DR EMBL; BC046819; AAH46819.1; -; mRNA.
DR EMBL; BC056440; AAH56440.1; -; mRNA.
DR CCDS; CCDS19901.1; -.
DR RefSeq; NP_075535.1; NM_023048.5.
DR RefSeq; XP_017177197.1; XM_017321708.1.
DR AlphaFoldDB; Q9WV71; -.
DR SMR; Q9WV71; -.
DR BioGRID; 211144; 3.
DR STRING; 10090.ENSMUSP00000040331; -.
DR iPTMnet; Q9WV71; -.
DR PhosphoSitePlus; Q9WV71; -.
DR MaxQB; Q9WV71; -.
DR PaxDb; Q9WV71; -.
DR PRIDE; Q9WV71; -.
DR ProteomicsDB; 277043; -.
DR Antibodypedia; 30158; 170 antibodies from 21 providers.
DR DNASU; 65255; -.
DR Ensembl; ENSMUST00000043294; ENSMUSP00000040331; ENSMUSG00000042607.
DR GeneID; 65255; -.
DR KEGG; mmu:65255; -.
DR UCSC; uc009awi.1; mouse.
DR CTD; 51666; -.
DR MGI; MGI:1929751; Asb4.
DR VEuPathDB; HostDB:ENSMUSG00000042607; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000158874; -.
DR HOGENOM; CLU_035721_1_0_1; -.
DR InParanoid; Q9WV71; -.
DR OMA; PIQYVLK; -.
DR OrthoDB; 529398at2759; -.
DR PhylomeDB; Q9WV71; -.
DR TreeFam; TF331836; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 65255; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Asb4; mouse.
DR PRO; PR:Q9WV71; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9WV71; protein.
DR Bgee; ENSMUSG00000042607; Expressed in humerus cartilage element and 208 other tissues.
DR ExpressionAtlas; Q9WV71; baseline and differential.
DR Genevisible; Q9WV71; MM.
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:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; IDA:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA: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 ANK repeat; Direct protein sequencing; Hydroxylation; Reference proteome;
KW Repeat; Ubl conjugation pathway.
FT CHAIN 1..426
FT /note="Ankyrin repeat and SOCS box protein 4"
FT /id="PRO_0000066929"
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:0000269|PubMed:17636018"
FT REGION 244..246
FT /note="Essential for interaction with HIF1AN"
FT /evidence="ECO:0000269|PubMed:17636018"
FT SITE 256
FT /note="Essential for interaction with HIF1AN"
FT MOD_RES 246
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:17636018"
FT MUTAGEN 238
FT /note="L->D: Abolishes interaction with HIF1AN."
FT /evidence="ECO:0000269|PubMed:17636018"
FT MUTAGEN 239
FT /note="L->D: Abolishes interaction with HIF1AN."
FT /evidence="ECO:0000269|PubMed:17636018"
FT MUTAGEN 244..246
FT /note="EVN->ATA: Abolishes interaction with HIF1AN. Fails
FT to induce expansion of the hematovascular lineage in
FT embryonic stem cells."
FT /evidence="ECO:0000269|PubMed:17636018"
FT MUTAGEN 244
FT /note="E->A: Impairs interaction with HIF1AN."
FT /evidence="ECO:0000269|PubMed:17636018"
FT MUTAGEN 245
FT /note="V->T: Impairs interaction with HIF1AN."
FT /evidence="ECO:0000269|PubMed:17636018"
FT MUTAGEN 246
FT /note="N->A: Abolishes interaction with HIF1AN."
FT /evidence="ECO:0000269|PubMed:17636018"
FT MUTAGEN 256
FT /note="L->D: Abolishes interaction with HIF1AN."
FT /evidence="ECO:0000269|PubMed:17636018"
SQ SEQUENCE 426 AA; 48098 MW; D8F52119CDF25648 CRC64;
MDGITAPISK AGAAKLVKKD FLEALKTNDF GKLKAILIER QIDVDTVFEV EDENMILASY
KQGYWLPSYK LKSSWATGLH LSVLLGHVEC LMVLLDHNAT INCRPNGKTP LHVACEIANL
ECVKILCDRG AKLNCYSLSG HTALHFCTTP SSILCAKQLV LRGANVNMKT NNQDEETPLH
TAAHFGLSEL VAFYVENGAI VDSMNAHMET PLAIATYWAL RFKEQEYSRE HHLICRTLLD
NNAEVNARDD DFKSPLHKAA WNCDHVLMHM MLEAGAEANL MDINGCAAIQ YVLKVTSVRP
AAQPEICYQL LLNHGAARIY PPQFHKVIQA CHSCPKAIEV VVNAYEHIRW NIKWRRAIPD
DDLEKHWDFY HSLFKVCCNT PRTLMHLSRC AIRKALHNRC HKAIPMLSLP LPLKKYLLLE
PEGIIY
