PRAM_HUMAN
ID PRAM_HUMAN Reviewed; 670 AA.
AC Q96QH2; Q8N6W7;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=PML-RARA-regulated adapter molecule 1;
DE Short=PRAM;
DE Short=PRAM-1;
GN Name=PRAM1;
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], INDUCTION, TISSUE SPECIFICITY, PHOSPHORYLATION,
RP INTERACTION WITH SKAP2; LCP2 AND LYN, AND VARIANT GLN-57.
RX PubMed=11301322; DOI=10.1074/jbc.m011683200;
RA Moog-Lutz C., Peterson E.J., Lutz P.G., Eliason S., Cave-Riant F.,
RA Singer A., Di Gioia Y., Dmovski S., Kamens J., Cayre Y.E., Koretzky G.;
RT "PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and
RT promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic
RT leukemia cells.";
RL J. Biol. Chem. 276:22375-22381(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
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 INTERACTION WITH DBNL, AND INDUCTION.
RX PubMed=15637062; DOI=10.1074/jbc.m413564200;
RA Denis F.M., Benecke A., Di Gioia Y., Touw I.P., Cayre Y.E., Lutz P.G.;
RT "PRAM-1 potentiates arsenic trioxide-induced JNK activation.";
RL J. Biol. Chem. 280:9043-9048(2005).
RN [5]
RP PHOSPHOINOSITIDE-BINDING.
RX PubMed=16831444; DOI=10.1016/j.jmb.2006.06.004;
RA Heuer K., Sylvester M., Kliche S., Pusch R., Thiemke K., Schraven B.,
RA Freund C.;
RT "Lipid-binding hSH3 domains in immune cell adapter proteins.";
RL J. Mol. Biol. 361:94-104(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
RP INTERACTION WITH NEK6.
RX PubMed=20873783; DOI=10.1021/pr100562w;
RA Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J.,
RA Paes Leme A.F., Kobarg J.;
RT "Characterization of hNek6 interactome reveals an important role for its
RT short N-terminal domain and colocalization with proteins at the
RT centrosome.";
RL J. Proteome Res. 9:6298-6316(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: May be involved in myeloid differentiation. May be involved
CC in integrin signaling in neutrophils. Binds to PtdIns(4)P.
CC -!- SUBUNIT: Interacts with SKAP2, LCP2 and DBNL. May interact with LYN.
CC Interacts with NEK6. {ECO:0000269|PubMed:11301322,
CC ECO:0000269|PubMed:15637062, ECO:0000269|PubMed:20873783}.
CC -!- INTERACTION:
CC Q96QH2; Q9NYB9: ABI2; NbExp=3; IntAct=EBI-2860740, EBI-743598;
CC Q96QH2; P56945: BCAR1; NbExp=3; IntAct=EBI-2860740, EBI-702093;
CC Q96QH2; P27797: CALR; NbExp=3; IntAct=EBI-2860740, EBI-1049597;
CC Q96QH2; Q2TAC2: CCDC57; NbExp=3; IntAct=EBI-2860740, EBI-2808286;
CC Q96QH2; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-2860740, EBI-10961624;
CC Q96QH2; P12830: CDH1; NbExp=3; IntAct=EBI-2860740, EBI-727477;
CC Q96QH2; Q15078: CDK5R1; NbExp=3; IntAct=EBI-2860740, EBI-746189;
CC Q96QH2; P02489: CRYAA; NbExp=3; IntAct=EBI-2860740, EBI-6875961;
CC Q96QH2; P36957: DLST; NbExp=3; IntAct=EBI-2860740, EBI-351007;
CC Q96QH2; Q14204: DYNC1H1; NbExp=3; IntAct=EBI-2860740, EBI-356015;
CC Q96QH2; P51114-2: FXR1; NbExp=3; IntAct=EBI-2860740, EBI-11022345;
CC Q96QH2; P51116: FXR2; NbExp=7; IntAct=EBI-2860740, EBI-740459;
CC Q96QH2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-2860740, EBI-618309;
CC Q96QH2; Q92876: KLK6; NbExp=3; IntAct=EBI-2860740, EBI-2432309;
CC Q96QH2; Q6A162: KRT40; NbExp=3; IntAct=EBI-2860740, EBI-10171697;
CC Q96QH2; Q14511-2: NEDD9; NbExp=4; IntAct=EBI-2860740, EBI-11746523;
CC Q96QH2; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-2860740, EBI-1055945;
CC Q96QH2; Q9H0A6: RNF32; NbExp=2; IntAct=EBI-2860740, EBI-724829;
CC Q96QH2; Q86WV1: SKAP1; NbExp=4; IntAct=EBI-2860740, EBI-2477305;
CC Q96QH2; Q86WV1-2: SKAP1; NbExp=3; IntAct=EBI-2860740, EBI-11995314;
CC Q96QH2; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-2860740, EBI-11952721;
CC Q96QH2; P14373: TRIM27; NbExp=3; IntAct=EBI-2860740, EBI-719493;
CC -!- TISSUE SPECIFICITY: Expressed in peripheral blood leukocytes and bone
CC marrow. Expressed in monocytes, and to a lesser extent in granulocytes
CC and lymphocytes. Not expressed in non hematopoietic tissues except in
CC lung. {ECO:0000269|PubMed:11301322}.
CC -!- INDUCTION: Down-regulated by the PML-RARA oncogene, a fusion protein
CC expressed in a vast majority of acute promyelocytic leukemia. Up-
CC regulated by retinoic acid or arsenic trioxide in cells expressing PML-
CC RARA. {ECO:0000269|PubMed:11301322, ECO:0000269|PubMed:15637062}.
CC -!- DOMAIN: The SH3 domain binds to PtdIns(4)P.
CC -!- PTM: May be phosphorylated on tyrosines. {ECO:0000269|PubMed:11301322}.
CC -!- POLYMORPHISM: Some transcripts displayed additional 12 amino acid
CC repeats of K-P-P-[PQ]-P-[EQ]-[VAF]-T-D-L-P-K (PubMed:11301322). We
CC cannot rule out that they may represent genetic variants.
CC {ECO:0000269|PubMed:11301322}.
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DR EMBL; AJ272324; CAC17767.1; -; mRNA.
DR EMBL; AC092298; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC136469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028012; AAH28012.1; -; mRNA.
DR CCDS; CCDS45954.2; -.
DR RefSeq; NP_115528.4; NM_032152.4.
DR AlphaFoldDB; Q96QH2; -.
DR SMR; Q96QH2; -.
DR BioGRID; 123894; 39.
DR IntAct; Q96QH2; 28.
DR STRING; 9606.ENSP00000408342; -.
DR iPTMnet; Q96QH2; -.
DR PhosphoSitePlus; Q96QH2; -.
DR BioMuta; PRAM1; -.
DR DMDM; 327478532; -.
DR EPD; Q96QH2; -.
DR jPOST; Q96QH2; -.
DR MassIVE; Q96QH2; -.
DR PeptideAtlas; Q96QH2; -.
DR PRIDE; Q96QH2; -.
DR Antibodypedia; 24911; 124 antibodies from 25 providers.
DR DNASU; 84106; -.
DR Ensembl; ENST00000423345.5; ENSP00000408342.2; ENSG00000133246.12.
DR GeneID; 84106; -.
DR KEGG; hsa:84106; -.
DR MANE-Select; ENST00000423345.5; ENSP00000408342.2; NM_032152.5; NP_115528.4.
DR UCSC; uc002mkd.4; human.
DR CTD; 84106; -.
DR DisGeNET; 84106; -.
DR GeneCards; PRAM1; -.
DR HGNC; HGNC:30091; PRAM1.
DR HPA; ENSG00000133246; Tissue enriched (bone).
DR MIM; 606466; gene.
DR neXtProt; NX_Q96QH2; -.
DR OpenTargets; ENSG00000133246; -.
DR PharmGKB; PA142671137; -.
DR VEuPathDB; HostDB:ENSG00000133246; -.
DR eggNOG; ENOG502SS22; Eukaryota.
DR GeneTree; ENSGT00530000063460; -.
DR HOGENOM; CLU_460488_0_0_1; -.
DR InParanoid; Q96QH2; -.
DR OMA; IVIQTRM; -.
DR OrthoDB; 203958at2759; -.
DR PhylomeDB; Q96QH2; -.
DR PathwayCommons; Q96QH2; -.
DR SignaLink; Q96QH2; -.
DR BioGRID-ORCS; 84106; 6 hits in 1065 CRISPR screens.
DR ChiTaRS; PRAM1; human.
DR GeneWiki; PRAM1; -.
DR GenomeRNAi; 84106; -.
DR Pharos; Q96QH2; Tbio.
DR PRO; PR:Q96QH2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96QH2; protein.
DR Bgee; ENSG00000133246; Expressed in monocyte and 101 other tissues.
DR ExpressionAtlas; Q96QH2; baseline and differential.
DR Genevisible; Q96QH2; HS.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR GO; GO:0043313; P:regulation of neutrophil degranulation; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR InterPro; IPR043443; FYB1/2-like.
DR InterPro; IPR029294; hSH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR16830; PTHR16830; 1.
DR Pfam; PF14603; hSH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Lipid-binding; Phosphoprotein; Reference proteome; Repeat; SH3 domain.
FT CHAIN 1..670
FT /note="PML-RARA-regulated adapter molecule 1"
FT /id="PRO_0000270171"
FT REPEAT 70..81
FT /note="1"
FT REPEAT 82..93
FT /note="2"
FT REPEAT 94..105
FT /note="3"
FT REPEAT 106..117
FT /note="4"
FT DOMAIN 571..649
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 1..561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 70..165
FT /note="4 X 12 AA repeats of K-P-P-[PQ]-P-[EQ]-[VAF]-T-D-L-
FT P-K"
FT COMPBIAS 33..58
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..115
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..465
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6BCL1"
FT VARIANT 57
FT /note="K -> Q (in dbSNP:rs4804305)"
FT /evidence="ECO:0000269|PubMed:11301322"
FT /id="VAR_029808"
FT VARIANT 73
FT /note="P -> Q (in dbSNP:rs4239541)"
FT /id="VAR_029809"
FT VARIANT 76
FT /note="V -> F (in dbSNP:rs4239540)"
FT /id="VAR_029810"
FT VARIANT 135
FT /note="G -> E (in dbSNP:rs58466313)"
FT /id="VAR_061692"
FT CONFLICT 11
FT /note="S -> N (in Ref. 3; AAH28012)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="P -> PQPQFTDLPKKPPPPEVTDLPKKPPPPEVTDLPKKPPPPEVTDLPKK
FT PP (in Ref. 1; CAC17767)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="V -> A (in Ref. 1; CAC17767)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 670 AA; 73969 MW; 6C05FFBC05CE739F CRC64;
MAHHLPAAME SHQDFRSIKA KFQASQPEPS DLPKKPPKPE FGKLKKFSQP ELSEHPKKAP
LPEFGAVSLK PPPPEVTDLP KKPPPPEVTD LPKKPPPPEV TDLPKKPPPP EVTDLPKKPS
KLELSDLSKK FPQLGATPFP RKPLQPEVGE APLKASLPEP GAPARKPLQP DELSHPARPP
SEPKSGAFPR KLWQPEAGEA TPRSPQPELS TFPKKPAQPE FNVYPKKPPQ PQVGGLPKKS
VPQPEFSEAA QTPLWKPQSS EPKRDSSAFP KKASQPPLSD FPKKPPQPEL GDLTRTSSEP
EVSVLPKRPR PAEFKALSKK PPQPELGGLP RTSSEPEFNS LPRKLLQPER RGPPRKFSQP
EPSAVLKRHP QPEFFGDLPR KPPLPSSASE SSLPAAVAGF SSRHPLSPGF GAAGTPRWRS
GGLVHSGGAR PGLRPSHPPR RRPLPPASSL GHPPAKPPLP PGPVDMQSFR RPSAASIDLR
RTRSAAGLHF QDRQPEDIPQ VPDEIYELYD DVEPRDDSSP SPKGRDEAPS VQQAARRPPQ
DPALRKEKDP QPQQLPPMDP KLLKQLRKAE KAEREFRKKF KFEGEIVVHT KMMIDPNAKT
RRGGGKHLGI RRGEILEVIE FTSNEEMLCR DPKGKYGYVP RTALLPLETE VYDDVDFCDP
LENQPLPLGR
