Q9NRF2 (SH2B1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SH2B adapter protein 1

Alternative name(s):
Pro-rich, PH and SH2 domain-containing signaling mediator
Short name=PSM
SH2 domain-containing protein 1B

Gene names

Name:	SH2B1
Synonyms:	KIAA1299, SH2B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptors of insulin (INS), insulin-like growth factor I (IGF1), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), platelet-derived growth factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity. Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis By similarity. Ref.1 Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15
Subunit structure	Self-associates. Homopentamer By similarity. Forms a heteromultimeric complex with SH2B2 By similarity. Interacts with SH2B2. Isoform 1 interacts via its SH2 domain with JAK2. Isoform 2 interacts via its SH2 domain and its N-terminus with JAK2; the SH2 domain is required for the major interaction with JAK2 phosphorylated on tyrosine residues; the N-terminus provides a low-affinity binding to JAK2 independent of JAK2 phosphorylation. Isoform 3 interacts via its SH2 domain with JAK2. Isoform 1 interacts via its SH2 domain with INSR; the interaction requires receptor activation. Isoform 3 interacts via its SH2 domain with INSR; the interaction requires receptor activation and requires INSR phosphorylation at 'Tyr-1185'. Isoform 1 interacts with IGF1R; the interaction requires receptor activation. Isoform 2 interacts with PRKAR1A/RET (PTC2) fusion protein; the interaction requires RET 'Tyr-905' and Tyr-981'. Isoform 2 interacts via its SH2 domain with FGFR3; the interaction requires FGFR3 'Tyr-724' and 'Tyr-760'. Isoform 2 interacts with RET; the interaction requires RET kinase activity and RET 'Tyr-981'. Isoform 2 interacts with RAC1. Isoform 2 interacts with PDGFRA and/or PDGFRB; the interaction requires receptor activation. Interacts with ISR1 and ISR2. Isoform 3 is probably part of a complex consisting of INSR, ISR1 and SH2B1. Probably part of a ternary complex consisting of SH2B1, JAK2 and ISR1 or ISR2. May interact with FCER1G By similarity. Interacts (via SH2 domain) with NTRK1 (phosphorylated) By similarity. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15
Subcellular location	Cytoplasm By similarity. Membrane Probable. Nucleus By similarity. Note: Shuttles between the nucleus and the cytoplasm By similarity.
Tissue specificity	Widely expressed with highest levels in skeletal muscle and ovary. Ref.1
Post-translational modification	Phosphorylated on tyrosine residues in response to receptor kinase stimulation. Phosphorylated by RET. Ref.1 Ref.8 Ref.11
Sequence similarities	Belongs to the SH2B adapter family. Contains 1 PH domain. Contains 1 SH2 domain.
Sequence caution	The sequence AAH10704.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAA92537.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAB55148.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome cellular component movement Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro lamellipodium assembly Inferred from electronic annotation. Source: Compara positive regulation of mitosis Inferred from electronic annotation. Source: Compara regulation of DNA biosynthetic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	phospholipid binding Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NRF2-1)

Also known as: Alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NRF2-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     633-756: EPTTSHDPPQ...RAINNQYSFV → GREQAGSHAG...ASDCVTDHLP

Isoform 3 (identifier: Q9NRF2-3)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     633-756: EPTTSHDPPQ...RAINNQYSFV → GEQSRSAGEE...PSCPSERVTV

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 756	756	SH2B adapter protein 1		PRO_0000323593
Regions
	Domain	267 – 376	110	PH
	Domain	527 – 625	99	SH2
	Region	1 – 555	555	Interaction with JAK2 (low-affinity binding; independent of JAK2 phosphorylation) By similarity
	Region	24 – 85	62	Required for self-association
	Region	85 – 196	112	Interaction with RAC1 By similarity
	Region	100 – 243	144	Required for NGF signaling By similarity
	Region	224 – 233	10	Required for nuclear localization By similarity
Amino acid modifications
	Modified residue	88	1	Phosphoserine
	Modified residue	96	1	Phosphoserine Ref.16 Ref.17
	Modified residue	125	1	Phosphoserine By similarity
	Modified residue	126	1	Phosphoserine By similarity
	Modified residue	439	1	Phosphotyrosine; by JAK1, JAK2 and PDGFR By similarity
	Modified residue	494	1	Phosphotyrosine; by JAK1, JAK2 By similarity
	Modified residue	624	1	Phosphotyrosine
Natural variations
	Alternative sequence	633 – 756	124	EPTTS…QYSFV → GREQAGSHAGVCEGDGCHPD ASCTLMPFGASDCVTDHLP in isoform 2.		VSP_032027
	Alternative sequence	633 – 756	124	EPTTS…QYSFV → GEQSRSAGEEVPVHPRSEAG SRLGAMRGCAREMDATPMPP APSCPSERVTV in isoform 3.		VSP_032028
	Natural variant	484	1	T → A. Ref.1 Ref.4 Corresponds to variant rs7498665 [ dbSNP | Ensembl ].		VAR_039550
	Natural variant	541	1	V → A. Ref.2 Corresponds to variant rs17850682 [ dbSNP | Ensembl ].		VAR_039551
Experimental info
	Mutagenesis	29	1	F → R: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Mutagenesis	34	1	A → D: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Mutagenesis	38	1	A → D: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Mutagenesis	41	1	F → A: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Mutagenesis	42	1	A → D: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Mutagenesis	48	1	Y → A: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Mutagenesis	68	1	F → A: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Mutagenesis	72	1	F → A: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Mutagenesis	555	1	R → A: Abolishes self-association and interaction with INSR and IGF1R. Ref.1
	Sequence conflict	197	1	N → D in BAF83021. Ref.3
	Sequence conflict	519	1	D → G in BAF83021. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified November 30, 2010. Version 3. Checksum: CF680B57114CB1D3	FASTA	756	79,366
	10 20 30 40 50 60 MNGAPSPEDG ASPSSPPLPP PPPPSWREFC ESHARAAALD FARRFRLYLA SHPQYAGPGA 70 80 90 100 110 120 EAAFSRRFAE LFLQHFEAEV ARASGSLSPP ILAPLSPGAE ISPHDLSLES CRVGGPLAVL 130 140 150 160 170 180 GPSRSSEDLA GPLPSSVSSS STTSSKPKLK KRFSLRSVGR SVRGSVRGIL QWRGTVDPPS 190 200 210 220 230 240 SAGPLETSSG PPVLGGNSNS NSSGGAGTVG RGLVSDGTSP GERWTHRFER LRLSRGGGAL 250 260 270 280 290 300 KDGAGMVQRE ELLSFMGAEE AAPDPAGVGR GGGVAGPPSG GGGQPQWQKC RLLLRSEGEG 310 320 330 340 350 360 GGGSRLEFFV PPKASRPRLS IPCSSITDVR TTTALEMPDR ENTFVVKVEG PSEYIMETVD 370 380 390 400 410 420 AQHVKAWVSD IQECLSPGPC PATSPRPMTL PLAPGTSFLT RENTDSLELS CLNHSESLPS 430 440 450 460 470 480 QDLLLGPSES NDRLSQGAYG GLSDRPSASI SPSSASIAAS HFDSMELLPP ELPPRIPIEE 490 500 510 520 530 540 GPPTGTVHPL SAPYPPLDTP ETATGSFLFQ GEPEGGEGDQ PLSGYPWFHG MLSRLKAAQL 550 560 570 580 590 600 VLTGGTGSHG VFLVRQSETR RGEYVLTFNF QGKAKHLRLS LNEEGQCRVQ HLWFQSIFDM 610 620 630 640 650 660 LEHFRVHPIP LESGGSSDVV LVSYVPSSQR QQEPTTSHDP PQPPEPPSWT DPPQPGAEEA 670 680 690 700 710 720 SRAPEVAAAA AAAAKERQEK EKAGGGGVPE ELVPVVELVP VVELEEAIAP GSEAQGAGSG 730 740 750 GDAGVPPMVQ LQQSPLGGDG EEGGHPRAIN NQYSFV
	Isoform 2 (Beta) [UniParc]. Checksum: 3EAD9A95F370FD94	FASTA	671	70,781
	10 20 30 40 50 60 MNGAPSPEDG ASPSSPPLPP PPPPSWREFC ESHARAAALD FARRFRLYLA SHPQYAGPGA 70 80 90 100 110 120 EAAFSRRFAE LFLQHFEAEV ARASGSLSPP ILAPLSPGAE ISPHDLSLES CRVGGPLAVL 130 140 150 160 170 180 GPSRSSEDLA GPLPSSVSSS STTSSKPKLK KRFSLRSVGR SVRGSVRGIL QWRGTVDPPS 190 200 210 220 230 240 SAGPLETSSG PPVLGGNSNS NSSGGAGTVG RGLVSDGTSP GERWTHRFER LRLSRGGGAL 250 260 270 280 290 300 KDGAGMVQRE ELLSFMGAEE AAPDPAGVGR GGGVAGPPSG GGGQPQWQKC RLLLRSEGEG 310 320 330 340 350 360 GGGSRLEFFV PPKASRPRLS IPCSSITDVR TTTALEMPDR ENTFVVKVEG PSEYIMETVD 370 380 390 400 410 420 AQHVKAWVSD IQECLSPGPC PATSPRPMTL PLAPGTSFLT RENTDSLELS CLNHSESLPS 430 440 450 460 470 480 QDLLLGPSES NDRLSQGAYG GLSDRPSASI SPSSASIAAS HFDSMELLPP ELPPRIPIEE 490 500 510 520 530 540 GPPTGTVHPL SAPYPPLDTP ETATGSFLFQ GEPEGGEGDQ PLSGYPWFHG MLSRLKAAQL 550 560 570 580 590 600 VLTGGTGSHG VFLVRQSETR RGEYVLTFNF QGKAKHLRLS LNEEGQCRVQ HLWFQSIFDM 610 620 630 640 650 660 LEHFRVHPIP LESGGSSDVV LVSYVPSSQR QQGREQAGSH AGVCEGDGCH PDASCTLMPF 670 GASDCVTDHL P
	Isoform 3 (Gamma) [UniParc]. Checksum: 353155178527B5A7	FASTA	683	72,188
	10 20 30 40 50 60 MNGAPSPEDG ASPSSPPLPP PPPPSWREFC ESHARAAALD FARRFRLYLA SHPQYAGPGA 70 80 90 100 110 120 EAAFSRRFAE LFLQHFEAEV ARASGSLSPP ILAPLSPGAE ISPHDLSLES CRVGGPLAVL 130 140 150 160 170 180 GPSRSSEDLA GPLPSSVSSS STTSSKPKLK KRFSLRSVGR SVRGSVRGIL QWRGTVDPPS 190 200 210 220 230 240 SAGPLETSSG PPVLGGNSNS NSSGGAGTVG RGLVSDGTSP GERWTHRFER LRLSRGGGAL 250 260 270 280 290 300 KDGAGMVQRE ELLSFMGAEE AAPDPAGVGR GGGVAGPPSG GGGQPQWQKC RLLLRSEGEG 310 320 330 340 350 360 GGGSRLEFFV PPKASRPRLS IPCSSITDVR TTTALEMPDR ENTFVVKVEG PSEYIMETVD 370 380 390 400 410 420 AQHVKAWVSD IQECLSPGPC PATSPRPMTL PLAPGTSFLT RENTDSLELS CLNHSESLPS 430 440 450 460 470 480 QDLLLGPSES NDRLSQGAYG GLSDRPSASI SPSSASIAAS HFDSMELLPP ELPPRIPIEE 490 500 510 520 530 540 GPPTGTVHPL SAPYPPLDTP ETATGSFLFQ GEPEGGEGDQ PLSGYPWFHG MLSRLKAAQL 550 560 570 580 590 600 VLTGGTGSHG VFLVRQSETR RGEYVLTFNF QGKAKHLRLS LNEEGQCRVQ HLWFQSIFDM 610 620 630 640 650 660 LEHFRVHPIP LESGGSSDVV LVSYVPSSQR QQGEQSRSAG EEVPVHPRSE AGSRLGAMRG 670 680 CAREMDATPM PPAPSCPSER VTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Kinase activation through dimerization by human SH2-B." Nishi M., Werner E.D., Oh B.C., Frantz J.D., Dhe-Paganon S., Hansen L., Lee J., Shoelson S.E. Mol. Cell. Biol. 25:2607-2621(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION IN JAK2 ACTIVATION, SELF-ASSOCIATION, INTERACTION WITH JAK2; SH2B2; INSR AND IGF1R, PHOSPHORYLATION, TISSUE SPECIFICITY, MUTAGENESIS OF PHE-29; ALA-34; ALA-38; PHE-41; ALA-42; TYR-48; PHE-68; PHE-72 AND ARG-555, VARIANT ALA-484.
[2]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ALA-541. Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Teratocarcinoma and Tongue.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-756 (ISOFORM 3), VARIANT ALA-484. Tissue: Mammary cancer.
[5]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 60-756 (ISOFORM 2). Tissue: Eye.
[7]	"PSM, an insulin-dependent, pro-rich, PH, SH2 domain containing partner of the insulin receptor." Riedel H., Wang J., Hansen H., Yousaf N. J. Biochem. 122:1105-1113(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INSR.
[8]	"SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase." Kotani K., Wilden P., Pillay T.S. Biochem. J. 335:103-109(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH INSR, PHOSPHORYLATION.
[9]	"Platelet-derived growth factor (PDGF) stimulates the association of SH2-Bbeta with PDGF receptor and phosphorylation of SH2-Bbeta." Rui L., Carter-Su C. J. Biol. Chem. 273:21239-21245(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PDGF SIGNALING, INTERACTION WITH PDGFRA/B.
[10]	"Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain." Nelms K., O'Neill T.J., Li S., Hubbard S.R., Gustafson T.A., Paul W.E. Mamm. Genome 10:1160-1167(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INSR AND ISR1.
[11]	"SH2-B family members differentially regulate JAK family tyrosine kinases." O'Brien K.B., O'Shea J.J., Carter-Su C. J. Biol. Chem. 277:8673-8681(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH JAK1; JAK2 AND JAK3, PHOSPHORYLATION.
[12]	"Interaction of fibroblast growth factor receptor 3 and the adapter protein SH2-B. A role in STAT5 activation." Kong M., Wang C.S., Donoghue D.J. J. Biol. Chem. 277:15962-15970(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN FGF SIGNALING, INTERACTION WITH FGFR3.
[13]	"SH2-B is a positive regulator of nerve growth factor-mediated activation of the Akt/Forkhead pathway in PC12 cells." Wang X., Chen L., Maures T.J., Herrington J., Carter-Su C. J. Biol. Chem. 279:133-141(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NGF SIGNALING.
[14]	"Interaction of SH2-Bbeta with RET is involved in signaling of GDNF-induced neurite outgrowth." Zhang Y., Zhu W., Wang Y.G., Liu X.J., Jiao L., Liu X., Zhang Z.H., Lu C.L., He C. J. Cell Sci. 119:1666-1676(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN GDNF SIGNALING, INTERACTION WITH RET.
[15]	"SH2B1beta adaptor is a key enhancer of RET tyrosine kinase signaling." Donatello S., Fiorino A., Degl'Innocenti D., Alberti L., Miranda C., Gorla L., Bongarzone I., Rizzetti M.G., Pierotti M.A., Borrello M.G. Oncogene 26:6546-6559(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RET SIGNALING, INTERACTION WITH PRKAR1A/RET.
[16]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF227967 mRNA. Translation: AAF73912.1. AF227968 mRNA. Translation: AAF73913.1. AF227969 mRNA. Translation: AAF73914.1. AB037720 mRNA. Translation: BAA92537.1. Different initiation. AK027488 mRNA. Translation: BAB55148.1. Different initiation. AK290332 mRNA. Translation: BAF83021.1. AL049924 mRNA. Translation: CAB43208.1. AL713760 mRNA. Translation: CAD28530.1. AC133550 Genomic DNA. No translation available. BC010704 mRNA. Translation: AAH10704.1. Different initiation.
IPI	IPI00016441. IPI00292988. IPI00385535.
PIR	T08662.
RefSeq	NP_001139267.1. NM_001145795.1. NP_001139268.1. NM_001145796.1. NP_001139269.1. NM_001145797.1. NP_001139284.1. NM_001145812.1. NP_056318.2. NM_015503.2.
UniGene	Hs.15744.
3D structure databases
HSSP	HSSP built from PDB template 1RQQ based on UniProtKB Q9Z200.
ProteinModelPortal	Q9NRF2.
SMR	Q9NRF2. Positions 24-82, 247-379, 520-654.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NRF2. 2 interactions.
MINT	MINT-1494470.
STRING	9606.ENSP00000337163.
PTM databases
PhosphoSite	Q9NRF2.
Polymorphism databases
DMDM	172046610.
Proteomic databases
PaxDb	Q9NRF2.
PRIDE	Q9NRF2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000322610; ENSP00000321221; ENSG00000178188. ENST00000337120; ENSP00000337163; ENSG00000178188. ENST00000359285; ENSP00000352232; ENSG00000178188. ENST00000395532; ENSP00000378903; ENSG00000178188.
GeneID	25970.
KEGG	hsa:25970.
UCSC	uc002dri.3. human. uc002drj.3. human. uc002drk.3. human.
Organism-specific databases
CTD	25970.
GeneCards	GC16P028875.
H-InvDB	HIX0017272.
HGNC	HGNC:30417. SH2B1.
MIM	608937. gene.
neXtProt	NX_Q9NRF2.
Orphanet	261197. 16p11.2 microdeletion syndrome. 261222. Distal 16p11.2 microdeletion syndrome.
PharmGKB	PA145148084.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG77816.
HOVERGEN	HBG006707.
InParanoid	Q9NRF2.
KO	K12459.
OMA	DGAGMVQ.
OrthoDB	EOG4ZPDV6.
PhylomeDB	Q9NRF2.
Enzyme and pathway databases
Pathway_Interaction_DB	trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
Reactome	REACT_111102. Signal Transduction. REACT_604. Hemostasis. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9NRF2.
Bgee	Q9NRF2.
CleanEx	HS_SH2B1.
Genevestigator	Q9NRF2.
Family and domain databases
Gene3D	2.30.29.30. 1 hit. 3.30.505.10. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR015012. Phe_ZIP. IPR001849. Pleckstrin_homology. IPR000980. SH2. [Graphical view]
Pfam	PF00169. PH. 1 hit. PF08916. Phe_ZIP. 1 hit. PF00017. SH2. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN.
SMART	SM00233. PH. 1 hit. SM00252. SH2. 1 hit. [Graphical view]
SUPFAM	SSF109805. Phe_ZIP. 1 hit.
PROSITE	PS50003. PH_DOMAIN. False negative. PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	25970.
NextBio	47602.
SOURCE	Search...

Entry information

Entry name

SH2B1_HUMAN

Accession

Primary (citable) accession number: Q9NRF2
Secondary accession number(s): A8K2R7 , Q96FK3, Q96SX3, Q9NRF1, Q9NRF3, Q9P2P7, Q9Y3Y3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.