P46109 (CRKL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Crk-like protein

Gene names

Name:

CRKL

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	303 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May mediate the transduction of intracellular signals.
Subunit structure	Interacts with INPP5D/SHIP1. Interacts with DOCK2 and EPOR. Interacts with phosphorylated CBLB and IRS4. Ref.6 Ref.7 Ref.8 Ref.9
Sequence similarities	Belongs to the CRK family. Contains 1 SH2 domain. Contains 2 SH3 domains.

Ontologies

Keywords
Domain	Repeat SH2 domain SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JNK cascade Traceable author statement PubMed 8798523. Source: ProtInc Ras protein signal transduction Traceable author statement PubMed 8798523. Source: ProtInc anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara blood vessel development Inferred from electronic annotation. Source: Compara heart development Inferred from electronic annotation. Source: Compara organ morphogenesis Inferred from electronic annotation. Source: Compara parathyroid gland development Inferred from electronic annotation. Source: Compara thymus development Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	SH3/SH2 adaptor activity Traceable author statement PubMed 8798523. Source: ProtInc signal transducer activity Traceable author statement Ref.1PubMed 8798523. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Kidins220	Q9EQG6	2	EBI-910,EBI-976654	From a different organism.
MAP4K1	Q92918	5	EBI-910,EBI-881

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 303

303

Crk-like protein

PRO_0000079347

Regions

Domain

14 – 102

89

SH2

Domain

123 – 183

61

SH3 1

Domain

235 – 296

62

SH3 2

Amino acid modifications

Modified residue

107

1

Phosphoserine By similarity

Modified residue

127

1

Phosphotyrosine Ref.12

Modified residue

132

1

Phosphotyrosine By similarity

Modified residue

207

1

Phosphotyrosine Ref.10

Modified residue

251

1

Phosphotyrosine By similarity

Secondary structure

1

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303

Helix Strand Turn

Details...

Helix

11 – 14

4

Beta strand

15 – 18

4

Helix

21 – 28

8

Beta strand

29 – 31

3

Beta strand

36 – 40

5

Beta strand

42 – 46

5

Beta strand

48 – 54

7

Beta strand

57 – 66

10

Turn

67 – 69

3

Beta strand

70 – 73

4

Beta strand

78 – 80

3

Helix

81 – 88

8

Beta strand

93 – 96

4

Beta strand

105 – 107

3

Beta strand

119 – 132

14

Beta strand

138 – 141

4

Beta strand

146 – 154

9

Beta strand

157 – 164

8

Beta strand

170 – 174

5

Helix

175 – 177

3

Beta strand

178 – 182

5

Helix

190 – 192

3

Helix

203 – 205

3

Beta strand

238 – 242

5

Beta strand

248 – 251

4

Beta strand

253 – 255

3

Beta strand

263 – 269

7

Beta strand

271 – 279

9

Beta strand

282 – 287

6

Helix

288 – 290

3

Beta strand

291 – 293

3

Beta strand

296 – 299

4

Sequences

	Sequence		Length	Mass (Da)
	P46109 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 294CF1EE2CD44B81	FASTA	303	33,777
	10 20 30 40 50 60 MSSARFDSSD RSAWYMGPVS RQEAQTRLQG QRHGMFLVRD SSTCPGDYVL SVSENSRVSH 70 80 90 100 110 120 YIINSLPNRR FKIGDQEFDH LPALLEFYKI HYLDTTTLIE PAPRYPSPPM GSVSAPNLPT 130 140 150 160 170 180 AEDNLEYVRT LYDFPGNDAE DLPFKKGEIL VIIEKPEEQW WSARNKDGRV GMIPVPYVEK 190 200 210 220 230 240 LVRSSPHGKH GNRNSNSYGI PEPAHAYAQP QTTTPLPAVS GSPGAAITPL PSTQNGPVFA 250 260 270 280 290 300 KAIQKRVPCA YDKTALALEV GDIVKVTRMN INGQWEGEVN GRKGLFPFTH VKIFDPQNPD ENE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and chromosomal localization of CRKL, a human crk-like gene." ten Hoeve J., Morris C., Heisterkamp N., Groffen J. Oncogene 8:2469-2474(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[2]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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]. Tissue: Trachea.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Skin.
[6]	"Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction." Koval A.P., Karas M., Zick Y., LeRoith D. J. Biol. Chem. 273:14780-14787(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IRS4.
[7]	"Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation." Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C. Oncogene 18:1147-1156(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CBLB.
[8]	"DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines." Nishihara H., Maeda M., Oda A., Tsuda M., Sawa H., Nagashima K., Tanaka S. Blood 100:3968-3974(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DOCK2.
[9]	"CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling." Arai A., Kanda E., Nosaka Y., Miyasaka N., Miura O. J. Biol. Chem. 276:33282-33290(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EPOR.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-207, MASS SPECTROMETRY.
[11]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-127, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Solution structures of the SH3 domain of human CRK-like protein." RIKEN structural genomics initiative (RSGI) Submitted (DEC-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 220-303.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X59656 mRNA. Translation: CAA42199.1.
CR456423 mRNA. Translation: CAG30309.1.
AK292909 mRNA. Translation: BAF85598.1.
CH471176 Genomic DNA. Translation: EAX02932.1.
CH471176 Genomic DNA. Translation: EAX02933.1.
CH471176 Genomic DNA. Translation: EAX02934.1.
BC043500 mRNA. Translation: AAH43500.1.

IPI

IPI00004839.

PIR

S41754.

RefSeq

NP_005198.1. NM_005207.3.

UniGene

Hs.5613.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BZX	X-ray	2.80	A	237-303	[»]
2BZY	X-ray	2.50	A/B	237-303	[»]
2DBK	NMR	-	A	229-303	[»]
2EO3	NMR	-	A	1-104	[»]
2LQN	NMR	-	A	1-303	[»]
2LQW	NMR	-	A	1-303	[»]

ProteinModelPortal

P46109.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29165N.

IntAct

P46109. 28 interactions.

MINT

MINT-137265.

STRING

9606.ENSP00000346300.

PTM databases

PhosphoSite

P46109.

Polymorphism databases

DMDM

1169094.

2D gel databases

OGP

P46109.

Proteomic databases

PaxDb

P46109.

PeptideAtlas

P46109.

PRIDE

P46109.

Protocols and materials databases

DNASU

1399.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000354336; ENSP00000346300; ENSG00000099942.
ENST00000411769; ENSP00000396646; ENSG00000099942.

GeneID

1399.

KEGG

hsa:1399.

UCSC

uc002ztf.2. human.

Organism-specific databases

CTD

1399.

GeneCards

GC22P021272.

HGNC

HGNC:2363. CRKL.

HPA

HPA001100.

MIM

602007. gene.

neXtProt

NX_P46109.

PharmGKB

PA26881.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG292767.

HOGENOM

HOG000236288.

HOVERGEN

HBG105616.

InParanoid

P46109.

KO

K04438.

OMA

SRNSNSY.

OrthoDB

EOG4NS3C3.

PhylomeDB

P46109.

Enzyme and pathway databases

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.
epopathway. EPO signaling pathway.
ifngpathway. IFN-gamma pathway.
igf1_pathway. IGF1 pathway.
tcrjnkpathway. JNK signaling in the CD4+ TCR pathway.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
pdgfrapathway. PDGFR-alpha signaling pathway.
reelinpathway. Reelin signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Reactome

REACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

Bgee

P46109.

CleanEx

HS_CRKL.

Genevestigator

P46109.

GermOnline

ENSG00000099942. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]

SUPFAM

SSF50044. SH3. 2 hits.

PROSITE

PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CRKL. human.

EvolutionaryTrace

P46109.

GenomeRNAi

1399.

NextBio

5727.

SOURCE

Search...

Entry information

Entry name

CRKL_HUMAN

Accession

Primary (citable) accession number: P46109
Secondary accession number(s): A8KA44, D3DX35

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 132 of the entry and version 1 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.